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{'Official Title': 'A Phase 3 Randomized, Double-Blind Study of Nivolumab Monotherapy or Nivolumab Combined With Ipilimumab vs Placebo in Participants With Localized Renal Cell Carcinoma Who Underwent Radical or Partial Nephrectomy and Who Are at High Risk of Relapse', 'Brief Summary': 'The purpose of this study is to determine whether nivolmab alone or the combination of nivolumab and ipilimumab versus placebo, is safe and effective for delaying or preventing recurrence of cancer in participants who have experienced partial or entire removal of a kidney.', 'Condition': 'Renal Cell Carcinoma', 'Detailed Description': 'The study has two primary endpoints. The first primary completion date is anticipated to be reached July 2022 (DFS in Part A). The second primary completion date is anticipated to be reached July 2024 (DFS in Part B).', 'Inclusion Criteria': 'Inclusion Criteria: Kidney tumor has been completely resected with negative surgical margins obtained. The randomization must occur greater than 4 weeks and less than (or equal to) 12 weeks from the date of nephrectomy Pathologic tumor, node, and metastasis (TNM) staging meeting one of the following: pT2a, G3 or G4, N0 M0; pT2b, G any, N0 M0; pT3, (a, b, c), G any, N0 M0; pT4, G any, N0 M0; pT any, G any, N1 M0 Post-nephrectomy tumor shows renal cell cancer (RCC) with a predominantly clear cell histology, including participants with sarcomatoid features Participants must have no clinical or radiological evidence of macroscopic residual disease or distant metastases after nephrectomy Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1 Women must agree to follow methods of contraception, if applicable', 'Exclusion Criteria': 'Exclusion Criteria: Participants with an active known or suspected autoimmune disease Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways Any severe or serious, acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation History of allergy or hypersensitivity to study drug components Participants with a condition requiring systemic treatment with corticosteroids Participants who have received a live/attenuated vaccine within 30 days of first treatment'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Exclude: PD-1, PD-L1, PD-L2, CTLA-4'}
|
{'Official Title': 'A Phase 3 Randomized, Double-Blind Study of Nivolumab Monotherapy or Nivolumab Combined With Ipilimumab vs Placebo in Participants With Localized Renal Cell Carcinoma Who Underwent Radical or Partial Nephrectomy and Who Are at High Risk of Relapse', 'Brief Summary': 'The purpose of this study is to determine whether nivolmab alone or the combination of nivolumab and ipilimumab versus placebo, is safe and effective for delaying or preventing recurrence of cancer in participants who have experienced partial or entire removal of a kidney.', 'Condition': 'Renal Cell Carcinoma', 'Detailed Description': 'The study has two primary endpoints. The first primary completion date is anticipated to be reached July 2022 (DFS in Part A). The second primary completion date is anticipated to be reached July 2024 (DFS in Part B).', 'Inclusion Criteria': 'Inclusion Criteria: Kidney tumor has been completely resected with negative surgical margins obtained. The randomization must occur greater than 4 weeks and less than (or equal to) 12 weeks from the date of nephrectomy Pathologic tumor, node, and metastasis (TNM) staging meeting one of the following: pT2a, G3 or G4, N0 M0; pT2b, G any, N0 M0; pT3, (a, b, c), G any, N0 M0; pT4, G any, N0 M0; pT any, G any, N1 M0 Post-nephrectomy tumor shows renal cell cancer (RCC) with a predominantly clear cell histology, including participants with sarcomatoid features Participants must have no clinical or radiological evidence of macroscopic residual disease or distant metastases after nephrectomy Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1 Women must agree to follow methods of contraception, if applicable', 'Exclusion Criteria': 'Exclusion Criteria: Participants with an active known or suspected autoimmune disease Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways Any severe or serious, acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation History of allergy or hypersensitivity to study drug components Participants with a condition requiring systemic treatment with corticosteroids Participants who have received a live/attenuated vaccine within 30 days of first treatment'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Exclude: PD-1, PD-L1, PD-L2, CTLA-4'}
|
{'Official Title': 'A Phase 3 Randomized, Double-Blind Study of Nivolumab Monotherapy or Nivolumab Combined With Ipilimumab vs Placebo in Participants With Localized Renal Cell Carcinoma Who Underwent Radical or Partial Nephrectomy and Who Are at High Risk of Relapse', 'Brief Summary': 'The purpose of this study is to determine whether nivolmab alone or the combination of nivolumab and ipilimumab versus placebo, is safe and effective for delaying or preventing recurrence of cancer in participants who have experienced partial or entire removal of a kidney.', 'Condition': 'Renal Cell Carcinoma', 'Detailed Description': 'The study has two primary endpoints. The first primary completion date is anticipated to be reached July 2022 (DFS in Part A). The second primary completion date is anticipated to be reached July 2024 (DFS in Part B).', 'Inclusion Criteria': 'Inclusion Criteria: Kidney tumor has been completely resected with negative surgical margins obtained. The randomization must occur greater than 4 weeks and less than (or equal to) 12 weeks from the date of nephrectomy Pathologic tumor, node, and metastasis (TNM) staging meeting one of the following: pT2a, G3 or G4, N0 M0; pT2b, G any, N0 M0; pT3, (a, b, c), G any, N0 M0; pT4, G any, N0 M0; pT any, G any, N1 M0 Post-nephrectomy tumor shows renal cell cancer (RCC) with a predominantly clear cell histology, including participants with sarcomatoid features Participants must have no clinical or radiological evidence of macroscopic residual disease or distant metastases after nephrectomy Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1 Women must agree to follow methods of contraception, if applicable', 'Exclusion Criteria': 'Exclusion Criteria: Participants with an active known or suspected autoimmune disease Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways Any severe or serious, acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation History of allergy or hypersensitivity to study drug components Participants with a condition requiring systemic treatment with corticosteroids Participants who have received a live/attenuated vaccine within 30 days of first treatment'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Exclude: PD-1, PD-L1, PD-L2, CTLA-4'}
|
{'Official Title': 'A Phase 3 Randomized, Double-Blind Study of Nivolumab Monotherapy or Nivolumab Combined With Ipilimumab vs Placebo in Participants With Localized Renal Cell Carcinoma Who Underwent Radical or Partial Nephrectomy and Who Are at High Risk of Relapse', 'Brief Summary': 'The purpose of this study is to determine whether nivolmab alone or the combination of nivolumab and ipilimumab versus placebo, is safe and effective for delaying or preventing recurrence of cancer in participants who have experienced partial or entire removal of a kidney.', 'Condition': 'Renal Cell Carcinoma', 'Detailed Description': 'The study has two primary endpoints. The first primary completion date is anticipated to be reached July 2022 (DFS in Part A). The second primary completion date is anticipated to be reached July 2024 (DFS in Part B).', 'Inclusion Criteria': 'Inclusion Criteria: Kidney tumor has been completely resected with negative surgical margins obtained. The randomization must occur greater than 4 weeks and less than (or equal to) 12 weeks from the date of nephrectomy Pathologic tumor, node, and metastasis (TNM) staging meeting one of the following: pT2a, G3 or G4, N0 M0; pT2b, G any, N0 M0; pT3, (a, b, c), G any, N0 M0; pT4, G any, N0 M0; pT any, G any, N1 M0 Post-nephrectomy tumor shows renal cell cancer (RCC) with a predominantly clear cell histology, including participants with sarcomatoid features Participants must have no clinical or radiological evidence of macroscopic residual disease or distant metastases after nephrectomy Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1 Women must agree to follow methods of contraception, if applicable', 'Exclusion Criteria': 'Exclusion Criteria: Participants with an active known or suspected autoimmune disease Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways Any severe or serious, acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation History of allergy or hypersensitivity to study drug components Participants with a condition requiring systemic treatment with corticosteroids Participants who have received a live/attenuated vaccine within 30 days of first treatment'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Exclude: PD-1, PD-L1, PD-L2, CTLA-4'}
|
{'Official Title': 'A Phase 3 Randomized, Double-Blind Study of Nivolumab Monotherapy or Nivolumab Combined With Ipilimumab vs Placebo in Participants With Localized Renal Cell Carcinoma Who Underwent Radical or Partial Nephrectomy and Who Are at High Risk of Relapse', 'Brief Summary': 'The purpose of this study is to determine whether nivolmab alone or the combination of nivolumab and ipilimumab versus placebo, is safe and effective for delaying or preventing recurrence of cancer in participants who have experienced partial or entire removal of a kidney.', 'Condition': 'Renal Cell Carcinoma', 'Detailed Description': 'The study has two primary endpoints. The first primary completion date is anticipated to be reached July 2022 (DFS in Part A). The second primary completion date is anticipated to be reached July 2024 (DFS in Part B).', 'Inclusion Criteria': 'Inclusion Criteria: Kidney tumor has been completely resected with negative surgical margins obtained. The randomization must occur greater than 4 weeks and less than (or equal to) 12 weeks from the date of nephrectomy Pathologic tumor, node, and metastasis (TNM) staging meeting one of the following: pT2a, G3 or G4, N0 M0; pT2b, G any, N0 M0; pT3, (a, b, c), G any, N0 M0; pT4, G any, N0 M0; pT any, G any, N1 M0 Post-nephrectomy tumor shows renal cell cancer (RCC) with a predominantly clear cell histology, including participants with sarcomatoid features Participants must have no clinical or radiological evidence of macroscopic residual disease or distant metastases after nephrectomy Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1 Women must agree to follow methods of contraception, if applicable', 'Exclusion Criteria': 'Exclusion Criteria: Participants with an active known or suspected autoimmune disease Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways Any severe or serious, acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation History of allergy or hypersensitivity to study drug components Participants with a condition requiring systemic treatment with corticosteroids Participants who have received a live/attenuated vaccine within 30 days of first treatment'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Exclude: PD-1, PD-L1, PD-L2, CTLA-4'}
|
{'Official Title': 'International,Multicenter,Randomized,Open-label, Phase II to Evaluate the Efficacy and Safety of Continuation of Palbociclib+2nd Line Endocrine Therapy in HR+/HER2- ABC Patients Who Had Clinical Benefit During 1st Line Palbociclib.', 'Brief Summary': 'Hormone Receptor (HR)-positive/Human Epidermal Growth Factor Receptor 2 (HER2)-negative advanced breast cancer (ABC)', 'Condition': 'Breast Cancer Advanced Breast Cancer Hormone Receptor Positive Tumor Human Epidermal Growth Factor 2 Negative Carcinoma of Breast', 'Detailed Description': 'Pre- and post-menopausal women age ≥ 18 years with HR-positive and HER2-negative with ABC that had previously received first-line endocrine therapy in combination with palbociclib and had achieved clinical benefit during palbociclib-based treatment. Patients relapsing on a palbociclib-based regimen in the adjuvant setting are also eligible. Patients are not eligible if they are candidates for a local treatment with a curative intention. Evidence of either measurable and biopsiable metastatic disease (as for Response Evaluation Criteria In Solid Tumors (RECIST v.1.1)) or non-measurable disease with bone lesion is required. Pre-menopausal women must be under treatment with luteinizing hormone-releasing hormone (LHRH)', 'Inclusion Criteria': "Inclusion Criteria: Female patients over 18 years of age. Pre-menopausal women provided they are being treated with a LHRH analogue for at least 28 days (if shorter, post-menopausal levels of serum estradiol/Follicle-stimulating hormone (FSH) must be confirmed analytically) prior to study entry or post- menopausal women as defined by any of the following criteria: Age ≥60 years; Age <60 years and cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and serum estradiol and/or FSH level within the laboratory's reference range for postmenopausal females; Documented bilateral oophorectomy. Eastern Cooperative Oncology Group (ECOG) performance status lower or equal to 1. Life expectancy greater or equal to 12 weeks. Histologically proven diagnosed of ABC not amenable to curative treatment. Documented recurrent ER-positive and/or progesterone receptor (PgR)-positive (with ≥1% positive stained cells (according to NCCN National Comprehensive Cancer Network and ASCO American Society of Clinical Oncology guidelines) and HER2-negative (0-1+ by immunohistochemistry (IHC) or 2+ and negative by in situ hybridization (ISH) test) breast cancer in the advanced setting. Radiological or clinical evidence of disease progression on first- line combination of palbociclib plus endocrine therapy (aromatase inhibitor (AI) or fulvestrant). Patients previously treated with the combination of palbociclib and tamoxifen will be excluded. Patients have achieved clinical benefit criteria to a first-line palbociclib-based endocrine regimen (defined as at least stable disease ≥ 24 weeks or partial or complete response confirmed or unconfirmed). Patients must have been treated with a stable minimum dose of 75 mg palbociclib during the last 2 cycles of the prior palbociclib-based regimen. Last dose of palbociclib administered not later than 8 weeks and not earlier than 7 days from study entry, with the exception of patients relapsing on a palbociclib-based regimen in the adjuvant setting. Patients should not have been treated in the advanced setting with at least one of these endocrine therapy options: either fulvestrant or AI. Patients must have measurable disease or evaluable disease according to RECIST criteria v.1.1. Patients with only bone lesions are eligible. Willingness and ability to provide tumor biopsy (if feasible) both at the time of the inclusion and after disease progression in order to perform exploratory studies. If not feasible, patient eligibility should be evaluated by a Sponsor's qualified designee. Patients agree to collection of blood samples (liquid biopsy) at the time of inclusion, after 2 weeks of treatment, and upon progression or study termination. Adequate organ function: (Hematological, hepatic and renal) Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. Patients have been informed about the nature of study, and have agreed to participate in the study, and signed the informed consent form prior to participation in any study-related activities. Resolution of all acute toxic effects of prior anti-cancer therapy to grade 1", 'Exclusion Criteria': 'Exclusion Criteria: HR or HER2 unknown disease. HER2-positive disease based on local laboratory results (performed by IHC / ISH test). Locally ABC candidate for curative treatment. Formal contraindication to endocrine therapy defined as visceral crisis and rapidly or symptomatic progressive visceral disease. Prior therapy with any other CDK4/6 inhibitor different from palbociclib. Known active uncontrolled or symptomatic Central Nervous System (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS metastases or cord compression are eligible if they have been definitively treated and are clinically stable off anticonvulsants and steroids for at least 4 weeks before randomization. Patients are currently receiving food or drugs known to be strong inducers or inhibitors of CYP3A4. Current or prior malignancy which could affect compliance with the protocol or interpretation of results. Patients with curatively- treated non-melanoma skin cancer, non-muscle-invasive bladder cancer, or carcinoma in situ, among others, are generally eligible. No other systemic therapy for metastatic disease including chemotherapy, immunotherapy, targeted therapy (small molecules/ monoclonal antibodies), or endocrine therapy excluding first-line palbociclib-based regimen. Major surgery (defined as requiring general anesthesia) or significant traumatic injury within 2 weeks of start of study drug, or patients who have not recovered from the side effects of any major surgery, or patients who may require major surgery during the study. Radiotherapy or limited-field palliative radiotherapy within 7 days prior to study enrolment, or patients who have not recovered from radiotherapy-related toxicities to baseline or grade ≤ 1 and/or from whom ≥ 25% of the bone marrow has been previously irradiated. Use of concurrent investigational agents or other concomitant anticancer therapies. Active bleeding diathesis, previous history of bleeding diathesis, or chronic anti-coagulation treatment (the use of low molecular weight heparin is allowed as soon as it is used as prophylaxis intention). Serious concomitant systemic disorder (e.g., active infection including HIV, or cardiac disease) incompatible with the study (at the discretion of investigator). Unable to swallow capsules or tablets. History of malabsorption syndrome or other condition that would interfere with enteral absorption. Any of the following within 6 months of randomization: myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI-CTCAE v.5.0 grade ≥2, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism. Uncontrolled electrolyte disorders of NCI-CTCAE v.5.0 grade ≥ 2. Known hypersensitivity to palbociclib or any of its excipients.'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: HR+, HER2- Exclude: HER2+'}
|
{'Official Title': 'International,Multicenter,Randomized,Open-label, Phase II to Evaluate the Efficacy and Safety of Continuation of Palbociclib+2nd Line Endocrine Therapy in HR+/HER2- ABC Patients Who Had Clinical Benefit During 1st Line Palbociclib.', 'Brief Summary': 'Hormone Receptor (HR)-positive/Human Epidermal Growth Factor Receptor 2 (HER2)-negative advanced breast cancer (ABC)', 'Condition': 'Breast Cancer Advanced Breast Cancer Hormone Receptor Positive Tumor Human Epidermal Growth Factor 2 Negative Carcinoma of Breast', 'Detailed Description': 'Pre- and post-menopausal women age ≥ 18 years with HR-positive and HER2-negative with ABC that had previously received first-line endocrine therapy in combination with palbociclib and had achieved clinical benefit during palbociclib-based treatment. Patients relapsing on a palbociclib-based regimen in the adjuvant setting are also eligible. Patients are not eligible if they are candidates for a local treatment with a curative intention. Evidence of either measurable and biopsiable metastatic disease (as for Response Evaluation Criteria In Solid Tumors (RECIST v.1.1)) or non-measurable disease with bone lesion is required. Pre-menopausal women must be under treatment with luteinizing hormone-releasing hormone (LHRH)', 'Inclusion Criteria': "Inclusion Criteria: Female patients over 18 years of age. Pre-menopausal women provided they are being treated with a LHRH analogue for at least 28 days (if shorter, post-menopausal levels of serum estradiol/Follicle-stimulating hormone (FSH) must be confirmed analytically) prior to study entry or post- menopausal women as defined by any of the following criteria: Age ≥60 years; Age <60 years and cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and serum estradiol and/or FSH level within the laboratory's reference range for postmenopausal females; Documented bilateral oophorectomy. Eastern Cooperative Oncology Group (ECOG) performance status lower or equal to 1. Life expectancy greater or equal to 12 weeks. Histologically proven diagnosed of ABC not amenable to curative treatment. Documented recurrent ER-positive and/or progesterone receptor (PgR)-positive (with ≥1% positive stained cells (according to NCCN National Comprehensive Cancer Network and ASCO American Society of Clinical Oncology guidelines) and HER2-negative (0-1+ by immunohistochemistry (IHC) or 2+ and negative by in situ hybridization (ISH) test) breast cancer in the advanced setting. Radiological or clinical evidence of disease progression on first- line combination of palbociclib plus endocrine therapy (aromatase inhibitor (AI) or fulvestrant). Patients previously treated with the combination of palbociclib and tamoxifen will be excluded. Patients have achieved clinical benefit criteria to a first-line palbociclib-based endocrine regimen (defined as at least stable disease ≥ 24 weeks or partial or complete response confirmed or unconfirmed). Patients must have been treated with a stable minimum dose of 75 mg palbociclib during the last 2 cycles of the prior palbociclib-based regimen. Last dose of palbociclib administered not later than 8 weeks and not earlier than 7 days from study entry, with the exception of patients relapsing on a palbociclib-based regimen in the adjuvant setting. Patients should not have been treated in the advanced setting with at least one of these endocrine therapy options: either fulvestrant or AI. Patients must have measurable disease or evaluable disease according to RECIST criteria v.1.1. Patients with only bone lesions are eligible. Willingness and ability to provide tumor biopsy (if feasible) both at the time of the inclusion and after disease progression in order to perform exploratory studies. If not feasible, patient eligibility should be evaluated by a Sponsor's qualified designee. Patients agree to collection of blood samples (liquid biopsy) at the time of inclusion, after 2 weeks of treatment, and upon progression or study termination. Adequate organ function: (Hematological, hepatic and renal) Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. Patients have been informed about the nature of study, and have agreed to participate in the study, and signed the informed consent form prior to participation in any study-related activities. Resolution of all acute toxic effects of prior anti-cancer therapy to grade 1", 'Exclusion Criteria': 'Exclusion Criteria: HR or HER2 unknown disease. HER2-positive disease based on local laboratory results (performed by IHC / ISH test). Locally ABC candidate for curative treatment. Formal contraindication to endocrine therapy defined as visceral crisis and rapidly or symptomatic progressive visceral disease. Prior therapy with any other CDK4/6 inhibitor different from palbociclib. Known active uncontrolled or symptomatic Central Nervous System (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS metastases or cord compression are eligible if they have been definitively treated and are clinically stable off anticonvulsants and steroids for at least 4 weeks before randomization. Patients are currently receiving food or drugs known to be strong inducers or inhibitors of CYP3A4. Current or prior malignancy which could affect compliance with the protocol or interpretation of results. Patients with curatively- treated non-melanoma skin cancer, non-muscle-invasive bladder cancer, or carcinoma in situ, among others, are generally eligible. No other systemic therapy for metastatic disease including chemotherapy, immunotherapy, targeted therapy (small molecules/ monoclonal antibodies), or endocrine therapy excluding first-line palbociclib-based regimen. Major surgery (defined as requiring general anesthesia) or significant traumatic injury within 2 weeks of start of study drug, or patients who have not recovered from the side effects of any major surgery, or patients who may require major surgery during the study. Radiotherapy or limited-field palliative radiotherapy within 7 days prior to study enrolment, or patients who have not recovered from radiotherapy-related toxicities to baseline or grade ≤ 1 and/or from whom ≥ 25% of the bone marrow has been previously irradiated. Use of concurrent investigational agents or other concomitant anticancer therapies. Active bleeding diathesis, previous history of bleeding diathesis, or chronic anti-coagulation treatment (the use of low molecular weight heparin is allowed as soon as it is used as prophylaxis intention). Serious concomitant systemic disorder (e.g., active infection including HIV, or cardiac disease) incompatible with the study (at the discretion of investigator). Unable to swallow capsules or tablets. History of malabsorption syndrome or other condition that would interfere with enteral absorption. Any of the following within 6 months of randomization: myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI-CTCAE v.5.0 grade ≥2, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism. Uncontrolled electrolyte disorders of NCI-CTCAE v.5.0 grade ≥ 2. Known hypersensitivity to palbociclib or any of its excipients.'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: HR+, HER2- Exclude: HER2+'}
|
{'Official Title': 'A Randomized, Double-Blind, Phase 3 Study of Pemetrexed + Platinum Chemotherapy With or Without Pembrolizumab (MK-3475) in TKI-resistant EGFR-mutated Tumors in Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) Participants (KEYNOTE-789)', 'Brief Summary': 'The purpose of this study is to evaluate the efficacy and safety of pemetrexed plus platinum chemotherapy (carboplatin or cisplatin) with or without pembrolizumab (MK-3475; KEYTRUDA®) in the treatment of adults with the following types of tyrosine kinase inhibitor (TKI)-resistant, epidermal growth factor receptor (EGFR)-mutated, metastatic non-squamous non-small cell lung cancer (NSCLC) tumors: 1) TKI-failures (including osimertinib [TAGRISSO®] failure) with T790M-negative mutation tumors, 2) T790M-positive mutation tumors with prior exposure to osimertinib, and 3) first-line osimertinib failure regardless of T790M mutation status. The primary study hypotheses are that the combination of pembrolizumab plus chemotherapy has superior efficacy compared to saline placebo plus chemotherapy in terms of: 1) Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) based on blinded independent central review, and 2) Overall Survival (OS). This study will be considered to have met its success criteria if the combination of pembrolizumab plus chemotherapy is superior to saline placebo plus chemotherapy in terms of PFS or OS. Upon study completion, participants are discontinued and may be enrolled in a pembrolizumab extension study, if available.', 'Condition': 'Non-small Cell Lung Cancer', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Histologically or cytologically confirmed diagnosis of Stage IV non-squamous NSCLC. Documentation of tumor activating EGFR mutation, specifically either DEL19 or L858R. Investigator-determined radiographic disease progression per RECIST 1.1 after treatment with an EGFR TKI therapy: a) Participants previously treated with 1st or 2nd generation EGFR TKI (e.g. erlotinib/afatinib/gefitinib) are required to have confirmed documented absence of EGFR T790M mutation; b) Participants with confirmed acquired T790M mutation after 1st or 2nd generation EGFR TKI (e.g. erlotinib/afatinib/gefitinib) are required to have osimertinib TKI treatment failure prior to enrollment; c) Participants previously failed osimertinib TKI treatment as 1st line therapy are eligible regardless of their EGFR T790M mutation status. Note: TKI washout period for all participants is 1 week or 2 half-lives after last treatment dose, whichever is longer. TKI washout should be completed prior to first dose of study treatment. Measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology. Provided archival tumor tissue sample or newly obtained (no anti-neoplastic therapy since biopsy) core or excisional biopsy of a tumor lesion not previously irradiated. Life expectancy of at least 3 months. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to the first dose of study treatment but before randomization. Male participants must agree to use contraception during the treatment period and for at least 120 days after the last dose of pembrolizumab and up to 180 days after last dose of chemotherapeutic agents. Female participants must not be pregnant, not breastfeeding, and must agree to use contraception during the treatment period and for at least 120 days after the last dose of pembrolizumab and up to 180 days after the last dose of chemotherapeutic agents. Adequate organ function.', 'Exclusion Criteria': 'Exclusion Criteria: Predominantly squamous cell histology NSCLC. Mixed tumors will be categorized by the predominant cell type; if small cell elements are present, the participant is ineligible. Symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible. Received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein-4 [CTLA-4], OX-40, CD137). Received prior systemic cytotoxic chemotherapy or investigational agent(s), excluding EGFR TKIs, for metastatic NSCLC. [Notes: 1) Prior treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of metastatic NSCLC. 2) If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment. 3) Prior exposure to traditional medicine(s) is allowed as long as therapy was discontinued at least 4 weeks prior to the first dose of study treatment.] Received prior radiotherapy within 2 weeks of start of study treatment or has received lung radiation therapy of >30 Gray (Gy) within 6 months before the first dose of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease. Received a live vaccine within 30 days prior to the first dose of study treatment. Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment. Known additional malignancy that is progressing or has required active treatment within the past 5 years. (Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.) Known active untreated CNS metastases and/or carcinomatous meningitis. Severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients. Known sensitivity to any component of cisplatin, carboplatin, or pemetrexed. Active autoimmune disease that has required systemic treatment in past 2 years. History of (non-infectious) pneumonitis that required steroids or has current pneumonitis. Active infection requiring systemic therapy. Known history of human immunodeficiency virus (HIV) infection. Known history of Hepatitis B or known active Hepatitis C virus. Known history of active tuberculosis (TB; Bacillus tuberculosis) Pregnant, breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of pembrolizumab and up to 180 days after the last dose of chemotherapeutic agents.'}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
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{'Arm - Disease - Biomarker': 'Include: EGFR mutation, specifically either DEL19 or L858R, confirmed acquired T790M mutation'}
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{'Official Title': 'A Randomized, Double-Blind, Phase 3 Study of Pemetrexed + Platinum Chemotherapy With or Without Pembrolizumab (MK-3475) in TKI-resistant EGFR-mutated Tumors in Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) Participants (KEYNOTE-789)', 'Brief Summary': 'The purpose of this study is to evaluate the efficacy and safety of pemetrexed plus platinum chemotherapy (carboplatin or cisplatin) with or without pembrolizumab (MK-3475; KEYTRUDA®) in the treatment of adults with the following types of tyrosine kinase inhibitor (TKI)-resistant, epidermal growth factor receptor (EGFR)-mutated, metastatic non-squamous non-small cell lung cancer (NSCLC) tumors: 1) TKI-failures (including osimertinib [TAGRISSO®] failure) with T790M-negative mutation tumors, 2) T790M-positive mutation tumors with prior exposure to osimertinib, and 3) first-line osimertinib failure regardless of T790M mutation status. The primary study hypotheses are that the combination of pembrolizumab plus chemotherapy has superior efficacy compared to saline placebo plus chemotherapy in terms of: 1) Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) based on blinded independent central review, and 2) Overall Survival (OS). This study will be considered to have met its success criteria if the combination of pembrolizumab plus chemotherapy is superior to saline placebo plus chemotherapy in terms of PFS or OS. Upon study completion, participants are discontinued and may be enrolled in a pembrolizumab extension study, if available.', 'Condition': 'Non-small Cell Lung Cancer', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Histologically or cytologically confirmed diagnosis of Stage IV non-squamous NSCLC. Documentation of tumor activating EGFR mutation, specifically either DEL19 or L858R. Investigator-determined radiographic disease progression per RECIST 1.1 after treatment with an EGFR TKI therapy: a) Participants previously treated with 1st or 2nd generation EGFR TKI (e.g. erlotinib/afatinib/gefitinib) are required to have confirmed documented absence of EGFR T790M mutation; b) Participants with confirmed acquired T790M mutation after 1st or 2nd generation EGFR TKI (e.g. erlotinib/afatinib/gefitinib) are required to have osimertinib TKI treatment failure prior to enrollment; c) Participants previously failed osimertinib TKI treatment as 1st line therapy are eligible regardless of their EGFR T790M mutation status. Note: TKI washout period for all participants is 1 week or 2 half-lives after last treatment dose, whichever is longer. TKI washout should be completed prior to first dose of study treatment. Measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology. Provided archival tumor tissue sample or newly obtained (no anti-neoplastic therapy since biopsy) core or excisional biopsy of a tumor lesion not previously irradiated. Life expectancy of at least 3 months. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to the first dose of study treatment but before randomization. Male participants must agree to use contraception during the treatment period and for at least 120 days after the last dose of pembrolizumab and up to 180 days after last dose of chemotherapeutic agents. Female participants must not be pregnant, not breastfeeding, and must agree to use contraception during the treatment period and for at least 120 days after the last dose of pembrolizumab and up to 180 days after the last dose of chemotherapeutic agents. Adequate organ function.', 'Exclusion Criteria': 'Exclusion Criteria: Predominantly squamous cell histology NSCLC. Mixed tumors will be categorized by the predominant cell type; if small cell elements are present, the participant is ineligible. Symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible. Received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein-4 [CTLA-4], OX-40, CD137). Received prior systemic cytotoxic chemotherapy or investigational agent(s), excluding EGFR TKIs, for metastatic NSCLC. [Notes: 1) Prior treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of metastatic NSCLC. 2) If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment. 3) Prior exposure to traditional medicine(s) is allowed as long as therapy was discontinued at least 4 weeks prior to the first dose of study treatment.] Received prior radiotherapy within 2 weeks of start of study treatment or has received lung radiation therapy of >30 Gray (Gy) within 6 months before the first dose of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease. Received a live vaccine within 30 days prior to the first dose of study treatment. Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment. Known additional malignancy that is progressing or has required active treatment within the past 5 years. (Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.) Known active untreated CNS metastases and/or carcinomatous meningitis. Severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients. Known sensitivity to any component of cisplatin, carboplatin, or pemetrexed. Active autoimmune disease that has required systemic treatment in past 2 years. History of (non-infectious) pneumonitis that required steroids or has current pneumonitis. Active infection requiring systemic therapy. Known history of human immunodeficiency virus (HIV) infection. Known history of Hepatitis B or known active Hepatitis C virus. Known history of active tuberculosis (TB; Bacillus tuberculosis) Pregnant, breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of pembrolizumab and up to 180 days after the last dose of chemotherapeutic agents.'}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
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{'Arm - Disease - Biomarker': 'Include: EGFR mutation, specifically either DEL19 or L858R, confirmed acquired T790M mutation'}
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{'Official Title': 'A Phase 1b-2 Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Various Regimens of Erdafitinib in Subjects With Metastatic or Locally Advanced Urothelial Cancer', 'Brief Summary': 'The purpose of this study is to: (a) characterize the safety and tolerability of and to identify the recommended Phase 2 dose (RP2D) and schedule for erdafitinib in combination with cetrelimab, and for erdafitinib in combination with cetrelimab and platinum (cisplatin and carboplatin) chemotherapy and; (b) to evaluate the safety and clinical activity of erdafitinib alone and in combination with cetrelimab in cisplatin-ineligible participants with metastatic or locally advanced urothelial cancer (UC) with select fibroblast growth factor receptor (FGFR) gene alterations and no prior systemic therapy for metastatic disease.', 'Condition': 'Urothelial Carcinoma', 'Detailed Description': 'This open-label (all people know identity of intervention) and multicenter (when more than one hospital or medical school team work on a medical research study) study to establish the recommended phase 2 dose (RP2D) for erdafitinib and cetrelimab and/or platinum (cisplatin or carboplatin) chemotherapy, and to evaluate the safety of erdafitinib in combination with cetrelimab and platinum chemotherapy in Phase 1b and to evaluate the safety and efficacy of the RP2D of erdafitinib plus cetrelimab versus erdafitinib in Phase 2 in participants with advanced urothelial cancer with select fibroblast growth factor receptor (FGFR) gene alterations. Participants enrolled in Phase 1b erdafitinib + cetrelimab cohort may have received any number of lines of prior therapy, and participants enrolled in Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort will have had no prior systemic therapy for metastatic disease and participants enrolled in Phase 2 will have had no prior systemic therapy for metastatic disease and will be cis-ineligible. Part 1 (Phase 1b: Dose Escalation) will identify safety and RP2Ds of erdafitinib + cetrelimab and erdafitinib + cetrelimab + platinum (cisplatin or carboplatin) chemotherapy, and Part 2 (Phase 2: Dose Expansion) will evaluate erdafitinib monotherapy and the RP2D regimen of the erdafitinib + cetrelimab combination to further characterize safety and clinical activity. The study will be conducted in 3 phases: screening phase, treatment phase, and follow-up phase. Study evaluations include efficacy, pharmacokinetics, pharmacodynamics, immunogenicity, biomarkers, and safety.', 'Inclusion Criteria': 'Inclusion Criteria: Histologic demonstration of transitional cell carcinoma of the urothelium. Variant urothelial carcinoma histologies such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or micropapillary change are acceptable Metastatic or locally advanced urothelial cancer Must have measurable disease by radiological imaging according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) at baseline Prior systemic therapy for metastatic urothelial cancer: (a) For Phase 1b erdafitinib + cetrelimab cohort: Any number of lines of prior therapy; (b) For Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: No prior systemic therapy for metastatic disease; and renal function for participants must have a creatinine clearance (CrCl) greater than (>) 30 milliliter per minute (mL/min) to receive carboplatin and >60 mL/min to receive cisplatin as calculated by Cockcroft Gault and (c) Phase 2: No prior systemic therapy for metastatic disease and cisplatin-ineligible based on: ECOG PS 0-1 and at least one of the following criteria: Renal function defined as creatinine clearance (CrCl) less than (˂) 60 mL/min as calculated by Cockcroft-Gault; Grade 2 or higher peripheral neuropathy per NCI-CTCAE version 5.0; Grade 2 or higher hearing loss per NCI-CTCAE version 5.0 OR ECOG PS 2 Eastern Cooperative Oncology Group (ECOG) performance status (PS) grade of: (a) Phase 1b erdafitinib + cetrelimab cohort: ECOG 0-2; (b) Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: ECOG 0-1 for cisplatin and 0-2 for carboplatin (c) Phase 2: ECOG 0-2', 'Exclusion Criteria': 'Exclusion Criteria: Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 30 days prior to Cycle 1 Day 1. For Phase 1b, participants who have received the following prior antitumor therapy: received nitrosoureas and mitomycin C within 6 weeks Phase 1b erdafitinib + cetrelimab cohort: Chemotherapy within 3 weeks of Cycle 1 Day 1; Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort and Phase 2: Prior neoadjuvant/adjuvant chemotherapy is allowed if the last dose was given >12 months prior to recurrent disease progression and did not result in drug-related toxicity leading to treatment discontinuation Prior anti-programmed death receptor-1 (PD-1), anti-programmed death ligand-1 (PD-L1), or anti-programmed death ligand-2 (PD-L2) therapy. Prior neoadjuvant/adjuvant checkpoint inhibitor therapy is allowed if the last dose was given more than (>)12 months prior to recurrent disease progression and did not result in drug-related toxicity leading to treatment discontinuation. PD-1 for non-muscle invasive bladder cancer is also allowed Active malignancies requiring concurrent therapy other than urothelial cancer Symptomatic central nervous system metastases'}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
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{'Arm - Disease - Biomarker': 'Include: Fibroblast growth factor receptor (FGFR) gene alterations '}
|
{'Official Title': 'A Phase 1b-2 Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Various Regimens of Erdafitinib in Subjects With Metastatic or Locally Advanced Urothelial Cancer', 'Brief Summary': 'The purpose of this study is to: (a) characterize the safety and tolerability of and to identify the recommended Phase 2 dose (RP2D) and schedule for erdafitinib in combination with cetrelimab, and for erdafitinib in combination with cetrelimab and platinum (cisplatin and carboplatin) chemotherapy and; (b) to evaluate the safety and clinical activity of erdafitinib alone and in combination with cetrelimab in cisplatin-ineligible participants with metastatic or locally advanced urothelial cancer (UC) with select fibroblast growth factor receptor (FGFR) gene alterations and no prior systemic therapy for metastatic disease.', 'Condition': 'Urothelial Carcinoma', 'Detailed Description': 'This open-label (all people know identity of intervention) and multicenter (when more than one hospital or medical school team work on a medical research study) study to establish the recommended phase 2 dose (RP2D) for erdafitinib and cetrelimab and/or platinum (cisplatin or carboplatin) chemotherapy, and to evaluate the safety of erdafitinib in combination with cetrelimab and platinum chemotherapy in Phase 1b and to evaluate the safety and efficacy of the RP2D of erdafitinib plus cetrelimab versus erdafitinib in Phase 2 in participants with advanced urothelial cancer with select fibroblast growth factor receptor (FGFR) gene alterations. Participants enrolled in Phase 1b erdafitinib + cetrelimab cohort may have received any number of lines of prior therapy, and participants enrolled in Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort will have had no prior systemic therapy for metastatic disease and participants enrolled in Phase 2 will have had no prior systemic therapy for metastatic disease and will be cis-ineligible. Part 1 (Phase 1b: Dose Escalation) will identify safety and RP2Ds of erdafitinib + cetrelimab and erdafitinib + cetrelimab + platinum (cisplatin or carboplatin) chemotherapy, and Part 2 (Phase 2: Dose Expansion) will evaluate erdafitinib monotherapy and the RP2D regimen of the erdafitinib + cetrelimab combination to further characterize safety and clinical activity. The study will be conducted in 3 phases: screening phase, treatment phase, and follow-up phase. Study evaluations include efficacy, pharmacokinetics, pharmacodynamics, immunogenicity, biomarkers, and safety.', 'Inclusion Criteria': 'Inclusion Criteria: Histologic demonstration of transitional cell carcinoma of the urothelium. Variant urothelial carcinoma histologies such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or micropapillary change are acceptable Metastatic or locally advanced urothelial cancer Must have measurable disease by radiological imaging according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) at baseline Prior systemic therapy for metastatic urothelial cancer: (a) For Phase 1b erdafitinib + cetrelimab cohort: Any number of lines of prior therapy; (b) For Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: No prior systemic therapy for metastatic disease; and renal function for participants must have a creatinine clearance (CrCl) greater than (>) 30 milliliter per minute (mL/min) to receive carboplatin and >60 mL/min to receive cisplatin as calculated by Cockcroft Gault and (c) Phase 2: No prior systemic therapy for metastatic disease and cisplatin-ineligible based on: ECOG PS 0-1 and at least one of the following criteria: Renal function defined as creatinine clearance (CrCl) less than (˂) 60 mL/min as calculated by Cockcroft-Gault; Grade 2 or higher peripheral neuropathy per NCI-CTCAE version 5.0; Grade 2 or higher hearing loss per NCI-CTCAE version 5.0 OR ECOG PS 2 Eastern Cooperative Oncology Group (ECOG) performance status (PS) grade of: (a) Phase 1b erdafitinib + cetrelimab cohort: ECOG 0-2; (b) Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: ECOG 0-1 for cisplatin and 0-2 for carboplatin (c) Phase 2: ECOG 0-2', 'Exclusion Criteria': 'Exclusion Criteria: Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 30 days prior to Cycle 1 Day 1. For Phase 1b, participants who have received the following prior antitumor therapy: received nitrosoureas and mitomycin C within 6 weeks Phase 1b erdafitinib + cetrelimab cohort: Chemotherapy within 3 weeks of Cycle 1 Day 1; Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort and Phase 2: Prior neoadjuvant/adjuvant chemotherapy is allowed if the last dose was given >12 months prior to recurrent disease progression and did not result in drug-related toxicity leading to treatment discontinuation Prior anti-programmed death receptor-1 (PD-1), anti-programmed death ligand-1 (PD-L1), or anti-programmed death ligand-2 (PD-L2) therapy. Prior neoadjuvant/adjuvant checkpoint inhibitor therapy is allowed if the last dose was given more than (>)12 months prior to recurrent disease progression and did not result in drug-related toxicity leading to treatment discontinuation. PD-1 for non-muscle invasive bladder cancer is also allowed Active malignancies requiring concurrent therapy other than urothelial cancer Symptomatic central nervous system metastases'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: Fibroblast growth factor receptor (FGFR) gene alterations '}
|
{'Official Title': 'A Phase II Study to Evaluate Neoadjuvant Osimertinib Therapy in Patients With Surgically Resectable, EGFR-Mutant Non-Small Cell Lung Cancer', 'Brief Summary': 'This phase II trial studies how well osimertinib works in treating participants with stage I-IIIA Epithelial Growth Factor Receptor (EGFR) -mutant non-small cell lung cancer before surgery. Osimertinib may stop the growth of tumor cells by blocking mutant EGFR signaling in cancer cells.', 'Condition': 'Stage I Non-Small Cell Lung Cancer Stage IA Non-Small Cell Lung Cancer Stage IB Non-Small Cell Lung Cancer Stage II Non-Small Cell Lung Cancer Stage IIA Non-Small Cell Lung Cancer Stage IIB Non-Small Cell Lung Cancer Stage IIIA Non-Small Cell Lung Cancer', 'Detailed Description': 'PRIMARY OBJECTIVES: I. To evaluate the efficacy of osimertinib as neoadjuvant therapy in patients with surgically resectable EGFR-mutant non-small cell lung cancer (NSCLC). SECONDARY OBJECTIVES: I. To evaluate the safety of osimertinib given as neoadjuvant therapy in early stage EGFR-mutant NSCLC participants. II. To evaluate whether neoadjuvant osimertinib treatment increases the frequency of tumors that are unresectable due to adverse events or disease progression. III. To evaluate secondary measures of clinical efficacy in early stage EGFR-mutant NSCLC patients treated with osimertinib induction therapy. TERTIARY OBJECTIVES: I. To evaluate long-term measures of efficacy in patients treated with osimertinib neoadjuvant therapy. II. To explore tissue and cell-free biomarkers that may be predictive of response or primary resistance to osimertinib neoadjuvant therapy. OUTLINE: Participants receive osimertinib orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgical resection of their cancer. After completion of study treatment, participants are followed up at 30 days then every 3 months for up to 1 year.', 'Inclusion Criteria': "Inclusion Criteria: Males and females >=18 years of age Histologically or cytologically confirmed non-small cell lung cancer (NSCLC), performed on a biopsy that occurred within the last 90 days. This biopsy can be deferred if the procedure is deemed to represent an unacceptable safety risk to the patient by the Principal Investigator and as long as the patient has a prior biopsy showing non-small cell lung cancer. Documented activating EGFR mutation (Exon 19 deletion, T790M, or L858R) on tumor samples by Clinical Laboratory Clinical Laboratory Improvement Amendments (CLIA)-approved test Patients treated with osimertinib or another EGFR tyrosine kinase inhibitors (TKI) (including erlotinib, afatinib, gefitinib, & rocelitinib) are eligible if they received no more than 28 days of treatment, and if there is no evidence of grade 2 or greater treatment adverse events possibly related to treatment with the EGFR TKI. Positron emission tomography (PET)-computed tomography (CT) within the last 60 days showing radiographic stage I to IIIa lung cancer (mediastinal staging biopsy is allowed but not required) Brain magnetic resonance imaging (MRI) (or CT if contraindication to MRI) within the last 60 days showing no evidence of metastatic disease Documentation that the patient is a candidate for surgical resection of their lung cancer by an American Board of Thoracic Surgery certified surgeon The patient must have a tumor size >=1 centimeter (cm) in its longest diameter. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-1 Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment, with the exception of alopecia and grade 2 prior platinumtherapy-related neuropathy is allowed Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN) Bilirubin =< 1.5 x ULN, (Patients with documented Gilbert's syndrome and conjugated bilirubin within the normal range may be allowed into the study; in this event, it will be documented that the patient was eligible based on conjugated bilirubin levels) Potassium and magnesium within normal range, patients may receive supplements to meet this requirement Leukocytes > 3,000/microliter (mcL) Hemoglobin >= 9 g/dL, with no blood transfusions in the 28 days prior to study entry Absolute neutrophil count > 1,500/mcL Platelets > 100,000/mcL Creatinine Clearance (CrCl) > 50 mL/min for patients with serum creatinine (SCr) > 1.5 x upper limit of normal (ULN) Ability to swallow oral medications Women of childbearing potential (WoCBP) must have a negative serum pregnancy test within 3 days prior to the first dose of study treatment and agree to use highly effective contraception, during the study and for 90 days following the last dose of osimertinib Women of childbearing potential (WoCBP): women between menarche and menopause who have not been permanently or surgically sterilized and are capable of procreation Women NOT of childbearing potential: women who are permanently or surgically sterilized or postmenopausal Permanent sterilization includes hysterectomy and/or bilateral oophorectomy and/or bilateral salpingectomy but excludes bilateral tubal occlusion; tubal occlusion is considered a highly effective method of birth control but does not absolutely exclude possibility of pregnancy; (the term occlusion refers to both occluding and ligating techniques that do not physically remove the oviducts) Women who have undergone tubal occlusion should be managed on trials as if they are of WoCBP (e.g. undergo pregnancy testing etc., as required by the study protocol) Women will be considered postmenopausal if they are amenorrhoeic for 12 months without an alternative medical cause; the following age-specific requirements apply: Women under 50 years old will be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone and follicle-stimulating hormone levels in the postmenopausal range Women over 50 years of age will be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatments Acceptable contraception methods are: Total sexual abstinence (abstinence must be for the total duration of the trial and the follow-up period) Vasectomized sexual partner plus male condom (with participant assurance that partner received post-vasectomy confirmation of azoospermia) Tubal occlusion plus male condom Intra-uterine device - provided coils are copper-banded, plus male condom Intra-uterine system (IUS) levonorgestrel IUS (e.g., Mirena), plus male condom Medroxyprogesterone injections (Depo-Provera) plus male condom Etonogestrel implants (e.g., Implanon, Norplan) plus male condom Normal and low dose combined oral contraceptive pills, plus male condom Norelgestromin / ethinylestradiol transdermal system plus male condom Intravaginal device (e.g., ethinylestradiol and etonogestrel) plus male condom Cerazette (desogestrel) plus male condom (Cerazette is currently the only highly efficacious progesterone based pill) Unacceptable Contraception Methods The following methods are considered not to be highly effective and are therefore not acceptable contraceptive methods: Triphasic combined oral contraceptives All progesterone only pills except, Cerazette All barrier methods, if intended to be used alone Non-copper containing intra-uterine devices Fertility awareness methods Coitus interruptus Men with a female partner of childbearing potential must have either had a prior vasectomy agree to use effective contraception as described in the full protocol for at least 14 days prior to administration of the first dose of study treatment, during the study, and for 90 days following the last dose of osimertinib", 'Exclusion Criteria': 'Exclusion Criteria: Leptomeningeal carcinomatosis or other central nervous system (CNS) metastases Stage IIIB, or distant metastases (including malignant pleural effusion) identified on PET-CT scan or biopsy (PET abnormalities that are negative for malignancy on biopsy will be considered on a case by case basis Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease Patients who are known to be serologically positive for human immunodeficiency virus (HIV) Active second malignancy, i.e. patient known to have potentially fatal cancer present for which he/she may be (but not necessarily) currently receiving treatment; patients with a history of malignancy that has been completely treated, with no evidence of that cancer currently, are permitted to enroll in the trial provided all chemotherapy for prior malignancy was completed > 12 months prior and/or bone marrow transplant > 2 years prior Patients who are currently receiving treatment with contraindicated corrected QT interval (QTc) prolonging medications or potent CYP3A4 inducers, if that treatment cannot be either discontinued or switched to a different medication prior to first day of study treatment. All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects Any of the following cardiac abnormalities or history: Mean resting corrected QT interval (QTc) > 470 msec, obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derived QTc value Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block and second degree heart block Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval Treatment with prohibited medications (concurrent anticancer therapy including chemotherapy, radiation, hormonal treatment [except corticosteroids and megesterolacetate], or immunotherapy) =< 14 days prior to treatment with osimertinib Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator?s opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol, or known active infection including chronic active hepatitis B, hepatitis C and human immunodeficiency virus (HIV); screening for chronic conditions is not required; patients with chronic hepatitis B virus (HBV) with negative HBV viral load on appropriate antiviral therapy will be permitted, if able to continue appropriate antiviral therapy throughout treatment period Active tuberculosis Signs or symptoms of infection within 2 weeks prior to first day of study Therapeutic oral or intravenous (IV) antibiotics within 2 weeks prior to first day of study treatment: Patients receiving prophylactic antibiotics (eg, to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible Class II to IV heart failure as defined by the New York Heart Association functional classification system Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction (LVEF) < 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate, to be eligible Patients who have experienced untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction (unstable angina, congestive heart failure, myocardial infarction within the previous 3 months; coronary angioplasty, or stenting or bypass grafting within the past 6 months; cardiac ventricular arrhythmias requiring medication; any history of second (2nd) or third (3rd) degree atrioventricular conduction defects) Females who are pregnant or breastfeeding Presence of active gastrointestinal (GI) disease (including GI bleeding or ulceration) or other condition that could affect GI absorption (e.g. malabsorption syndrome, history of biliary tract disease), including refractory nausea or vomiting, or chronic GI disease which may affect absorption or tolerance to oral medications History of hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib Involvement in the planning and/or conduct of the study (applies to both investigator staff and/or staff at the study site) Participation in another clinical study with an investigational product during the last 2 months or within five half-lives of the compound, whichever is longer Uncontrolled medical, psychological, familial, sociological, or geographical conditions that interfere with the patient?s safety, ability to provide informed consent, or ability to comply with the protocol'}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: EGFR mutation (Exon 19 deletion, T790M, or L858R) on tumor samples'}
|
{'Official Title': 'A Randomized, Open-Label, Phase 3 Study of Abemaciclib Combined With Standard Adjuvant Endocrine Therapy Versus Standard Adjuvant Endocrine Therapy Alone in Patients With High Risk, Node Positive, Early Stage, Hormone Receptor Positive, Human Epidermal Receptor 2 Negative, Breast Cancer', 'Brief Summary': 'The purpose of this study is to evaluate the safety and efficacy of the study drug abemaciclib in participants with high risk, node positive, early stage, hormone receptor positive (HR+), human epidermal receptor 2 negative (HER2-), breast cancer.', 'Condition': 'Breast Cancer', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Women (regardless of menopausal status) or men ≥18 years of age (or per local regulations). The participant has confirmed HR+, HER2-, early stage resected invasive breast cancer without evidence of distant metastases. The participant must have undergone definitive surgery of the primary breast tumor. The participant must have tumor tissue from breast (preferred) or lymph node for exploratory biomarker analysis available prior to randomization. Pathologic lymph node involvement and at least one of the following indicating a higher risk of recurrence: 4 or more positive axillary lymph nodes Tumor size of at least 5 centimeters Grade 3 defined as at least 8 points on the Bloom Richardson grading system Ki-67 index by central analysis of ≥20% on untreated breast tissue The participant must be randomized within 16 months from the time of definitive breast cancer surgery. The participant may receive up to 12 weeks of endocrine therapy until randomization following the last non-endocrine therapy (surgery, chemotherapy, or radiation) whichever is last. Participants must have recovered (grade ≤1) from the acute effects of chemotherapy and radiotherapy and from surgical side effects following definitive breast surgery. Women of reproductive potential must have a negative blood pregnancy test and agree to use highly effective contraceptive methods. The participant has a Eastern Cooperative Oncology Group (ECOG) performance status ≤1. The participant has adequate organ function. The participant is able to swallow oral medications.', 'Exclusion Criteria': 'Exclusion Criteria: Metastatic disease (including contralateral axillary lymph nodes) or node-negative disease. Participants with inflammatory breast cancer. Participants with a history of previous breast cancer, with the exception of ipsilateral ductal carcinoma in situ (DCIS) treated by locoregional therapy alone ≥5 years ago. Participants with a history of contralateral DCIS treated by local regional therapy at any time may be eligible. Participants with a history of any other cancer (except non-melanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission with no therapy for a minimum of 5 years from the date of randomization are excluded. Females who are pregnant or lactating. The participant has previously received treatment with any CDK4 and CDK6 inhibitor. The participant is receiving concurrent exogenous reproductive hormone therapy (for example, birth control pills, hormone replacement therapy, or megestrol acetate). The participant has previously received endocrine therapy for breast cancer prevention (tamoxifen or aromatase inhibitors) or raloxifene. The participant has serious preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study. The participant has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin or sudden cardiac arrest. Any participant with a history of venous thromboembolism (VTE). The participant has active systemic infections or viral load. The participant has received an experimental treatment in a clinical trial within the last 30 days or 5 half-lives, whichever is longer.'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: HR-Positive, HER2-Negative'}
|
{'Official Title': 'A Randomized, Open-Label, Phase 3 Study of Abemaciclib Combined With Standard Adjuvant Endocrine Therapy Versus Standard Adjuvant Endocrine Therapy Alone in Patients With High Risk, Node Positive, Early Stage, Hormone Receptor Positive, Human Epidermal Receptor 2 Negative, Breast Cancer', 'Brief Summary': 'The purpose of this study is to evaluate the safety and efficacy of the study drug abemaciclib in participants with high risk, node positive, early stage, hormone receptor positive (HR+), human epidermal receptor 2 negative (HER2-), breast cancer.', 'Condition': 'Breast Cancer', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Women (regardless of menopausal status) or men ≥18 years of age (or per local regulations). The participant has confirmed HR+, HER2-, early stage resected invasive breast cancer without evidence of distant metastases. The participant must have undergone definitive surgery of the primary breast tumor. The participant must have tumor tissue from breast (preferred) or lymph node for exploratory biomarker analysis available prior to randomization. Pathologic lymph node involvement and at least one of the following indicating a higher risk of recurrence: 4 or more positive axillary lymph nodes Tumor size of at least 5 centimeters Grade 3 defined as at least 8 points on the Bloom Richardson grading system Ki-67 index by central analysis of ≥20% on untreated breast tissue The participant must be randomized within 16 months from the time of definitive breast cancer surgery. The participant may receive up to 12 weeks of endocrine therapy until randomization following the last non-endocrine therapy (surgery, chemotherapy, or radiation) whichever is last. Participants must have recovered (grade ≤1) from the acute effects of chemotherapy and radiotherapy and from surgical side effects following definitive breast surgery. Women of reproductive potential must have a negative blood pregnancy test and agree to use highly effective contraceptive methods. The participant has a Eastern Cooperative Oncology Group (ECOG) performance status ≤1. The participant has adequate organ function. The participant is able to swallow oral medications.', 'Exclusion Criteria': 'Exclusion Criteria: Metastatic disease (including contralateral axillary lymph nodes) or node-negative disease. Participants with inflammatory breast cancer. Participants with a history of previous breast cancer, with the exception of ipsilateral ductal carcinoma in situ (DCIS) treated by locoregional therapy alone ≥5 years ago. Participants with a history of contralateral DCIS treated by local regional therapy at any time may be eligible. Participants with a history of any other cancer (except non-melanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission with no therapy for a minimum of 5 years from the date of randomization are excluded. Females who are pregnant or lactating. The participant has previously received treatment with any CDK4 and CDK6 inhibitor. The participant is receiving concurrent exogenous reproductive hormone therapy (for example, birth control pills, hormone replacement therapy, or megestrol acetate). The participant has previously received endocrine therapy for breast cancer prevention (tamoxifen or aromatase inhibitors) or raloxifene. The participant has serious preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study. The participant has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin or sudden cardiac arrest. Any participant with a history of venous thromboembolism (VTE). The participant has active systemic infections or viral load. The participant has received an experimental treatment in a clinical trial within the last 30 days or 5 half-lives, whichever is longer.'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: HR-Positive, HER2-Negative'}
|
{'Official Title': 'A Phase II Study of U3-1402 in Patients With Metastatic Breast Cancer', 'Brief Summary': 'This study is to evaluate safety and efficacy of an antibody drug conjugate U3-1402 in patients with locally advanced or metastatic breast cancer (MBC).', 'Condition': 'Metastatic Breast Cancer Locally Advanced Breast Cancer', 'Detailed Description': 'U3-1302 is an antibody drug conjugate comprising a recombinant fully human anti HER3 monoclonal antibody linked to a linker containing topoisomerase I inhibitor. This study is a phase II study of U3-1402 in subjects with MBC who have received no prior anti HER2 therapy. The study will be conducted in 3 parts (Part A, Part B, and Part Z). All enrolled subjects in part A will undergo pretreatment biopsies to determine if subjects with particular biomarker expression (ER/PR/HER2/HER3) show preliminary efficacy after an analysis is performed at 24 weeks. Part B will enroll subgroups of subjects that will be defined from part A based on ER/PR/HER2/HER3 expression and will be evaluated for efficacy analysis. Part Z will enroll additional 21 subjects with HER2+ MBC.', 'Inclusion Criteria': "Inclusion Criteria: Patients must meet the following criteria in order to be included in the research study: Written informed consent, according to local guidelines, signed and dated by the patient or by a legal guardian prior to the performance of any study-specific procedures, sampling, or analyses Women and men at least 18 years-of-age at the time of signature of the informed consent form (ICF) Histologically documented locally advanced or metastatic breast cancer Triple-negative breast cancer patients should have received at least 1 but no more than 3 prior lines of chemotherapy in the metastatic setting Parts A and B (HER2-negative, ER-positive) patients only: HR+ breast cancer patients should have received prior treatment with endocrine therapy +CDK 4/6 inhibitor. No limit to prior endocrine therapy regimens but no more than 2 prior chemotherapy regimens in the metastatic setting Part Z patients only should have documented HER2-positive expression as per American Society of Clinical Oncology - College of American Pathologists guidelines based on local testing. Part Z patients only should have had prior treatment with at least 2 anti-HER2 therapies, 1 of which must be T-DXd. These patients must have experienced disease progression after receiving T-DXd. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (bone-only disease excluded) Patients who have received radiation or surgery for brain metastases are eligible if therapy was completed ≥4 weeks prior to initiation of study treatment (2 weeks for patients who received palliative radiation therapy), there is no evidence of central nervous system disease progression on a scan or mild neurologic symptoms, and there is no requirement for chronic corticosteroid therapy for the treatment of brain metastases Willingness to undergo pre-treatment biopsy and on-treatment biopsies. Must have a tumor amenable to pre-treatment biopsy (unless archived tissue is available and was obtained within 2 months prior to starting treatment) and on-treatment biopsy (excludes bone lesions and previously irradiated lesions). Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1 Has adequate organ function within 7 days before the start of study treatment, defined as: Platelet count ≥100 × 10^9/L Hemoglobin (Hb) ≥9 g/dL (transfusion and/or growth factor support allowed) Absolute neutrophil count ≥1.5 × 10^9/L Prothrombin time (PT) and partial thromboplastin time (PTT) ≤1.5 × the upper limit of normal (ULN), except for patients on coumadin-derivative anticoagulants or other similar anticoagulant therapy, who must have PT-international normalized ratio (INR) within therapeutic range as deemed appropriate by the Investigator. Serum creatinine ≤1.5 × ULN, or creatinine clearance ≥ 50 mL/min as calculated using the modified Cockcroft-Gault equation; confirmation of creatinine clearance is only required when creatinine is >1.5 × ULN. AST/ALT ≤3 × ULN (if liver metastases are present, ≤5 × ULN) Total bilirubin ≤1.5 × ULN if no liver metastases or < 3 × ULN in the presence of documented Gilbert's syndrome or liver metastases Serum albumin ≥ 2.5 g/dL Male patients with female partners of childbearing potential and female patients of childbearing potential are required to use two forms of acceptable contraception, including one barrier method, during their participation in the study and for at least 7 months following last dose. Male patients must also refrain from donating sperm during their participation in the study.", 'Exclusion Criteria': "Exclusion Criteria: Patients who meet any of the following criteria will be excluded from study entry: Exclusion criteria for Part A and B (HER2-negative) and Part Z (HER2-positive) cohorts: Treatment with any of the following: Any systemic anti-cancer chemotherapy, small molecule, biologic, hormonal agent, or immune checkpoint inhibitor therapy from a previous treatment regimen or clinical study within 21 days prior to the first dose of U3-1402. Prior treatment with any HER3 targeting agent Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study drug treatment Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug treatment, or palliative radiation therapy within 2 weeks of the first dose of study drug treatment Chloroquine /hydroxychloroquine ≤14 days prior to the first dose of study drug treatment. Has any hypersensitivity to drug substances or inactive ingredients in drug product. Has any history of ILD (including pulmonary fibrosis or radiation pneumonitis), has clinically significant ILD, or is suspected to have such disease by imaging during screening. If imaging findings are unlikely to indicate a history of pneumonitis, then the Investigator should discuss the considerations with the Medical Monitor about potential enrollment and record the reasoning in the source documentation. Clinically severe pulmonary compromise (based on Investigator's assessment) resulting from intercurrent pulmonary illnesses including, but not limited to: any underlying pulmonary disorder (e.g., pulmonary emboli, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion) any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement (e.g., rheumatoid arthritis, Sjögren's syndrome, sarcoidosis) OR prior pneumonectomy With the exception of alopecia, any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or baseline at the time of starting study treatment. Note: patients with chronic Grade 2 toxicities who are asymptomatic or adequately managed with stable medication may be eligible with approval by the Medical Monitor. Leptomeningeal metastases or spinal cord compression due to disease Women who are pregnant, nursing, or plan to become pregnant while in the study and for at least 7 months after the last administration of study treatment Men who plan to father a child while in the study and for at least 7 months after the last administration of study treatment Any of the following cardiac criteria currently or within the last 6 months: Mean resting corrected QT interval using Fridericia's formula (QTcF) prolongation to >470 ms for females and >450 ms for males in three successive screening measurements Any clinically important abnormalities (as assessed by the Investigator) in rhythm, conduction, or morphology of resting electrocardiograms (ECGs), e.g., complete left bundle branch block, third-degree heart block Congestive heart failure (New York Heart Association ≥ Grade 2 [Appendix D]) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age Patients with a left ventricular ejection fraction (LVEF) <50% Has known clinically significant corneal disease from prior therapies such as drug-induced keratitis Is receiving chronic systemic corticosteroids dosed at >10 mg prednisone or equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior to Cycle 1 Day 1. Patients who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the study. As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, uncontrolled diabetes mellitus, active bleeding diatheses, or active infection, including hepatitis B, hepatitis C, and human immunodeficiency virus. Screening for chronic conditions is not required. Presence of other active invasive cancers other than the one treated in this study within 3 years prior to screening, except appropriately treated basal cell carcinoma of the skin, in situ carcinoma of uterine cervix, or other local tumors considered cured by local treatment Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol and/or follow-up procedures outlined in the protocol. Additional exclusion criteria only for Part A and B (HER2-negative) cohorts: Prior treatment with an antibody drug conjugate that consists of an exatecan derivative that is a topoisomerase I inhibitor (e.g., T-DXd, DS-1062a, and DS-7300a) Patients with HER2+ breast cancer per ASCO-CAP guidelines Additional exclusion criteria only for Part Z (HER2-positive) cohort: Treatment with any of the following: Prior treatment with an antibody drug conjugate that consists of an exatecan derivative that is a topoisomerase I inhibitor except T-DXd Prior treatment with T-DXd within 4 weeks prior to the first dose of U3-1402 Uncontrolled or significant cardiovascular disease, including history of myocardial infarction within 6 months before enrollment A severe reaction or severe tolerability issues that necessitated stopping treatment with T-DXd Any unresolved toxicities from prior therapy with T-DXd."}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: HER2-Negative, HR-Positive Exclude: HER2-positive'}
|
{'Official Title': 'A Phase II Study of U3-1402 in Patients With Metastatic Breast Cancer', 'Brief Summary': 'This study is to evaluate safety and efficacy of an antibody drug conjugate U3-1402 in patients with locally advanced or metastatic breast cancer (MBC).', 'Condition': 'Metastatic Breast Cancer Locally Advanced Breast Cancer', 'Detailed Description': 'U3-1302 is an antibody drug conjugate comprising a recombinant fully human anti HER3 monoclonal antibody linked to a linker containing topoisomerase I inhibitor. This study is a phase II study of U3-1402 in subjects with MBC who have received no prior anti HER2 therapy. The study will be conducted in 3 parts (Part A, Part B, and Part Z). All enrolled subjects in part A will undergo pretreatment biopsies to determine if subjects with particular biomarker expression (ER/PR/HER2/HER3) show preliminary efficacy after an analysis is performed at 24 weeks. Part B will enroll subgroups of subjects that will be defined from part A based on ER/PR/HER2/HER3 expression and will be evaluated for efficacy analysis. Part Z will enroll additional 21 subjects with HER2+ MBC.', 'Inclusion Criteria': "Inclusion Criteria: Patients must meet the following criteria in order to be included in the research study: Written informed consent, according to local guidelines, signed and dated by the patient or by a legal guardian prior to the performance of any study-specific procedures, sampling, or analyses Women and men at least 18 years-of-age at the time of signature of the informed consent form (ICF) Histologically documented locally advanced or metastatic breast cancer Triple-negative breast cancer patients should have received at least 1 but no more than 3 prior lines of chemotherapy in the metastatic setting Parts A and B (HER2-negative, ER-positive) patients only: HR+ breast cancer patients should have received prior treatment with endocrine therapy +CDK 4/6 inhibitor. No limit to prior endocrine therapy regimens but no more than 2 prior chemotherapy regimens in the metastatic setting Part Z patients only should have documented HER2-positive expression as per American Society of Clinical Oncology - College of American Pathologists guidelines based on local testing. Part Z patients only should have had prior treatment with at least 2 anti-HER2 therapies, 1 of which must be T-DXd. These patients must have experienced disease progression after receiving T-DXd. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (bone-only disease excluded) Patients who have received radiation or surgery for brain metastases are eligible if therapy was completed ≥4 weeks prior to initiation of study treatment (2 weeks for patients who received palliative radiation therapy), there is no evidence of central nervous system disease progression on a scan or mild neurologic symptoms, and there is no requirement for chronic corticosteroid therapy for the treatment of brain metastases Willingness to undergo pre-treatment biopsy and on-treatment biopsies. Must have a tumor amenable to pre-treatment biopsy (unless archived tissue is available and was obtained within 2 months prior to starting treatment) and on-treatment biopsy (excludes bone lesions and previously irradiated lesions). Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1 Has adequate organ function within 7 days before the start of study treatment, defined as: Platelet count ≥100 × 10^9/L Hemoglobin (Hb) ≥9 g/dL (transfusion and/or growth factor support allowed) Absolute neutrophil count ≥1.5 × 10^9/L Prothrombin time (PT) and partial thromboplastin time (PTT) ≤1.5 × the upper limit of normal (ULN), except for patients on coumadin-derivative anticoagulants or other similar anticoagulant therapy, who must have PT-international normalized ratio (INR) within therapeutic range as deemed appropriate by the Investigator. Serum creatinine ≤1.5 × ULN, or creatinine clearance ≥ 50 mL/min as calculated using the modified Cockcroft-Gault equation; confirmation of creatinine clearance is only required when creatinine is >1.5 × ULN. AST/ALT ≤3 × ULN (if liver metastases are present, ≤5 × ULN) Total bilirubin ≤1.5 × ULN if no liver metastases or < 3 × ULN in the presence of documented Gilbert's syndrome or liver metastases Serum albumin ≥ 2.5 g/dL Male patients with female partners of childbearing potential and female patients of childbearing potential are required to use two forms of acceptable contraception, including one barrier method, during their participation in the study and for at least 7 months following last dose. Male patients must also refrain from donating sperm during their participation in the study.", 'Exclusion Criteria': "Exclusion Criteria: Patients who meet any of the following criteria will be excluded from study entry: Exclusion criteria for Part A and B (HER2-negative) and Part Z (HER2-positive) cohorts: Treatment with any of the following: Any systemic anti-cancer chemotherapy, small molecule, biologic, hormonal agent, or immune checkpoint inhibitor therapy from a previous treatment regimen or clinical study within 21 days prior to the first dose of U3-1402. Prior treatment with any HER3 targeting agent Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study drug treatment Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug treatment, or palliative radiation therapy within 2 weeks of the first dose of study drug treatment Chloroquine /hydroxychloroquine ≤14 days prior to the first dose of study drug treatment. Has any hypersensitivity to drug substances or inactive ingredients in drug product. Has any history of ILD (including pulmonary fibrosis or radiation pneumonitis), has clinically significant ILD, or is suspected to have such disease by imaging during screening. If imaging findings are unlikely to indicate a history of pneumonitis, then the Investigator should discuss the considerations with the Medical Monitor about potential enrollment and record the reasoning in the source documentation. Clinically severe pulmonary compromise (based on Investigator's assessment) resulting from intercurrent pulmonary illnesses including, but not limited to: any underlying pulmonary disorder (e.g., pulmonary emboli, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion) any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement (e.g., rheumatoid arthritis, Sjögren's syndrome, sarcoidosis) OR prior pneumonectomy With the exception of alopecia, any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or baseline at the time of starting study treatment. Note: patients with chronic Grade 2 toxicities who are asymptomatic or adequately managed with stable medication may be eligible with approval by the Medical Monitor. Leptomeningeal metastases or spinal cord compression due to disease Women who are pregnant, nursing, or plan to become pregnant while in the study and for at least 7 months after the last administration of study treatment Men who plan to father a child while in the study and for at least 7 months after the last administration of study treatment Any of the following cardiac criteria currently or within the last 6 months: Mean resting corrected QT interval using Fridericia's formula (QTcF) prolongation to >470 ms for females and >450 ms for males in three successive screening measurements Any clinically important abnormalities (as assessed by the Investigator) in rhythm, conduction, or morphology of resting electrocardiograms (ECGs), e.g., complete left bundle branch block, third-degree heart block Congestive heart failure (New York Heart Association ≥ Grade 2 [Appendix D]) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age Patients with a left ventricular ejection fraction (LVEF) <50% Has known clinically significant corneal disease from prior therapies such as drug-induced keratitis Is receiving chronic systemic corticosteroids dosed at >10 mg prednisone or equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior to Cycle 1 Day 1. Patients who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the study. As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, uncontrolled diabetes mellitus, active bleeding diatheses, or active infection, including hepatitis B, hepatitis C, and human immunodeficiency virus. Screening for chronic conditions is not required. Presence of other active invasive cancers other than the one treated in this study within 3 years prior to screening, except appropriately treated basal cell carcinoma of the skin, in situ carcinoma of uterine cervix, or other local tumors considered cured by local treatment Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol and/or follow-up procedures outlined in the protocol. Additional exclusion criteria only for Part A and B (HER2-negative) cohorts: Prior treatment with an antibody drug conjugate that consists of an exatecan derivative that is a topoisomerase I inhibitor (e.g., T-DXd, DS-1062a, and DS-7300a) Patients with HER2+ breast cancer per ASCO-CAP guidelines Additional exclusion criteria only for Part Z (HER2-positive) cohort: Treatment with any of the following: Prior treatment with an antibody drug conjugate that consists of an exatecan derivative that is a topoisomerase I inhibitor except T-DXd Prior treatment with T-DXd within 4 weeks prior to the first dose of U3-1402 Uncontrolled or significant cardiovascular disease, including history of myocardial infarction within 6 months before enrollment A severe reaction or severe tolerability issues that necessitated stopping treatment with T-DXd Any unresolved toxicities from prior therapy with T-DXd."}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: HER2-Negative, HR-Positive, Regardless of HER3 expression Exclude: HER2-positive'}
|
{'Official Title': 'A Phase II Study of U3-1402 in Patients With Metastatic Breast Cancer', 'Brief Summary': 'This study is to evaluate safety and efficacy of an antibody drug conjugate U3-1402 in patients with locally advanced or metastatic breast cancer (MBC).', 'Condition': 'Metastatic Breast Cancer Locally Advanced Breast Cancer', 'Detailed Description': 'U3-1302 is an antibody drug conjugate comprising a recombinant fully human anti HER3 monoclonal antibody linked to a linker containing topoisomerase I inhibitor. This study is a phase II study of U3-1402 in subjects with MBC who have received no prior anti HER2 therapy. The study will be conducted in 3 parts (Part A, Part B, and Part Z). All enrolled subjects in part A will undergo pretreatment biopsies to determine if subjects with particular biomarker expression (ER/PR/HER2/HER3) show preliminary efficacy after an analysis is performed at 24 weeks. Part B will enroll subgroups of subjects that will be defined from part A based on ER/PR/HER2/HER3 expression and will be evaluated for efficacy analysis. Part Z will enroll additional 21 subjects with HER2+ MBC.', 'Inclusion Criteria': "Inclusion Criteria: Patients must meet the following criteria in order to be included in the research study: Written informed consent, according to local guidelines, signed and dated by the patient or by a legal guardian prior to the performance of any study-specific procedures, sampling, or analyses Women and men at least 18 years-of-age at the time of signature of the informed consent form (ICF) Histologically documented locally advanced or metastatic breast cancer Triple-negative breast cancer patients should have received at least 1 but no more than 3 prior lines of chemotherapy in the metastatic setting Parts A and B (HER2-negative, ER-positive) patients only: HR+ breast cancer patients should have received prior treatment with endocrine therapy +CDK 4/6 inhibitor. No limit to prior endocrine therapy regimens but no more than 2 prior chemotherapy regimens in the metastatic setting Part Z patients only should have documented HER2-positive expression as per American Society of Clinical Oncology - College of American Pathologists guidelines based on local testing. Part Z patients only should have had prior treatment with at least 2 anti-HER2 therapies, 1 of which must be T-DXd. These patients must have experienced disease progression after receiving T-DXd. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (bone-only disease excluded) Patients who have received radiation or surgery for brain metastases are eligible if therapy was completed ≥4 weeks prior to initiation of study treatment (2 weeks for patients who received palliative radiation therapy), there is no evidence of central nervous system disease progression on a scan or mild neurologic symptoms, and there is no requirement for chronic corticosteroid therapy for the treatment of brain metastases Willingness to undergo pre-treatment biopsy and on-treatment biopsies. Must have a tumor amenable to pre-treatment biopsy (unless archived tissue is available and was obtained within 2 months prior to starting treatment) and on-treatment biopsy (excludes bone lesions and previously irradiated lesions). Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1 Has adequate organ function within 7 days before the start of study treatment, defined as: Platelet count ≥100 × 10^9/L Hemoglobin (Hb) ≥9 g/dL (transfusion and/or growth factor support allowed) Absolute neutrophil count ≥1.5 × 10^9/L Prothrombin time (PT) and partial thromboplastin time (PTT) ≤1.5 × the upper limit of normal (ULN), except for patients on coumadin-derivative anticoagulants or other similar anticoagulant therapy, who must have PT-international normalized ratio (INR) within therapeutic range as deemed appropriate by the Investigator. Serum creatinine ≤1.5 × ULN, or creatinine clearance ≥ 50 mL/min as calculated using the modified Cockcroft-Gault equation; confirmation of creatinine clearance is only required when creatinine is >1.5 × ULN. AST/ALT ≤3 × ULN (if liver metastases are present, ≤5 × ULN) Total bilirubin ≤1.5 × ULN if no liver metastases or < 3 × ULN in the presence of documented Gilbert's syndrome or liver metastases Serum albumin ≥ 2.5 g/dL Male patients with female partners of childbearing potential and female patients of childbearing potential are required to use two forms of acceptable contraception, including one barrier method, during their participation in the study and for at least 7 months following last dose. Male patients must also refrain from donating sperm during their participation in the study.", 'Exclusion Criteria': "Exclusion Criteria: Patients who meet any of the following criteria will be excluded from study entry: Exclusion criteria for Part A and B (HER2-negative) and Part Z (HER2-positive) cohorts: Treatment with any of the following: Any systemic anti-cancer chemotherapy, small molecule, biologic, hormonal agent, or immune checkpoint inhibitor therapy from a previous treatment regimen or clinical study within 21 days prior to the first dose of U3-1402. Prior treatment with any HER3 targeting agent Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study drug treatment Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug treatment, or palliative radiation therapy within 2 weeks of the first dose of study drug treatment Chloroquine /hydroxychloroquine ≤14 days prior to the first dose of study drug treatment. Has any hypersensitivity to drug substances or inactive ingredients in drug product. Has any history of ILD (including pulmonary fibrosis or radiation pneumonitis), has clinically significant ILD, or is suspected to have such disease by imaging during screening. If imaging findings are unlikely to indicate a history of pneumonitis, then the Investigator should discuss the considerations with the Medical Monitor about potential enrollment and record the reasoning in the source documentation. Clinically severe pulmonary compromise (based on Investigator's assessment) resulting from intercurrent pulmonary illnesses including, but not limited to: any underlying pulmonary disorder (e.g., pulmonary emboli, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion) any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement (e.g., rheumatoid arthritis, Sjögren's syndrome, sarcoidosis) OR prior pneumonectomy With the exception of alopecia, any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or baseline at the time of starting study treatment. Note: patients with chronic Grade 2 toxicities who are asymptomatic or adequately managed with stable medication may be eligible with approval by the Medical Monitor. Leptomeningeal metastases or spinal cord compression due to disease Women who are pregnant, nursing, or plan to become pregnant while in the study and for at least 7 months after the last administration of study treatment Men who plan to father a child while in the study and for at least 7 months after the last administration of study treatment Any of the following cardiac criteria currently or within the last 6 months: Mean resting corrected QT interval using Fridericia's formula (QTcF) prolongation to >470 ms for females and >450 ms for males in three successive screening measurements Any clinically important abnormalities (as assessed by the Investigator) in rhythm, conduction, or morphology of resting electrocardiograms (ECGs), e.g., complete left bundle branch block, third-degree heart block Congestive heart failure (New York Heart Association ≥ Grade 2 [Appendix D]) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age Patients with a left ventricular ejection fraction (LVEF) <50% Has known clinically significant corneal disease from prior therapies such as drug-induced keratitis Is receiving chronic systemic corticosteroids dosed at >10 mg prednisone or equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior to Cycle 1 Day 1. Patients who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the study. As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, uncontrolled diabetes mellitus, active bleeding diatheses, or active infection, including hepatitis B, hepatitis C, and human immunodeficiency virus. Screening for chronic conditions is not required. Presence of other active invasive cancers other than the one treated in this study within 3 years prior to screening, except appropriately treated basal cell carcinoma of the skin, in situ carcinoma of uterine cervix, or other local tumors considered cured by local treatment Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol and/or follow-up procedures outlined in the protocol. Additional exclusion criteria only for Part A and B (HER2-negative) cohorts: Prior treatment with an antibody drug conjugate that consists of an exatecan derivative that is a topoisomerase I inhibitor (e.g., T-DXd, DS-1062a, and DS-7300a) Patients with HER2+ breast cancer per ASCO-CAP guidelines Additional exclusion criteria only for Part Z (HER2-positive) cohort: Treatment with any of the following: Prior treatment with an antibody drug conjugate that consists of an exatecan derivative that is a topoisomerase I inhibitor except T-DXd Prior treatment with T-DXd within 4 weeks prior to the first dose of U3-1402 Uncontrolled or significant cardiovascular disease, including history of myocardial infarction within 6 months before enrollment A severe reaction or severe tolerability issues that necessitated stopping treatment with T-DXd Any unresolved toxicities from prior therapy with T-DXd."}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: HER2-Positive Exclude:HER2-Negative'}
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{'Official Title': 'A Phase 3 Multicenter, Randomized, Open Label, Active-controlled, Study of AMG 510 Versus Docetaxel for the Treatment of Previously Treated Locally Advanced and Unresectable or Metastatic NSCLC Subjects With Mutated KRAS p.G12C', 'Brief Summary': 'A Phase 3 Study to Compare AMG 510 with Docetaxel in Non Small Cell Lung Cancer (NSCLC) subjects with KRAS p. G12c mutation', 'Condition': 'KRAS p, G12c Mutated /Advanced Metastatic NSCLC', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Men or women greater than or equal to 18 years old. ECOG ≤ 1 Pathologically documented, previously treated, locally-advanced and unresectable or metastatic NSCLC with KRAS p.G12C mutation confirmed through central testing or have documentation of KRAS p.G12C mutation through Amgen Study 20190294 prior to enrollment', 'Exclusion Criteria': 'Exclusion Criteria: Active brain metastases Myocardial infarction within 6 months of study day 1 Gastrointestinal (GI) tract disease causing the inability to take oral medication'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'KRASG12C mutated'}
|
{'Official Title': 'A Phase 3 Multicenter, Randomized, Open Label, Active-controlled, Study of AMG 510 Versus Docetaxel for the Treatment of Previously Treated Locally Advanced and Unresectable or Metastatic NSCLC Subjects With Mutated KRAS p.G12C', 'Brief Summary': 'A Phase 3 Study to Compare AMG 510 with Docetaxel in Non Small Cell Lung Cancer (NSCLC) subjects with KRAS p. G12c mutation', 'Condition': 'KRAS p, G12c Mutated /Advanced Metastatic NSCLC', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Men or women greater than or equal to 18 years old. ECOG ≤ 1 Pathologically documented, previously treated, locally-advanced and unresectable or metastatic NSCLC with KRAS p.G12C mutation confirmed through central testing or have documentation of KRAS p.G12C mutation through Amgen Study 20190294 prior to enrollment', 'Exclusion Criteria': 'Exclusion Criteria: Active brain metastases Myocardial infarction within 6 months of study day 1 Gastrointestinal (GI) tract disease causing the inability to take oral medication'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'KRASG12C mutated'}
|
{'Official Title': 'A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Advanced Liver Cancers (Morpheus-Liver)', 'Brief Summary': 'This is a Phase Ib/II, open-label, multicenter, randomized umbrella study in participants with advanced liver cancers. The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, modify the participant population, or introduce additional cohorts of participants with other types of advanced primary liver cancer. Cohort 1 will enroll participants with locally advanced or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy for their disease. Eligible participants will initially be randomly assigned to one of several treatment arms (Stage 1). Participants who experience loss of clinical benefit or unacceptable toxicity during Stage 1 may be eligible to receive treatment with a different treatment combination (Stage 2). When a Stage 2 treatment combination is available, this will be introduced by amending the protocol.', 'Condition': 'Advanced Liver Cancers', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Stage 1 Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 within 7 days prior to randomization Locally advanced or metastatic and/or unresectable hepatocellular carcinoma (HCC) with diagnosis confirmed by histology/cytology or clinically by American Association for the Study of Liver Diseases criteria in cirrhotic patients Child-Pugh class A within 7 days prior to randomization Disease that is not amenable to curative surgical and/or locoregional therapies No prior systemic treatment for HCC Life expectancy >= 3 months Availability of a representative tumor specimen that is suitable for determination of PD-L1 and/or additional biomarker status via central testing Stage 1 and Stage 2 Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1 Adequate hematologic and end-organ function within 7 days prior to initiation of study treatment Documented virology status of hepatitis, as confirmed by screening tests for hepatitis B virus - (HBV) and hepatitis C virus (HCV) Negative HIV test at screening For women of childbearing potential: agreement to remain abstinent or use contraception and for men: agreement to remain abstinent or use contraception, and agreement to refrain from donating sperm Stage 2 ECOG Performance Status of 0, 1, or 2 Ability to initiate Stage 2 treatment within 3 months after experiencing unacceptable toxicity not related to atezolizumab or RO7247669 or loss of clinical benefit as determined by the investigator while receiving Stage 1 treatment Availability of a tumor specimen from a biopsy performed upon discontinuation of Stage 1 (if deemed clinically feasible)', 'Exclusion Criteria': 'Exclusion Criteria: Stage 1 Prior treatment with CD137 agonists or immune checkpoint inhibitors Treatment with investigational therapy within 28 days prior to initiation of study Treatment with locoregional therapy to liver within 28 days prior to initiation of study, or non-recovery from side effects of any such procedure Untreated or incompletely treated esophageal and/or gastric varices with bleeding or at high risk for bleeding Prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study AEs from prior anti-cancer therapy that have not resolved to Grade <= 1 or better, with the exception of alopecia of any grade Inadequately controlled hypertension History of hypertensive crisis or hypertensive encephalopathy Significant vascular disease History of hemoptysis within 1 month prior to initiation of study Evidence of bleeding diathesis or significant coagulopathy Current or recent use of asprin (>325 mg/day) or treatment with clopidogrel, dipyramidole, ticlopidine, or cilostazol Current or recent use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purpose Core biopsy or other minor surgical procedure within 3 days prior to initiation of study History of abdominal or tracheoesophageal fistula, GI perforation, or intra-abdominal abscess, intestinal obstruction and/or clinical signs/symptoms of GI obstruction Evidence of abdominal free air not explained by paracentesis or recent surgery Serious, non-healing/dehiscing wound, active ulcer, or untreated bone fracture Grade >=2 proteinuria Metastatic disease involving major airways/blood vessels, or centrally located mediastinal tumor masses of large volume History of intra-abdominal inflammatory process Radiotherapy within 28 days or abdominal/pelvic radiotherapy within 60 days prior to initiation of study with the exception of palliative radiotherapy to bone lesions within 7 days prior to initiation of study Major surgery, open biopsy, or significant traumatic injury within 28 days prior to initiation of study; or abdominal surgery, abdominal interventions or significant abdominal traumatic injury within 60 days prior to initiation of study; or anticipation of need for major surgery during study or non-recovery from side effects of any such procedure Chronic daily treatment with NSAID Eligible only for control arm Stage 1 and 2 Fibrolamellar or sarcomatoid HCC, or mixed cholangiocarcinoma and HCC History of hepatic encephalopathy Moderate or severe ascites HBV and HCV coinfection Symptomatic, untreated, or actively progressing CNS metastases History of leptomeningeal disease Uncontrolled tumor-related pain Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures Uncontrolled or symptomatic hypercalcemia Active or history of autoimmune disease or immune deficiency History of IPF, organizing pneumonia, drug-induced or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan Active TB Significant CV disease within 3 months prior to initiation of study, unstable arrhythmia, or unstable angina Major surgery, other than for diagnosis, within 4 weeks prior to initiation of study, or anticipated major surgery during study History of malignancy other than HCC within 5 years prior to screening Severe infection within 4 weeks prior to initiation of study Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study Prior allogeneic stem cell or solid organ transplantation Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins Known allergy or hypersensitivity to any of the study drugs or any of their excipients Treatment with systemic immunostimulatory, immunosuppressive agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study Patients entering Stage 2: immunotherapy-related adverse events that have not resolved to Grade 1 or better or to baseline at time of consent'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: PD-L1'}
|
{'Official Title': 'A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Advanced Liver Cancers (Morpheus-Liver)', 'Brief Summary': 'This is a Phase Ib/II, open-label, multicenter, randomized umbrella study in participants with advanced liver cancers. The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, modify the participant population, or introduce additional cohorts of participants with other types of advanced primary liver cancer. Cohort 1 will enroll participants with locally advanced or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy for their disease. Eligible participants will initially be randomly assigned to one of several treatment arms (Stage 1). Participants who experience loss of clinical benefit or unacceptable toxicity during Stage 1 may be eligible to receive treatment with a different treatment combination (Stage 2). When a Stage 2 treatment combination is available, this will be introduced by amending the protocol.', 'Condition': 'Advanced Liver Cancers', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Stage 1 Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 within 7 days prior to randomization Locally advanced or metastatic and/or unresectable hepatocellular carcinoma (HCC) with diagnosis confirmed by histology/cytology or clinically by American Association for the Study of Liver Diseases criteria in cirrhotic patients Child-Pugh class A within 7 days prior to randomization Disease that is not amenable to curative surgical and/or locoregional therapies No prior systemic treatment for HCC Life expectancy >= 3 months Availability of a representative tumor specimen that is suitable for determination of PD-L1 and/or additional biomarker status via central testing Stage 1 and Stage 2 Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1 Adequate hematologic and end-organ function within 7 days prior to initiation of study treatment Documented virology status of hepatitis, as confirmed by screening tests for hepatitis B virus - (HBV) and hepatitis C virus (HCV) Negative HIV test at screening For women of childbearing potential: agreement to remain abstinent or use contraception and for men: agreement to remain abstinent or use contraception, and agreement to refrain from donating sperm Stage 2 ECOG Performance Status of 0, 1, or 2 Ability to initiate Stage 2 treatment within 3 months after experiencing unacceptable toxicity not related to atezolizumab or RO7247669 or loss of clinical benefit as determined by the investigator while receiving Stage 1 treatment Availability of a tumor specimen from a biopsy performed upon discontinuation of Stage 1 (if deemed clinically feasible)', 'Exclusion Criteria': 'Exclusion Criteria: Stage 1 Prior treatment with CD137 agonists or immune checkpoint inhibitors Treatment with investigational therapy within 28 days prior to initiation of study Treatment with locoregional therapy to liver within 28 days prior to initiation of study, or non-recovery from side effects of any such procedure Untreated or incompletely treated esophageal and/or gastric varices with bleeding or at high risk for bleeding Prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study AEs from prior anti-cancer therapy that have not resolved to Grade <= 1 or better, with the exception of alopecia of any grade Inadequately controlled hypertension History of hypertensive crisis or hypertensive encephalopathy Significant vascular disease History of hemoptysis within 1 month prior to initiation of study Evidence of bleeding diathesis or significant coagulopathy Current or recent use of asprin (>325 mg/day) or treatment with clopidogrel, dipyramidole, ticlopidine, or cilostazol Current or recent use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purpose Core biopsy or other minor surgical procedure within 3 days prior to initiation of study History of abdominal or tracheoesophageal fistula, GI perforation, or intra-abdominal abscess, intestinal obstruction and/or clinical signs/symptoms of GI obstruction Evidence of abdominal free air not explained by paracentesis or recent surgery Serious, non-healing/dehiscing wound, active ulcer, or untreated bone fracture Grade >=2 proteinuria Metastatic disease involving major airways/blood vessels, or centrally located mediastinal tumor masses of large volume History of intra-abdominal inflammatory process Radiotherapy within 28 days or abdominal/pelvic radiotherapy within 60 days prior to initiation of study with the exception of palliative radiotherapy to bone lesions within 7 days prior to initiation of study Major surgery, open biopsy, or significant traumatic injury within 28 days prior to initiation of study; or abdominal surgery, abdominal interventions or significant abdominal traumatic injury within 60 days prior to initiation of study; or anticipation of need for major surgery during study or non-recovery from side effects of any such procedure Chronic daily treatment with NSAID Eligible only for control arm Stage 1 and 2 Fibrolamellar or sarcomatoid HCC, or mixed cholangiocarcinoma and HCC History of hepatic encephalopathy Moderate or severe ascites HBV and HCV coinfection Symptomatic, untreated, or actively progressing CNS metastases History of leptomeningeal disease Uncontrolled tumor-related pain Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures Uncontrolled or symptomatic hypercalcemia Active or history of autoimmune disease or immune deficiency History of IPF, organizing pneumonia, drug-induced or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan Active TB Significant CV disease within 3 months prior to initiation of study, unstable arrhythmia, or unstable angina Major surgery, other than for diagnosis, within 4 weeks prior to initiation of study, or anticipated major surgery during study History of malignancy other than HCC within 5 years prior to screening Severe infection within 4 weeks prior to initiation of study Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study Prior allogeneic stem cell or solid organ transplantation Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins Known allergy or hypersensitivity to any of the study drugs or any of their excipients Treatment with systemic immunostimulatory, immunosuppressive agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study Patients entering Stage 2: immunotherapy-related adverse events that have not resolved to Grade 1 or better or to baseline at time of consent'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: PD-L1'}
|
{'Official Title': 'A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Advanced Liver Cancers (Morpheus-Liver)', 'Brief Summary': 'This is a Phase Ib/II, open-label, multicenter, randomized umbrella study in participants with advanced liver cancers. The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, modify the participant population, or introduce additional cohorts of participants with other types of advanced primary liver cancer. Cohort 1 will enroll participants with locally advanced or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy for their disease. Eligible participants will initially be randomly assigned to one of several treatment arms (Stage 1). Participants who experience loss of clinical benefit or unacceptable toxicity during Stage 1 may be eligible to receive treatment with a different treatment combination (Stage 2). When a Stage 2 treatment combination is available, this will be introduced by amending the protocol.', 'Condition': 'Advanced Liver Cancers', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Stage 1 Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 within 7 days prior to randomization Locally advanced or metastatic and/or unresectable hepatocellular carcinoma (HCC) with diagnosis confirmed by histology/cytology or clinically by American Association for the Study of Liver Diseases criteria in cirrhotic patients Child-Pugh class A within 7 days prior to randomization Disease that is not amenable to curative surgical and/or locoregional therapies No prior systemic treatment for HCC Life expectancy >= 3 months Availability of a representative tumor specimen that is suitable for determination of PD-L1 and/or additional biomarker status via central testing Stage 1 and Stage 2 Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1 Adequate hematologic and end-organ function within 7 days prior to initiation of study treatment Documented virology status of hepatitis, as confirmed by screening tests for hepatitis B virus - (HBV) and hepatitis C virus (HCV) Negative HIV test at screening For women of childbearing potential: agreement to remain abstinent or use contraception and for men: agreement to remain abstinent or use contraception, and agreement to refrain from donating sperm Stage 2 ECOG Performance Status of 0, 1, or 2 Ability to initiate Stage 2 treatment within 3 months after experiencing unacceptable toxicity not related to atezolizumab or RO7247669 or loss of clinical benefit as determined by the investigator while receiving Stage 1 treatment Availability of a tumor specimen from a biopsy performed upon discontinuation of Stage 1 (if deemed clinically feasible)', 'Exclusion Criteria': 'Exclusion Criteria: Stage 1 Prior treatment with CD137 agonists or immune checkpoint inhibitors Treatment with investigational therapy within 28 days prior to initiation of study Treatment with locoregional therapy to liver within 28 days prior to initiation of study, or non-recovery from side effects of any such procedure Untreated or incompletely treated esophageal and/or gastric varices with bleeding or at high risk for bleeding Prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study AEs from prior anti-cancer therapy that have not resolved to Grade <= 1 or better, with the exception of alopecia of any grade Inadequately controlled hypertension History of hypertensive crisis or hypertensive encephalopathy Significant vascular disease History of hemoptysis within 1 month prior to initiation of study Evidence of bleeding diathesis or significant coagulopathy Current or recent use of asprin (>325 mg/day) or treatment with clopidogrel, dipyramidole, ticlopidine, or cilostazol Current or recent use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purpose Core biopsy or other minor surgical procedure within 3 days prior to initiation of study History of abdominal or tracheoesophageal fistula, GI perforation, or intra-abdominal abscess, intestinal obstruction and/or clinical signs/symptoms of GI obstruction Evidence of abdominal free air not explained by paracentesis or recent surgery Serious, non-healing/dehiscing wound, active ulcer, or untreated bone fracture Grade >=2 proteinuria Metastatic disease involving major airways/blood vessels, or centrally located mediastinal tumor masses of large volume History of intra-abdominal inflammatory process Radiotherapy within 28 days or abdominal/pelvic radiotherapy within 60 days prior to initiation of study with the exception of palliative radiotherapy to bone lesions within 7 days prior to initiation of study Major surgery, open biopsy, or significant traumatic injury within 28 days prior to initiation of study; or abdominal surgery, abdominal interventions or significant abdominal traumatic injury within 60 days prior to initiation of study; or anticipation of need for major surgery during study or non-recovery from side effects of any such procedure Chronic daily treatment with NSAID Eligible only for control arm Stage 1 and 2 Fibrolamellar or sarcomatoid HCC, or mixed cholangiocarcinoma and HCC History of hepatic encephalopathy Moderate or severe ascites HBV and HCV coinfection Symptomatic, untreated, or actively progressing CNS metastases History of leptomeningeal disease Uncontrolled tumor-related pain Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures Uncontrolled or symptomatic hypercalcemia Active or history of autoimmune disease or immune deficiency History of IPF, organizing pneumonia, drug-induced or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan Active TB Significant CV disease within 3 months prior to initiation of study, unstable arrhythmia, or unstable angina Major surgery, other than for diagnosis, within 4 weeks prior to initiation of study, or anticipated major surgery during study History of malignancy other than HCC within 5 years prior to screening Severe infection within 4 weeks prior to initiation of study Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study Prior allogeneic stem cell or solid organ transplantation Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins Known allergy or hypersensitivity to any of the study drugs or any of their excipients Treatment with systemic immunostimulatory, immunosuppressive agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study Patients entering Stage 2: immunotherapy-related adverse events that have not resolved to Grade 1 or better or to baseline at time of consent'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: PD-L1'}
|
{'Official Title': 'A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Advanced Liver Cancers (Morpheus-Liver)', 'Brief Summary': 'This is a Phase Ib/II, open-label, multicenter, randomized umbrella study in participants with advanced liver cancers. The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, modify the participant population, or introduce additional cohorts of participants with other types of advanced primary liver cancer. Cohort 1 will enroll participants with locally advanced or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy for their disease. Eligible participants will initially be randomly assigned to one of several treatment arms (Stage 1). Participants who experience loss of clinical benefit or unacceptable toxicity during Stage 1 may be eligible to receive treatment with a different treatment combination (Stage 2). When a Stage 2 treatment combination is available, this will be introduced by amending the protocol.', 'Condition': 'Advanced Liver Cancers', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Stage 1 Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 within 7 days prior to randomization Locally advanced or metastatic and/or unresectable hepatocellular carcinoma (HCC) with diagnosis confirmed by histology/cytology or clinically by American Association for the Study of Liver Diseases criteria in cirrhotic patients Child-Pugh class A within 7 days prior to randomization Disease that is not amenable to curative surgical and/or locoregional therapies No prior systemic treatment for HCC Life expectancy >= 3 months Availability of a representative tumor specimen that is suitable for determination of PD-L1 and/or additional biomarker status via central testing Stage 1 and Stage 2 Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1 Adequate hematologic and end-organ function within 7 days prior to initiation of study treatment Documented virology status of hepatitis, as confirmed by screening tests for hepatitis B virus - (HBV) and hepatitis C virus (HCV) Negative HIV test at screening For women of childbearing potential: agreement to remain abstinent or use contraception and for men: agreement to remain abstinent or use contraception, and agreement to refrain from donating sperm Stage 2 ECOG Performance Status of 0, 1, or 2 Ability to initiate Stage 2 treatment within 3 months after experiencing unacceptable toxicity not related to atezolizumab or RO7247669 or loss of clinical benefit as determined by the investigator while receiving Stage 1 treatment Availability of a tumor specimen from a biopsy performed upon discontinuation of Stage 1 (if deemed clinically feasible)', 'Exclusion Criteria': 'Exclusion Criteria: Stage 1 Prior treatment with CD137 agonists or immune checkpoint inhibitors Treatment with investigational therapy within 28 days prior to initiation of study Treatment with locoregional therapy to liver within 28 days prior to initiation of study, or non-recovery from side effects of any such procedure Untreated or incompletely treated esophageal and/or gastric varices with bleeding or at high risk for bleeding Prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study AEs from prior anti-cancer therapy that have not resolved to Grade <= 1 or better, with the exception of alopecia of any grade Inadequately controlled hypertension History of hypertensive crisis or hypertensive encephalopathy Significant vascular disease History of hemoptysis within 1 month prior to initiation of study Evidence of bleeding diathesis or significant coagulopathy Current or recent use of asprin (>325 mg/day) or treatment with clopidogrel, dipyramidole, ticlopidine, or cilostazol Current or recent use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purpose Core biopsy or other minor surgical procedure within 3 days prior to initiation of study History of abdominal or tracheoesophageal fistula, GI perforation, or intra-abdominal abscess, intestinal obstruction and/or clinical signs/symptoms of GI obstruction Evidence of abdominal free air not explained by paracentesis or recent surgery Serious, non-healing/dehiscing wound, active ulcer, or untreated bone fracture Grade >=2 proteinuria Metastatic disease involving major airways/blood vessels, or centrally located mediastinal tumor masses of large volume History of intra-abdominal inflammatory process Radiotherapy within 28 days or abdominal/pelvic radiotherapy within 60 days prior to initiation of study with the exception of palliative radiotherapy to bone lesions within 7 days prior to initiation of study Major surgery, open biopsy, or significant traumatic injury within 28 days prior to initiation of study; or abdominal surgery, abdominal interventions or significant abdominal traumatic injury within 60 days prior to initiation of study; or anticipation of need for major surgery during study or non-recovery from side effects of any such procedure Chronic daily treatment with NSAID Eligible only for control arm Stage 1 and 2 Fibrolamellar or sarcomatoid HCC, or mixed cholangiocarcinoma and HCC History of hepatic encephalopathy Moderate or severe ascites HBV and HCV coinfection Symptomatic, untreated, or actively progressing CNS metastases History of leptomeningeal disease Uncontrolled tumor-related pain Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures Uncontrolled or symptomatic hypercalcemia Active or history of autoimmune disease or immune deficiency History of IPF, organizing pneumonia, drug-induced or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan Active TB Significant CV disease within 3 months prior to initiation of study, unstable arrhythmia, or unstable angina Major surgery, other than for diagnosis, within 4 weeks prior to initiation of study, or anticipated major surgery during study History of malignancy other than HCC within 5 years prior to screening Severe infection within 4 weeks prior to initiation of study Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study Prior allogeneic stem cell or solid organ transplantation Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins Known allergy or hypersensitivity to any of the study drugs or any of their excipients Treatment with systemic immunostimulatory, immunosuppressive agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study Patients entering Stage 2: immunotherapy-related adverse events that have not resolved to Grade 1 or better or to baseline at time of consent'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: PD-L1'}
|
{'Official Title': 'A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Advanced Liver Cancers (Morpheus-Liver)', 'Brief Summary': 'This is a Phase Ib/II, open-label, multicenter, randomized umbrella study in participants with advanced liver cancers. The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, modify the participant population, or introduce additional cohorts of participants with other types of advanced primary liver cancer. Cohort 1 will enroll participants with locally advanced or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy for their disease. Eligible participants will initially be randomly assigned to one of several treatment arms (Stage 1). Participants who experience loss of clinical benefit or unacceptable toxicity during Stage 1 may be eligible to receive treatment with a different treatment combination (Stage 2). When a Stage 2 treatment combination is available, this will be introduced by amending the protocol.', 'Condition': 'Advanced Liver Cancers', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Stage 1 Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 within 7 days prior to randomization Locally advanced or metastatic and/or unresectable hepatocellular carcinoma (HCC) with diagnosis confirmed by histology/cytology or clinically by American Association for the Study of Liver Diseases criteria in cirrhotic patients Child-Pugh class A within 7 days prior to randomization Disease that is not amenable to curative surgical and/or locoregional therapies No prior systemic treatment for HCC Life expectancy >= 3 months Availability of a representative tumor specimen that is suitable for determination of PD-L1 and/or additional biomarker status via central testing Stage 1 and Stage 2 Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1 Adequate hematologic and end-organ function within 7 days prior to initiation of study treatment Documented virology status of hepatitis, as confirmed by screening tests for hepatitis B virus - (HBV) and hepatitis C virus (HCV) Negative HIV test at screening For women of childbearing potential: agreement to remain abstinent or use contraception and for men: agreement to remain abstinent or use contraception, and agreement to refrain from donating sperm Stage 2 ECOG Performance Status of 0, 1, or 2 Ability to initiate Stage 2 treatment within 3 months after experiencing unacceptable toxicity not related to atezolizumab or RO7247669 or loss of clinical benefit as determined by the investigator while receiving Stage 1 treatment Availability of a tumor specimen from a biopsy performed upon discontinuation of Stage 1 (if deemed clinically feasible)', 'Exclusion Criteria': 'Exclusion Criteria: Stage 1 Prior treatment with CD137 agonists or immune checkpoint inhibitors Treatment with investigational therapy within 28 days prior to initiation of study Treatment with locoregional therapy to liver within 28 days prior to initiation of study, or non-recovery from side effects of any such procedure Untreated or incompletely treated esophageal and/or gastric varices with bleeding or at high risk for bleeding Prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study AEs from prior anti-cancer therapy that have not resolved to Grade <= 1 or better, with the exception of alopecia of any grade Inadequately controlled hypertension History of hypertensive crisis or hypertensive encephalopathy Significant vascular disease History of hemoptysis within 1 month prior to initiation of study Evidence of bleeding diathesis or significant coagulopathy Current or recent use of asprin (>325 mg/day) or treatment with clopidogrel, dipyramidole, ticlopidine, or cilostazol Current or recent use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purpose Core biopsy or other minor surgical procedure within 3 days prior to initiation of study History of abdominal or tracheoesophageal fistula, GI perforation, or intra-abdominal abscess, intestinal obstruction and/or clinical signs/symptoms of GI obstruction Evidence of abdominal free air not explained by paracentesis or recent surgery Serious, non-healing/dehiscing wound, active ulcer, or untreated bone fracture Grade >=2 proteinuria Metastatic disease involving major airways/blood vessels, or centrally located mediastinal tumor masses of large volume History of intra-abdominal inflammatory process Radiotherapy within 28 days or abdominal/pelvic radiotherapy within 60 days prior to initiation of study with the exception of palliative radiotherapy to bone lesions within 7 days prior to initiation of study Major surgery, open biopsy, or significant traumatic injury within 28 days prior to initiation of study; or abdominal surgery, abdominal interventions or significant abdominal traumatic injury within 60 days prior to initiation of study; or anticipation of need for major surgery during study or non-recovery from side effects of any such procedure Chronic daily treatment with NSAID Eligible only for control arm Stage 1 and 2 Fibrolamellar or sarcomatoid HCC, or mixed cholangiocarcinoma and HCC History of hepatic encephalopathy Moderate or severe ascites HBV and HCV coinfection Symptomatic, untreated, or actively progressing CNS metastases History of leptomeningeal disease Uncontrolled tumor-related pain Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures Uncontrolled or symptomatic hypercalcemia Active or history of autoimmune disease or immune deficiency History of IPF, organizing pneumonia, drug-induced or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan Active TB Significant CV disease within 3 months prior to initiation of study, unstable arrhythmia, or unstable angina Major surgery, other than for diagnosis, within 4 weeks prior to initiation of study, or anticipated major surgery during study History of malignancy other than HCC within 5 years prior to screening Severe infection within 4 weeks prior to initiation of study Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study Prior allogeneic stem cell or solid organ transplantation Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins Known allergy or hypersensitivity to any of the study drugs or any of their excipients Treatment with systemic immunostimulatory, immunosuppressive agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study Patients entering Stage 2: immunotherapy-related adverse events that have not resolved to Grade 1 or better or to baseline at time of consent'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: PD-L1'}
|
{'Official Title': 'A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Advanced Liver Cancers (Morpheus-Liver)', 'Brief Summary': 'This is a Phase Ib/II, open-label, multicenter, randomized umbrella study in participants with advanced liver cancers. The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, modify the participant population, or introduce additional cohorts of participants with other types of advanced primary liver cancer. Cohort 1 will enroll participants with locally advanced or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy for their disease. Eligible participants will initially be randomly assigned to one of several treatment arms (Stage 1). Participants who experience loss of clinical benefit or unacceptable toxicity during Stage 1 may be eligible to receive treatment with a different treatment combination (Stage 2). When a Stage 2 treatment combination is available, this will be introduced by amending the protocol.', 'Condition': 'Advanced Liver Cancers', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Stage 1 Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 within 7 days prior to randomization Locally advanced or metastatic and/or unresectable hepatocellular carcinoma (HCC) with diagnosis confirmed by histology/cytology or clinically by American Association for the Study of Liver Diseases criteria in cirrhotic patients Child-Pugh class A within 7 days prior to randomization Disease that is not amenable to curative surgical and/or locoregional therapies No prior systemic treatment for HCC Life expectancy >= 3 months Availability of a representative tumor specimen that is suitable for determination of PD-L1 and/or additional biomarker status via central testing Stage 1 and Stage 2 Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1 Adequate hematologic and end-organ function within 7 days prior to initiation of study treatment Documented virology status of hepatitis, as confirmed by screening tests for hepatitis B virus - (HBV) and hepatitis C virus (HCV) Negative HIV test at screening For women of childbearing potential: agreement to remain abstinent or use contraception and for men: agreement to remain abstinent or use contraception, and agreement to refrain from donating sperm Stage 2 ECOG Performance Status of 0, 1, or 2 Ability to initiate Stage 2 treatment within 3 months after experiencing unacceptable toxicity not related to atezolizumab or RO7247669 or loss of clinical benefit as determined by the investigator while receiving Stage 1 treatment Availability of a tumor specimen from a biopsy performed upon discontinuation of Stage 1 (if deemed clinically feasible)', 'Exclusion Criteria': 'Exclusion Criteria: Stage 1 Prior treatment with CD137 agonists or immune checkpoint inhibitors Treatment with investigational therapy within 28 days prior to initiation of study Treatment with locoregional therapy to liver within 28 days prior to initiation of study, or non-recovery from side effects of any such procedure Untreated or incompletely treated esophageal and/or gastric varices with bleeding or at high risk for bleeding Prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study AEs from prior anti-cancer therapy that have not resolved to Grade <= 1 or better, with the exception of alopecia of any grade Inadequately controlled hypertension History of hypertensive crisis or hypertensive encephalopathy Significant vascular disease History of hemoptysis within 1 month prior to initiation of study Evidence of bleeding diathesis or significant coagulopathy Current or recent use of asprin (>325 mg/day) or treatment with clopidogrel, dipyramidole, ticlopidine, or cilostazol Current or recent use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purpose Core biopsy or other minor surgical procedure within 3 days prior to initiation of study History of abdominal or tracheoesophageal fistula, GI perforation, or intra-abdominal abscess, intestinal obstruction and/or clinical signs/symptoms of GI obstruction Evidence of abdominal free air not explained by paracentesis or recent surgery Serious, non-healing/dehiscing wound, active ulcer, or untreated bone fracture Grade >=2 proteinuria Metastatic disease involving major airways/blood vessels, or centrally located mediastinal tumor masses of large volume History of intra-abdominal inflammatory process Radiotherapy within 28 days or abdominal/pelvic radiotherapy within 60 days prior to initiation of study with the exception of palliative radiotherapy to bone lesions within 7 days prior to initiation of study Major surgery, open biopsy, or significant traumatic injury within 28 days prior to initiation of study; or abdominal surgery, abdominal interventions or significant abdominal traumatic injury within 60 days prior to initiation of study; or anticipation of need for major surgery during study or non-recovery from side effects of any such procedure Chronic daily treatment with NSAID Eligible only for control arm Stage 1 and 2 Fibrolamellar or sarcomatoid HCC, or mixed cholangiocarcinoma and HCC History of hepatic encephalopathy Moderate or severe ascites HBV and HCV coinfection Symptomatic, untreated, or actively progressing CNS metastases History of leptomeningeal disease Uncontrolled tumor-related pain Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures Uncontrolled or symptomatic hypercalcemia Active or history of autoimmune disease or immune deficiency History of IPF, organizing pneumonia, drug-induced or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan Active TB Significant CV disease within 3 months prior to initiation of study, unstable arrhythmia, or unstable angina Major surgery, other than for diagnosis, within 4 weeks prior to initiation of study, or anticipated major surgery during study History of malignancy other than HCC within 5 years prior to screening Severe infection within 4 weeks prior to initiation of study Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study Prior allogeneic stem cell or solid organ transplantation Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins Known allergy or hypersensitivity to any of the study drugs or any of their excipients Treatment with systemic immunostimulatory, immunosuppressive agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study Patients entering Stage 2: immunotherapy-related adverse events that have not resolved to Grade 1 or better or to baseline at time of consent'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: PD-L1'}
|
{'Official Title': 'A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Advanced Liver Cancers (Morpheus-Liver)', 'Brief Summary': 'This is a Phase Ib/II, open-label, multicenter, randomized umbrella study in participants with advanced liver cancers. The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, modify the participant population, or introduce additional cohorts of participants with other types of advanced primary liver cancer. Cohort 1 will enroll participants with locally advanced or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy for their disease. Eligible participants will initially be randomly assigned to one of several treatment arms (Stage 1). Participants who experience loss of clinical benefit or unacceptable toxicity during Stage 1 may be eligible to receive treatment with a different treatment combination (Stage 2). When a Stage 2 treatment combination is available, this will be introduced by amending the protocol.', 'Condition': 'Advanced Liver Cancers', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Stage 1 Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 within 7 days prior to randomization Locally advanced or metastatic and/or unresectable hepatocellular carcinoma (HCC) with diagnosis confirmed by histology/cytology or clinically by American Association for the Study of Liver Diseases criteria in cirrhotic patients Child-Pugh class A within 7 days prior to randomization Disease that is not amenable to curative surgical and/or locoregional therapies No prior systemic treatment for HCC Life expectancy >= 3 months Availability of a representative tumor specimen that is suitable for determination of PD-L1 and/or additional biomarker status via central testing Stage 1 and Stage 2 Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1 Adequate hematologic and end-organ function within 7 days prior to initiation of study treatment Documented virology status of hepatitis, as confirmed by screening tests for hepatitis B virus - (HBV) and hepatitis C virus (HCV) Negative HIV test at screening For women of childbearing potential: agreement to remain abstinent or use contraception and for men: agreement to remain abstinent or use contraception, and agreement to refrain from donating sperm Stage 2 ECOG Performance Status of 0, 1, or 2 Ability to initiate Stage 2 treatment within 3 months after experiencing unacceptable toxicity not related to atezolizumab or RO7247669 or loss of clinical benefit as determined by the investigator while receiving Stage 1 treatment Availability of a tumor specimen from a biopsy performed upon discontinuation of Stage 1 (if deemed clinically feasible)', 'Exclusion Criteria': 'Exclusion Criteria: Stage 1 Prior treatment with CD137 agonists or immune checkpoint inhibitors Treatment with investigational therapy within 28 days prior to initiation of study Treatment with locoregional therapy to liver within 28 days prior to initiation of study, or non-recovery from side effects of any such procedure Untreated or incompletely treated esophageal and/or gastric varices with bleeding or at high risk for bleeding Prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study AEs from prior anti-cancer therapy that have not resolved to Grade <= 1 or better, with the exception of alopecia of any grade Inadequately controlled hypertension History of hypertensive crisis or hypertensive encephalopathy Significant vascular disease History of hemoptysis within 1 month prior to initiation of study Evidence of bleeding diathesis or significant coagulopathy Current or recent use of asprin (>325 mg/day) or treatment with clopidogrel, dipyramidole, ticlopidine, or cilostazol Current or recent use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purpose Core biopsy or other minor surgical procedure within 3 days prior to initiation of study History of abdominal or tracheoesophageal fistula, GI perforation, or intra-abdominal abscess, intestinal obstruction and/or clinical signs/symptoms of GI obstruction Evidence of abdominal free air not explained by paracentesis or recent surgery Serious, non-healing/dehiscing wound, active ulcer, or untreated bone fracture Grade >=2 proteinuria Metastatic disease involving major airways/blood vessels, or centrally located mediastinal tumor masses of large volume History of intra-abdominal inflammatory process Radiotherapy within 28 days or abdominal/pelvic radiotherapy within 60 days prior to initiation of study with the exception of palliative radiotherapy to bone lesions within 7 days prior to initiation of study Major surgery, open biopsy, or significant traumatic injury within 28 days prior to initiation of study; or abdominal surgery, abdominal interventions or significant abdominal traumatic injury within 60 days prior to initiation of study; or anticipation of need for major surgery during study or non-recovery from side effects of any such procedure Chronic daily treatment with NSAID Eligible only for control arm Stage 1 and 2 Fibrolamellar or sarcomatoid HCC, or mixed cholangiocarcinoma and HCC History of hepatic encephalopathy Moderate or severe ascites HBV and HCV coinfection Symptomatic, untreated, or actively progressing CNS metastases History of leptomeningeal disease Uncontrolled tumor-related pain Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures Uncontrolled or symptomatic hypercalcemia Active or history of autoimmune disease or immune deficiency History of IPF, organizing pneumonia, drug-induced or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan Active TB Significant CV disease within 3 months prior to initiation of study, unstable arrhythmia, or unstable angina Major surgery, other than for diagnosis, within 4 weeks prior to initiation of study, or anticipated major surgery during study History of malignancy other than HCC within 5 years prior to screening Severe infection within 4 weeks prior to initiation of study Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study Prior allogeneic stem cell or solid organ transplantation Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins Known allergy or hypersensitivity to any of the study drugs or any of their excipients Treatment with systemic immunostimulatory, immunosuppressive agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study Patients entering Stage 2: immunotherapy-related adverse events that have not resolved to Grade 1 or better or to baseline at time of consent'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: PD-L1'}
|
{'Official Title': 'A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Advanced Liver Cancers (Morpheus-Liver)', 'Brief Summary': 'This is a Phase Ib/II, open-label, multicenter, randomized umbrella study in participants with advanced liver cancers. The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, modify the participant population, or introduce additional cohorts of participants with other types of advanced primary liver cancer. Cohort 1 will enroll participants with locally advanced or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy for their disease. Eligible participants will initially be randomly assigned to one of several treatment arms (Stage 1). Participants who experience loss of clinical benefit or unacceptable toxicity during Stage 1 may be eligible to receive treatment with a different treatment combination (Stage 2). When a Stage 2 treatment combination is available, this will be introduced by amending the protocol.', 'Condition': 'Advanced Liver Cancers', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Stage 1 Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 within 7 days prior to randomization Locally advanced or metastatic and/or unresectable hepatocellular carcinoma (HCC) with diagnosis confirmed by histology/cytology or clinically by American Association for the Study of Liver Diseases criteria in cirrhotic patients Child-Pugh class A within 7 days prior to randomization Disease that is not amenable to curative surgical and/or locoregional therapies No prior systemic treatment for HCC Life expectancy >= 3 months Availability of a representative tumor specimen that is suitable for determination of PD-L1 and/or additional biomarker status via central testing Stage 1 and Stage 2 Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1 Adequate hematologic and end-organ function within 7 days prior to initiation of study treatment Documented virology status of hepatitis, as confirmed by screening tests for hepatitis B virus - (HBV) and hepatitis C virus (HCV) Negative HIV test at screening For women of childbearing potential: agreement to remain abstinent or use contraception and for men: agreement to remain abstinent or use contraception, and agreement to refrain from donating sperm Stage 2 ECOG Performance Status of 0, 1, or 2 Ability to initiate Stage 2 treatment within 3 months after experiencing unacceptable toxicity not related to atezolizumab or RO7247669 or loss of clinical benefit as determined by the investigator while receiving Stage 1 treatment Availability of a tumor specimen from a biopsy performed upon discontinuation of Stage 1 (if deemed clinically feasible)', 'Exclusion Criteria': 'Exclusion Criteria: Stage 1 Prior treatment with CD137 agonists or immune checkpoint inhibitors Treatment with investigational therapy within 28 days prior to initiation of study Treatment with locoregional therapy to liver within 28 days prior to initiation of study, or non-recovery from side effects of any such procedure Untreated or incompletely treated esophageal and/or gastric varices with bleeding or at high risk for bleeding Prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study AEs from prior anti-cancer therapy that have not resolved to Grade <= 1 or better, with the exception of alopecia of any grade Inadequately controlled hypertension History of hypertensive crisis or hypertensive encephalopathy Significant vascular disease History of hemoptysis within 1 month prior to initiation of study Evidence of bleeding diathesis or significant coagulopathy Current or recent use of asprin (>325 mg/day) or treatment with clopidogrel, dipyramidole, ticlopidine, or cilostazol Current or recent use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purpose Core biopsy or other minor surgical procedure within 3 days prior to initiation of study History of abdominal or tracheoesophageal fistula, GI perforation, or intra-abdominal abscess, intestinal obstruction and/or clinical signs/symptoms of GI obstruction Evidence of abdominal free air not explained by paracentesis or recent surgery Serious, non-healing/dehiscing wound, active ulcer, or untreated bone fracture Grade >=2 proteinuria Metastatic disease involving major airways/blood vessels, or centrally located mediastinal tumor masses of large volume History of intra-abdominal inflammatory process Radiotherapy within 28 days or abdominal/pelvic radiotherapy within 60 days prior to initiation of study with the exception of palliative radiotherapy to bone lesions within 7 days prior to initiation of study Major surgery, open biopsy, or significant traumatic injury within 28 days prior to initiation of study; or abdominal surgery, abdominal interventions or significant abdominal traumatic injury within 60 days prior to initiation of study; or anticipation of need for major surgery during study or non-recovery from side effects of any such procedure Chronic daily treatment with NSAID Eligible only for control arm Stage 1 and 2 Fibrolamellar or sarcomatoid HCC, or mixed cholangiocarcinoma and HCC History of hepatic encephalopathy Moderate or severe ascites HBV and HCV coinfection Symptomatic, untreated, or actively progressing CNS metastases History of leptomeningeal disease Uncontrolled tumor-related pain Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures Uncontrolled or symptomatic hypercalcemia Active or history of autoimmune disease or immune deficiency History of IPF, organizing pneumonia, drug-induced or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan Active TB Significant CV disease within 3 months prior to initiation of study, unstable arrhythmia, or unstable angina Major surgery, other than for diagnosis, within 4 weeks prior to initiation of study, or anticipated major surgery during study History of malignancy other than HCC within 5 years prior to screening Severe infection within 4 weeks prior to initiation of study Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study Prior allogeneic stem cell or solid organ transplantation Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins Known allergy or hypersensitivity to any of the study drugs or any of their excipients Treatment with systemic immunostimulatory, immunosuppressive agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study Patients entering Stage 2: immunotherapy-related adverse events that have not resolved to Grade 1 or better or to baseline at time of consent'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: PD-L1'}
|
{'Official Title': 'A Phase 1/2 Multiple Expansion Cohort Trial of MRTX849 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL-1', 'Brief Summary': 'This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumors that have a KRAS G12C mutation.', 'Condition': 'Advanced Cancer Metastatic Cancer Malignant Neoplastic Disease', 'Detailed Description': 'This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumors with a KRAS G12C mutation. MRTX849 (adagrasib) is an orally-available small molecule inhibitor of KRAS G12C.', 'Inclusion Criteria': 'Inclusion Criteria: Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation Unresectable or metastatic disease Standard treatment is not available or patient declines; first-line treatment for NSCLC for certain cohorts Adequate organ function', 'Exclusion Criteria': 'Exclusion Criteria: History of intestinal disease or major gastric surgery or inability to swallow oral medications Other active cancer'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: KRAS G12C mutation'}
|
{'Official Title': 'A Phase 1/2 Multiple Expansion Cohort Trial of MRTX849 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL-1', 'Brief Summary': 'This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumors that have a KRAS G12C mutation.', 'Condition': 'Advanced Cancer Metastatic Cancer Malignant Neoplastic Disease', 'Detailed Description': 'This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumors with a KRAS G12C mutation. MRTX849 (adagrasib) is an orally-available small molecule inhibitor of KRAS G12C.', 'Inclusion Criteria': 'Inclusion Criteria: Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation Unresectable or metastatic disease Standard treatment is not available or patient declines; first-line treatment for NSCLC for certain cohorts Adequate organ function', 'Exclusion Criteria': 'Exclusion Criteria: History of intestinal disease or major gastric surgery or inability to swallow oral medications Other active cancer'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: KRAS G12C mutation'}
|
{'Official Title': 'A Phase 1/2 Multiple Expansion Cohort Trial of MRTX849 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL-1', 'Brief Summary': 'This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumors that have a KRAS G12C mutation.', 'Condition': 'Advanced Cancer Metastatic Cancer Malignant Neoplastic Disease', 'Detailed Description': 'This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumors with a KRAS G12C mutation. MRTX849 (adagrasib) is an orally-available small molecule inhibitor of KRAS G12C.', 'Inclusion Criteria': 'Inclusion Criteria: Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation Unresectable or metastatic disease Standard treatment is not available or patient declines; first-line treatment for NSCLC for certain cohorts Adequate organ function', 'Exclusion Criteria': 'Exclusion Criteria: History of intestinal disease or major gastric surgery or inability to swallow oral medications Other active cancer'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: KRAS G12C mutation'}
|
{'Official Title': 'A Phase 1/2 Multiple Expansion Cohort Trial of MRTX849 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL-1', 'Brief Summary': 'This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumors that have a KRAS G12C mutation.', 'Condition': 'Advanced Cancer Metastatic Cancer Malignant Neoplastic Disease', 'Detailed Description': 'This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumors with a KRAS G12C mutation. MRTX849 (adagrasib) is an orally-available small molecule inhibitor of KRAS G12C.', 'Inclusion Criteria': 'Inclusion Criteria: Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation Unresectable or metastatic disease Standard treatment is not available or patient declines; first-line treatment for NSCLC for certain cohorts Adequate organ function', 'Exclusion Criteria': 'Exclusion Criteria: History of intestinal disease or major gastric surgery or inability to swallow oral medications Other active cancer'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: KRAS G12C mutation'}
|
{'Official Title': 'A Phase 1/2 Multiple Expansion Cohort Trial of MRTX849 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL-1', 'Brief Summary': 'This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumors that have a KRAS G12C mutation.', 'Condition': 'Advanced Cancer Metastatic Cancer Malignant Neoplastic Disease', 'Detailed Description': 'This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumors with a KRAS G12C mutation. MRTX849 (adagrasib) is an orally-available small molecule inhibitor of KRAS G12C.', 'Inclusion Criteria': 'Inclusion Criteria: Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation Unresectable or metastatic disease Standard treatment is not available or patient declines; first-line treatment for NSCLC for certain cohorts Adequate organ function', 'Exclusion Criteria': 'Exclusion Criteria: History of intestinal disease or major gastric surgery or inability to swallow oral medications Other active cancer'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: KRAS G12C mutation'}
|
{'Official Title': 'A Phase 1/2 Multiple Expansion Cohort Trial of MRTX849 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL-1', 'Brief Summary': 'This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumors that have a KRAS G12C mutation.', 'Condition': 'Advanced Cancer Metastatic Cancer Malignant Neoplastic Disease', 'Detailed Description': 'This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumors with a KRAS G12C mutation. MRTX849 (adagrasib) is an orally-available small molecule inhibitor of KRAS G12C.', 'Inclusion Criteria': 'Inclusion Criteria: Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation Unresectable or metastatic disease Standard treatment is not available or patient declines; first-line treatment for NSCLC for certain cohorts Adequate organ function', 'Exclusion Criteria': 'Exclusion Criteria: History of intestinal disease or major gastric surgery or inability to swallow oral medications Other active cancer'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: KRAS G12C mutation'}
|
{'Official Title': 'A Phase 1/2 Multiple Expansion Cohort Trial of MRTX849 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL-1', 'Brief Summary': 'This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumors that have a KRAS G12C mutation.', 'Condition': 'Advanced Cancer Metastatic Cancer Malignant Neoplastic Disease', 'Detailed Description': 'This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumors with a KRAS G12C mutation. MRTX849 (adagrasib) is an orally-available small molecule inhibitor of KRAS G12C.', 'Inclusion Criteria': 'Inclusion Criteria: Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation Unresectable or metastatic disease Standard treatment is not available or patient declines; first-line treatment for NSCLC for certain cohorts Adequate organ function', 'Exclusion Criteria': 'Exclusion Criteria: History of intestinal disease or major gastric surgery or inability to swallow oral medications Other active cancer'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: KRAS G12C mutation'}
|
{'Official Title': 'A Phase 1/2 Multiple Expansion Cohort Trial of MRTX849 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL-1', 'Brief Summary': 'This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumors that have a KRAS G12C mutation.', 'Condition': 'Advanced Cancer Metastatic Cancer Malignant Neoplastic Disease', 'Detailed Description': 'This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumors with a KRAS G12C mutation. MRTX849 (adagrasib) is an orally-available small molecule inhibitor of KRAS G12C.', 'Inclusion Criteria': 'Inclusion Criteria: Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation Unresectable or metastatic disease Standard treatment is not available or patient declines; first-line treatment for NSCLC for certain cohorts Adequate organ function', 'Exclusion Criteria': 'Exclusion Criteria: History of intestinal disease or major gastric surgery or inability to swallow oral medications Other active cancer'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: KRAS G12C mutation'}
|
{'Official Title': 'A Phase 1/2 Multiple Expansion Cohort Trial of MRTX849 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL-1', 'Brief Summary': 'This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumors that have a KRAS G12C mutation.', 'Condition': 'Advanced Cancer Metastatic Cancer Malignant Neoplastic Disease', 'Detailed Description': 'This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumors with a KRAS G12C mutation. MRTX849 (adagrasib) is an orally-available small molecule inhibitor of KRAS G12C.', 'Inclusion Criteria': 'Inclusion Criteria: Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation Unresectable or metastatic disease Standard treatment is not available or patient declines; first-line treatment for NSCLC for certain cohorts Adequate organ function', 'Exclusion Criteria': 'Exclusion Criteria: History of intestinal disease or major gastric surgery or inability to swallow oral medications Other active cancer'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: KRAS G12C mutation'}
|
{'Official Title': 'A Phase III Randomised, Double-Blind, Placebo-Controlled, Multicentre Study of Durvalumab in Combination With Chemotherapy and Bevacizumab, Followed by Maintenance Durvalumab, Bevacizumab and Olaparib in Newly Diagnosed Advanced Ovarian Cancer Patients (DUO-O).', 'Brief Summary': 'This is a Phase III randomised, double-blind, multi-centre study to evaluate the efficacy and safety of durvalumab in combination with standard of care platinum based chemotherapy and bevacizumab followed by maintenance durvalumab and bevacizumab or durvalumab, bevacizumab and olaparib in patients with newly diagnosed advanced ovarian cancer.', 'Condition': 'Advanced Ovarian Cancer', 'Detailed Description': "Eligible patients will be those patients with newly diagnosed, histologically confirmed advanced (Fédération Internationale de Gynécologie et d'Obstétrique [FIGO] Stage III-IV) ovarian, primary peritoneal cancer and/or fallopian-tube cancer. All patients should be candidates for cytoreductive surgery which could be conducted as immediate upfront primary surgery following diagnosis or can be conducted after initiation of platinum based neoadjuvant chemotherapy. All patients should be eligible to start first line platinum based chemotherapy in combination with bevacizumab. The study aims to evaluate the efficacy and safety of standard of care (SoC) platinum-based chemotherapy and bevacizumab followed by maintenance bevacizumab either as monotherapy, or in combination with durvalumab, or in combination with durvalumab and olaparib. Therefore, this study aims to see which combination allows patients to live longer without the cancer coming back or getting worse. The study is also looking to see which combination makes patients live longer and how the treatment and the cancer affects their quality of life.", 'Inclusion Criteria': 'Key Inclusion Criteria: Female patients with newly diagnosed, histologically confirmed, advanced (Stage III-IV) high grade epithelial ovarian cancer including high grade serious, high grade endometriod, clear cell ovarian cancer or carcinosarcoma, primary peritoneal cancer and / or fallopian-tube cancer Patients must be aged ≥18 years of age. For patients enrolled in Japan that are aged <20 year All patients should be candidates for cytoreductive surgery either: upfront primary surgery OR plan to undergo chemotherapy with interval debulking surgery Evidence of presence or absence of BRCA1/2 mutation in tumour tissue Mandatory provision of tumour sample for centralised tBRCA testing ECOG performance status 0-1 Patients must have preserved organ and bone marrow function Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test', 'Exclusion Criteria': 'Key Exclusion Criteria: Non-epithelial ovarian cancer, borderline tumors, low grade epithelial tumors or mucinous histology Prior systemic anti-cancer therapy for ovarian cancer Inability to determine the presence or absence of a deleterious or suspected deleterious BRCA mutation Prior treatment with PARP inhibitor or immune mediated therapy Planned intraperitoneal cytotoxic chemotherapy Active or prior documented autoimmune or inflammatory disorders Patients considered a poor medical risk due to a serious, uncontrolled intercurrent illness Clinically significant cardiovascular disease Patients with known brain metastases History of another primary malignancy except for: Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study treatment and of low potential risk for recurrence (patients who have received prior adjuvant chemotherapy for early stage breast cancer may be eligible, provided that it was completed ≥3 years prior to registration, and that the patient remains free of recurrent or metastatic disease) Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease Adequately treated carcinoma in situ without evidence of disease Endometrial cancer FIGO Stage IA, Grade 1 or Grade 2 Persistent toxicities CTCAE Grade >2 caused by previous cancer therapy Patients with a known hypersensitivity to olaparib, durvalumab or any of the excipients of these products and to the combination/comparator agents Breast feeding women'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: BRCA1/2 mutation'}
|
{'Official Title': 'A Phase III Randomised, Double-Blind, Placebo-Controlled, Multicentre Study of Durvalumab in Combination With Chemotherapy and Bevacizumab, Followed by Maintenance Durvalumab, Bevacizumab and Olaparib in Newly Diagnosed Advanced Ovarian Cancer Patients (DUO-O).', 'Brief Summary': 'This is a Phase III randomised, double-blind, multi-centre study to evaluate the efficacy and safety of durvalumab in combination with standard of care platinum based chemotherapy and bevacizumab followed by maintenance durvalumab and bevacizumab or durvalumab, bevacizumab and olaparib in patients with newly diagnosed advanced ovarian cancer.', 'Condition': 'Advanced Ovarian Cancer', 'Detailed Description': "Eligible patients will be those patients with newly diagnosed, histologically confirmed advanced (Fédération Internationale de Gynécologie et d'Obstétrique [FIGO] Stage III-IV) ovarian, primary peritoneal cancer and/or fallopian-tube cancer. All patients should be candidates for cytoreductive surgery which could be conducted as immediate upfront primary surgery following diagnosis or can be conducted after initiation of platinum based neoadjuvant chemotherapy. All patients should be eligible to start first line platinum based chemotherapy in combination with bevacizumab. The study aims to evaluate the efficacy and safety of standard of care (SoC) platinum-based chemotherapy and bevacizumab followed by maintenance bevacizumab either as monotherapy, or in combination with durvalumab, or in combination with durvalumab and olaparib. Therefore, this study aims to see which combination allows patients to live longer without the cancer coming back or getting worse. The study is also looking to see which combination makes patients live longer and how the treatment and the cancer affects their quality of life.", 'Inclusion Criteria': 'Key Inclusion Criteria: Female patients with newly diagnosed, histologically confirmed, advanced (Stage III-IV) high grade epithelial ovarian cancer including high grade serious, high grade endometriod, clear cell ovarian cancer or carcinosarcoma, primary peritoneal cancer and / or fallopian-tube cancer Patients must be aged ≥18 years of age. For patients enrolled in Japan that are aged <20 year All patients should be candidates for cytoreductive surgery either: upfront primary surgery OR plan to undergo chemotherapy with interval debulking surgery Evidence of presence or absence of BRCA1/2 mutation in tumour tissue Mandatory provision of tumour sample for centralised tBRCA testing ECOG performance status 0-1 Patients must have preserved organ and bone marrow function Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test', 'Exclusion Criteria': 'Key Exclusion Criteria: Non-epithelial ovarian cancer, borderline tumors, low grade epithelial tumors or mucinous histology Prior systemic anti-cancer therapy for ovarian cancer Inability to determine the presence or absence of a deleterious or suspected deleterious BRCA mutation Prior treatment with PARP inhibitor or immune mediated therapy Planned intraperitoneal cytotoxic chemotherapy Active or prior documented autoimmune or inflammatory disorders Patients considered a poor medical risk due to a serious, uncontrolled intercurrent illness Clinically significant cardiovascular disease Patients with known brain metastases History of another primary malignancy except for: Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study treatment and of low potential risk for recurrence (patients who have received prior adjuvant chemotherapy for early stage breast cancer may be eligible, provided that it was completed ≥3 years prior to registration, and that the patient remains free of recurrent or metastatic disease) Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease Adequately treated carcinoma in situ without evidence of disease Endometrial cancer FIGO Stage IA, Grade 1 or Grade 2 Persistent toxicities CTCAE Grade >2 caused by previous cancer therapy Patients with a known hypersensitivity to olaparib, durvalumab or any of the excipients of these products and to the combination/comparator agents Breast feeding women'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: BRCA1/2 mutation'}
|
{'Official Title': 'A Phase III Randomised, Double-Blind, Placebo-Controlled, Multicentre Study of Durvalumab in Combination With Chemotherapy and Bevacizumab, Followed by Maintenance Durvalumab, Bevacizumab and Olaparib in Newly Diagnosed Advanced Ovarian Cancer Patients (DUO-O).', 'Brief Summary': 'This is a Phase III randomised, double-blind, multi-centre study to evaluate the efficacy and safety of durvalumab in combination with standard of care platinum based chemotherapy and bevacizumab followed by maintenance durvalumab and bevacizumab or durvalumab, bevacizumab and olaparib in patients with newly diagnosed advanced ovarian cancer.', 'Condition': 'Advanced Ovarian Cancer', 'Detailed Description': "Eligible patients will be those patients with newly diagnosed, histologically confirmed advanced (Fédération Internationale de Gynécologie et d'Obstétrique [FIGO] Stage III-IV) ovarian, primary peritoneal cancer and/or fallopian-tube cancer. All patients should be candidates for cytoreductive surgery which could be conducted as immediate upfront primary surgery following diagnosis or can be conducted after initiation of platinum based neoadjuvant chemotherapy. All patients should be eligible to start first line platinum based chemotherapy in combination with bevacizumab. The study aims to evaluate the efficacy and safety of standard of care (SoC) platinum-based chemotherapy and bevacizumab followed by maintenance bevacizumab either as monotherapy, or in combination with durvalumab, or in combination with durvalumab and olaparib. Therefore, this study aims to see which combination allows patients to live longer without the cancer coming back or getting worse. The study is also looking to see which combination makes patients live longer and how the treatment and the cancer affects their quality of life.", 'Inclusion Criteria': 'Key Inclusion Criteria: Female patients with newly diagnosed, histologically confirmed, advanced (Stage III-IV) high grade epithelial ovarian cancer including high grade serious, high grade endometriod, clear cell ovarian cancer or carcinosarcoma, primary peritoneal cancer and / or fallopian-tube cancer Patients must be aged ≥18 years of age. For patients enrolled in Japan that are aged <20 year All patients should be candidates for cytoreductive surgery either: upfront primary surgery OR plan to undergo chemotherapy with interval debulking surgery Evidence of presence or absence of BRCA1/2 mutation in tumour tissue Mandatory provision of tumour sample for centralised tBRCA testing ECOG performance status 0-1 Patients must have preserved organ and bone marrow function Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test', 'Exclusion Criteria': 'Key Exclusion Criteria: Non-epithelial ovarian cancer, borderline tumors, low grade epithelial tumors or mucinous histology Prior systemic anti-cancer therapy for ovarian cancer Inability to determine the presence or absence of a deleterious or suspected deleterious BRCA mutation Prior treatment with PARP inhibitor or immune mediated therapy Planned intraperitoneal cytotoxic chemotherapy Active or prior documented autoimmune or inflammatory disorders Patients considered a poor medical risk due to a serious, uncontrolled intercurrent illness Clinically significant cardiovascular disease Patients with known brain metastases History of another primary malignancy except for: Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study treatment and of low potential risk for recurrence (patients who have received prior adjuvant chemotherapy for early stage breast cancer may be eligible, provided that it was completed ≥3 years prior to registration, and that the patient remains free of recurrent or metastatic disease) Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease Adequately treated carcinoma in situ without evidence of disease Endometrial cancer FIGO Stage IA, Grade 1 or Grade 2 Persistent toxicities CTCAE Grade >2 caused by previous cancer therapy Patients with a known hypersensitivity to olaparib, durvalumab or any of the excipients of these products and to the combination/comparator agents Breast feeding women'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: BRCA1/2 mutation'}
|
{'Official Title': 'A Phase III Randomised, Double-Blind, Placebo-Controlled, Multicentre Study of Durvalumab in Combination With Chemotherapy and Bevacizumab, Followed by Maintenance Durvalumab, Bevacizumab and Olaparib in Newly Diagnosed Advanced Ovarian Cancer Patients (DUO-O).', 'Brief Summary': 'This is a Phase III randomised, double-blind, multi-centre study to evaluate the efficacy and safety of durvalumab in combination with standard of care platinum based chemotherapy and bevacizumab followed by maintenance durvalumab and bevacizumab or durvalumab, bevacizumab and olaparib in patients with newly diagnosed advanced ovarian cancer.', 'Condition': 'Advanced Ovarian Cancer', 'Detailed Description': "Eligible patients will be those patients with newly diagnosed, histologically confirmed advanced (Fédération Internationale de Gynécologie et d'Obstétrique [FIGO] Stage III-IV) ovarian, primary peritoneal cancer and/or fallopian-tube cancer. All patients should be candidates for cytoreductive surgery which could be conducted as immediate upfront primary surgery following diagnosis or can be conducted after initiation of platinum based neoadjuvant chemotherapy. All patients should be eligible to start first line platinum based chemotherapy in combination with bevacizumab. The study aims to evaluate the efficacy and safety of standard of care (SoC) platinum-based chemotherapy and bevacizumab followed by maintenance bevacizumab either as monotherapy, or in combination with durvalumab, or in combination with durvalumab and olaparib. Therefore, this study aims to see which combination allows patients to live longer without the cancer coming back or getting worse. The study is also looking to see which combination makes patients live longer and how the treatment and the cancer affects their quality of life.", 'Inclusion Criteria': 'Key Inclusion Criteria: Female patients with newly diagnosed, histologically confirmed, advanced (Stage III-IV) high grade epithelial ovarian cancer including high grade serious, high grade endometriod, clear cell ovarian cancer or carcinosarcoma, primary peritoneal cancer and / or fallopian-tube cancer Patients must be aged ≥18 years of age. For patients enrolled in Japan that are aged <20 year All patients should be candidates for cytoreductive surgery either: upfront primary surgery OR plan to undergo chemotherapy with interval debulking surgery Evidence of presence or absence of BRCA1/2 mutation in tumour tissue Mandatory provision of tumour sample for centralised tBRCA testing ECOG performance status 0-1 Patients must have preserved organ and bone marrow function Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test', 'Exclusion Criteria': 'Key Exclusion Criteria: Non-epithelial ovarian cancer, borderline tumors, low grade epithelial tumors or mucinous histology Prior systemic anti-cancer therapy for ovarian cancer Inability to determine the presence or absence of a deleterious or suspected deleterious BRCA mutation Prior treatment with PARP inhibitor or immune mediated therapy Planned intraperitoneal cytotoxic chemotherapy Active or prior documented autoimmune or inflammatory disorders Patients considered a poor medical risk due to a serious, uncontrolled intercurrent illness Clinically significant cardiovascular disease Patients with known brain metastases History of another primary malignancy except for: Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study treatment and of low potential risk for recurrence (patients who have received prior adjuvant chemotherapy for early stage breast cancer may be eligible, provided that it was completed ≥3 years prior to registration, and that the patient remains free of recurrent or metastatic disease) Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease Adequately treated carcinoma in situ without evidence of disease Endometrial cancer FIGO Stage IA, Grade 1 or Grade 2 Persistent toxicities CTCAE Grade >2 caused by previous cancer therapy Patients with a known hypersensitivity to olaparib, durvalumab or any of the excipients of these products and to the combination/comparator agents Breast feeding women'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: BRCA1/2 mutation'}
|
{'Official Title': 'A Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center Clinical Study to Evaluate the Efficacy and Safety of Toripalimab Injection (JS001) or Placebo Combined With First-line Standard Chemotherapy in Treatment-naive Advanced Non-small Cell Lung Cancer (NSCLC)', 'Brief Summary': 'This is one randomized, double-blind, placebo-controlled, multi-center, phase III clinical study to evaluate the efficacy and safety of Toripalimab injection (JS001) or placebo combined with standard 1st-line chemotherapy in treatment-naïve advanced non-small cell lung cancer (NSCLC); and evaluate the population with the best predictive biomarkers, i.e., positive diagnosis population. About 450 subjects with advanced non-small cell lung cancer without activated EGFR mutation (exon 19 deletion, or exon 21 L858R, exon 21 L861Q, exon 18 G719X or exon 20 S768I mutations) and ALK fusion will be 2:1 randomized into two groups, JS001 combined with the standard 1st-line chemotherapy will be given in the study group whereas placebo combined with standard 1st-line chemotherapy will be given in the control group. The stratification will be based on the following factors: PD-L1 expression (TC≥1% vs TC<1%); Smoking state (often smoking vs no smoking or infrequent smoking); Pathological type (squamous cell carcinoma vs non-squamous cell carcinoma).', 'Condition': 'Treatment-naive Advanced Non-small Cell Lung Cancer', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Only the patients meeting all the following criteria can be eligible to participate in the trial: Histologically and/or cytologically confirmed stage IV non-small cell lung cancer and ALK fusion At least one measurable lesion 3 No history of any systemic anti-tumor therapy. 4. Agreement on providing formalin fixed tumor tissue specimen or fresh biopsy tissue from tumor lesions after diagnosis of metastasis 6. Age of 18-75 years 7. ECOG Scores 0-1; 8. Expected survival ≥ 3 months;', 'Exclusion Criteria': 'Exclusion Criteria: Known allergy to recombinant humanized anti-PD-1 monoclonal antibody drug and its components; Histologically or cytopathologically confirmed combination with small cell lung cancer component or sarcomatoid lesion; Current participation in and receiving other study treatment, or participation in treatment of one study drug within 4 weeks prior to administration of JS001; Previous use of systematic chemotherapy for advanced NSCLC; targeted therapy for advanced NSCLC Previous use of anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody or anti-CTLA-4 antibody (or any other antibody acting on T cells synergetic stimulation or checkpoint pathway, such as IDO, IL-2R, GITR); Chest (lung) radiotherapy > 30 Gy within 6 months prior to the start of study treatment. Active tuberculosis (TB), receiving anti-tuberculosis therapy currently or within one year prior to screening; Known active central nervous system (CNS) metastasis and/or cancerous meningitis; Spinal cord compression for which operation and/or radical radiotherapy has not been given, or no clinical evidence of stable disease for ≥4 weeks prior to enrollment after treatment for previously diagnosed spinal cord compression Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage Uncontrollable or symptomatic hypercalcemia Clinically uncontrolled active infection, including but not limited to acute pneumonia; Uncontrollable major epileptic seizure or superior vena cava syndrome Previous or current combination with other malignancies ; History of idiopathic pulmonary fibrosis, organized pneumonia (e.g., obliterating bronchiolitis), drug induced pneumonia, idiopathic pneumonia or evidence of active pneumonia during chest CT scanning for screening; Known hepatic diseases of clinical significance, including active viral hepatitis, alcoholic hepatitis or other hepatitis, liver cirrhosis, fatty liver, hereditary liver disease; Use of systemic immunosuppressive therapy for any active autoimmune disease within two years prior to Day 1 of the 1st cycle; Vaccination of live-virus vaccine within 30 days after the start of planned treatment'}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
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{'Arm - Disease - Biomarker': 'Include: PD-L1 expression'}
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{'Official Title': 'A Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center Clinical Study to Evaluate the Efficacy and Safety of Toripalimab Injection (JS001) or Placebo Combined With First-line Standard Chemotherapy in Treatment-naive Advanced Non-small Cell Lung Cancer (NSCLC)', 'Brief Summary': 'This is one randomized, double-blind, placebo-controlled, multi-center, phase III clinical study to evaluate the efficacy and safety of Toripalimab injection (JS001) or placebo combined with standard 1st-line chemotherapy in treatment-naïve advanced non-small cell lung cancer (NSCLC); and evaluate the population with the best predictive biomarkers, i.e., positive diagnosis population. About 450 subjects with advanced non-small cell lung cancer without activated EGFR mutation (exon 19 deletion, or exon 21 L858R, exon 21 L861Q, exon 18 G719X or exon 20 S768I mutations) and ALK fusion will be 2:1 randomized into two groups, JS001 combined with the standard 1st-line chemotherapy will be given in the study group whereas placebo combined with standard 1st-line chemotherapy will be given in the control group. The stratification will be based on the following factors: PD-L1 expression (TC≥1% vs TC<1%); Smoking state (often smoking vs no smoking or infrequent smoking); Pathological type (squamous cell carcinoma vs non-squamous cell carcinoma).', 'Condition': 'Treatment-naive Advanced Non-small Cell Lung Cancer', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Only the patients meeting all the following criteria can be eligible to participate in the trial: Histologically and/or cytologically confirmed stage IV non-small cell lung cancer and ALK fusion At least one measurable lesion 3 No history of any systemic anti-tumor therapy. 4. Agreement on providing formalin fixed tumor tissue specimen or fresh biopsy tissue from tumor lesions after diagnosis of metastasis 6. Age of 18-75 years 7. ECOG Scores 0-1; 8. Expected survival ≥ 3 months;', 'Exclusion Criteria': 'Exclusion Criteria: Known allergy to recombinant humanized anti-PD-1 monoclonal antibody drug and its components; Histologically or cytopathologically confirmed combination with small cell lung cancer component or sarcomatoid lesion; Current participation in and receiving other study treatment, or participation in treatment of one study drug within 4 weeks prior to administration of JS001; Previous use of systematic chemotherapy for advanced NSCLC; targeted therapy for advanced NSCLC Previous use of anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody or anti-CTLA-4 antibody (or any other antibody acting on T cells synergetic stimulation or checkpoint pathway, such as IDO, IL-2R, GITR); Chest (lung) radiotherapy > 30 Gy within 6 months prior to the start of study treatment. Active tuberculosis (TB), receiving anti-tuberculosis therapy currently or within one year prior to screening; Known active central nervous system (CNS) metastasis and/or cancerous meningitis; Spinal cord compression for which operation and/or radical radiotherapy has not been given, or no clinical evidence of stable disease for ≥4 weeks prior to enrollment after treatment for previously diagnosed spinal cord compression Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage Uncontrollable or symptomatic hypercalcemia Clinically uncontrolled active infection, including but not limited to acute pneumonia; Uncontrollable major epileptic seizure or superior vena cava syndrome Previous or current combination with other malignancies ; History of idiopathic pulmonary fibrosis, organized pneumonia (e.g., obliterating bronchiolitis), drug induced pneumonia, idiopathic pneumonia or evidence of active pneumonia during chest CT scanning for screening; Known hepatic diseases of clinical significance, including active viral hepatitis, alcoholic hepatitis or other hepatitis, liver cirrhosis, fatty liver, hereditary liver disease; Use of systemic immunosuppressive therapy for any active autoimmune disease within two years prior to Day 1 of the 1st cycle; Vaccination of live-virus vaccine within 30 days after the start of planned treatment'}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
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{'Arm - Disease - Biomarker': 'Include: PD-L1 expression'}
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{'Official Title': 'A Phase 2b, Open-label, Single-arm Study of ZW25 Monotherapy in Subjects With Advanced or Metastatic HER2-amplified Biliary Tract Cancers', 'Brief Summary': 'This multicenter, open-label, single-arm trial will evaluate the anti-tumor activity of ZW25 (zanidatamab) monotherapy in subjects with human epidermal growth factor receptor 2 (HER2)-amplified, inoperable and advanced or metastatic biliary tract cancer (BTC), including intra-hepatic cholangiocarcinoma (ICC), extra-hepatic cholangiocarcinoma (ECC), and gallbladder cancer (GBC).', 'Condition': 'HER2-amplified Biliary Tract Cancers', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Histologically- or cytologically-confirmed BTC, including ICC, ECC or GBC. Locally advanced or metastatic BTC and not eligible for curative resection, transplantation, or ablative therapies. Received at least 1 prior gemcitabine-containing systemic chemotherapy regimen for advanced disease, and experienced disease progression after or developed intolerance to the most recent prior therapy. For subjects who received gemcitabine in prior adjuvant or neoadjuvant treatment, if progression occurred < 6 months from the latter of primary surgical resection or completion of gemcitabine-containing adjuvant therapy, they will be considered as having received 1 prior line of therapy for advanced disease. Subjects must test positive for HER2 amplification by ISH-assay at a central laboratory on a new biopsy or archival tissue. Note that fine needle aspirates (FNAs; cytology samples) and biopsies from sites of bone metastases are not acceptable. Testing may occur at any time after diagnosis of advanced or metastatic disease and before study enrollment. Male or female, ≥18 years of age (or the legal age of adulthood per country-specific regulations). Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1. Adequate organ function. Adequate cardiac function, as defined by left ventricular ejection fraction ≥ 50%.', 'Exclusion Criteria': 'Exclusion Criteria: Received systemic anti-cancer therapy within 3 weeks of the first dose of ZW25. Received radiotherapy within 2 weeks of the first dose of ZW25. Prior treatment with HER2-targeted agents. Untreated central nervous system (CNS) metastases, symptomatic CNS metastases, or radiation treatment for CNS metastases within 4 weeks of start of study treatment. Stable, treated brain metastases are allowed (defined as subjects who are off steroids and anticonvulsants and are neurologically stable with no evidence of radiographic progression for at least 4 weeks at the time of screening). Known leptomeningeal disease (LMD). If LMD has been reported radiographically on baseline MRI, but is not suspected clinically by the investigator, the subject must be free of neurological symptoms of LMD. Concurrent uncontrolled or active hepatobiliary disorders or untreated or ongoing complications after laparoscopic procedures or stent placement, including but not limited to active cholangitis, unresolved biliary obstruction, infected biloma or abscess. Any complications must be resolved more than 2 weeks prior to the first dose of ZW25. Prior or concurrent malignancy whose natural history or treatment has, in the opinion of the investigator or medical monitor, the potential to interfere with the safety or efficacy assessment of the investigational regimen. Active hepatitis Infection with human immunodeficiency virus (HIV)-1 or HIV-2 QTc Fridericia (QTcF) > 470 ms. History of myocardial infarction or unstable angina within 6 months prior to enrollment, troponin levels consistent with myocardial infarction, or clinically significant cardiac disease. Acute or chronic uncontrolled pancreatitis or Child-Pugh Class C liver disease.'}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
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{'Arm - Disease - Biomarker': 'Include: HER2 Amplification '}
|
{'Official Title': 'Phase I/II Study of Dabrafenib, Trametinib, and Navitoclax in BRAF Mutant Melanoma (Phase I and II) and Other Solid Tumors (Phase I Only)', 'Brief Summary': 'This phase I/II trial studies the side effects and best dose of dabrafenib, trametinib, and navitoclax and to see how well they work in treating patients with BRAF mutant melanoma or solid tumors that have spread to other parts of the body (metastatic) or cannot be removed by surgery (unresectable). Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Navitoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving navitoclax, dabrafenib, and trametinib may help shrink tumors in patients with melanoma.', 'Condition': 'Clinical Stage III Cutaneous Melanoma AJCC v8 Clinical Stage IV Cutaneous Melanoma AJCC v8 Malignant Solid Neoplasm Metastatic Melanoma Unresectable Melanoma', 'Detailed Description': 'PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD), toxicity, and safety profile of navitoclax when given in combination with dabrafenib and trametinib in patients with BRAF-mutant solid tumors. (Phase I) II. To estimate the complete response (CR) rate in patients with BRAF-mutant melanoma treated with dabrafenib, trametinib, and navitoclax as compared to the historical control dabrafenib and trametinib combination (DT). (Phase II) III. To compare the maximal tumor regression in patients with BRAF-mutant melanoma treated with dabrafenib, trametinib versus dabrafenib, trametinib, and navitoclax. (Phase II) SECONDARY OBJECTIVES: I. To describe pharmacodynamics effects of treatment with dabrafenib, trametinib, and navitoclax on both serial tumor biopsies and serial blood draws in a small subset of patients treated with BRAF-mutant melanoma. (Phase I) II. To describe the pharmacokinetics of treatment with dabrafenib, trametinib, and navitoclax. (Phase I) III. To compare the progression-free survival (PFS), overall survival (OS), and overall response rate (ORR) in patients with BRAF-mutant melanoma treated with dabrafenib, trametinib, versus dabrafenib, trametinib, and navitoclax. (Phase II) IV. To compare the degree of apoptosis induced in on-treatment biopsies of patients with BRAF-mutant melanoma treated with dabrafenib, trametinib versus dabrafenib, trametinib, and navitoclax. (Phase II) V. To explore other pharmacodynamic effects in on-treatment biopsies of patients with BRAF-mutant melanoma treated with either dabrafenib, trametinib versus dabrafenib, trametinib, and navitoclax including cell proliferation (Ki-67), proteomics (reverse-phase protein microarrays [RPPA]), and B-cell chronic lymphocytic leukemia (CLL)/lymphoma 2 (BCL-2) family gene expression analysis. (Phase II) OUTLINE: This is a phase I, dose-escalation study of dabrafenib, trametinib, and navitoclax followed by a randomized phase II study. PHASE I: Patients receive navitoclax orally (PO) once daily (QD) on days -7 to -1 of cycle 1 only. Patients also receive dabrafenib PO twice daily (BID), trametinib PO QD, and navitoclax PO QD days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo magnetic resonance imaging (MRI) or computed tomography (CT), also undergo biopsy, and collection of blood samples throughout the trial. PHASE II: Patients are randomized to 1 of 2 arms. ARM I: Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT, biopsy, and collection of blood samples throughout the trial. ARM II: Patients receive navitoclax PO QD days -7 to -1 of cycle 1 only. Patients also receive dabrafenib PO BID, trametinib PO QD, and navitoclax PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT, biopsy, and collection of blood samples throughout the trial. After the completion of study treatment, patients are followed up for clinical evaluation at 28 days and every 3 months thereafter until disease progression or death, whichever comes first. For survival follow up, patients are followed every 12 months for 3 years.', 'Inclusion Criteria': 'Inclusion Criteria: PHASE I SUBJECTS ONLY: Prior therapy is allowed; for patients enrolled in the Phase I portion of the study, patients may have received any number of prior lines of therapy including treatment with a BRAF and/or MEK inhibitor; prior navitoclax use will not be allowed, unless the patient received < 7 days of navitoclax lead-in on this or another study and had to stop for reasons other than toxicity or disease progression Patients must have histologically confirmed, BRAF-mutant (V600E/K) melanoma (molecularly confirmed using validated, commercially available assay performed in a Clinical Laboratory Improvement Act [CLIA]-approved laboratory) that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective If test at CLIA-certified lab used a non-Food and Drug Administration (FDA) approved method, information about the assay must be provided; (FDA approved tests for BRAF V600 mutations in melanoma include: THxID BRAF Detection Kit and Cobas 4800 BRAF V600 Mutation Test) Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam Prior therapy is allowed; for patients enrolled in the Phase II portion of the study, patients may have received prior immunotherapy (including high-dose IL-2, ipilimumab, nivolumab, and other anti-PD1/PDL1 antibodies) or chemotherapy; however prior navitoclax, BRAF inhibitor and/or MEK inhibitor therapy will not be allowed Age >= 18 years. Because no dosing or adverse event data are currently available on the use of navitoclax in combination with dabrafenib and trametinib in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%) Life expectancy of greater than 3 months Leukocytes >= 3,000/mcL Absolute neutrophil count >= 1 x 10^9/L Hemoglobin >= 9 g/dl (patients may be transfused to this level) Platelets >= 100,000/mcL Total bilirubin =< 1.5 x institutional upper limit of normal OR > 1.5 x institutional upper limit of normal allowed if direct bilirubin is within normal range Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) < 1.3 x upper limit of normal (ULN) Serum creatinine =< 1.5 mg/dL OR creatinine clearance >= 50 mL/min/1.73 m^2 Left ventricular ejection fraction >= institutional lower limit of normal (LLN) by echocardiogram (ECHO) Patients must have a corrected QT (QTc) interval of less than 480 msec The effects of navitoclax, dabrafenib, and trametinib on the developing human fetus are unknown; for this reason, women of child-bearing potential and men with partners of childbearing potential must agree to use adequate contraception (barrier method of birth control, or abstinence; hormonal contraception is not allowed due to drug-drug interactions which can render hormonal contraceptives ineffective) prior to study entry, for the duration of study participation, and for 4 months after completion of study drug administration; should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately; based on studies in animals, it is also known that dabrafenib may cause damage to the tissue that makes sperm; this may cause sperm to be abnormal in shape and size and could lead to infertility, which may be irreversible; safety and efficacy of the combination of dabrafenib and trametinib in pediatric populations have not been investigated; dabrafenib or trametinib-dabrafenib combination should not be administered to pediatric populations outside clinical trials Able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels Ability to understand and the willingness to sign a written informed consent document; if a patient has impaired decision-making capacity, a legally authorized representative, patients will be allowed to participate', 'Exclusion Criteria': "Exclusion Criteria: PHASE I SUBJECTS ONLY: Patients must not have received prior navitoclax, unless the patient received < 7 days of navitoclax lead-in on this or another study and had to stop for reasons other than toxicity or disease progression Patients who have had immunotherapy, chemotherapy or radiotherapy within 14 days prior to the first dose of navitoclax, or prior systemic anti-cancer therapy (chemotherapy with delayed toxicity, extensive radiation therapy, immunotherapy, biologic therapy, or vaccine therapy) within the last 3 weeks prior to first dose of dabrafenib and/or trametinib; chemotherapy regimens without delayed toxicity within the last 2 weeks preceding the first dose of study treatment; biologics will not be allowed within 30 days prior to, or during, navitoclax administration Prior navitoclax, BRAF inhibitor, and MEK inhibitor is prohibited; (exceptions for Phase I are described above) Patients who are receiving any other investigational agents have received any other investigational drugs within 28 days (or five half-lives, whichever is shorter; with a minimum of 14 days from the last dose) preceding the first dose of study treatment and during the study Patients with treated leptomeningeal or brain metastasis are not eligible unless there is demonstrated stability (documented by imaging) for >= 3 months from any prior treatment of leptomeningeal or brain metastasis. Treatment may include surgery, radiation or systemic therapy. Patients with untreated leptomeningeal or brain metastasis or requiring corticosteroids are not eligible. Subjects on a stable dose of corticosteroids > 1 month or who have been off of corticosteroids for at least 2 weeks can be enrolled with approval of the Cancer Therapy Evaluation Program (CTEP) medical monitor. Subjects must also be off of enzyme-inducing anticonvulsants for > 4 weeks History of allergic reactions attributed to compounds of similar chemical or biologic composition to navitoclax, dabrafenib, or trametinib, or excipients or to dimethyl sulfoxide (DMSO) Uncontrolled intercurrent illness including, but not limited to, ongoing or active serious infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled diabetes, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant women are excluded from this study because navitoclax, dabrafenib, and trametinib may have teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the study drugs, breastfeeding should be discontinued if the mother is treated with the study drugs Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy that predict to interact with any of the study drugs are ineligible because of the potential for pharmacokinetic interactions with the study drugs; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated; it is not necessary to conduct HIV testing at screening; patients who are HIV-positive with undetectable viral loads, not on interacting antiretroviral therapy, and have CD4 counts above 300/mm^3 may be eligible after discussion with the principal investigator History of another malignancy; exception: patients who have been disease-free for 3 years (depending upon tumor type studied or clinical setting, 3 or 5 years can be used; e.g., for advanced melanoma and pancreatic studies 3 years is more appropriate due to aggressiveness of the disease, while 5 years can be more appropriate for prostate or ovarian cancer or adjuvant setting when life expectancy is longer), or patients with a history of completely resected non-melanoma skin cancer and/or patients with indolent secondary malignancies, are eligible; consult the CTEP medical monitor if unsure whether second malignancies meet the requirements specified above; exception: patients with history of RAS mutation-positive tumors are not eligible regardless of interval from the current study; prospective RAS testing is not required; however, if the results of previous RAS testing are known, they must be used in assessing eligibility History of interstitial lung disease or pneumonitis History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR): History of RVO or CSR, or predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes) Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or CSR such as evidence of new optic disc cupping, evidence of new visual field defects, and intraocular pressure > 21 mmHg History or evidence of cardiovascular risk including any of the following: A QT interval corrected for heart rate using the Bazett's formula QTcB >= 480 msec on screening electrocardiography (ECG) History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible) History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy Abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study Known history of hepatitis B virus (HBV), or hepatitis C virus (HCV) infection (patients with chronic or cleared HBV and HCV infection are eligible); it is not necessary to conduct HBV and HCV testing at screening Subject has an underlying condition predisposing them to bleeding or currently exhibits signs of clinically significant bleeding Subject has a recent history of non-chemotherapy-induced thrombocytopenic-associated bleeding within 1 year prior to the first dose of study drug A history of glucose-6-phosphate dehydrogenase (G6PD) deficiency Unresolved toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v. 5.0) grade 2 or higher from previous anti-cancer therapy, except alopecia or an endocrine toxicity related to immunotherapy (e.g. thyroiditis/hypothyroidism, adrenal insufficiency, hypophysitis) requiring replacement therapy, at the time of randomization Due to the expected dose-limiting toxicity of thrombocytopenia, the following concomitant medications are not allowed during navitoclax administration: clopidogrel, ibuprofen, tirofiban, warfarin, and other anticoagulants, drugs, or herbal supplements that affect platelet function are excluded, with the exception of low-dose anticoagulation medications (such as heparin) that are used to maintain the patency of a central intravenous catheter; aspirin will not be allowed within 7 days prior to the first dose of navitoclax or during navitoclax administration; however, subjects who have previously received aspirin therapy for thrombosis prevention may resume a low dose (i.e., maximum 100 mg QD) of aspirin if platelet counts are stable (>= 50,000/mm^3) through 6 weeks of navitoclax administration; all decisions regarding treatment with aspirin therapy will be determined by the investigator in conjunction with the medical monitor Current use of a prohibited medication; the following medications or non-drug therapies are prohibited: Other anti-cancer therapy while on study treatment; (note: megestrol [Megace] if used as an appetite stimulant is allowed) Concurrent treatment with bisphosphonates is permitted; however, treatment must be initiated prior to the first dose of study therapy; prophylactic use of bisphosphonates in patients without bone disease is not permitted, except for the treatment of osteoporosis Because the composition, pharmacokinetics (PK), and metabolism of many herbal supplements are unknown, the concurrent use of all herbal supplements is prohibited during the study (including, but not limited to, St. John's wort, kava, ephedra [ma huang], ginkgo biloba, dehydroepiandrosterone [DHEA], yohimbe, saw palmetto, or ginseng) Anticoagulants or antiplatelet agents except for low-dose, aspirin Preclinical studies indicate that navitoclax is metabolized by CYP3A4, is a moderate inhibitor of CYP2C8, and is a strong inhibitor of CYP2C9; there is also evidence of interactions with dabrafenib; therefore, caution should be exercised when dosing navitoclax concurrently with CYP2C8 and CYP2C9 substrates; common CYP2C8 substrates include paclitaxel, statins, and glitazones, whereas CYP2C9 substrates include phenytoin; when possible, investigators should switch to alternative medications or monitor the patients closely; CYP3A inhibitors such as ketoconazole and clarithromycin are not allowed 7 days prior to the first dose of navitoclax or during navitoclax administration Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A or CYP2C8 are ineligible; current use of, or intended ongoing treatment with: herbal remedies (e.g., St. John's wort), or strong inhibitors or inducers of permeability-glycoprotein (Pgp) or breast cancer resistance protein 1 (Bcrp1) should also be excluded; below are a few examples of the agents: Strong inducers of CYP3A or CYP2C8, since concentrations of dabrafenib may be decreased: Antibiotics: rifamycin class agents (e.g., rifampin, rifabutin, rifapentine) Anticonvulsants: carbamazepine, oxcarbazepine, phenobarbital, phenytoin, s-mephenytoin Miscellaneous: bosentan, St. John's wort Strong inhibitors of CYP3A or CYP2C8 since concentrations of dabrafenib may be increased: Antibiotics: clarithromycin, telithromycin, troleandomycin Antidepressants: nefazodone Antifungals: itraconazole, ketoconazole, posaconazole, voriconazole Hyperlipidemia: gemfibrozil Antiretroviral: ritonavir, saquinavir, atazanavir Miscellaneous: conivaptan"}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: BRAF-mutant (V600E/K)'}
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{'Official Title': 'Phase I/II Study of Dabrafenib, Trametinib, and Navitoclax in BRAF Mutant Melanoma (Phase I and II) and Other Solid Tumors (Phase I Only)', 'Brief Summary': 'This phase I/II trial studies the side effects and best dose of dabrafenib, trametinib, and navitoclax and to see how well they work in treating patients with BRAF mutant melanoma or solid tumors that have spread to other parts of the body (metastatic) or cannot be removed by surgery (unresectable). Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Navitoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving navitoclax, dabrafenib, and trametinib may help shrink tumors in patients with melanoma.', 'Condition': 'Clinical Stage III Cutaneous Melanoma AJCC v8 Clinical Stage IV Cutaneous Melanoma AJCC v8 Malignant Solid Neoplasm Metastatic Melanoma Unresectable Melanoma', 'Detailed Description': 'PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD), toxicity, and safety profile of navitoclax when given in combination with dabrafenib and trametinib in patients with BRAF-mutant solid tumors. (Phase I) II. To estimate the complete response (CR) rate in patients with BRAF-mutant melanoma treated with dabrafenib, trametinib, and navitoclax as compared to the historical control dabrafenib and trametinib combination (DT). (Phase II) III. To compare the maximal tumor regression in patients with BRAF-mutant melanoma treated with dabrafenib, trametinib versus dabrafenib, trametinib, and navitoclax. (Phase II) SECONDARY OBJECTIVES: I. To describe pharmacodynamics effects of treatment with dabrafenib, trametinib, and navitoclax on both serial tumor biopsies and serial blood draws in a small subset of patients treated with BRAF-mutant melanoma. (Phase I) II. To describe the pharmacokinetics of treatment with dabrafenib, trametinib, and navitoclax. (Phase I) III. To compare the progression-free survival (PFS), overall survival (OS), and overall response rate (ORR) in patients with BRAF-mutant melanoma treated with dabrafenib, trametinib, versus dabrafenib, trametinib, and navitoclax. (Phase II) IV. To compare the degree of apoptosis induced in on-treatment biopsies of patients with BRAF-mutant melanoma treated with dabrafenib, trametinib versus dabrafenib, trametinib, and navitoclax. (Phase II) V. To explore other pharmacodynamic effects in on-treatment biopsies of patients with BRAF-mutant melanoma treated with either dabrafenib, trametinib versus dabrafenib, trametinib, and navitoclax including cell proliferation (Ki-67), proteomics (reverse-phase protein microarrays [RPPA]), and B-cell chronic lymphocytic leukemia (CLL)/lymphoma 2 (BCL-2) family gene expression analysis. (Phase II) OUTLINE: This is a phase I, dose-escalation study of dabrafenib, trametinib, and navitoclax followed by a randomized phase II study. PHASE I: Patients receive navitoclax orally (PO) once daily (QD) on days -7 to -1 of cycle 1 only. Patients also receive dabrafenib PO twice daily (BID), trametinib PO QD, and navitoclax PO QD days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo magnetic resonance imaging (MRI) or computed tomography (CT), also undergo biopsy, and collection of blood samples throughout the trial. PHASE II: Patients are randomized to 1 of 2 arms. ARM I: Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT, biopsy, and collection of blood samples throughout the trial. ARM II: Patients receive navitoclax PO QD days -7 to -1 of cycle 1 only. Patients also receive dabrafenib PO BID, trametinib PO QD, and navitoclax PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT, biopsy, and collection of blood samples throughout the trial. After the completion of study treatment, patients are followed up for clinical evaluation at 28 days and every 3 months thereafter until disease progression or death, whichever comes first. For survival follow up, patients are followed every 12 months for 3 years.', 'Inclusion Criteria': 'Inclusion Criteria: PHASE I SUBJECTS ONLY: Prior therapy is allowed; for patients enrolled in the Phase I portion of the study, patients may have received any number of prior lines of therapy including treatment with a BRAF and/or MEK inhibitor; prior navitoclax use will not be allowed, unless the patient received < 7 days of navitoclax lead-in on this or another study and had to stop for reasons other than toxicity or disease progression Patients must have histologically confirmed, BRAF-mutant (V600E/K) melanoma (molecularly confirmed using validated, commercially available assay performed in a Clinical Laboratory Improvement Act [CLIA]-approved laboratory) that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective If test at CLIA-certified lab used a non-Food and Drug Administration (FDA) approved method, information about the assay must be provided; (FDA approved tests for BRAF V600 mutations in melanoma include: THxID BRAF Detection Kit and Cobas 4800 BRAF V600 Mutation Test) Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam Prior therapy is allowed; for patients enrolled in the Phase II portion of the study, patients may have received prior immunotherapy (including high-dose IL-2, ipilimumab, nivolumab, and other anti-PD1/PDL1 antibodies) or chemotherapy; however prior navitoclax, BRAF inhibitor and/or MEK inhibitor therapy will not be allowed Age >= 18 years. Because no dosing or adverse event data are currently available on the use of navitoclax in combination with dabrafenib and trametinib in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%) Life expectancy of greater than 3 months Leukocytes >= 3,000/mcL Absolute neutrophil count >= 1 x 10^9/L Hemoglobin >= 9 g/dl (patients may be transfused to this level) Platelets >= 100,000/mcL Total bilirubin =< 1.5 x institutional upper limit of normal OR > 1.5 x institutional upper limit of normal allowed if direct bilirubin is within normal range Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) < 1.3 x upper limit of normal (ULN) Serum creatinine =< 1.5 mg/dL OR creatinine clearance >= 50 mL/min/1.73 m^2 Left ventricular ejection fraction >= institutional lower limit of normal (LLN) by echocardiogram (ECHO) Patients must have a corrected QT (QTc) interval of less than 480 msec The effects of navitoclax, dabrafenib, and trametinib on the developing human fetus are unknown; for this reason, women of child-bearing potential and men with partners of childbearing potential must agree to use adequate contraception (barrier method of birth control, or abstinence; hormonal contraception is not allowed due to drug-drug interactions which can render hormonal contraceptives ineffective) prior to study entry, for the duration of study participation, and for 4 months after completion of study drug administration; should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately; based on studies in animals, it is also known that dabrafenib may cause damage to the tissue that makes sperm; this may cause sperm to be abnormal in shape and size and could lead to infertility, which may be irreversible; safety and efficacy of the combination of dabrafenib and trametinib in pediatric populations have not been investigated; dabrafenib or trametinib-dabrafenib combination should not be administered to pediatric populations outside clinical trials Able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels Ability to understand and the willingness to sign a written informed consent document; if a patient has impaired decision-making capacity, a legally authorized representative, patients will be allowed to participate', 'Exclusion Criteria': "Exclusion Criteria: PHASE I SUBJECTS ONLY: Patients must not have received prior navitoclax, unless the patient received < 7 days of navitoclax lead-in on this or another study and had to stop for reasons other than toxicity or disease progression Patients who have had immunotherapy, chemotherapy or radiotherapy within 14 days prior to the first dose of navitoclax, or prior systemic anti-cancer therapy (chemotherapy with delayed toxicity, extensive radiation therapy, immunotherapy, biologic therapy, or vaccine therapy) within the last 3 weeks prior to first dose of dabrafenib and/or trametinib; chemotherapy regimens without delayed toxicity within the last 2 weeks preceding the first dose of study treatment; biologics will not be allowed within 30 days prior to, or during, navitoclax administration Prior navitoclax, BRAF inhibitor, and MEK inhibitor is prohibited; (exceptions for Phase I are described above) Patients who are receiving any other investigational agents have received any other investigational drugs within 28 days (or five half-lives, whichever is shorter; with a minimum of 14 days from the last dose) preceding the first dose of study treatment and during the study Patients with treated leptomeningeal or brain metastasis are not eligible unless there is demonstrated stability (documented by imaging) for >= 3 months from any prior treatment of leptomeningeal or brain metastasis. Treatment may include surgery, radiation or systemic therapy. Patients with untreated leptomeningeal or brain metastasis or requiring corticosteroids are not eligible. Subjects on a stable dose of corticosteroids > 1 month or who have been off of corticosteroids for at least 2 weeks can be enrolled with approval of the Cancer Therapy Evaluation Program (CTEP) medical monitor. Subjects must also be off of enzyme-inducing anticonvulsants for > 4 weeks History of allergic reactions attributed to compounds of similar chemical or biologic composition to navitoclax, dabrafenib, or trametinib, or excipients or to dimethyl sulfoxide (DMSO) Uncontrolled intercurrent illness including, but not limited to, ongoing or active serious infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled diabetes, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant women are excluded from this study because navitoclax, dabrafenib, and trametinib may have teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the study drugs, breastfeeding should be discontinued if the mother is treated with the study drugs Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy that predict to interact with any of the study drugs are ineligible because of the potential for pharmacokinetic interactions with the study drugs; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated; it is not necessary to conduct HIV testing at screening; patients who are HIV-positive with undetectable viral loads, not on interacting antiretroviral therapy, and have CD4 counts above 300/mm^3 may be eligible after discussion with the principal investigator History of another malignancy; exception: patients who have been disease-free for 3 years (depending upon tumor type studied or clinical setting, 3 or 5 years can be used; e.g., for advanced melanoma and pancreatic studies 3 years is more appropriate due to aggressiveness of the disease, while 5 years can be more appropriate for prostate or ovarian cancer or adjuvant setting when life expectancy is longer), or patients with a history of completely resected non-melanoma skin cancer and/or patients with indolent secondary malignancies, are eligible; consult the CTEP medical monitor if unsure whether second malignancies meet the requirements specified above; exception: patients with history of RAS mutation-positive tumors are not eligible regardless of interval from the current study; prospective RAS testing is not required; however, if the results of previous RAS testing are known, they must be used in assessing eligibility History of interstitial lung disease or pneumonitis History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR): History of RVO or CSR, or predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes) Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or CSR such as evidence of new optic disc cupping, evidence of new visual field defects, and intraocular pressure > 21 mmHg History or evidence of cardiovascular risk including any of the following: A QT interval corrected for heart rate using the Bazett's formula QTcB >= 480 msec on screening electrocardiography (ECG) History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible) History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy Abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study Known history of hepatitis B virus (HBV), or hepatitis C virus (HCV) infection (patients with chronic or cleared HBV and HCV infection are eligible); it is not necessary to conduct HBV and HCV testing at screening Subject has an underlying condition predisposing them to bleeding or currently exhibits signs of clinically significant bleeding Subject has a recent history of non-chemotherapy-induced thrombocytopenic-associated bleeding within 1 year prior to the first dose of study drug A history of glucose-6-phosphate dehydrogenase (G6PD) deficiency Unresolved toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v. 5.0) grade 2 or higher from previous anti-cancer therapy, except alopecia or an endocrine toxicity related to immunotherapy (e.g. thyroiditis/hypothyroidism, adrenal insufficiency, hypophysitis) requiring replacement therapy, at the time of randomization Due to the expected dose-limiting toxicity of thrombocytopenia, the following concomitant medications are not allowed during navitoclax administration: clopidogrel, ibuprofen, tirofiban, warfarin, and other anticoagulants, drugs, or herbal supplements that affect platelet function are excluded, with the exception of low-dose anticoagulation medications (such as heparin) that are used to maintain the patency of a central intravenous catheter; aspirin will not be allowed within 7 days prior to the first dose of navitoclax or during navitoclax administration; however, subjects who have previously received aspirin therapy for thrombosis prevention may resume a low dose (i.e., maximum 100 mg QD) of aspirin if platelet counts are stable (>= 50,000/mm^3) through 6 weeks of navitoclax administration; all decisions regarding treatment with aspirin therapy will be determined by the investigator in conjunction with the medical monitor Current use of a prohibited medication; the following medications or non-drug therapies are prohibited: Other anti-cancer therapy while on study treatment; (note: megestrol [Megace] if used as an appetite stimulant is allowed) Concurrent treatment with bisphosphonates is permitted; however, treatment must be initiated prior to the first dose of study therapy; prophylactic use of bisphosphonates in patients without bone disease is not permitted, except for the treatment of osteoporosis Because the composition, pharmacokinetics (PK), and metabolism of many herbal supplements are unknown, the concurrent use of all herbal supplements is prohibited during the study (including, but not limited to, St. John's wort, kava, ephedra [ma huang], ginkgo biloba, dehydroepiandrosterone [DHEA], yohimbe, saw palmetto, or ginseng) Anticoagulants or antiplatelet agents except for low-dose, aspirin Preclinical studies indicate that navitoclax is metabolized by CYP3A4, is a moderate inhibitor of CYP2C8, and is a strong inhibitor of CYP2C9; there is also evidence of interactions with dabrafenib; therefore, caution should be exercised when dosing navitoclax concurrently with CYP2C8 and CYP2C9 substrates; common CYP2C8 substrates include paclitaxel, statins, and glitazones, whereas CYP2C9 substrates include phenytoin; when possible, investigators should switch to alternative medications or monitor the patients closely; CYP3A inhibitors such as ketoconazole and clarithromycin are not allowed 7 days prior to the first dose of navitoclax or during navitoclax administration Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A or CYP2C8 are ineligible; current use of, or intended ongoing treatment with: herbal remedies (e.g., St. John's wort), or strong inhibitors or inducers of permeability-glycoprotein (Pgp) or breast cancer resistance protein 1 (Bcrp1) should also be excluded; below are a few examples of the agents: Strong inducers of CYP3A or CYP2C8, since concentrations of dabrafenib may be decreased: Antibiotics: rifamycin class agents (e.g., rifampin, rifabutin, rifapentine) Anticonvulsants: carbamazepine, oxcarbazepine, phenobarbital, phenytoin, s-mephenytoin Miscellaneous: bosentan, St. John's wort Strong inhibitors of CYP3A or CYP2C8 since concentrations of dabrafenib may be increased: Antibiotics: clarithromycin, telithromycin, troleandomycin Antidepressants: nefazodone Antifungals: itraconazole, ketoconazole, posaconazole, voriconazole Hyperlipidemia: gemfibrozil Antiretroviral: ritonavir, saquinavir, atazanavir Miscellaneous: conivaptan"}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
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{'Arm - Disease - Biomarker': 'Include: BRAF-mutant (V600E/K)'}
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{'Official Title': 'Efficacy and Safety of Neoadjuvant Therapy of Pembrolizumab Combined With Ramucirumab for PD-L1 Positive Stage IB-IIIA Lung Cancer: An Open-label Single-arm Phase II Study', 'Brief Summary': 'The efficacy and safety of the neoadjuvant therapy of pembrolizumab+ ramucirumab', 'Condition': 'Non-small Cell Lung Cancer Stage IB Non-small Cell Lung Cancer Stage II Non-small Cell Lung Cancer Stage ⅢA', 'Detailed Description': 'To demonstrate the antitumor activity and safety of neoadjuvant pembrolizumab plus ramucirumab followed by surgery in patients with PD-L1 positive stage IB-IIIA non-small cell lung cancer', 'Inclusion Criteria': "Inclusion Criteria: Male/female participants who are at least 20 years of age on the day of signing informed consent Previously untreated and histologically proven NSCLC harboring PD-L1 expression (≥1% in a biopsy specimen), as measured by immunohistochemistry (22C3). Resectable clinical stage IB-IIIA NSCLC carefully evaluated by experienced thoracic surgeons. (If N2 disease is suspected, the histological or cytological confirmation is mandatory) (UICC version 8) Pulmonary resection more than lobectomy and lymph node dissection is considered to be possible for complete resection of the tumor.Be able to undergo protocol therapy, including necessary surgery. Has adequate pulmonary function for pulmonary resection. Predicted postoperative FEV1.0 is 800 mL or more. ｛(predicted postoperative FEV1.0) = (preoperative FEV1.0) x (18-number of resected segment) / 18｝ ECOG performance status of 0 to 1. Has measurable disease as defined by RECIST 1.1 as determined by investigator. Has adequate organ function as defined in the following criteria. Clinical test data must meet the following criteria within 14 days of the registration. The registration day is the standard, including the same day of the week two weeks prior. a Neutrophil count: ≥ 1500/mm3 b Hemoglobin (Hb) ≥ 9.0 g/dL c Platelet count: ≥ 10.0 × 104/mm3 d AST (SGOT) ≤ 100 IU/L e ALT (SGPT): ≤ 100 IU/L f Total bilirubin: ≤ 1.5 mg/dL (Total bilirubin: ≤ 3.0 mg/dL for patient with Gilbert's syndrome) g Creatinine: CRE ≤ 1.5 mg/dL, or creatinine clearance of 40 mL/minute or higher [Even when the value is less than 40 mL/min in the Cockcroft-Gault equation, if the measured value from a 24-hour urine collection is 40 mL/min or higher, the patient qualifies.] * Cockcroft-Gault equation: Male: Ccr=｛(140-age) × body weight (kg)｝/｛72 × serum CRE value (mg/dL）｝Female: Ccr=0.85 × ｛(140-age) × body weight (kg)｝/｛72 × serum CRE value (mg/dL) h SpO(2) ≥ 92% (room air) i International normalized ratio (INR) ≤ 1.5 j PTT(aPTT) ≤ 1.5 × ULN k Urinary protein ≤1+ (if it is ≥2+, store the urine for 24 hours, and if the urinary protein is <1,000 mg, the patient is qualified). Female who are likely to become pregnant are negative with pregnancy tests (urine or serum) within 7 days prior to enrollment. They agree to conduct proper contraception (total abstinence, intrauterine contraceptive device, hormone release system, or contraceptive implant and oral contraceptive) for both men and women during the trial and from the final investigational dosing up to 120 days The participant is willing and able to provide written informed consent/assent for the trial.", 'Exclusion Criteria': "Exclusion Criteria: Has one of the following tumor locations/types: NSCLC involving the superior sulcus Large cell neuro-endocrine cancer (LCNEC) Sarcomatoid tumor Synchronous lung cancer (within 5 years), current non-pure GGN on TSCT, or pure GGN with 15mm or more on TSCT Has an active infection requiring systemic therapy. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (dose exceeding 10mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of trial drug. Has a known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. Hypersensitivity or allergy to pembrolizumab, ramucirumab, or any of their excipients. Has a known history of, or any evidence of active, interstitial lung disease. Has a hypertension that is difficult to control (systolic blood pressure ≥160 mmHg and diastolic blood pressure ≥90 mmHg) despite treatment with several hypotensive agents. Has an acute coronary syndrome (including myocardial infarction and unstable angina), and with a history of coronary angioplasty or stent placement performed within 6 months before enrollment Has a history of New York Heart Association congestive heart failure of grade II or above, unstable angina, myocardial infarction within the past 6 months, or serious cardiac arrhythmia associated with significant cardiovascular impairment within the past 6 months Has a severe (hospitalization required) complications (intestinal palsy, intestinal obstruction, pulmonary fibrosis, diabetes difficult to control, heart failure, myocardial infarction, unstable angina, renal failure, liver failure, liver cirrhosis, mental disease, cerebrovascular disease etc). Has a known history of human immunodeficiency virus (HIV) infection. No HIV resting is required unless mandated by local health authority. Has a known history of active TB (Bacillus Tuberculosis) Positivefor HBs antigens, HBs antibodies, and HBc antibodies. However, if positive for HBs and/or HBc antibodies, the patient can be registered as long as they are negative for HBV-DNA. Positive for HCV antibody. However, if positive for HCV antibody, the patient can be registered as long as they are negative for HCV-RNA. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. Has a known additional malignancy that is progressing or requires active treatment within the past (5 years) or received anti-cancer drug including hormone therapy. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, bladder carcinoma, or carcinoma in situ (eg, in situ cervical cancer, breast carcinoma, CIS and AIS of the lung) that have undergone potentially curative therapy are not excluded. Has received a live vaccine within 30 days prior to the first dose of trial drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist) are live attenuated vaccines and are not allowed. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the screening or screening visit through 120 days after the last dose of trial treatment. Has history of hemoptysis (more than 1/2 cups in teaspoon) in 2 months before registration, or invasion of major vessels by cancer or major vessel narrowing is recognized on the image. Image shows cavity formation in the tumor. Is considered highly likely to have complications related to bleeding. * Obvious tumor invasion to the chest great vessel, cavity formation of the lung lesion, or the existence of obvious thrombus on the image are recognized, etc. Has past history of gastrointestinal perforation, peptic ulcer, diverticulosis or fistula within 6 months. ※ As for peptic ulcer, registration is permitted when disease condition is controlled by appropriate treatment. Has a history of pulmonary embolism / deep vein thrombosis, or other thromboembolism within 3 months before registration. Received major surgery within 28 days before registration, or received procedures for placement of subcutaneous venous access devices within seven days before registration. Severe wounds, ulcers or fractures within 28 days before registration. Has undergone long-term treatment using aspirin, nonsteroidal anti-inflammatory drugs (such as ibuprofen, naproxen), dipyridamole, clopidogrel or similar drugs. However, use of aspirin up to 325 mg / day once a day is acceptable. Patients who are receiving anticoagulant therapy and whose dose of oral anticoagulant or low molecular weight heparin is not stable. In case of taking warfarin, registration is permitted if there is no active bleeding or no risk of bleeding. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of registration. Note: Participants who have entered the follow-up phase of an investigational trial may participate as long as it has been 4 weeks after the last dose of the previous investigational agent. Has no intention to comply with the study protocol or it is impossible to comply. Investigator or clinical trial doctor judged unsuitable as subject of this trial."}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
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{'Arm - Disease - Biomarker': 'Include: PD-L1-Positive'}
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{'Official Title': 'A Phase Ib/II Open-label, Multi-center Dose Escalation Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation', 'Brief Summary': 'This is a phase Ib/II open label study. The escalation part will characterize the safety and tolerability of JDQ443 single agent and JDQ443 in combination with the other study treatments (TNO155 and tislelizumab) in advanced solid tumor patients. After the determination of the maximum tolerated dose / recommended dose for a particular treatment arm, dose expansion will assess the anti-tumor activity and further assess the safety, tolerability, and PK/PD of each regimen at the maximum tolerated dose / recommended dose or lower dose.', 'Condition': 'KRAS G12C Mutant Solid Tumors Carcinoma, Non-Small-Cell Lung Carcinoma, Colorectal Cancer of Lung Cancer of the Lung Lung Cancer Neoplasms, Lung Neoplasms, Pulmonary Pulmonary Cancer Pulmonary Neoplasms', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Adult patients with advanced (metastatic or unresectable) KRAS G12C mutant solid tumors who have received standard of care or are intolerant or ineligible to approved therapies ECOG Performance Status of 0 or 1 At least one measurable lesion as defined by RECIST 1.1 Prior treatment with a KRAS G12C inhibitor may be allowed for dose escalations of combinations and a subset of groups in dose expansion', 'Exclusion Criteria': 'Exclusion Criteria: Tumors harboring driver mutations that have approved targeted therapies, with the exception of KRAS G12C mutations Symptomatic brain metastases or known leptomeningeal disease. Patients with asymptomatic treated or untreated brain metastases may be eligible Clinically significant cardiac disease or risk factors at screening A medical condition that results in increased photosensitivity Other protocol-defined inclusion/exclusion criteria may apply.'}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
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{'Arm - Disease - Biomarker': 'Include: KRAS G12C mutant Exclude: Tumors harboring driver mutations that have approved targeted therapies, with the exception of KRAS G12C mutations'}
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{'Official Title': 'A Phase Ib/II Open-label, Multi-center Dose Escalation Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation', 'Brief Summary': 'This is a phase Ib/II open label study. The escalation part will characterize the safety and tolerability of JDQ443 single agent and JDQ443 in combination with the other study treatments (TNO155 and tislelizumab) in advanced solid tumor patients. After the determination of the maximum tolerated dose / recommended dose for a particular treatment arm, dose expansion will assess the anti-tumor activity and further assess the safety, tolerability, and PK/PD of each regimen at the maximum tolerated dose / recommended dose or lower dose.', 'Condition': 'KRAS G12C Mutant Solid Tumors Carcinoma, Non-Small-Cell Lung Carcinoma, Colorectal Cancer of Lung Cancer of the Lung Lung Cancer Neoplasms, Lung Neoplasms, Pulmonary Pulmonary Cancer Pulmonary Neoplasms', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Adult patients with advanced (metastatic or unresectable) KRAS G12C mutant solid tumors who have received standard of care or are intolerant or ineligible to approved therapies ECOG Performance Status of 0 or 1 At least one measurable lesion as defined by RECIST 1.1 Prior treatment with a KRAS G12C inhibitor may be allowed for dose escalations of combinations and a subset of groups in dose expansion', 'Exclusion Criteria': 'Exclusion Criteria: Tumors harboring driver mutations that have approved targeted therapies, with the exception of KRAS G12C mutations Symptomatic brain metastases or known leptomeningeal disease. Patients with asymptomatic treated or untreated brain metastases may be eligible Clinically significant cardiac disease or risk factors at screening A medical condition that results in increased photosensitivity Other protocol-defined inclusion/exclusion criteria may apply.'}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
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{'Arm - Disease - Biomarker': 'Include: KRAS G12C mutant Exclude: Tumors harboring driver mutations that have approved targeted therapies, with the exception of KRAS G12C mutations'}
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{'Official Title': 'A Phase Ib/II Open-label, Multi-center Dose Escalation Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation', 'Brief Summary': 'This is a phase Ib/II open label study. The escalation part will characterize the safety and tolerability of JDQ443 single agent and JDQ443 in combination with the other study treatments (TNO155 and tislelizumab) in advanced solid tumor patients. After the determination of the maximum tolerated dose / recommended dose for a particular treatment arm, dose expansion will assess the anti-tumor activity and further assess the safety, tolerability, and PK/PD of each regimen at the maximum tolerated dose / recommended dose or lower dose.', 'Condition': 'KRAS G12C Mutant Solid Tumors Carcinoma, Non-Small-Cell Lung Carcinoma, Colorectal Cancer of Lung Cancer of the Lung Lung Cancer Neoplasms, Lung Neoplasms, Pulmonary Pulmonary Cancer Pulmonary Neoplasms', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Adult patients with advanced (metastatic or unresectable) KRAS G12C mutant solid tumors who have received standard of care or are intolerant or ineligible to approved therapies ECOG Performance Status of 0 or 1 At least one measurable lesion as defined by RECIST 1.1 Prior treatment with a KRAS G12C inhibitor may be allowed for dose escalations of combinations and a subset of groups in dose expansion', 'Exclusion Criteria': 'Exclusion Criteria: Tumors harboring driver mutations that have approved targeted therapies, with the exception of KRAS G12C mutations Symptomatic brain metastases or known leptomeningeal disease. Patients with asymptomatic treated or untreated brain metastases may be eligible Clinically significant cardiac disease or risk factors at screening A medical condition that results in increased photosensitivity Other protocol-defined inclusion/exclusion criteria may apply.'}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: KRAS G12C mutant Exclude: Tumors harboring driver mutations that have approved targeted therapies, with the exception of KRAS G12C mutations'}
|
{'Official Title': 'A Phase Ib/II Open-label, Multi-center Dose Escalation Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation', 'Brief Summary': 'This is a phase Ib/II open label study. The escalation part will characterize the safety and tolerability of JDQ443 single agent and JDQ443 in combination with the other study treatments (TNO155 and tislelizumab) in advanced solid tumor patients. After the determination of the maximum tolerated dose / recommended dose for a particular treatment arm, dose expansion will assess the anti-tumor activity and further assess the safety, tolerability, and PK/PD of each regimen at the maximum tolerated dose / recommended dose or lower dose.', 'Condition': 'KRAS G12C Mutant Solid Tumors Carcinoma, Non-Small-Cell Lung Carcinoma, Colorectal Cancer of Lung Cancer of the Lung Lung Cancer Neoplasms, Lung Neoplasms, Pulmonary Pulmonary Cancer Pulmonary Neoplasms', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Adult patients with advanced (metastatic or unresectable) KRAS G12C mutant solid tumors who have received standard of care or are intolerant or ineligible to approved therapies ECOG Performance Status of 0 or 1 At least one measurable lesion as defined by RECIST 1.1 Prior treatment with a KRAS G12C inhibitor may be allowed for dose escalations of combinations and a subset of groups in dose expansion', 'Exclusion Criteria': 'Exclusion Criteria: Tumors harboring driver mutations that have approved targeted therapies, with the exception of KRAS G12C mutations Symptomatic brain metastases or known leptomeningeal disease. Patients with asymptomatic treated or untreated brain metastases may be eligible Clinically significant cardiac disease or risk factors at screening A medical condition that results in increased photosensitivity Other protocol-defined inclusion/exclusion criteria may apply.'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: KRAS G12C mutant Exclude: Tumors harboring driver mutations that have approved targeted therapies, with the exception of KRAS G12C mutations'}
|
{'Official Title': 'FIREFLY-1: A Phase 2, Open-Label, Multicenter Study to Evaluate the Safety and Efficacy of the Oral Pan-RAF Inhibitor DAY101 in Pediatric Patients With BRAF-Altered, Recurrent or Progressive Low-Grade Glioma and Advanced Solid Tumors', 'Brief Summary': 'FIREFLY-1 is a Phase 2, multi center, open-label study to evaluate the safety and efficacy of oral pan-RAF inhibitor DAY101 in pediatric, adolescent, and young adult patients with recurrent or progressive low-grade glioma or an advanced solid tumor harboring a known BRAF alteration.', 'Condition': 'Low-grade Glioma Advanced Solid Tumor', 'Detailed Description': 'The study will consist of the following treatment arms: Arm 1 (Low-Grade Glioma): Patients aged 6 months to 25 years, inclusive, with recurrent or progressive low-grade glioma harboring a known activating BRAF alteration, including BRAF V600 mutations and KIAA1549:BRAF fusions. Arm 2 (Low-Grade Glioma Expanded Access): Patients aged 6 months to 25 years, inclusive, with recurrent or progressive low-grade glioma harboring a known or expected to be activating RAF alteration (e.g., BRAF or CRAF/RAF1 fusion or BRAF V600 mutations). Opening of Arm 2 to enrollment will be based on the recommendation of the Data Safety Monitoring Board (DSMB). Arm 3 (Advanced Solid Tumor): Patients aged 6 months to 25 years, inclusive, with advanced solid tumors harboring a known or expected to be activating RAF fusion (e.g., BRAF or CRAF/RAF1 fusion). Qualifying genomic alterations will be identified through molecular assays as routinely performed at Clinical Laboratory Improvement Amendments (CLIA) of 1988 or other similarly certified laboratories prior to enrollment into any of the aforementioned arms. Patients will be treated with DAY101, an oral pan-RAF inhibitor, for a planned period of 26 cycles will be treated with DAY101 for a planned period of 26 cycles (approximately 24 months). DAY101 will be administered at the recommended Phase 2 dose (RP2D) of 420 mg/m2 (not to exceed 600 mg) orally once weekly (QW) for each 28-day treatment cycle. Treatment cycles will repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients will undergo radiographic evaluation of their disease at the end of every third cycle. Patients will continue on DAY101 until radiographic evidence of disease progression by RANO (Arms 1 & 2) or RECIST v1.1 criteria (Arm 3) as determined by treating investigator, unacceptable toxicity, patient withdrawal of consent, or death. Patients who have radiographic evidence of disease progression may be allowed to continue DAY101 if, in the opinion of the investigator and approval by the Sponsor, the patient is deriving clinical benefit from continuing study treatment. Disease assessments for patients being treated beyond progression should continue as per regular schedule. DAY101 is an oral pan-RAF inhibitor administered as an oral tablet at 420 mg/m2 (not to exceed 600 mg).', 'Inclusion Criteria': 'Inclusion Criteria: Age 6 months to 25 years with: Arms 1 & 2: a relapsed or progressive LGG with documented known activating BRAF alteration Arm 3: locally advanced or metastatic solid tumor with documented known or expected to be activating RAF fusion Confirmation of histopathologic diagnosis of LGG and molecular diagnosis of activating BRAF alteration Must have received at least one line of systemic therapy and have evidence of radiographic progression Must have at least 1 measurable lesion as defined by RANO (Arms 1 & 2) or RECIST v1.1 (Arm 3) criteria', 'Exclusion Criteria': "Exclusion Criteria: Patient's tumor has additional previously-known activating molecular alterations Patient has symptoms of clinical progression in the absence of radiographic progression Known or suspected diagnosis of neurofibromatosis type 1 (NF-1) Other inclusion/exclusion criteria as stipulated by protocol may apply"}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
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{'Arm - Disease - Biomarker': 'BRAF or CRAF/RAF1 fusion or BRAF V600 mutations and KIAA1549:BRAF fusions'}
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{'Official Title': 'FIREFLY-1: A Phase 2, Open-Label, Multicenter Study to Evaluate the Safety and Efficacy of the Oral Pan-RAF Inhibitor DAY101 in Pediatric Patients With BRAF-Altered, Recurrent or Progressive Low-Grade Glioma and Advanced Solid Tumors', 'Brief Summary': 'FIREFLY-1 is a Phase 2, multi center, open-label study to evaluate the safety and efficacy of oral pan-RAF inhibitor DAY101 in pediatric, adolescent, and young adult patients with recurrent or progressive low-grade glioma or an advanced solid tumor harboring a known BRAF alteration.', 'Condition': 'Low-grade Glioma Advanced Solid Tumor', 'Detailed Description': 'The study will consist of the following treatment arms: Arm 1 (Low-Grade Glioma): Patients aged 6 months to 25 years, inclusive, with recurrent or progressive low-grade glioma harboring a known activating BRAF alteration, including BRAF V600 mutations and KIAA1549:BRAF fusions. Arm 2 (Low-Grade Glioma Expanded Access): Patients aged 6 months to 25 years, inclusive, with recurrent or progressive low-grade glioma harboring a known or expected to be activating RAF alteration (e.g., BRAF or CRAF/RAF1 fusion or BRAF V600 mutations). Opening of Arm 2 to enrollment will be based on the recommendation of the Data Safety Monitoring Board (DSMB). Arm 3 (Advanced Solid Tumor): Patients aged 6 months to 25 years, inclusive, with advanced solid tumors harboring a known or expected to be activating RAF fusion (e.g., BRAF or CRAF/RAF1 fusion). Qualifying genomic alterations will be identified through molecular assays as routinely performed at Clinical Laboratory Improvement Amendments (CLIA) of 1988 or other similarly certified laboratories prior to enrollment into any of the aforementioned arms. Patients will be treated with DAY101, an oral pan-RAF inhibitor, for a planned period of 26 cycles will be treated with DAY101 for a planned period of 26 cycles (approximately 24 months). DAY101 will be administered at the recommended Phase 2 dose (RP2D) of 420 mg/m2 (not to exceed 600 mg) orally once weekly (QW) for each 28-day treatment cycle. Treatment cycles will repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients will undergo radiographic evaluation of their disease at the end of every third cycle. Patients will continue on DAY101 until radiographic evidence of disease progression by RANO (Arms 1 & 2) or RECIST v1.1 criteria (Arm 3) as determined by treating investigator, unacceptable toxicity, patient withdrawal of consent, or death. Patients who have radiographic evidence of disease progression may be allowed to continue DAY101 if, in the opinion of the investigator and approval by the Sponsor, the patient is deriving clinical benefit from continuing study treatment. Disease assessments for patients being treated beyond progression should continue as per regular schedule. DAY101 is an oral pan-RAF inhibitor administered as an oral tablet at 420 mg/m2 (not to exceed 600 mg).', 'Inclusion Criteria': 'Inclusion Criteria: Age 6 months to 25 years with: Arms 1 & 2: a relapsed or progressive LGG with documented known activating BRAF alteration Arm 3: locally advanced or metastatic solid tumor with documented known or expected to be activating RAF fusion Confirmation of histopathologic diagnosis of LGG and molecular diagnosis of activating BRAF alteration Must have received at least one line of systemic therapy and have evidence of radiographic progression Must have at least 1 measurable lesion as defined by RANO (Arms 1 & 2) or RECIST v1.1 (Arm 3) criteria', 'Exclusion Criteria': "Exclusion Criteria: Patient's tumor has additional previously-known activating molecular alterations Patient has symptoms of clinical progression in the absence of radiographic progression Known or suspected diagnosis of neurofibromatosis type 1 (NF-1) Other inclusion/exclusion criteria as stipulated by protocol may apply"}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'BRAF or CRAF/RAF1 fusion or BRAF V600 mutations and KIAA1549:BRAF fusions'}
|
{'Official Title': 'FIREFLY-1: A Phase 2, Open-Label, Multicenter Study to Evaluate the Safety and Efficacy of the Oral Pan-RAF Inhibitor DAY101 in Pediatric Patients With BRAF-Altered, Recurrent or Progressive Low-Grade Glioma and Advanced Solid Tumors', 'Brief Summary': 'FIREFLY-1 is a Phase 2, multi center, open-label study to evaluate the safety and efficacy of oral pan-RAF inhibitor DAY101 in pediatric, adolescent, and young adult patients with recurrent or progressive low-grade glioma or an advanced solid tumor harboring a known BRAF alteration.', 'Condition': 'Low-grade Glioma Advanced Solid Tumor', 'Detailed Description': 'The study will consist of the following treatment arms: Arm 1 (Low-Grade Glioma): Patients aged 6 months to 25 years, inclusive, with recurrent or progressive low-grade glioma harboring a known activating BRAF alteration, including BRAF V600 mutations and KIAA1549:BRAF fusions. Arm 2 (Low-Grade Glioma Expanded Access): Patients aged 6 months to 25 years, inclusive, with recurrent or progressive low-grade glioma harboring a known or expected to be activating RAF alteration (e.g., BRAF or CRAF/RAF1 fusion or BRAF V600 mutations). Opening of Arm 2 to enrollment will be based on the recommendation of the Data Safety Monitoring Board (DSMB). Arm 3 (Advanced Solid Tumor): Patients aged 6 months to 25 years, inclusive, with advanced solid tumors harboring a known or expected to be activating RAF fusion (e.g., BRAF or CRAF/RAF1 fusion). Qualifying genomic alterations will be identified through molecular assays as routinely performed at Clinical Laboratory Improvement Amendments (CLIA) of 1988 or other similarly certified laboratories prior to enrollment into any of the aforementioned arms. Patients will be treated with DAY101, an oral pan-RAF inhibitor, for a planned period of 26 cycles will be treated with DAY101 for a planned period of 26 cycles (approximately 24 months). DAY101 will be administered at the recommended Phase 2 dose (RP2D) of 420 mg/m2 (not to exceed 600 mg) orally once weekly (QW) for each 28-day treatment cycle. Treatment cycles will repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients will undergo radiographic evaluation of their disease at the end of every third cycle. Patients will continue on DAY101 until radiographic evidence of disease progression by RANO (Arms 1 & 2) or RECIST v1.1 criteria (Arm 3) as determined by treating investigator, unacceptable toxicity, patient withdrawal of consent, or death. Patients who have radiographic evidence of disease progression may be allowed to continue DAY101 if, in the opinion of the investigator and approval by the Sponsor, the patient is deriving clinical benefit from continuing study treatment. Disease assessments for patients being treated beyond progression should continue as per regular schedule. DAY101 is an oral pan-RAF inhibitor administered as an oral tablet at 420 mg/m2 (not to exceed 600 mg).', 'Inclusion Criteria': 'Inclusion Criteria: Age 6 months to 25 years with: Arms 1 & 2: a relapsed or progressive LGG with documented known activating BRAF alteration Arm 3: locally advanced or metastatic solid tumor with documented known or expected to be activating RAF fusion Confirmation of histopathologic diagnosis of LGG and molecular diagnosis of activating BRAF alteration Must have received at least one line of systemic therapy and have evidence of radiographic progression Must have at least 1 measurable lesion as defined by RANO (Arms 1 & 2) or RECIST v1.1 (Arm 3) criteria', 'Exclusion Criteria': "Exclusion Criteria: Patient's tumor has additional previously-known activating molecular alterations Patient has symptoms of clinical progression in the absence of radiographic progression Known or suspected diagnosis of neurofibromatosis type 1 (NF-1) Other inclusion/exclusion criteria as stipulated by protocol may apply"}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'BRAF or CRAF/RAF1 fusion or BRAF V600 mutations and KIAA1549:BRAF fusions'}
|
{'Official Title': 'PALbociclib CoLlaborative Adjuvant Study: A Randomized Phase III Trial of Palbociclib With Standard Adjuvant Endocrine Therapy Versus Standard Adjuvant Endocrine Therapy Alone for Hormone Receptor Positive (HR+) / Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Early Breast Cancer', 'Brief Summary': 'This is a prospective, two arm, international, multicenter, randomized, open-label Phase III study evaluating the addition of 2 years of palbociclib to standard adjuvant endocrine therapy for patients with HR+ / HER2- early breast cancer (EBC). The purpose of the PALLAS study is to determine whether the addition of palbociclib to adjuvant endocrine therapy will improve outcomes over endocrine therapy alone for HR+/HER2- early breast cancer. Assessment of a variety of correlative analysis, including evaluation of the effect of palbociclib in genomically defined tumor subgroups, is planned.', 'Condition': 'Breast Cancer', 'Detailed Description': '-', 'Inclusion Criteria': "Inclusion Criteria: Signed informed consent prior to study specific procedures. Age ≥18 years (or per national guidelines). Pre- and postmenopausal women or men with Stage II (Stage IIA limited to max. 1000 patients) or Stage III early invasive breast cancer Patients with multicentric and/or multifocal and/or bilateral early invasive breast cancer are eligible if all histopathologically examined tumors meet pathologic criteria for ER+ and/or PR+ and HER2-. Patients must have histologically confirmed ER+ and/or PR+, HER2-, early invasive breast cancer. Patients must have undergone adequate (definitive) breast surgery for the current malignancy. FFPE tumor tissue block must be confirmed to be received at the central sample repository prior to randomization. ECOG performance status 0-1. Patients must be able and willing to swallow and retain oral medication. Serum or urine pregnancy test must be negative in premenopausal women within 14 days of randomization, or in women with amenorrhea of less than 12 months at time of randomization. Patients who received neo/adjuvant therapy must be after last dose of chemotherapy and/or biologic therapy and must have sufficient resolution of side effects. Patients who received breast/axilla/post-mastectomy chest wall radiotherapy must be after last dose of radiotherapy and must have sufficient resolution of side effects. Patients must have sufficient resolution of any surgical side effects (no active wound healing complications). -Patients must either be initiating or have already started adjuvant hormonal treatment. - Patients who already received neo/adjuvant endocrine therapy are eligible as long as they are enrolled within 12 months of initial histological diagnosis and after completing no more than 6 months of adjuvant endocrine therapy. Absolute neutrophil count ≥ 1,500/µL Platelets ≥ 100,000/ mm3 Hemoglobin ≥ 10g/dL Total serum bilirubin ≤ ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin within normal range in patients with documented Gilbert's Syndrome. Aspartate amino transferase (AST or SGOT) and alanine amino transferase (ALT or SGPT) ≤ 1.5 × institutional ULN. Serum creatinine below the upper limit of the institutional normal range (ULN) or creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with serum creatinine levels above institutional ULN.", 'Exclusion Criteria': 'Exclusion Criteria: Concurrent therapy with other Investigational Products. Prior therapy with any CDK inhibitor. Patients with Stage I or IV breast cancer are not eligible. History of allergic reactions attributed to compounds of chemical or biologic composition similar to palbociclib. Patients receiving any medications or substances that are potent inhibitors or inducers of CYP3A isoenzymes within 7 days of randomization. Uncontrolled intercurrent illness that would limit compliance with study requirements. Pregnant women, or women of childbearing potential without a negative pregnancy test within 14 days prior to randomization. Patients with a history of any malignancy are ineligible Patients who previously received endocrine therapy within 5 years prior to diagnosis of the current malignancy. Patients on antiretroviral therapy. Patients with clinically significant history of any chronic liver disease. Patients receiving concurrent exogenous hormone therapy (topical vaginal estrogen therapy is allowable).'}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: ER+ and/or PR+, HER2-'}
|
{'Official Title': 'PALbociclib CoLlaborative Adjuvant Study: A Randomized Phase III Trial of Palbociclib With Standard Adjuvant Endocrine Therapy Versus Standard Adjuvant Endocrine Therapy Alone for Hormone Receptor Positive (HR+) / Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Early Breast Cancer', 'Brief Summary': 'This is a prospective, two arm, international, multicenter, randomized, open-label Phase III study evaluating the addition of 2 years of palbociclib to standard adjuvant endocrine therapy for patients with HR+ / HER2- early breast cancer (EBC). The purpose of the PALLAS study is to determine whether the addition of palbociclib to adjuvant endocrine therapy will improve outcomes over endocrine therapy alone for HR+/HER2- early breast cancer. Assessment of a variety of correlative analysis, including evaluation of the effect of palbociclib in genomically defined tumor subgroups, is planned.', 'Condition': 'Breast Cancer', 'Detailed Description': '-', 'Inclusion Criteria': "Inclusion Criteria: Signed informed consent prior to study specific procedures. Age ≥18 years (or per national guidelines). Pre- and postmenopausal women or men with Stage II (Stage IIA limited to max. 1000 patients) or Stage III early invasive breast cancer Patients with multicentric and/or multifocal and/or bilateral early invasive breast cancer are eligible if all histopathologically examined tumors meet pathologic criteria for ER+ and/or PR+ and HER2-. Patients must have histologically confirmed ER+ and/or PR+, HER2-, early invasive breast cancer. Patients must have undergone adequate (definitive) breast surgery for the current malignancy. FFPE tumor tissue block must be confirmed to be received at the central sample repository prior to randomization. ECOG performance status 0-1. Patients must be able and willing to swallow and retain oral medication. Serum or urine pregnancy test must be negative in premenopausal women within 14 days of randomization, or in women with amenorrhea of less than 12 months at time of randomization. Patients who received neo/adjuvant therapy must be after last dose of chemotherapy and/or biologic therapy and must have sufficient resolution of side effects. Patients who received breast/axilla/post-mastectomy chest wall radiotherapy must be after last dose of radiotherapy and must have sufficient resolution of side effects. Patients must have sufficient resolution of any surgical side effects (no active wound healing complications). -Patients must either be initiating or have already started adjuvant hormonal treatment. - Patients who already received neo/adjuvant endocrine therapy are eligible as long as they are enrolled within 12 months of initial histological diagnosis and after completing no more than 6 months of adjuvant endocrine therapy. Absolute neutrophil count ≥ 1,500/µL Platelets ≥ 100,000/ mm3 Hemoglobin ≥ 10g/dL Total serum bilirubin ≤ ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin within normal range in patients with documented Gilbert's Syndrome. Aspartate amino transferase (AST or SGOT) and alanine amino transferase (ALT or SGPT) ≤ 1.5 × institutional ULN. Serum creatinine below the upper limit of the institutional normal range (ULN) or creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with serum creatinine levels above institutional ULN.", 'Exclusion Criteria': 'Exclusion Criteria: Concurrent therapy with other Investigational Products. Prior therapy with any CDK inhibitor. Patients with Stage I or IV breast cancer are not eligible. History of allergic reactions attributed to compounds of chemical or biologic composition similar to palbociclib. Patients receiving any medications or substances that are potent inhibitors or inducers of CYP3A isoenzymes within 7 days of randomization. Uncontrolled intercurrent illness that would limit compliance with study requirements. Pregnant women, or women of childbearing potential without a negative pregnancy test within 14 days prior to randomization. Patients with a history of any malignancy are ineligible Patients who previously received endocrine therapy within 5 years prior to diagnosis of the current malignancy. Patients on antiretroviral therapy. Patients with clinically significant history of any chronic liver disease. Patients receiving concurrent exogenous hormone therapy (topical vaginal estrogen therapy is allowable).'}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: ER+ and/or PR+, HER2-'}
|
{'Official Title': 'A Phase 3 Study of Erdafitinib Compared With Vinflunine or Docetaxel or Pembrolizumab in Subjects With Advanced Urothelial Cancer and Selected FGFR Gene Aberrations', 'Brief Summary': 'The purpose of this study is to evaluate efficacy of erdafitinib versus chemotherapy or pembrolizumab in participants with advanced urothelial cancer harboring selected fibroblast growth factor receptor (FGFR) aberrations who have progressed after 1 or 2 prior treatments, at least 1 of which includes an anti-programmed death ligand 1(PD-[L]1) agent (cohort 1) or 1 prior treatment not containing an anti-PD-(L) 1 agent (cohort 2).', 'Condition': 'Urothelial Cancer', 'Detailed Description': 'A study of erdafitinib versus standard of care, consisting of chemotherapy (docetaxel or vinflunine) or anti-PD-(L) 1 agent pembrolizumab, in participants with advanced urothelial cancer and selected FGFR aberrations who have progressed on or after 1 or 2 prior treatments, at least 1 of which includes an anti-PD-(L) 1 agent (cohort 1) or 1 prior treatment not containing an anti-PD-(L) 1 agent (cohort 2). It will consist of screening, treatment phase (from randomization until disease progression, intolerable toxicity, withdrawal of consent or decision by investigator to discontinue treatment, post-treatment follow-up (from end-of-treatment to participants death, withdraws consent, lost to follow-up study completion for the respective cohort, whichever comes first). The study will have long term extension (LTE) period after clinical cutoff date is achieved for final analysis of each cohort and participants eligible in the opinion of the investigator, will continue to benefit from the study intervention. Efficacy, pharmacokinetics, biomarkers, patient reported outcomes, medical resource utilization and safety will be assessed.', 'Inclusion Criteria': 'Inclusion Criteria: Histologic demonstration of transitional cell carcinoma of the urothelium. Minor components ( less than [<] 50 percent [%] overall) of variant histology such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or micropapillary change are acceptable Metastatic or surgically unresectable urothelial cancer Documented progression of disease, defined as any progression that requires a change in treatment, prior to randomization Cohort 1: Prior treatment with an anti-PD-(L) 1 agent as monotherapy or as combination therapy; no more than 2 prior lines of systemic treatment. Cohort 2: No prior treatment with an anti-PD-(L) 1 agent; only 1 line of prior systemic treatment. Subjects who received neoadjuvant or adjuvant chemotherapy and showed disease progression within 12 months of the last dose are considered to have received systemic therapy in the metastatic setting. A woman of childbearing potential who is sexually active must have a negative pregnancy test (beta human chorionic gonadotropin [beta hCG]) at Screening (urine or serum) Participants must meet appropriate molecular eligibility criteria Eastern Cooperative Oncology Group (ECOG) performance status Grade 0, 1, or 2 Adequate bone marrow, liver, and renal function', 'Exclusion Criteria': 'Exclusion Criteria: Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 30 days prior to randomization Active malignancies (that is, requiring treatment change in the last 24 months). The only allowed exceptions are: urothelial cancer, skin cancer treated within the last 24 months that is considered completely cured, localized prostate cancer with a gleason score of 6 (treated within the last 24 months or untreated and under surveillance) and localized prostate cancer with a gleason score of 3+4 that has been treated more than 6 months prior to full study screening and considered to have a very low risk of recurrence. Symptomatic central nervous system metastases Received prior fibroblast growth factor receptor (FGFR) inhibitor treatment Known allergies, hypersensitivity, or intolerance to erdafitinib or its excipients Current central serous retinopathy (CSR) or retinal pigment epithelial detachment of any grade. History of uncontrolled cardiovascular disease Impaired wound healing capacity defined as skin/decubitus ulcers, chronic leg ulcers, known gastric ulcers, or unhealed incisions'}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: fibroblast growth factor receptor (FGFR) aberrations'}
|
{'Official Title': 'A Phase 3 Study of Erdafitinib Compared With Vinflunine or Docetaxel or Pembrolizumab in Subjects With Advanced Urothelial Cancer and Selected FGFR Gene Aberrations', 'Brief Summary': 'The purpose of this study is to evaluate efficacy of erdafitinib versus chemotherapy or pembrolizumab in participants with advanced urothelial cancer harboring selected fibroblast growth factor receptor (FGFR) aberrations who have progressed after 1 or 2 prior treatments, at least 1 of which includes an anti-programmed death ligand 1(PD-[L]1) agent (cohort 1) or 1 prior treatment not containing an anti-PD-(L) 1 agent (cohort 2).', 'Condition': 'Urothelial Cancer', 'Detailed Description': 'A study of erdafitinib versus standard of care, consisting of chemotherapy (docetaxel or vinflunine) or anti-PD-(L) 1 agent pembrolizumab, in participants with advanced urothelial cancer and selected FGFR aberrations who have progressed on or after 1 or 2 prior treatments, at least 1 of which includes an anti-PD-(L) 1 agent (cohort 1) or 1 prior treatment not containing an anti-PD-(L) 1 agent (cohort 2). It will consist of screening, treatment phase (from randomization until disease progression, intolerable toxicity, withdrawal of consent or decision by investigator to discontinue treatment, post-treatment follow-up (from end-of-treatment to participants death, withdraws consent, lost to follow-up study completion for the respective cohort, whichever comes first). The study will have long term extension (LTE) period after clinical cutoff date is achieved for final analysis of each cohort and participants eligible in the opinion of the investigator, will continue to benefit from the study intervention. Efficacy, pharmacokinetics, biomarkers, patient reported outcomes, medical resource utilization and safety will be assessed.', 'Inclusion Criteria': 'Inclusion Criteria: Histologic demonstration of transitional cell carcinoma of the urothelium. Minor components ( less than [<] 50 percent [%] overall) of variant histology such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or micropapillary change are acceptable Metastatic or surgically unresectable urothelial cancer Documented progression of disease, defined as any progression that requires a change in treatment, prior to randomization Cohort 1: Prior treatment with an anti-PD-(L) 1 agent as monotherapy or as combination therapy; no more than 2 prior lines of systemic treatment. Cohort 2: No prior treatment with an anti-PD-(L) 1 agent; only 1 line of prior systemic treatment. Subjects who received neoadjuvant or adjuvant chemotherapy and showed disease progression within 12 months of the last dose are considered to have received systemic therapy in the metastatic setting. A woman of childbearing potential who is sexually active must have a negative pregnancy test (beta human chorionic gonadotropin [beta hCG]) at Screening (urine or serum) Participants must meet appropriate molecular eligibility criteria Eastern Cooperative Oncology Group (ECOG) performance status Grade 0, 1, or 2 Adequate bone marrow, liver, and renal function', 'Exclusion Criteria': 'Exclusion Criteria: Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 30 days prior to randomization Active malignancies (that is, requiring treatment change in the last 24 months). The only allowed exceptions are: urothelial cancer, skin cancer treated within the last 24 months that is considered completely cured, localized prostate cancer with a gleason score of 6 (treated within the last 24 months or untreated and under surveillance) and localized prostate cancer with a gleason score of 3+4 that has been treated more than 6 months prior to full study screening and considered to have a very low risk of recurrence. Symptomatic central nervous system metastases Received prior fibroblast growth factor receptor (FGFR) inhibitor treatment Known allergies, hypersensitivity, or intolerance to erdafitinib or its excipients Current central serous retinopathy (CSR) or retinal pigment epithelial detachment of any grade. History of uncontrolled cardiovascular disease Impaired wound healing capacity defined as skin/decubitus ulcers, chronic leg ulcers, known gastric ulcers, or unhealed incisions'}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: fibroblast growth factor receptor (FGFR) aberrations'}
|
{'Official Title': 'A Phase 3 Study of Erdafitinib Compared With Vinflunine or Docetaxel or Pembrolizumab in Subjects With Advanced Urothelial Cancer and Selected FGFR Gene Aberrations', 'Brief Summary': 'The purpose of this study is to evaluate efficacy of erdafitinib versus chemotherapy or pembrolizumab in participants with advanced urothelial cancer harboring selected fibroblast growth factor receptor (FGFR) aberrations who have progressed after 1 or 2 prior treatments, at least 1 of which includes an anti-programmed death ligand 1(PD-[L]1) agent (cohort 1) or 1 prior treatment not containing an anti-PD-(L) 1 agent (cohort 2).', 'Condition': 'Urothelial Cancer', 'Detailed Description': 'A study of erdafitinib versus standard of care, consisting of chemotherapy (docetaxel or vinflunine) or anti-PD-(L) 1 agent pembrolizumab, in participants with advanced urothelial cancer and selected FGFR aberrations who have progressed on or after 1 or 2 prior treatments, at least 1 of which includes an anti-PD-(L) 1 agent (cohort 1) or 1 prior treatment not containing an anti-PD-(L) 1 agent (cohort 2). It will consist of screening, treatment phase (from randomization until disease progression, intolerable toxicity, withdrawal of consent or decision by investigator to discontinue treatment, post-treatment follow-up (from end-of-treatment to participants death, withdraws consent, lost to follow-up study completion for the respective cohort, whichever comes first). The study will have long term extension (LTE) period after clinical cutoff date is achieved for final analysis of each cohort and participants eligible in the opinion of the investigator, will continue to benefit from the study intervention. Efficacy, pharmacokinetics, biomarkers, patient reported outcomes, medical resource utilization and safety will be assessed.', 'Inclusion Criteria': 'Inclusion Criteria: Histologic demonstration of transitional cell carcinoma of the urothelium. Minor components ( less than [<] 50 percent [%] overall) of variant histology such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or micropapillary change are acceptable Metastatic or surgically unresectable urothelial cancer Documented progression of disease, defined as any progression that requires a change in treatment, prior to randomization Cohort 1: Prior treatment with an anti-PD-(L) 1 agent as monotherapy or as combination therapy; no more than 2 prior lines of systemic treatment. Cohort 2: No prior treatment with an anti-PD-(L) 1 agent; only 1 line of prior systemic treatment. Subjects who received neoadjuvant or adjuvant chemotherapy and showed disease progression within 12 months of the last dose are considered to have received systemic therapy in the metastatic setting. A woman of childbearing potential who is sexually active must have a negative pregnancy test (beta human chorionic gonadotropin [beta hCG]) at Screening (urine or serum) Participants must meet appropriate molecular eligibility criteria Eastern Cooperative Oncology Group (ECOG) performance status Grade 0, 1, or 2 Adequate bone marrow, liver, and renal function', 'Exclusion Criteria': 'Exclusion Criteria: Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 30 days prior to randomization Active malignancies (that is, requiring treatment change in the last 24 months). The only allowed exceptions are: urothelial cancer, skin cancer treated within the last 24 months that is considered completely cured, localized prostate cancer with a gleason score of 6 (treated within the last 24 months or untreated and under surveillance) and localized prostate cancer with a gleason score of 3+4 that has been treated more than 6 months prior to full study screening and considered to have a very low risk of recurrence. Symptomatic central nervous system metastases Received prior fibroblast growth factor receptor (FGFR) inhibitor treatment Known allergies, hypersensitivity, or intolerance to erdafitinib or its excipients Current central serous retinopathy (CSR) or retinal pigment epithelial detachment of any grade. History of uncontrolled cardiovascular disease Impaired wound healing capacity defined as skin/decubitus ulcers, chronic leg ulcers, known gastric ulcers, or unhealed incisions'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: fibroblast growth factor receptor (FGFR) aberrations'}
|
{'Official Title': 'A Phase 3 Study of Erdafitinib Compared With Vinflunine or Docetaxel or Pembrolizumab in Subjects With Advanced Urothelial Cancer and Selected FGFR Gene Aberrations', 'Brief Summary': 'The purpose of this study is to evaluate efficacy of erdafitinib versus chemotherapy or pembrolizumab in participants with advanced urothelial cancer harboring selected fibroblast growth factor receptor (FGFR) aberrations who have progressed after 1 or 2 prior treatments, at least 1 of which includes an anti-programmed death ligand 1(PD-[L]1) agent (cohort 1) or 1 prior treatment not containing an anti-PD-(L) 1 agent (cohort 2).', 'Condition': 'Urothelial Cancer', 'Detailed Description': 'A study of erdafitinib versus standard of care, consisting of chemotherapy (docetaxel or vinflunine) or anti-PD-(L) 1 agent pembrolizumab, in participants with advanced urothelial cancer and selected FGFR aberrations who have progressed on or after 1 or 2 prior treatments, at least 1 of which includes an anti-PD-(L) 1 agent (cohort 1) or 1 prior treatment not containing an anti-PD-(L) 1 agent (cohort 2). It will consist of screening, treatment phase (from randomization until disease progression, intolerable toxicity, withdrawal of consent or decision by investigator to discontinue treatment, post-treatment follow-up (from end-of-treatment to participants death, withdraws consent, lost to follow-up study completion for the respective cohort, whichever comes first). The study will have long term extension (LTE) period after clinical cutoff date is achieved for final analysis of each cohort and participants eligible in the opinion of the investigator, will continue to benefit from the study intervention. Efficacy, pharmacokinetics, biomarkers, patient reported outcomes, medical resource utilization and safety will be assessed.', 'Inclusion Criteria': 'Inclusion Criteria: Histologic demonstration of transitional cell carcinoma of the urothelium. Minor components ( less than [<] 50 percent [%] overall) of variant histology such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or micropapillary change are acceptable Metastatic or surgically unresectable urothelial cancer Documented progression of disease, defined as any progression that requires a change in treatment, prior to randomization Cohort 1: Prior treatment with an anti-PD-(L) 1 agent as monotherapy or as combination therapy; no more than 2 prior lines of systemic treatment. Cohort 2: No prior treatment with an anti-PD-(L) 1 agent; only 1 line of prior systemic treatment. Subjects who received neoadjuvant or adjuvant chemotherapy and showed disease progression within 12 months of the last dose are considered to have received systemic therapy in the metastatic setting. A woman of childbearing potential who is sexually active must have a negative pregnancy test (beta human chorionic gonadotropin [beta hCG]) at Screening (urine or serum) Participants must meet appropriate molecular eligibility criteria Eastern Cooperative Oncology Group (ECOG) performance status Grade 0, 1, or 2 Adequate bone marrow, liver, and renal function', 'Exclusion Criteria': 'Exclusion Criteria: Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 30 days prior to randomization Active malignancies (that is, requiring treatment change in the last 24 months). The only allowed exceptions are: urothelial cancer, skin cancer treated within the last 24 months that is considered completely cured, localized prostate cancer with a gleason score of 6 (treated within the last 24 months or untreated and under surveillance) and localized prostate cancer with a gleason score of 3+4 that has been treated more than 6 months prior to full study screening and considered to have a very low risk of recurrence. Symptomatic central nervous system metastases Received prior fibroblast growth factor receptor (FGFR) inhibitor treatment Known allergies, hypersensitivity, or intolerance to erdafitinib or its excipients Current central serous retinopathy (CSR) or retinal pigment epithelial detachment of any grade. History of uncontrolled cardiovascular disease Impaired wound healing capacity defined as skin/decubitus ulcers, chronic leg ulcers, known gastric ulcers, or unhealed incisions'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: fibroblast growth factor receptor (FGFR) aberrations'}
|
{'Official Title': 'A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase III Clinical Study on Toripalimab Combined With Platinum-Based Doublet Drug Chemotherapy for Resectable, Stage II-III, Non-Small Cell Lung Cancer', 'Brief Summary': 'This is a randomized, double-blind, placebo-controlled, multi-center, phase III clinical study to evaluate the efficacy and safety of Toripalimab injection (JS001) combined with platinum-based doublet drug chemotherapy versus placebo combined with platinum-based doublet drug chemotherapy for subjects with resectable, stage II-III NSCLC.', 'Condition': 'Stage II-III Non-small Cell Lung Cancer', 'Detailed Description': 'Subjects who meet all the inclusion criteria but do not meet any exclusion criteria are randomized into two groups at a ratio of 1:1: according to the stratification factors as below: Disease stage: II vs IIIA vs IIIB PD-L1 status: PD-L1 expression ≥1% vs. PD-L1 <1% or not evaluable Planned surgical operation: pneumonectomy vs. lobectomy Pathological type: non-squamous cell carcinoma vs. squamous cell carcinoma Neoadjuvant therapy should be started within 3 days after randomization. Toripalimab IV 240 mg Q3W /plaecbo will be given combined with platinum-based doublet drug chemotherapy for three cycles in the preoperative neoadjuvant therapy period for trial group; Every 3 weeks of treatment is regarded as one cycle, in which combined therapy is given in the first day of every cycle. All the subjects will receive preoperative radiological and surgical evaluation 3-5 weeks after neoadjuvant therapy. After 3 cycles of preoperative neoadjuvant therapy, all the subjects who still have surgical indications will receive radical excision based on the surgical operation criteria of the World Association for Lung Cancer Research within 4-6 weeks after 3 cycles of preoperative neoadjuvant therapy. The pTNM will be staged in accordance with AJCC Cancer Staging Manual (version 8). All the specimens taken during the operation will be evaluated by local pathologists for the surgical margin. The tumor tissue samples collected from subjects during the study will be submitted to the authorized central laboratory for blinded evaluation of pathological response and translational research. All the subjects who have completed the radical operation will receive one cycle of postoperative adjuvant therapy, i.e., Toripalimab IV 240 mg/placebo + platinum-based doublet drug chemotherapy in 30 days after the operation. If there is no adjuvant radiotherapy plan, it will proceed to consolidation treatment period three weeks after adjuvant therapy; if adjuvant radiotherapy is planned then the consolidation treatment period will start 30 days after adjuvant radiotherapy. In the consolidation treatment period, Toripalimab IV 240 mg/placebo is given in each cycle of every 3 weeks for a total of 13 cycles . Adverse events (AEs) will be monitored throughout the study, and the severity will be graded to the guidelines listed in National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) version 5.0 or above. The safety will be followed up in the subjects who have received study treatment and discontinued the drug prematurely. All the subjects will be followed up for overall survival, until death, withdrawal of informed consent or end of study.', 'Inclusion Criteria': 'Having sufficient understanding of this study and being willing to sign the informed consent form (ICF); Aged 18-70 years, male or female; Treatment-naive, histologically confirmed resectable, stage II, IIIA, IIIB (N2) (AJCC staging system, version 8) NSCLC; cTNM stage can be confirmed through PET-CT or pathological biopsy; resectable stage II non-small cell lung cancer is defined as eligible for radical resection evaluated by a qualified thoracic surgeon; resectable stage III is defined as the resectable and potential resectable according to the Chinese expert consensus on the multidisciplinary diagnosis and treatment for stage III non-small cell lung cancer (2019)in which resectable includes IIIA(N0-1), partial N2 with single-station mediastinal lymph node metastasis and the short diameter of lymph node<2 cm， partial T4 (satellite nodules in the adjacent lobe) N1 and potential resectable includes partial stage IIIA and IIIB with the short diameter of single-station N2 mediastinal lymph node<3 cm, other potentially resectable T3 or T4 central tumor ; Any suspected lesions which could change the TNM stage, such as contralateral mediastinal lymph node, supraclavicular lymph mode, solid/sub-solid pulmonary node and non-isolated ground glass opacity (GGO), pathological confirmation is strongly recommended. Measurable lesions based on the response evaluation criteria in solid tumors version 1.1; Tumor tissue specimens available for pathological diagnosis, detection of PD-L1 expression and biomarkers prior to randomization (the tumor tissue specimens must be freshly obtained or archived samples within 3 months prior to enrollment; tumor tissue specimens must be the samples of histological category, including but not limited to the tissue punctured by core needle and hollow needle, tissue acquired by bronchoscopic clamp, surgically resected samples; the samples acquired by fine needle puncture and bronchial brushing are not acceptable); ECOG score 0-1; Good organ function: Being willing and able to comply with the visits, treatment plan, laboratory examinations and other study procedures scheduled in the study; pulmonary function test being able to withstand the planned pneumonectomy evaluated by surgeons; Women of childbearing potential must undergo serum pregnancy test within 3 hours prior to the first dose and the result must be negative. Female subjects of childbearing potential and male subjects whose partners are women of childbearing potential must agree to use highly effective contraceptive methods during the study period and within 180 days after the last dose of study drug. Women of childbearing potential must undergo serum pregnancy test within 3 days prior to the first dose and the result must be negative. Female subjects of childbearing potential and male subjects whose partners are women of childbearing potential must agree to use highly effective contraceptive methods during the study period and within 180 days after the last dose of study drug', 'Exclusion Criteria': "Presence of locally advanced, unresectable or metastatic disease; unresectable includes the unresectable defined in the Chinese expert consensus on the multidisciplinary diagnosis and treatment for stage III non-small cell lung cancer (2019), including partial stage IIIA and IIIB and all the stage IIIC; N2: single station mediastinal lymph node metastasis with short diameter ≥3cm; N2: multiple station mediastinal lymph node metastasis with lymph node fusion and the short diameter of lymph node ≥2cm on CT; ALL the N3; T4: invading esophagus, heart, aorta; NSCLC involving superior sulcus, large cell neuroendocrine carcinoma (LCNEC), sarcomatoid tumor; Participants with known EGFR sensitive mutations or ALK translocation, EGFR and ALK mutation status needs to be identified for the subjects with non-squamous cell carcinoma; Previous treatment with systemic antitumor therapy for early NSCLC, including investigational product; History of (non-infectious) pneumonitis/interstitial lung disease requiring steroid treatment, or ongoing pneumonitis/interstitial lung disease requiring steroid treatment; Active tuberculosis; Active infection requiring systemic treatment; Subjects with any known or suspected autoimmune disorder or immunodeficiency, with the following exceptions: hypothyroidism, hormone therapy is not needed, or well controlled at physiological dose; controlled type I diabetes; Uncontrolled active hepatitis B (defined as positive hepatitis B surface antigen [HBsAg] in screening period with HBV-DNA detected higher than the upper limit of normal at the clinical laboratory of the study center); (the subjects with HBV-DNA assay <500 IU/mL within 28 days prior to randomization who have received local standard antiviral therapy for at least 14 days and are willing to receive antiviral therapy continuously during the study can be enrolled); active hepatitis C (defined as positive hepatitis C surface antibody [HCsAb] in screening period and positive HCV-RNA); Known human immunodeficiency virus (HIV) infection (known positive HIV antibody); Vaccination of live vaccine within 30 days prior to the first dose. Including but not limited to the following: parotitis, rubella, measles, varicella/ herpes zoster (varicella), yellow fever, Rabies, Bacille Calmette-Guérin (BCG) and typhoid vaccine (inactivated virus vaccine allowed); ≥ Grade 2 peripheral neuropathy; Previous use of PD-1/PD-L1 agent or the drug acting on another targeted T cell receptor (e.g., CTLA-4, OX-40); Severe allergic reaction to other monoclonal antibodies; History of serious allergy to Pemetrexed, paclitaxel or docetaxel, cisplatin, carboplatin or its preventive medications; Known serious or uncontrolled pre-existing diseases; including but not limited to cardiovascular events with hemodynamic instability, symptomatic cerebrovascular events, and hepatic cirrhosis above Child-Pugh A within 6 months; History or current evidence of any disease, therapy or abnormal laboratory examination that may confuse the study results, interfere with subject's participation in the full course of the study or not meet the best interest of subject's participation in the study, as judged by investigators; Other malignant tumors within 5 years prior to the first dose, except non-small cell lung cancer. The malignant tumors with negligible risk of metastasis or death (e.g., expected disease-free survival > 5 years) and expected to achieve radical outcomes after treatment (e.g., sufficiently treated carcinoma in situ of cervix, basal or squamous cell skin cancer, ductal carcinoma in situ treated for radical surgery) can be excluded."}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include : PD-L1 Exclude : EGFR sensitive mutations, ALK translocation'}
|
{'Official Title': 'A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase III Clinical Study on Toripalimab Combined With Platinum-Based Doublet Drug Chemotherapy for Resectable, Stage II-III, Non-Small Cell Lung Cancer', 'Brief Summary': 'This is a randomized, double-blind, placebo-controlled, multi-center, phase III clinical study to evaluate the efficacy and safety of Toripalimab injection (JS001) combined with platinum-based doublet drug chemotherapy versus placebo combined with platinum-based doublet drug chemotherapy for subjects with resectable, stage II-III NSCLC.', 'Condition': 'Stage II-III Non-small Cell Lung Cancer', 'Detailed Description': 'Subjects who meet all the inclusion criteria but do not meet any exclusion criteria are randomized into two groups at a ratio of 1:1: according to the stratification factors as below: Disease stage: II vs IIIA vs IIIB PD-L1 status: PD-L1 expression ≥1% vs. PD-L1 <1% or not evaluable Planned surgical operation: pneumonectomy vs. lobectomy Pathological type: non-squamous cell carcinoma vs. squamous cell carcinoma Neoadjuvant therapy should be started within 3 days after randomization. Toripalimab IV 240 mg Q3W /plaecbo will be given combined with platinum-based doublet drug chemotherapy for three cycles in the preoperative neoadjuvant therapy period for trial group; Every 3 weeks of treatment is regarded as one cycle, in which combined therapy is given in the first day of every cycle. All the subjects will receive preoperative radiological and surgical evaluation 3-5 weeks after neoadjuvant therapy. After 3 cycles of preoperative neoadjuvant therapy, all the subjects who still have surgical indications will receive radical excision based on the surgical operation criteria of the World Association for Lung Cancer Research within 4-6 weeks after 3 cycles of preoperative neoadjuvant therapy. The pTNM will be staged in accordance with AJCC Cancer Staging Manual (version 8). All the specimens taken during the operation will be evaluated by local pathologists for the surgical margin. The tumor tissue samples collected from subjects during the study will be submitted to the authorized central laboratory for blinded evaluation of pathological response and translational research. All the subjects who have completed the radical operation will receive one cycle of postoperative adjuvant therapy, i.e., Toripalimab IV 240 mg/placebo + platinum-based doublet drug chemotherapy in 30 days after the operation. If there is no adjuvant radiotherapy plan, it will proceed to consolidation treatment period three weeks after adjuvant therapy; if adjuvant radiotherapy is planned then the consolidation treatment period will start 30 days after adjuvant radiotherapy. In the consolidation treatment period, Toripalimab IV 240 mg/placebo is given in each cycle of every 3 weeks for a total of 13 cycles . Adverse events (AEs) will be monitored throughout the study, and the severity will be graded to the guidelines listed in National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) version 5.0 or above. The safety will be followed up in the subjects who have received study treatment and discontinued the drug prematurely. All the subjects will be followed up for overall survival, until death, withdrawal of informed consent or end of study.', 'Inclusion Criteria': 'Having sufficient understanding of this study and being willing to sign the informed consent form (ICF); Aged 18-70 years, male or female; Treatment-naive, histologically confirmed resectable, stage II, IIIA, IIIB (N2) (AJCC staging system, version 8) NSCLC; cTNM stage can be confirmed through PET-CT or pathological biopsy; resectable stage II non-small cell lung cancer is defined as eligible for radical resection evaluated by a qualified thoracic surgeon; resectable stage III is defined as the resectable and potential resectable according to the Chinese expert consensus on the multidisciplinary diagnosis and treatment for stage III non-small cell lung cancer (2019)in which resectable includes IIIA(N0-1), partial N2 with single-station mediastinal lymph node metastasis and the short diameter of lymph node<2 cm， partial T4 (satellite nodules in the adjacent lobe) N1 and potential resectable includes partial stage IIIA and IIIB with the short diameter of single-station N2 mediastinal lymph node<3 cm, other potentially resectable T3 or T4 central tumor ; Any suspected lesions which could change the TNM stage, such as contralateral mediastinal lymph node, supraclavicular lymph mode, solid/sub-solid pulmonary node and non-isolated ground glass opacity (GGO), pathological confirmation is strongly recommended. Measurable lesions based on the response evaluation criteria in solid tumors version 1.1; Tumor tissue specimens available for pathological diagnosis, detection of PD-L1 expression and biomarkers prior to randomization (the tumor tissue specimens must be freshly obtained or archived samples within 3 months prior to enrollment; tumor tissue specimens must be the samples of histological category, including but not limited to the tissue punctured by core needle and hollow needle, tissue acquired by bronchoscopic clamp, surgically resected samples; the samples acquired by fine needle puncture and bronchial brushing are not acceptable); ECOG score 0-1; Good organ function: Being willing and able to comply with the visits, treatment plan, laboratory examinations and other study procedures scheduled in the study; pulmonary function test being able to withstand the planned pneumonectomy evaluated by surgeons; Women of childbearing potential must undergo serum pregnancy test within 3 hours prior to the first dose and the result must be negative. Female subjects of childbearing potential and male subjects whose partners are women of childbearing potential must agree to use highly effective contraceptive methods during the study period and within 180 days after the last dose of study drug. Women of childbearing potential must undergo serum pregnancy test within 3 days prior to the first dose and the result must be negative. Female subjects of childbearing potential and male subjects whose partners are women of childbearing potential must agree to use highly effective contraceptive methods during the study period and within 180 days after the last dose of study drug', 'Exclusion Criteria': "Presence of locally advanced, unresectable or metastatic disease; unresectable includes the unresectable defined in the Chinese expert consensus on the multidisciplinary diagnosis and treatment for stage III non-small cell lung cancer (2019), including partial stage IIIA and IIIB and all the stage IIIC; N2: single station mediastinal lymph node metastasis with short diameter ≥3cm; N2: multiple station mediastinal lymph node metastasis with lymph node fusion and the short diameter of lymph node ≥2cm on CT; ALL the N3; T4: invading esophagus, heart, aorta; NSCLC involving superior sulcus, large cell neuroendocrine carcinoma (LCNEC), sarcomatoid tumor; Participants with known EGFR sensitive mutations or ALK translocation, EGFR and ALK mutation status needs to be identified for the subjects with non-squamous cell carcinoma; Previous treatment with systemic antitumor therapy for early NSCLC, including investigational product; History of (non-infectious) pneumonitis/interstitial lung disease requiring steroid treatment, or ongoing pneumonitis/interstitial lung disease requiring steroid treatment; Active tuberculosis; Active infection requiring systemic treatment; Subjects with any known or suspected autoimmune disorder or immunodeficiency, with the following exceptions: hypothyroidism, hormone therapy is not needed, or well controlled at physiological dose; controlled type I diabetes; Uncontrolled active hepatitis B (defined as positive hepatitis B surface antigen [HBsAg] in screening period with HBV-DNA detected higher than the upper limit of normal at the clinical laboratory of the study center); (the subjects with HBV-DNA assay <500 IU/mL within 28 days prior to randomization who have received local standard antiviral therapy for at least 14 days and are willing to receive antiviral therapy continuously during the study can be enrolled); active hepatitis C (defined as positive hepatitis C surface antibody [HCsAb] in screening period and positive HCV-RNA); Known human immunodeficiency virus (HIV) infection (known positive HIV antibody); Vaccination of live vaccine within 30 days prior to the first dose. Including but not limited to the following: parotitis, rubella, measles, varicella/ herpes zoster (varicella), yellow fever, Rabies, Bacille Calmette-Guérin (BCG) and typhoid vaccine (inactivated virus vaccine allowed); ≥ Grade 2 peripheral neuropathy; Previous use of PD-1/PD-L1 agent or the drug acting on another targeted T cell receptor (e.g., CTLA-4, OX-40); Severe allergic reaction to other monoclonal antibodies; History of serious allergy to Pemetrexed, paclitaxel or docetaxel, cisplatin, carboplatin or its preventive medications; Known serious or uncontrolled pre-existing diseases; including but not limited to cardiovascular events with hemodynamic instability, symptomatic cerebrovascular events, and hepatic cirrhosis above Child-Pugh A within 6 months; History or current evidence of any disease, therapy or abnormal laboratory examination that may confuse the study results, interfere with subject's participation in the full course of the study or not meet the best interest of subject's participation in the study, as judged by investigators; Other malignant tumors within 5 years prior to the first dose, except non-small cell lung cancer. The malignant tumors with negligible risk of metastasis or death (e.g., expected disease-free survival > 5 years) and expected to achieve radical outcomes after treatment (e.g., sufficiently treated carcinoma in situ of cervix, basal or squamous cell skin cancer, ductal carcinoma in situ treated for radical surgery) can be excluded."}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include : PD-L1 Exclude : EGFR sensitive mutations, ALK translocation'}
|
{'Official Title': 'A Phase 2, Multicenter, Randomized, Study of Trastuzumab Deruxtecan in Participants With HER2-overexpressing Locally Advanced, Unresectable or Metastatic Colorectal Cancer (DESTINY-CRC02)', 'Brief Summary': 'This study will evaluate the efficacy, safety, and pharmacokinetics of Trastuzumab deruxtecan (T-DXd) in participants with human epidermal growth factor 2 (HER2)-overexpressing locally advanced, unresectable, or metastatic colorectal cancer (mCRC).', 'Condition': 'Advanced Colorectal Cancer', 'Detailed Description': 'This 2-stage study will evaluate participants with locally advanced, unresectable, or metastatic HER2-overexpressing colorectal cancer (CRC) (immunohistochemistry [IHC] 3+ or IHC 2+/ in situ hybridization [ISH]+) of v-raf murine sarcoma viral oncogene homologue B1 (BRAF) wild-type and either rat sarcoma viral oncogenes homologue (RAS) wild-type or mutant tumor type, previously treated with standard therapy. In the first stage, participants will be randomized 1:1 with 2 doses of T-DXd. After Stage 1 enrollment is complete, all further eligible participants will be registered to T-DXd administered IV in Stage 2. Participants will receive the assigned dose of T-DXd until progression of disease or the participant meets one of the discontinuation criteria.', 'Inclusion Criteria': 'KEY Inclusion Criteria: Participants must meet all of the following criteria to be eligible for randomization/registration into the study: Adults aged ≥20 years in Japan, Taiwan, and Korea, or those aged ≥18 years in other countries, at the time the Informed Consent Forms (ICFs) are signed. Pathologically-documented, unresectable, recurrent, or metastatic colorectal adenocarcinoma. Participants must have v-raf murine sarcoma viral oncogene homologue B1 (BRAF) wild-type cancer and rat sarcoma viral oncogenes homologue (RAS) status identified in primary or metastatic site. The following therapies should be included in prior lines of therapy: Fluoropyrimidine, oxaliplatin, and irinotecan, unless contraindicated Anti-epidermal growth factor receptor (EGFR) treatment, if RAS wild-type and if clinically indicated Anti-vascular endothelial growth factor (VEGF) treatment, if clinically indicated Anti-programmed death ligand 1 (PD-(L)-1) therapy, if the tumor is microsatellite instability (MSI)-high/deficient mismatch repair (dMMR), or tumor mutational burden (TMB)-high, if clinically indicated Confirmed human epidermal growth factor 2 (HER2)-overexpressing status assessed by central laboratory and defined as immunohistochemistry (IHC) 3+ or IHC 2+/ in situ hybridization (ISH) +. Presence of at least one measurable lesion assessed by the Investigator per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1. Has left ventricular ejection fraction (LVEF) ≥50% within 28 days before randomization/registration.', 'Exclusion Criteria': "KEY Exclusion Criteria: Participants who meet any of the following criteria will be disqualified from entering the study: Medical history of myocardial infarction (MI) within 6 months before randomization/registration, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV). Participants with troponin levels above the upper limit of normal (ULN) at Screening (as defined by the manufacturer), and without any MI-related symptoms, should have a cardiologic consultation before randomization/registration to rule out MI. Has a corrected QT interval corrected with Fridericia's formula (QTcF) prolongation to >470 msec (female participants) or >450 msec (male participants) based on the average of the Screening triplicate 12-lead electrocardiograms (ECGs). Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening. Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within 3 months of the randomization/registration, severe asthma, severe chronic obstructive pulmonary disease [COPD], restrictive lung disease, pleural effusion, etc.). Any autoimmune, connective tissue, or inflammatory disorders (eg, rheumatoid arthritis, Sjögren syndrome, sarcoidosis, etc.) where there is documented, or a suspicion of, pulmonary involvement at the time of Screening. Prior pneumonectomy. Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Participants with clinically inactive brain metastases may be included in the study. Participants with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole-brain radiotherapy and randomization/registration. Participants with leptomeningeal carcinomatosis. Has known human immunodeficiency virus (HIV) infection. Active hepatitis B and/or hepatitis C infection, such as those with serologic evidence of viral infection within 28 days before study randomization/registration. Participants with past or resolved hepatitis B virus (HBV) infection are eligible if hepatitis B surface antigen (HBsAg) negative (-) and antibody to hepatitis B core antigen (anti-HBc) positive (+). Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA). Previous treatment with a DXd-containing antibody-drug conjugate (ADC)."}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
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{'Arm - Disease - Biomarker': 'Include: HER2-Overexpressing, BRAF Wild-type'}
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{'Official Title': 'A Phase 2, Multicenter, Randomized, Study of Trastuzumab Deruxtecan in Participants With HER2-overexpressing Locally Advanced, Unresectable or Metastatic Colorectal Cancer (DESTINY-CRC02)', 'Brief Summary': 'This study will evaluate the efficacy, safety, and pharmacokinetics of Trastuzumab deruxtecan (T-DXd) in participants with human epidermal growth factor 2 (HER2)-overexpressing locally advanced, unresectable, or metastatic colorectal cancer (mCRC).', 'Condition': 'Advanced Colorectal Cancer', 'Detailed Description': 'This 2-stage study will evaluate participants with locally advanced, unresectable, or metastatic HER2-overexpressing colorectal cancer (CRC) (immunohistochemistry [IHC] 3+ or IHC 2+/ in situ hybridization [ISH]+) of v-raf murine sarcoma viral oncogene homologue B1 (BRAF) wild-type and either rat sarcoma viral oncogenes homologue (RAS) wild-type or mutant tumor type, previously treated with standard therapy. In the first stage, participants will be randomized 1:1 with 2 doses of T-DXd. After Stage 1 enrollment is complete, all further eligible participants will be registered to T-DXd administered IV in Stage 2. Participants will receive the assigned dose of T-DXd until progression of disease or the participant meets one of the discontinuation criteria.', 'Inclusion Criteria': 'KEY Inclusion Criteria: Participants must meet all of the following criteria to be eligible for randomization/registration into the study: Adults aged ≥20 years in Japan, Taiwan, and Korea, or those aged ≥18 years in other countries, at the time the Informed Consent Forms (ICFs) are signed. Pathologically-documented, unresectable, recurrent, or metastatic colorectal adenocarcinoma. Participants must have v-raf murine sarcoma viral oncogene homologue B1 (BRAF) wild-type cancer and rat sarcoma viral oncogenes homologue (RAS) status identified in primary or metastatic site. The following therapies should be included in prior lines of therapy: Fluoropyrimidine, oxaliplatin, and irinotecan, unless contraindicated Anti-epidermal growth factor receptor (EGFR) treatment, if RAS wild-type and if clinically indicated Anti-vascular endothelial growth factor (VEGF) treatment, if clinically indicated Anti-programmed death ligand 1 (PD-(L)-1) therapy, if the tumor is microsatellite instability (MSI)-high/deficient mismatch repair (dMMR), or tumor mutational burden (TMB)-high, if clinically indicated Confirmed human epidermal growth factor 2 (HER2)-overexpressing status assessed by central laboratory and defined as immunohistochemistry (IHC) 3+ or IHC 2+/ in situ hybridization (ISH) +. Presence of at least one measurable lesion assessed by the Investigator per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1. Has left ventricular ejection fraction (LVEF) ≥50% within 28 days before randomization/registration.', 'Exclusion Criteria': "KEY Exclusion Criteria: Participants who meet any of the following criteria will be disqualified from entering the study: Medical history of myocardial infarction (MI) within 6 months before randomization/registration, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV). Participants with troponin levels above the upper limit of normal (ULN) at Screening (as defined by the manufacturer), and without any MI-related symptoms, should have a cardiologic consultation before randomization/registration to rule out MI. Has a corrected QT interval corrected with Fridericia's formula (QTcF) prolongation to >470 msec (female participants) or >450 msec (male participants) based on the average of the Screening triplicate 12-lead electrocardiograms (ECGs). Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening. Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within 3 months of the randomization/registration, severe asthma, severe chronic obstructive pulmonary disease [COPD], restrictive lung disease, pleural effusion, etc.). Any autoimmune, connective tissue, or inflammatory disorders (eg, rheumatoid arthritis, Sjögren syndrome, sarcoidosis, etc.) where there is documented, or a suspicion of, pulmonary involvement at the time of Screening. Prior pneumonectomy. Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Participants with clinically inactive brain metastases may be included in the study. Participants with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole-brain radiotherapy and randomization/registration. Participants with leptomeningeal carcinomatosis. Has known human immunodeficiency virus (HIV) infection. Active hepatitis B and/or hepatitis C infection, such as those with serologic evidence of viral infection within 28 days before study randomization/registration. Participants with past or resolved hepatitis B virus (HBV) infection are eligible if hepatitis B surface antigen (HBsAg) negative (-) and antibody to hepatitis B core antigen (anti-HBc) positive (+). Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA). Previous treatment with a DXd-containing antibody-drug conjugate (ADC)."}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
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{'Arm - Disease - Biomarker': 'Include: HER2-Overexpressing, BRAF Wild-type'}
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{'Official Title': 'Phase II Randomized Study of Maintenance Atezolizumab Versus Atezolizumab in Combination With Talazoparib in Patients With SLFN11 Positive Extensive Stage Small Cell Lung Cancer (ES-SCLC)', 'Brief Summary': "This phase II trial studies whether atezolizumab in combination with talazoparib works better than atezolizumab alone as maintenance therapy for patients with SLFN11-positive extensive-stage small cell lung cancer. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. PARPs are proteins that help repair damage to DNA, the genetic material that serves as the body's instruction book. Changes (mutations) in DNA can cause tumor cells to grow quickly and out of control, but PARP inhibitors like talazoparib may keep PARP from working, so tumor cells can't repair themselves, and they stop growing. Giving atezolizumab in combination with talazoparib may help lower the chance of extensive-stage small cell lung cancer growing and spreading compared to atezolizumab alone.", 'Condition': 'Extensive Stage Lung Small Cell Carcinoma', 'Detailed Description': 'PRIMARY OBJECTIVE: I. To compare progression free survival (PFS) among participants with Schlafen family member 11 (SLFN11) positive extensive stage small cell lung cancer (ES-SCLC) randomized to atezolizumab or atezolizumab plus talazoparib as maintenance therapy. SECONDARY OBJECTIVES: I. To compare overall survival (OS) between the arms. II. To compare objective response rate (ORR) among participants with measurable disease between the arms, including complete response (CR) and partial response (PR) (confirmed and unconfirmed) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. III. To evaluate the frequency and severity of adverse events within each treatment arm. TRANSLATIONAL MEDICINE OBJECTIVE: I. To bank specimens for future correlative studies. OUTLINE: Patients are screened for SLFN11 biomarker during Step 1: Screening Registration by submitting tumor tissue to MDACC. Patients with SLFN11 biomarker are registered to Step 2: Randomization and are randomized to 1 or 2 arms. ARM I: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive atezolizumab IV over 30-60 minutes on day 1 and talazoparib orally (PO) once daily (QD) on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo magnetic resonance imaging (MRI) during screening. Patients undergo tumor biopsy while on study. Patients undergo computed tomography (CT) scan and blood sample collection throughout the study.', 'Inclusion Criteria': 'STEP 1: SCREENING REGISTRATION: Participants must have histologically or pathologically confirmed diagnosis of extensive stage small cell lung cancer (ES-SCLC) at the time of protocol entry. Participants who have transformed to SCLC from lung non-small cell carcinoma (NSCLC) or have SCLC with mixed histology are not eligible STEP 1: SCREENING REGISTRATION: Participants must have completed at least day 3 of cycle 1 dosing of frontline induction treatment with platinum plus etoposide plus atezolizumab prior to Step 1 Screening Registration. Cycle 1 of frontline induction treatment may or may not contain atezolizumab NOTE: Participants may be screened while receiving consolidation thoracic radiation or during prophylactic cranial irradiation (PCI) at the time of Step 1 Screening Registration. Participants may or may not receive consolidation thoracic radiation and/or PCI per the discretion of their treating investigator STEP 1: SCREENING REGISTRATION: Participants must not have received any immunotherapy for SCLC prior to starting the frontline induction treatment for ES-SCLC STEP 1: SCREENING REGISTRATION: Participants must not have received any investigational agent for the treatment of ES-SCLC STEP 1: SCREENING REGISTRATION: Participants must be >= 18 years of age at the time of Step 1 Screening Registration STEP 1: SCREENING REGISTRATION: Participants must have adequate tumor tissue available from a core biopsy or fine needle aspiration (FNA) defined as: At least two (3-5 microns) (three slides preferred) unstained slides, or; One (3-5 microns) (two slides preferred) unstained slide plus one H&E stained slide Participants must agree to have this tissue submitted to M.D. Anderson Cancer Center (MDACC) for SLFN11 immunohistochemistry (IHC) testing. Note: A histologic review will be performed at MDACC to confirm adequate cellularity for the testing. If inadequate cellularity, additional unstained slides from the same participant may be submitted if it doesn\'t exceed the window of starting maintenance therapy STEP 1: SCREENING REGISTRATION: Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines STEP 1: SCREENING REGISTRATION: As a part of the Oncology Participant Enrollment Network (OPEN) registration process the treating institution\'s identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system STEP 1: SCREENING REGISTRATION: Participants with impaired decision-making capacity are eligible as long as their neurological or psychological condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator) STEP 2: RANDOMIZATION: Site must have received notification from the SWOG Statistics and Data Management Center (SDMC) that the participant\'s tumor sample is SLFN11 positive STEP 2: RANDOMIZATION: Participants must have their disease assessed either by computed tomography (CT) of chest/abdomen/pelvis (with contrast, unless contraindicated) within 28 days prior to Step 2 Registration for measurable disease or by positron emission tomography (PET)PET/CT of chest/abdomen/pelvis (with contrast, unless contraindicated) within 42 days prior to Step 2 Registration for non-measurable disease. Participants may have a complete response to induction therapy. All known sites of disease must be assessed and documented on the Baseline Tumor Assessment Form (RECIST 1.1). Study participants will not be considered eligible if a non-diagnostic PET/CT of chest/abdomen/pelvis is used to assess measurable disease prior to Step 2 Registration STEP 2: RANDOMIZATION: Patients must have a CT or magnetic resonance imaging (MRI) scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to Step 2 randomization. Patient must not have leptomeningeal disease, spinal cord compression or brain metastases unless: (1) metastases have been locally treated and have remained clinically controlled and asymptomatic for at least 14 days following treatment, and prior to Step 2 randomization, AND (2) participant has no residual neurological dysfunction and has been off corticosteroids for at least 24 hours prior to Step 2 randomization STEP 2: RANDOMIZATION: Participants must not have had disease progression based on post induction imaging in the opinion of treating investigator STEP 2: RANDOMIZATION: Participants must be registered to Step 2 Randomization prior to the start of maintenance atezolizumab STEP 2: RANDOMIZATION: Participants must have received no fewer than 2 cycles and no more than 4 cycles of induction treatment with platinum/etoposide/atezolizumab STEP 2: RANDOMIZATION: Participant must not have received radiation treatment (RT) or prophylactic cranial irradiation (PCI) within 14 days prior to Step 2 Randomization STEP 2: RANDOMIZATION: Participants must not be taking strong P-glycoprotein (P-gp) inhibitors (e.g., dronedarone, quinidine, ranolazine), P-gp inducers (e.g., rifampin), or breast cancer resistance protein (BCRP) inhibitors (e.g., elacridar) within 7 days prior to randomization. Participants must not plan to receive the therapies listed above while on protocol treatment) STEP 2: RANDOMIZATION: Participants must not have experienced the following during induction treatment: Any grade 3 or worse immune-related adverse event (irAE) in the opinion of the treating investigator. Exception: asymptomatic nonbullous/nonexfoliative rash Any unresolved grade 2 irAE Any toxicity that led to permanent discontinuation of prior anti-PD-1/PD-L1 immunotherapy. Exception to the above: Toxicities of any grade that require replacement therapy and have stabilized on therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) are allowed STEP 2: RANDOMIZATION: History and physical exam must be obtained within 28 days prior to Step 2 randomization STEP 2: RANDOMIZATION: Participants must have adequate cardiac function. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function and be considered class 2B or better on the New York Heart Association Functional Classification STEP 2: RANDOMIZATION: Participants must have Zubrod performance status 0-2 documented within 28 days prior to Step 2 Randomization. STEP 2: RANDOMIZATION: Leukocytes >= 3 x 10^3/mL (within 28 days prior to Step 2 Randomization) STEP 2: RANDOMIZATION: Absolute neutrophil count >= 1.5 x 10^3/mL (within 28 days prior to Step 2 Randomization) STEP 2: RANDOMIZATION: Platelets >= 100 x 10^3/mL (within 28 days prior to Step 2 Randomization) STEP 2: RANDOMIZATION: Total bilirubin =< institutional upper limit of normal (ULN) (within 28 days prior to Step 2 Randomization) STEP 2: RANDOMIZATION: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x institutional ULN (within 28 days prior to Step 2 Randomization) STEP 2: RANDOMIZATION: Creatinine =< institutional ULN OR estimated creatinine clearance > 30 mL/min (within 28 days prior to Step 2 Randomization) STEP 2: RANDOMIZATION: Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load on suppressive therapy within in 6 months prior to Step 2 Randomization STEP 2: RANDOMIZATION: Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment must have an undetectable HCV viral load within in 6 months prior to Step 2 Randomization STEP 2: RANDOMIZATION: Participants with known human immunodeficiency virus (HIV) infection must be on effective anti-retroviral therapy and must have undetectable viral load at their most recent viral load test and within 6 months prior to Step 2 Randomization STEP 2: RANDOMIZATION: Participants must be able to swallow capsule whole STEP 2: RANDOMIZATION: Participants with known diabetes must not have uncontrolled diabetes. (Uncontrolled diabetes is defined as glycosylated hemoglobin [HgA1C] > 7%) STEP 2: RANDOMIZATION: Participants must not have any known clinically significant liver disease, including cirrhosis, fatty liver, or inherited liver disease STEP 2: RANDOMIZATION: Participants must not have end stage renal or other serious medical illness that may limit survival or the ability to participate in this study STEP 2: RANDOMIZATION: Participants must not have a history of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted STEP 2: RANDOMIZATION: Participants must not have known active tuberculosis (TB) STEP 2: RANDOMIZATION: Participants must not have undergone prior allogeneic bone marrow transplantation or prior solid organ transplantation STEP 2: RANDOMIZATION: Participants must not have history of allergic reaction attributed to compounds of similar chemical or biological composition to atezolizumab and/or talazoparib STEP 2: RANDOMIZATION: Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen STEP 2: RANDOMIZATION: Participants must not be on corticosteroids at doses greater than prednisone 10 mg daily or equivalent within 7 days prior to Step 2 Randomization STEP 2: RANDOMIZATION: Participants must not receive any live attenuated vaccines within 28 days prior to Step 2 Randomization or at any time during the study and until 5 months after the last dose of protocol treatment STEP 2: RANDOMIZATION: Participants must not have severe infections in the form of severe sepsis or septic shock including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia within 14 days prior to Step 2 Randomization STEP 2: RANDOMIZATION: Participants must not be pregnant due to the potential teratogenic side effects of the protocol treatment. Women of reproductive potential and men must have agreed to use an effective contraception method for the duration of protocol treatment, and for 7 months after the last dose of protocol treatment. A woman is considered to be of "reproductive potential" if she has had a menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate participant chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with atezolizumab, breastfeeding must be discontinued prior to Step 2 Randomization STEP 2: RANDOMIZATION: Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the SWOG Specimen Tracking System STEP 2: RANDOMIZATION: Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines STEP 2: RANDOMIZATION: As a part of the OPEN registration process the treating institution\'s identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system STEP 2: RANDOMIZATION: Participants with impaired decision-making capacity are eligible as long as their neurological or psychological condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator)', 'Exclusion Criteria': '-'}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
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{'Arm - Disease - Biomarker': 'Include: SLFN11-Positive'}
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{'Official Title': 'Phase II Randomized Study of Maintenance Atezolizumab Versus Atezolizumab in Combination With Talazoparib in Patients With SLFN11 Positive Extensive Stage Small Cell Lung Cancer (ES-SCLC)', 'Brief Summary': "This phase II trial studies whether atezolizumab in combination with talazoparib works better than atezolizumab alone as maintenance therapy for patients with SLFN11-positive extensive-stage small cell lung cancer. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. PARPs are proteins that help repair damage to DNA, the genetic material that serves as the body's instruction book. Changes (mutations) in DNA can cause tumor cells to grow quickly and out of control, but PARP inhibitors like talazoparib may keep PARP from working, so tumor cells can't repair themselves, and they stop growing. Giving atezolizumab in combination with talazoparib may help lower the chance of extensive-stage small cell lung cancer growing and spreading compared to atezolizumab alone.", 'Condition': 'Extensive Stage Lung Small Cell Carcinoma', 'Detailed Description': 'PRIMARY OBJECTIVE: I. To compare progression free survival (PFS) among participants with Schlafen family member 11 (SLFN11) positive extensive stage small cell lung cancer (ES-SCLC) randomized to atezolizumab or atezolizumab plus talazoparib as maintenance therapy. SECONDARY OBJECTIVES: I. To compare overall survival (OS) between the arms. II. To compare objective response rate (ORR) among participants with measurable disease between the arms, including complete response (CR) and partial response (PR) (confirmed and unconfirmed) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. III. To evaluate the frequency and severity of adverse events within each treatment arm. TRANSLATIONAL MEDICINE OBJECTIVE: I. To bank specimens for future correlative studies. OUTLINE: Patients are screened for SLFN11 biomarker during Step 1: Screening Registration by submitting tumor tissue to MDACC. Patients with SLFN11 biomarker are registered to Step 2: Randomization and are randomized to 1 or 2 arms. ARM I: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive atezolizumab IV over 30-60 minutes on day 1 and talazoparib orally (PO) once daily (QD) on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo magnetic resonance imaging (MRI) during screening. Patients undergo tumor biopsy while on study. Patients undergo computed tomography (CT) scan and blood sample collection throughout the study.', 'Inclusion Criteria': 'STEP 1: SCREENING REGISTRATION: Participants must have histologically or pathologically confirmed diagnosis of extensive stage small cell lung cancer (ES-SCLC) at the time of protocol entry. Participants who have transformed to SCLC from lung non-small cell carcinoma (NSCLC) or have SCLC with mixed histology are not eligible STEP 1: SCREENING REGISTRATION: Participants must have completed at least day 3 of cycle 1 dosing of frontline induction treatment with platinum plus etoposide plus atezolizumab prior to Step 1 Screening Registration. Cycle 1 of frontline induction treatment may or may not contain atezolizumab NOTE: Participants may be screened while receiving consolidation thoracic radiation or during prophylactic cranial irradiation (PCI) at the time of Step 1 Screening Registration. Participants may or may not receive consolidation thoracic radiation and/or PCI per the discretion of their treating investigator STEP 1: SCREENING REGISTRATION: Participants must not have received any immunotherapy for SCLC prior to starting the frontline induction treatment for ES-SCLC STEP 1: SCREENING REGISTRATION: Participants must not have received any investigational agent for the treatment of ES-SCLC STEP 1: SCREENING REGISTRATION: Participants must be >= 18 years of age at the time of Step 1 Screening Registration STEP 1: SCREENING REGISTRATION: Participants must have adequate tumor tissue available from a core biopsy or fine needle aspiration (FNA) defined as: At least two (3-5 microns) (three slides preferred) unstained slides, or; One (3-5 microns) (two slides preferred) unstained slide plus one H&E stained slide Participants must agree to have this tissue submitted to M.D. Anderson Cancer Center (MDACC) for SLFN11 immunohistochemistry (IHC) testing. Note: A histologic review will be performed at MDACC to confirm adequate cellularity for the testing. If inadequate cellularity, additional unstained slides from the same participant may be submitted if it doesn\'t exceed the window of starting maintenance therapy STEP 1: SCREENING REGISTRATION: Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines STEP 1: SCREENING REGISTRATION: As a part of the Oncology Participant Enrollment Network (OPEN) registration process the treating institution\'s identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system STEP 1: SCREENING REGISTRATION: Participants with impaired decision-making capacity are eligible as long as their neurological or psychological condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator) STEP 2: RANDOMIZATION: Site must have received notification from the SWOG Statistics and Data Management Center (SDMC) that the participant\'s tumor sample is SLFN11 positive STEP 2: RANDOMIZATION: Participants must have their disease assessed either by computed tomography (CT) of chest/abdomen/pelvis (with contrast, unless contraindicated) within 28 days prior to Step 2 Registration for measurable disease or by positron emission tomography (PET)PET/CT of chest/abdomen/pelvis (with contrast, unless contraindicated) within 42 days prior to Step 2 Registration for non-measurable disease. Participants may have a complete response to induction therapy. All known sites of disease must be assessed and documented on the Baseline Tumor Assessment Form (RECIST 1.1). Study participants will not be considered eligible if a non-diagnostic PET/CT of chest/abdomen/pelvis is used to assess measurable disease prior to Step 2 Registration STEP 2: RANDOMIZATION: Patients must have a CT or magnetic resonance imaging (MRI) scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to Step 2 randomization. Patient must not have leptomeningeal disease, spinal cord compression or brain metastases unless: (1) metastases have been locally treated and have remained clinically controlled and asymptomatic for at least 14 days following treatment, and prior to Step 2 randomization, AND (2) participant has no residual neurological dysfunction and has been off corticosteroids for at least 24 hours prior to Step 2 randomization STEP 2: RANDOMIZATION: Participants must not have had disease progression based on post induction imaging in the opinion of treating investigator STEP 2: RANDOMIZATION: Participants must be registered to Step 2 Randomization prior to the start of maintenance atezolizumab STEP 2: RANDOMIZATION: Participants must have received no fewer than 2 cycles and no more than 4 cycles of induction treatment with platinum/etoposide/atezolizumab STEP 2: RANDOMIZATION: Participant must not have received radiation treatment (RT) or prophylactic cranial irradiation (PCI) within 14 days prior to Step 2 Randomization STEP 2: RANDOMIZATION: Participants must not be taking strong P-glycoprotein (P-gp) inhibitors (e.g., dronedarone, quinidine, ranolazine), P-gp inducers (e.g., rifampin), or breast cancer resistance protein (BCRP) inhibitors (e.g., elacridar) within 7 days prior to randomization. Participants must not plan to receive the therapies listed above while on protocol treatment) STEP 2: RANDOMIZATION: Participants must not have experienced the following during induction treatment: Any grade 3 or worse immune-related adverse event (irAE) in the opinion of the treating investigator. Exception: asymptomatic nonbullous/nonexfoliative rash Any unresolved grade 2 irAE Any toxicity that led to permanent discontinuation of prior anti-PD-1/PD-L1 immunotherapy. Exception to the above: Toxicities of any grade that require replacement therapy and have stabilized on therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) are allowed STEP 2: RANDOMIZATION: History and physical exam must be obtained within 28 days prior to Step 2 randomization STEP 2: RANDOMIZATION: Participants must have adequate cardiac function. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function and be considered class 2B or better on the New York Heart Association Functional Classification STEP 2: RANDOMIZATION: Participants must have Zubrod performance status 0-2 documented within 28 days prior to Step 2 Randomization. STEP 2: RANDOMIZATION: Leukocytes >= 3 x 10^3/mL (within 28 days prior to Step 2 Randomization) STEP 2: RANDOMIZATION: Absolute neutrophil count >= 1.5 x 10^3/mL (within 28 days prior to Step 2 Randomization) STEP 2: RANDOMIZATION: Platelets >= 100 x 10^3/mL (within 28 days prior to Step 2 Randomization) STEP 2: RANDOMIZATION: Total bilirubin =< institutional upper limit of normal (ULN) (within 28 days prior to Step 2 Randomization) STEP 2: RANDOMIZATION: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x institutional ULN (within 28 days prior to Step 2 Randomization) STEP 2: RANDOMIZATION: Creatinine =< institutional ULN OR estimated creatinine clearance > 30 mL/min (within 28 days prior to Step 2 Randomization) STEP 2: RANDOMIZATION: Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load on suppressive therapy within in 6 months prior to Step 2 Randomization STEP 2: RANDOMIZATION: Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment must have an undetectable HCV viral load within in 6 months prior to Step 2 Randomization STEP 2: RANDOMIZATION: Participants with known human immunodeficiency virus (HIV) infection must be on effective anti-retroviral therapy and must have undetectable viral load at their most recent viral load test and within 6 months prior to Step 2 Randomization STEP 2: RANDOMIZATION: Participants must be able to swallow capsule whole STEP 2: RANDOMIZATION: Participants with known diabetes must not have uncontrolled diabetes. (Uncontrolled diabetes is defined as glycosylated hemoglobin [HgA1C] > 7%) STEP 2: RANDOMIZATION: Participants must not have any known clinically significant liver disease, including cirrhosis, fatty liver, or inherited liver disease STEP 2: RANDOMIZATION: Participants must not have end stage renal or other serious medical illness that may limit survival or the ability to participate in this study STEP 2: RANDOMIZATION: Participants must not have a history of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted STEP 2: RANDOMIZATION: Participants must not have known active tuberculosis (TB) STEP 2: RANDOMIZATION: Participants must not have undergone prior allogeneic bone marrow transplantation or prior solid organ transplantation STEP 2: RANDOMIZATION: Participants must not have history of allergic reaction attributed to compounds of similar chemical or biological composition to atezolizumab and/or talazoparib STEP 2: RANDOMIZATION: Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen STEP 2: RANDOMIZATION: Participants must not be on corticosteroids at doses greater than prednisone 10 mg daily or equivalent within 7 days prior to Step 2 Randomization STEP 2: RANDOMIZATION: Participants must not receive any live attenuated vaccines within 28 days prior to Step 2 Randomization or at any time during the study and until 5 months after the last dose of protocol treatment STEP 2: RANDOMIZATION: Participants must not have severe infections in the form of severe sepsis or septic shock including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia within 14 days prior to Step 2 Randomization STEP 2: RANDOMIZATION: Participants must not be pregnant due to the potential teratogenic side effects of the protocol treatment. Women of reproductive potential and men must have agreed to use an effective contraception method for the duration of protocol treatment, and for 7 months after the last dose of protocol treatment. A woman is considered to be of "reproductive potential" if she has had a menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate participant chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with atezolizumab, breastfeeding must be discontinued prior to Step 2 Randomization STEP 2: RANDOMIZATION: Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the SWOG Specimen Tracking System STEP 2: RANDOMIZATION: Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines STEP 2: RANDOMIZATION: As a part of the OPEN registration process the treating institution\'s identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system STEP 2: RANDOMIZATION: Participants with impaired decision-making capacity are eligible as long as their neurological or psychological condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator)', 'Exclusion Criteria': '-'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: SLFN11-Positive'}
|
{'Official Title': 'A Phase 2, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of Trastuzumab Deruxtecan (T-DXd, DS-8201a) for the Treatment of Selected HER2 Expressing Tumors (DESTINY-PanTumor02)', 'Brief Summary': 'This is an open-label, multi-center, multi-cohort, Phase 2 study to evaluate the efficacy and safety of trastuzumab deruxtecan (T-DXd) for the treatment of selected HER2-expressing tumors. This study will enroll 7 cohorts: urothelial bladder cancer, biliary tract cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer, and rare tumors. Study hypothesis: Trastuzumab deruxtecan will show meaningful clinical activity and a favorable risk benefit profile in selected HER2-expressing solid tumors.', 'Condition': 'Bladder Cancer, Biliary Tract Cancer, Cervical Cancer, Endometrial Cancer, Ovarian Cancer, Pancreatic Cancer, Rare Tumors', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Locally advanced, unresectable, or metastatic disease based on most recent imaging. The respective cohorts for patient inclusion are: Cohort 1: Biliary tract cancer Cohort 2: Bladder cancer Cohort 3: Cervical cancer Cohort 4: Endometrial cancer Cohort 5: Epithelial ovarian cancer Cohort 6: Pancreatic cancer Cohort 7: Rare tumors: This cohort will consist of patients with tumors that express HER2, excluding the tumors mentioned above, and breast, non-small cell lung cancer, gastric cancer, and colorectal cancer. Progressed following prior treatment or who have no satisfactory alternative treatment option. Prior HER2 targeting therapy is permitted. HER2 expression for eligibility may be based on local or central assessment. Has measurable target disease assessed by the Investigator based on RECIST version 1.1. Has protocol- defined adequate organ function including cardiac, renal and hepatic function.', 'Exclusion Criteria': "Exclusion Criteria: History of non-infectious pneumonitis/ILD that required steroids, current ILD, or where suspected ILD that cannot be ruled out by imaging at screening Lung-specific intercurrent clinically significant severe illnesses Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART Known Somatic DNA mutation of HER2 (ERBB2) without tumoral HER2 protein expression. Primary diagnosis of adenocarcinoma of the breast, adenocarcinoma of the colon or rectum, adenocarcinoma of the gastric body or gastro-esophageal junction, or non-small cell lung cancer. Medical conditions that may interfere with the subject's participation in the study."}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: HER2-Expressing, Exclude: known Somatic DNA mutation of HER2 without tumoral HER2 protein expression'}
|
{'Official Title': 'A Phase 2, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of Trastuzumab Deruxtecan (T-DXd, DS-8201a) for the Treatment of Selected HER2 Expressing Tumors (DESTINY-PanTumor02)', 'Brief Summary': 'This is an open-label, multi-center, multi-cohort, Phase 2 study to evaluate the efficacy and safety of trastuzumab deruxtecan (T-DXd) for the treatment of selected HER2-expressing tumors. This study will enroll 7 cohorts: urothelial bladder cancer, biliary tract cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer, and rare tumors. Study hypothesis: Trastuzumab deruxtecan will show meaningful clinical activity and a favorable risk benefit profile in selected HER2-expressing solid tumors.', 'Condition': 'Bladder Cancer, Biliary Tract Cancer, Cervical Cancer, Endometrial Cancer, Ovarian Cancer, Pancreatic Cancer, Rare Tumors', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Locally advanced, unresectable, or metastatic disease based on most recent imaging. The respective cohorts for patient inclusion are: Cohort 1: Biliary tract cancer Cohort 2: Bladder cancer Cohort 3: Cervical cancer Cohort 4: Endometrial cancer Cohort 5: Epithelial ovarian cancer Cohort 6: Pancreatic cancer Cohort 7: Rare tumors: This cohort will consist of patients with tumors that express HER2, excluding the tumors mentioned above, and breast, non-small cell lung cancer, gastric cancer, and colorectal cancer. Progressed following prior treatment or who have no satisfactory alternative treatment option. Prior HER2 targeting therapy is permitted. HER2 expression for eligibility may be based on local or central assessment. Has measurable target disease assessed by the Investigator based on RECIST version 1.1. Has protocol- defined adequate organ function including cardiac, renal and hepatic function.', 'Exclusion Criteria': "Exclusion Criteria: History of non-infectious pneumonitis/ILD that required steroids, current ILD, or where suspected ILD that cannot be ruled out by imaging at screening Lung-specific intercurrent clinically significant severe illnesses Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART Known Somatic DNA mutation of HER2 (ERBB2) without tumoral HER2 protein expression. Primary diagnosis of adenocarcinoma of the breast, adenocarcinoma of the colon or rectum, adenocarcinoma of the gastric body or gastro-esophageal junction, or non-small cell lung cancer. Medical conditions that may interfere with the subject's participation in the study."}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: HER2-Expressing, Exclude: known Somatic DNA mutation of HER2 without tumoral HER2 protein expression'}
|
{'Official Title': 'A Phase 2, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of Trastuzumab Deruxtecan (T-DXd, DS-8201a) for the Treatment of Selected HER2 Expressing Tumors (DESTINY-PanTumor02)', 'Brief Summary': 'This is an open-label, multi-center, multi-cohort, Phase 2 study to evaluate the efficacy and safety of trastuzumab deruxtecan (T-DXd) for the treatment of selected HER2-expressing tumors. This study will enroll 7 cohorts: urothelial bladder cancer, biliary tract cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer, and rare tumors. Study hypothesis: Trastuzumab deruxtecan will show meaningful clinical activity and a favorable risk benefit profile in selected HER2-expressing solid tumors.', 'Condition': 'Bladder Cancer, Biliary Tract Cancer, Cervical Cancer, Endometrial Cancer, Ovarian Cancer, Pancreatic Cancer, Rare Tumors', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Locally advanced, unresectable, or metastatic disease based on most recent imaging. The respective cohorts for patient inclusion are: Cohort 1: Biliary tract cancer Cohort 2: Bladder cancer Cohort 3: Cervical cancer Cohort 4: Endometrial cancer Cohort 5: Epithelial ovarian cancer Cohort 6: Pancreatic cancer Cohort 7: Rare tumors: This cohort will consist of patients with tumors that express HER2, excluding the tumors mentioned above, and breast, non-small cell lung cancer, gastric cancer, and colorectal cancer. Progressed following prior treatment or who have no satisfactory alternative treatment option. Prior HER2 targeting therapy is permitted. HER2 expression for eligibility may be based on local or central assessment. Has measurable target disease assessed by the Investigator based on RECIST version 1.1. Has protocol- defined adequate organ function including cardiac, renal and hepatic function.', 'Exclusion Criteria': "Exclusion Criteria: History of non-infectious pneumonitis/ILD that required steroids, current ILD, or where suspected ILD that cannot be ruled out by imaging at screening Lung-specific intercurrent clinically significant severe illnesses Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART Known Somatic DNA mutation of HER2 (ERBB2) without tumoral HER2 protein expression. Primary diagnosis of adenocarcinoma of the breast, adenocarcinoma of the colon or rectum, adenocarcinoma of the gastric body or gastro-esophageal junction, or non-small cell lung cancer. Medical conditions that may interfere with the subject's participation in the study."}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: HER2-Expressing, Exclude: known Somatic DNA mutation of HER2 without tumoral HER2 protein expression'}
|
{'Official Title': 'A Phase 2, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of Trastuzumab Deruxtecan (T-DXd, DS-8201a) for the Treatment of Selected HER2 Expressing Tumors (DESTINY-PanTumor02)', 'Brief Summary': 'This is an open-label, multi-center, multi-cohort, Phase 2 study to evaluate the efficacy and safety of trastuzumab deruxtecan (T-DXd) for the treatment of selected HER2-expressing tumors. This study will enroll 7 cohorts: urothelial bladder cancer, biliary tract cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer, and rare tumors. Study hypothesis: Trastuzumab deruxtecan will show meaningful clinical activity and a favorable risk benefit profile in selected HER2-expressing solid tumors.', 'Condition': 'Bladder Cancer, Biliary Tract Cancer, Cervical Cancer, Endometrial Cancer, Ovarian Cancer, Pancreatic Cancer, Rare Tumors', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Locally advanced, unresectable, or metastatic disease based on most recent imaging. The respective cohorts for patient inclusion are: Cohort 1: Biliary tract cancer Cohort 2: Bladder cancer Cohort 3: Cervical cancer Cohort 4: Endometrial cancer Cohort 5: Epithelial ovarian cancer Cohort 6: Pancreatic cancer Cohort 7: Rare tumors: This cohort will consist of patients with tumors that express HER2, excluding the tumors mentioned above, and breast, non-small cell lung cancer, gastric cancer, and colorectal cancer. Progressed following prior treatment or who have no satisfactory alternative treatment option. Prior HER2 targeting therapy is permitted. HER2 expression for eligibility may be based on local or central assessment. Has measurable target disease assessed by the Investigator based on RECIST version 1.1. Has protocol- defined adequate organ function including cardiac, renal and hepatic function.', 'Exclusion Criteria': "Exclusion Criteria: History of non-infectious pneumonitis/ILD that required steroids, current ILD, or where suspected ILD that cannot be ruled out by imaging at screening Lung-specific intercurrent clinically significant severe illnesses Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART Known Somatic DNA mutation of HER2 (ERBB2) without tumoral HER2 protein expression. Primary diagnosis of adenocarcinoma of the breast, adenocarcinoma of the colon or rectum, adenocarcinoma of the gastric body or gastro-esophageal junction, or non-small cell lung cancer. Medical conditions that may interfere with the subject's participation in the study."}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: HER2-Expressing, Exclude: known Somatic DNA mutation of HER2 without tumoral HER2 protein expression'}
|
{'Official Title': 'A Phase 2, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of Trastuzumab Deruxtecan (T-DXd, DS-8201a) for the Treatment of Selected HER2 Expressing Tumors (DESTINY-PanTumor02)', 'Brief Summary': 'This is an open-label, multi-center, multi-cohort, Phase 2 study to evaluate the efficacy and safety of trastuzumab deruxtecan (T-DXd) for the treatment of selected HER2-expressing tumors. This study will enroll 7 cohorts: urothelial bladder cancer, biliary tract cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer, and rare tumors. Study hypothesis: Trastuzumab deruxtecan will show meaningful clinical activity and a favorable risk benefit profile in selected HER2-expressing solid tumors.', 'Condition': 'Bladder Cancer, Biliary Tract Cancer, Cervical Cancer, Endometrial Cancer, Ovarian Cancer, Pancreatic Cancer, Rare Tumors', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Locally advanced, unresectable, or metastatic disease based on most recent imaging. The respective cohorts for patient inclusion are: Cohort 1: Biliary tract cancer Cohort 2: Bladder cancer Cohort 3: Cervical cancer Cohort 4: Endometrial cancer Cohort 5: Epithelial ovarian cancer Cohort 6: Pancreatic cancer Cohort 7: Rare tumors: This cohort will consist of patients with tumors that express HER2, excluding the tumors mentioned above, and breast, non-small cell lung cancer, gastric cancer, and colorectal cancer. Progressed following prior treatment or who have no satisfactory alternative treatment option. Prior HER2 targeting therapy is permitted. HER2 expression for eligibility may be based on local or central assessment. Has measurable target disease assessed by the Investigator based on RECIST version 1.1. Has protocol- defined adequate organ function including cardiac, renal and hepatic function.', 'Exclusion Criteria': "Exclusion Criteria: History of non-infectious pneumonitis/ILD that required steroids, current ILD, or where suspected ILD that cannot be ruled out by imaging at screening Lung-specific intercurrent clinically significant severe illnesses Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART Known Somatic DNA mutation of HER2 (ERBB2) without tumoral HER2 protein expression. Primary diagnosis of adenocarcinoma of the breast, adenocarcinoma of the colon or rectum, adenocarcinoma of the gastric body or gastro-esophageal junction, or non-small cell lung cancer. Medical conditions that may interfere with the subject's participation in the study."}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: HER2-Expressing, Exclude: known Somatic DNA mutation of HER2 without tumoral HER2 protein expression'}
|
{'Official Title': 'A Phase 2, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of Trastuzumab Deruxtecan (T-DXd, DS-8201a) for the Treatment of Selected HER2 Expressing Tumors (DESTINY-PanTumor02)', 'Brief Summary': 'This is an open-label, multi-center, multi-cohort, Phase 2 study to evaluate the efficacy and safety of trastuzumab deruxtecan (T-DXd) for the treatment of selected HER2-expressing tumors. This study will enroll 7 cohorts: urothelial bladder cancer, biliary tract cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer, and rare tumors. Study hypothesis: Trastuzumab deruxtecan will show meaningful clinical activity and a favorable risk benefit profile in selected HER2-expressing solid tumors.', 'Condition': 'Bladder Cancer, Biliary Tract Cancer, Cervical Cancer, Endometrial Cancer, Ovarian Cancer, Pancreatic Cancer, Rare Tumors', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Locally advanced, unresectable, or metastatic disease based on most recent imaging. The respective cohorts for patient inclusion are: Cohort 1: Biliary tract cancer Cohort 2: Bladder cancer Cohort 3: Cervical cancer Cohort 4: Endometrial cancer Cohort 5: Epithelial ovarian cancer Cohort 6: Pancreatic cancer Cohort 7: Rare tumors: This cohort will consist of patients with tumors that express HER2, excluding the tumors mentioned above, and breast, non-small cell lung cancer, gastric cancer, and colorectal cancer. Progressed following prior treatment or who have no satisfactory alternative treatment option. Prior HER2 targeting therapy is permitted. HER2 expression for eligibility may be based on local or central assessment. Has measurable target disease assessed by the Investigator based on RECIST version 1.1. Has protocol- defined adequate organ function including cardiac, renal and hepatic function.', 'Exclusion Criteria': "Exclusion Criteria: History of non-infectious pneumonitis/ILD that required steroids, current ILD, or where suspected ILD that cannot be ruled out by imaging at screening Lung-specific intercurrent clinically significant severe illnesses Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART Known Somatic DNA mutation of HER2 (ERBB2) without tumoral HER2 protein expression. Primary diagnosis of adenocarcinoma of the breast, adenocarcinoma of the colon or rectum, adenocarcinoma of the gastric body or gastro-esophageal junction, or non-small cell lung cancer. Medical conditions that may interfere with the subject's participation in the study."}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: HER2-Expressing, Exclude: known Somatic DNA mutation of HER2 without tumoral HER2 protein expression'}
|
{'Official Title': 'A Phase 2, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of Trastuzumab Deruxtecan (T-DXd, DS-8201a) for the Treatment of Selected HER2 Expressing Tumors (DESTINY-PanTumor02)', 'Brief Summary': 'This is an open-label, multi-center, multi-cohort, Phase 2 study to evaluate the efficacy and safety of trastuzumab deruxtecan (T-DXd) for the treatment of selected HER2-expressing tumors. This study will enroll 7 cohorts: urothelial bladder cancer, biliary tract cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer, and rare tumors. Study hypothesis: Trastuzumab deruxtecan will show meaningful clinical activity and a favorable risk benefit profile in selected HER2-expressing solid tumors.', 'Condition': 'Bladder Cancer, Biliary Tract Cancer, Cervical Cancer, Endometrial Cancer, Ovarian Cancer, Pancreatic Cancer, Rare Tumors', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Locally advanced, unresectable, or metastatic disease based on most recent imaging. The respective cohorts for patient inclusion are: Cohort 1: Biliary tract cancer Cohort 2: Bladder cancer Cohort 3: Cervical cancer Cohort 4: Endometrial cancer Cohort 5: Epithelial ovarian cancer Cohort 6: Pancreatic cancer Cohort 7: Rare tumors: This cohort will consist of patients with tumors that express HER2, excluding the tumors mentioned above, and breast, non-small cell lung cancer, gastric cancer, and colorectal cancer. Progressed following prior treatment or who have no satisfactory alternative treatment option. Prior HER2 targeting therapy is permitted. HER2 expression for eligibility may be based on local or central assessment. Has measurable target disease assessed by the Investigator based on RECIST version 1.1. Has protocol- defined adequate organ function including cardiac, renal and hepatic function.', 'Exclusion Criteria': "Exclusion Criteria: History of non-infectious pneumonitis/ILD that required steroids, current ILD, or where suspected ILD that cannot be ruled out by imaging at screening Lung-specific intercurrent clinically significant severe illnesses Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART Known Somatic DNA mutation of HER2 (ERBB2) without tumoral HER2 protein expression. Primary diagnosis of adenocarcinoma of the breast, adenocarcinoma of the colon or rectum, adenocarcinoma of the gastric body or gastro-esophageal junction, or non-small cell lung cancer. Medical conditions that may interfere with the subject's participation in the study."}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: HER2-Expressing, Exclude: known Somatic DNA mutation of HER2 without tumoral HER2 protein expression'}
|
{'Official Title': 'Palbociclib Plus Letrozole Treatment After Progression to Second Line Chemotherapy for Women With ER/PR-positive Ovarian Cancer.', 'Brief Summary': 'The primary objective of this study is to evaluate 12 weeks progression-free survival (PFS) rate of Palbociclib plus Letrozole in ER/PR positive endometrioid or high-grade serous ovarian cancer who have disease progression on second-line chemotherapy.', 'Condition': 'Ovarian Cancer', 'Detailed Description': 'Letrozole (Femara®) is an oral non-steroidal aromatase inhibitor that is approved worldwide for the treatment of postmenopausal women with breast cancer. It is administered orally on a continuous 2.5 mg daily dosing regimen and has a good toxicity profile. Palbociclib (Ibrance®) is an active potent and highly selective reversible inhibitor of cyclin- dependent kinases 4 and 6 (CDK4/6). Palbociclib was approved by the United States Food and Drug Administration (U.S. FDA) and the European Medicines Agency (EMA) for the treatment of postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in combination with an aromatase inhibitor based on a randomized, double-blind, placebo-controlled, international clinical trial PALOMA-2. It is administered orally on a dose of 125 mg per day in 4-week cycles (3 weeks of treatment followed by 1 week off). This trial was based on preclinical studies that showed a synergistic effect between targeting the ER and cyclin-D-CDK4/6-Rb pathway. The principal toxicity was myelotoxicity but it was managed with appropriate supportive care and dose reductions13. Based on the results of phase 1 and 2 clinical trials of CDK4/6 inhibitors used as monotherapy to treat patients with recurrent ovarian cancer, we hypothesized that, as Palbociclibe is active in this population and many ovarian cancer show ER/PR expression, its combination with Letrozole can improve outcomes in ER/PR positive endometrioid or high-grade serous Ovarian Cancer who have disease progression on second-line chemotherapy, similar to what is seen in breast cancer studies.', 'Inclusion Criteria': "Inclusion Criteria: Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study; Subject is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures; 18 years of age or older; Patient agrees not to participate in another interventional study while on treatment; Histology confirmed ovarian cancer serous or endometrioid high degree, fallopian tube or with locoregional recurrence peritoneum (not amenable to curative treatment) or metastatic; Estrogen (ER) and/or progesterone (RP) receptor positive tumor, defined as > 10% by immunohistochemical examination in the local laboratory; Availability of tumor sample from the primary tumor or metastasis, fixed in formalin and embedded in paraffin, for confirmation of positivity for ER and/or RP in a central laboratory; Disease measurable by RECIST 1.1 as assessed by the local investigator or radiologist; Patients must have chemotherapy application for recurrence locoregional or metastatic according to the following criteria: at least one platinum-based chemotherapy regimen; have confirmed no more than 3 chemotherapy regimens for locally advanced or metastatic disease Patient must have radiographic disease progression to last treatment; Functional capacity by the Eastern Cooperative Oncology Group (ECOG) ≤ 2; Adequate bone marrow function: Absolute neutrophil count (CAN) ≥ 1,500/mm3 (≥ 1.5x109/L) Plates ≥ 100,000/mm3 or ≥ 100 x 109/L Hemoglobin ≥ 9.0 g/dL; 12. Adequate liver function: Total serum bilirubin ≤ 1.5 x upper limit of normal (ULN) (≤ 3.0 x ULN if there is Gilbert's Syndrome) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN (≤ 5.0 x ULN if liver tumor was involved) Alkaline phosphatase ≤ 2.5 x ULN (≤ 5.0 x ULN if any liver tumor involvement); 13. Adequate kidney function: Estimated creatinine clearance ≥ 15 mL/min; 14. Evidence of lack of potential to become pregnant: Post-menopause (defined as at least 1 year without menstruation) before selection, or Radiotherapy-induced oophorectomy with the last menstruation > 1 year ago, or Surgical sterilization (bilateral oophorectomy or hysterectomy).", 'Exclusion Criteria': "Exclusion Criteria: Patients with a known hypersensitivity to Palbociclib or Letrozole or any of the excipients of the product; Previous treatment with CDK4/6 inhibitors or endocrine therapy; Disease progression during or within 6 months of the first platinum-based chemotherapy regimen. Persistent toxicities (Grade 2 or higher) caused by previous anticancer therapy (excluding alopecia); Patients with a second primary cancer, except: adequately treated non-melanoma skin cancer, cervical cancer in situ curatively treated, Ductal carcinoma in situ (DCIS), stage 1 grade 1 endometrial carcinoma curatively treated with no evidence of illness for 3 years; Last dose of chemotherapy or radiotherapy within 3 weeks of study enrollment; Patients with symptomatic uncontrolled brain metastases. An exam to confirm the absence of brain metastases is not necessary; Major surgical procedure within 3 weeks prior to study randomization, or planned during the course of the study; Patients considered a precarious medical risk due to a disorder uncontrolled serious medical, non-malignant systemic disease, or uncontrolled active infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent myocardial infarction (within 6 months), stroke, gastrointestinal bleeding, or any psychiatric disorder that precludes informed consent; Patients who have difficulty taking oral medication or any digestive tract dysfunction or inflammatory bowel disease that interferes with intestinal absorption of medications (eg, partial bowel obstruction or malabsorption); Patients received potent inhibitors or inducers of CYP3A4 within 7 days of randomization; Pregnant or nursing women; The patient has a known history of testing positive for human immunodeficiency virus (HIV); Patients with known liver disease (ie, Hepatitis B or C); Treatment with any product under investigation during the last 28 days; Other acute or chronic medical or psychiatric condition or severe laboratory abnormality that could increase the risk associated with participation in the study or that could interfere with the interpretation of the study results and, in the investigator's judgment, would make the research participant unsuitable for entry into this study."}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
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{'Arm - Disease - Biomarker': 'Include: PR-Positive, ER-Positive'}
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{'Official Title': 'Phase II Randomized Study of Maintenance Regorafenib vs Placebo in no Progression Patients After First-line Platinum and Fluoropyrimidines Based Chemotherapy in HER2 Negative Locally Advanced/Metastatic Gastric or Gastroesophagel Junction Cancer (a-MANTRA Study)', 'Brief Summary': 'Randomized, double-blind, placebo-controlled, multicenter Phase-II study. Approximately 120 subjects with CR/PR/SD after platinum compounds and fluoropyrimidines based regimens: up to 6 cycles of cisplatin and 5-fluorouracil or capecitabine, up to 12 cycles of FOLFOX, up to 8 cycles of XELOX, will be randomly assigned (1:1 ratio) to one of the following treatment groups: Arm A: Placebo 4 tablets once daily on day 1-21, every 4 weeks, until intolerance or progression disease Arm B: Regorafenib 160 mg, 4 tablets once daily on days 1-21, every 4 weeks, until intolerance or progression disease Primary Variable: PFS1', 'Condition': 'Gastric Cancer', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Male of female ≥ 18 years of age Have an Eastern Cooperative Oncology Group performance status of 0 or 1 within 14 days prior to the initiation of study treatment Diagnosis of histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction HER2 negative gastric or gastroesophagel junction cancer ( ICH 0, IHC 1+, IHC + FISH -) Locally advanced/metastatic gastric or gastroesophageal junction cancer CR/PR/SD after first-line platinum compound and Fluoropyrimidines based chemotherapy Measurable disease according to RECIST 1.1 criteria Have adequate bone marrow function, liver function, and renal function, as measured by the following laboratory assessments conducted within 7 days prior to the initiation of study treatment: Total bilirubin 1.5 times the upper limit of normal (ULN) Alanine aminotransferase and aspartate aminotransferase 3 times the ULN Lipase 1.5 times the ULN Serum creatinine 1.5 times the ULN Glomerular filtration rate 30 mL/min/1,73 m2 according to the Modified Diet in Renal Disease abbreviated formula International normalized ratio of prothrombin time and activated partial thromboplastin time 1.5 times the ULN. Subjects who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate if no underlying abnormality in coagulation parameters exists per medical history. Platelet count 100,000 /mm3, hemoglobin 9 g/dL, absolute neutrophil count 1500/mm3 without transfusions or granulocyte colony stimulating factor and other hematopoietic growth factors Alkaline phosphatase ≤ 2.5 times the ULN Understand, be willing to give consent, and sign the written informed consent form (ICF) prior to undergoing any study-specific procedure. If female and of childbearing potential, have a negative result on a pregnancy test performed a maximum of 7 days before initiation of study treatment. If female and of childbearing potential, or if male, agree to use adequate contraception (eg, abstinence, intrauterine device, oral contraceptive, or double-barrier method) based on the judgment of the investigator or a designated associate from the date on which the ICF is signed until 8 weeks after the last dose of study drug.', 'Exclusion Criteria': "Exclusion Criteria: Are taking strong cytochrome P (CYP) CYP3A4 inhibitors (eg, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, voriconazole) or strong CYP3A4 inducers (eg, carbamazepine, phenobarbital, phenytoin, rifampin, St. John's Wort) Have used biologic response modifiers, such as G-CSF, within 3 weeks of study entry Have had prior treatment with regorafenib or any other VEGFR-targeting kinase inhibitor. Completed their last dose of chemotherapy more than 8 weeks, whichever came later, prior to randomization. Have had prior or concurrent cancer distinct in primary site or histology from GC or GJC within 5 years prior to randomization EXCEPT for curatively treated cervical cancer in situ, no-melanoma skin cancer, or superficial bladder tumors classified as noninvasive tumor (Ta), carcinoma in situ (Tis), or tumor invades lamina propria (T1). Have had systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy, and/or hormonal therapy within 4 weeks prior to initiation of study treatment. Have unresolved toxicity higher than National Cancer Institute-Common Terminology for Adverse Events version 4.0 (NCI-CTCAE v 4.0) Grade 1 attributed to any prior therapy/procedure, excluding alopecia and/or oxaliplatin-induced neurotoxicity ≤ Grade 2 and hemoglobin ≥ 9 g/dL as per inclusion criteria Have had a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to initiation of study treatment. Are pregnant. Are breastfeeding. Are unable to swallow oral tablets (crushing of study treatment tablets is not allowed). Have congestive heart failure classified as New York Heart Association Class 2 or higher Have had unstable angina (angina symptoms at rest) or new-onset angina 3 months prior to screening. Have had a myocardial infarction 6 months prior to initiation of study treatment. Have cardiac arrhythmias requiring anti-arrhythmic therapy, with the exception of beta blockers or digoxin. Have uncontrolled hypertension (systolic blood pressure [SBP] 140 mmHg or diastolic blood pressure [DBP] 90 mmHg) despite optimal medical management. Have had arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within 6 months prior to the initiation of study treatment. Have an ongoing infection with severity of Grade 2 or above (NCI-CTCAE v 4.0). Have a known history of human immunodeficiency virus infection. Have either active or chronic hepatitis B or C requiring treatment with antiviral therapy. Have a seizure disorder requiring medication. Have a history of organ allograft. Have evidence or history of any bleeding diathesis (including mild hemophilia), irrespective of severity. Have had a hemorrhage or a bleeding event Grade 3 (NCI-CTCAE v 4.0) within 4 weeks prior to the initiation of study treatment. Have a nonhealing wound, ulcer, or bone fracture. Have renal failure requiring hemodialysis or peritoneal dialysis. Have dehydration Grade 1 (NCI-CTCAE v 4.0). Have interstitial lung disease with ongoing signs and symptoms at the time informed consent is obtained. Have persistent proteinuria > 3.5 g/24 hours measured by urine protein creatinine ratio from a random urine sample (Grade 3, NCI-CTCAE v 4.0). Have any other serious or unstable illness, or medical, psychological, or social condition, that could jeopardize the safety of the subject and/or his/her compliance with study procedures, or may interfere with the subject's participation in the study or evaluation of the study results. Have a known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs. Have any malabsorption condition. Have a close affiliation with the investigational site (eg, be a close relative of the investigator) or be a dependent person (eg, be an employee or student working at the investigational site). Untreated gastro-esophageus varices"}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
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{'Arm - Disease - Biomarker': 'Include: HER2 negative'}
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{'Official Title': 'Phase II Randomized Study of Maintenance Regorafenib vs Placebo in no Progression Patients After First-line Platinum and Fluoropyrimidines Based Chemotherapy in HER2 Negative Locally Advanced/Metastatic Gastric or Gastroesophagel Junction Cancer (a-MANTRA Study)', 'Brief Summary': 'Randomized, double-blind, placebo-controlled, multicenter Phase-II study. Approximately 120 subjects with CR/PR/SD after platinum compounds and fluoropyrimidines based regimens: up to 6 cycles of cisplatin and 5-fluorouracil or capecitabine, up to 12 cycles of FOLFOX, up to 8 cycles of XELOX, will be randomly assigned (1:1 ratio) to one of the following treatment groups: Arm A: Placebo 4 tablets once daily on day 1-21, every 4 weeks, until intolerance or progression disease Arm B: Regorafenib 160 mg, 4 tablets once daily on days 1-21, every 4 weeks, until intolerance or progression disease Primary Variable: PFS1', 'Condition': 'Gastric Cancer', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Male of female ≥ 18 years of age Have an Eastern Cooperative Oncology Group performance status of 0 or 1 within 14 days prior to the initiation of study treatment Diagnosis of histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction HER2 negative gastric or gastroesophagel junction cancer ( ICH 0, IHC 1+, IHC + FISH -) Locally advanced/metastatic gastric or gastroesophageal junction cancer CR/PR/SD after first-line platinum compound and Fluoropyrimidines based chemotherapy Measurable disease according to RECIST 1.1 criteria Have adequate bone marrow function, liver function, and renal function, as measured by the following laboratory assessments conducted within 7 days prior to the initiation of study treatment: Total bilirubin 1.5 times the upper limit of normal (ULN) Alanine aminotransferase and aspartate aminotransferase 3 times the ULN Lipase 1.5 times the ULN Serum creatinine 1.5 times the ULN Glomerular filtration rate 30 mL/min/1,73 m2 according to the Modified Diet in Renal Disease abbreviated formula International normalized ratio of prothrombin time and activated partial thromboplastin time 1.5 times the ULN. Subjects who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate if no underlying abnormality in coagulation parameters exists per medical history. Platelet count 100,000 /mm3, hemoglobin 9 g/dL, absolute neutrophil count 1500/mm3 without transfusions or granulocyte colony stimulating factor and other hematopoietic growth factors Alkaline phosphatase ≤ 2.5 times the ULN Understand, be willing to give consent, and sign the written informed consent form (ICF) prior to undergoing any study-specific procedure. If female and of childbearing potential, have a negative result on a pregnancy test performed a maximum of 7 days before initiation of study treatment. If female and of childbearing potential, or if male, agree to use adequate contraception (eg, abstinence, intrauterine device, oral contraceptive, or double-barrier method) based on the judgment of the investigator or a designated associate from the date on which the ICF is signed until 8 weeks after the last dose of study drug.', 'Exclusion Criteria': "Exclusion Criteria: Are taking strong cytochrome P (CYP) CYP3A4 inhibitors (eg, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, voriconazole) or strong CYP3A4 inducers (eg, carbamazepine, phenobarbital, phenytoin, rifampin, St. John's Wort) Have used biologic response modifiers, such as G-CSF, within 3 weeks of study entry Have had prior treatment with regorafenib or any other VEGFR-targeting kinase inhibitor. Completed their last dose of chemotherapy more than 8 weeks, whichever came later, prior to randomization. Have had prior or concurrent cancer distinct in primary site or histology from GC or GJC within 5 years prior to randomization EXCEPT for curatively treated cervical cancer in situ, no-melanoma skin cancer, or superficial bladder tumors classified as noninvasive tumor (Ta), carcinoma in situ (Tis), or tumor invades lamina propria (T1). Have had systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy, and/or hormonal therapy within 4 weeks prior to initiation of study treatment. Have unresolved toxicity higher than National Cancer Institute-Common Terminology for Adverse Events version 4.0 (NCI-CTCAE v 4.0) Grade 1 attributed to any prior therapy/procedure, excluding alopecia and/or oxaliplatin-induced neurotoxicity ≤ Grade 2 and hemoglobin ≥ 9 g/dL as per inclusion criteria Have had a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to initiation of study treatment. Are pregnant. Are breastfeeding. Are unable to swallow oral tablets (crushing of study treatment tablets is not allowed). Have congestive heart failure classified as New York Heart Association Class 2 or higher Have had unstable angina (angina symptoms at rest) or new-onset angina 3 months prior to screening. Have had a myocardial infarction 6 months prior to initiation of study treatment. Have cardiac arrhythmias requiring anti-arrhythmic therapy, with the exception of beta blockers or digoxin. Have uncontrolled hypertension (systolic blood pressure [SBP] 140 mmHg or diastolic blood pressure [DBP] 90 mmHg) despite optimal medical management. Have had arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within 6 months prior to the initiation of study treatment. Have an ongoing infection with severity of Grade 2 or above (NCI-CTCAE v 4.0). Have a known history of human immunodeficiency virus infection. Have either active or chronic hepatitis B or C requiring treatment with antiviral therapy. Have a seizure disorder requiring medication. Have a history of organ allograft. Have evidence or history of any bleeding diathesis (including mild hemophilia), irrespective of severity. Have had a hemorrhage or a bleeding event Grade 3 (NCI-CTCAE v 4.0) within 4 weeks prior to the initiation of study treatment. Have a nonhealing wound, ulcer, or bone fracture. Have renal failure requiring hemodialysis or peritoneal dialysis. Have dehydration Grade 1 (NCI-CTCAE v 4.0). Have interstitial lung disease with ongoing signs and symptoms at the time informed consent is obtained. Have persistent proteinuria > 3.5 g/24 hours measured by urine protein creatinine ratio from a random urine sample (Grade 3, NCI-CTCAE v 4.0). Have any other serious or unstable illness, or medical, psychological, or social condition, that could jeopardize the safety of the subject and/or his/her compliance with study procedures, or may interfere with the subject's participation in the study or evaluation of the study results. Have a known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs. Have any malabsorption condition. Have a close affiliation with the investigational site (eg, be a close relative of the investigator) or be a dependent person (eg, be an employee or student working at the investigational site). Untreated gastro-esophageus varices"}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
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{'Arm - Disease - Biomarker': 'Include: HER2 negative'}
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{'Official Title': 'Single-center, Multi-cohort Exploratory Phase Ib/II Clinical Study of First-line Treatment of Unresectable Locally Advanced/Advanced Adenocarcinoma of the Stomach or Gastroesophageal Junction Based on Different Genotypes', 'Brief Summary': 'Abstract Study title: Single-center, Multi-cohort Exploratory Phase Ib/II Clinical Study of First-line Treatment of Unresectable Locally Advanced/Advanced Adenocarcinoma of the Stomach or Gastroesophageal Junction Based on Different Genotypes Protocol No: GC-MATCH Initiator: Henan Cancer Hospital Nature of study Investigator-initiated exploratory study Subjects Advanced first-line gastric cancer or adenocarcinoma of the gastroesophageal junction Objective: To evaluate the efficacy and safety of different first-line treatment options for unresectable locally advanced/advanced gastric or combined gastroesophageal adenocarcinoma with different gene/protein types. Evaluation criteria: To evaluate the adverse effects of drugs using the NCI CTCAE V5.0 criteria. RECIST1.1 criteria were used to evaluate drug efficacy Study endpoints: Primary indicators Objective Response Rate (ORR) Secondary indicators 1. drug safety. 2. disease control rate DCR (CR+PR+SD). 3. duration of remission DoR. 4. disease-free survival (PFS) and overall survival time (OS). 5. R0/R1 surgical resection rate Study design: Single-center umbrella clinical trial Planned number of enrollment: Total 39-45 cases Sample size estimation: This is an exploratory study and sample size was not calculated Statistical methods: Selection of data for statistical analysis Full Analysis Set (FAS): The efficacy analysis was performed on all patients who were enrolled and used the drug at least once, according to the principle of intentional analysis (ITT). Per-protocol Set: Cases with at least one oncologic efficacy assessment, compliance with the trial protocol, good compliance, no prohibited drugs during the trial, and completion of the case report form. Safety Analysis Set: All patients who had used the trial drug at least once and had a safety record after the drug was administered were enrolled in the Safety Analysis Set. Statistical analysis plan Validity analysis: for the efficacy index PFS, the Kaplan-Meier method will be used to estimate its median time and column Statistical methods: Out of two-sided 95% confidence intervals. Disease control rate (DCR = CR+PR+SD) and objective remission rate (ORR = CR+PR) were calculated using Fisher exact probability and bilateral 95% confidence intervals were presented. Safety analysis: descriptive statistical analysis was used to tabulate the AEs that occurred in this trial. laboratory test results were described as normal before the trial but abnormal after treatment and in relation to the trial drug when abnormal changes occurred. Treatment protocol: All subjects in this study were first tested for genes/proteins (HER2 protein, HER2FISH, PD-L1 protein 22C3, Claudin18.2, MMR) and received treatment in different groups according to gene/protein expression. Group 1 HER protein positive 3+ or FISH amplification or HER protein 2+ but FISH amplification Initial treatment (4-6 cycles): IBI315 injection, oxaliplatin, capecitabine Group 2 Claudin18.2 protein-positive Initial treatment (4-6 cycles): PD-L1 monoclonal antibody, TST001 injection, oxaliplatin, capecitabine Group 3 Her protein and Claudin18.2 protein were negative Initial treatment (4-6 cycles): TQB2450 injection, Anrotinib, Oxaliplatin, Capecitabine Patients can undergo radical gastric cancer surgery or radical gastric cancer surgery + local treatment during the maintenance treatment phase if their condition is stable and after in-hospital MDT consultation. The duration of maintenance treatment was 2 years from the time of enrollment. Principal Investigator: Luo Suxia, Li Ning Group leader unit: Henan Cancer Hospital', 'Condition': 'Gastric Cancer Gastroesophageal-junction Cancer', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Voluntarily sign the informed consent form for this study. Male or female patients aged 18-75 years. unresectable advanced or metastatic gastric cancer or adenocarcinoma of the gastroesophageal junction (including indolent cell carcinoma, mucinous adenocarcinoma, hepatoid adenocarcinoma) confirmed by pathological (histological or cytological) examination. >6 months from the end of prior (neo)adjuvant chemotherapy/adjuvant radiotherapy to the time of disease recurrence at least one measurable lesion or evaluable lesion according to RECIST version 1.1; measurable lesions should not have received local treatment such as radiotherapy (lesions located within the area of previous radiotherapy may also be optional targets if progression is confirmed and they meet RECIST 1.1 criteria) ECOG score: 0 to 1. Life expectancy ≥ 3 months. Adequate organ function, with the following laboratory test values required at screening. Routine blood test criteria to be met. Hemoglobin level (HB) ≥ 90 g/L (no blood transfusion within 14 days). Absolute neutrophil count (ANC) ≥ 1.5 x 109/L. Platelet count (PLT) ≥100×109/L (no interleukin 11 or TPO within 14 days). White blood cell count (WBC) ≥4.0×109/L (no granulocyte stimulating factor within 14 days). Biochemical tests are required to meet the following criteria. Serum total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN). ALT and AST ≤ 2.5 ULN. Cr ≤ 1.5 ULN or creatinine clearance (CCr) ≥ 60 ml/min, (Cockcroft-Gault formula). Serum albumin ≥ 25 g/L (2.5 g/dL). For subjects with liver metastases, AST and ALT must be ≤ 5 x ULN, leukocytes ≥ 4 x 109/L, untransfused platelets ≥ 100 x 109/L, absolute neutrophil value (ANC) without granulocyte-stimulating factor treatment ≥ 1.5 x 109/L, hemoglobin ≥ 90 g/L Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ low limit of normal (50%). Adequate coagulation, defined as an international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN. Women of childbearing potential are required to use highly effective contraception for the duration of the study, and for the period after the last dose and for at least 180 days after chemotherapy. It is recommended that contraception be initiated at least 3 months prior to study drug administration; non-sterile men are required to use highly effective contraception for the duration of the study and for at least 180 days after both the last dose and chemotherapy. It is recommended that contraception be initiated at least 3 months prior to study drug administration. If local treatment of metastases, such as radiotherapy or ablation, is performed, they may also be enrolled after 14 days of washout as long as an assessable lesion is still present and the local treatment is not followed by anti-tumor therapy such as targeted, chemotherapy or immunotherapy.', 'Exclusion Criteria': "Exclusion Criteria: Hypersensitivity to any of the test drugs and their excipients, or a history of severe allergy, or a contraindication to the test drug. A history or active stage of autoimmune disease. symptomatic/asymptomatic brain metastases CT suggestive of definite ulcerative lesions or positive fecal occult blood (risk of bleeding and suitability for enrollment as determined by the investigator) History of abnormal bleeding (except epistaxis) complained of 14 days prior to enrollment previous allogeneic bone marrow transplantation or organ transplantation congenital pulmonary fibrosis, drug-induced pneumonia, mechanized pneumonia, or CT-confirmed active pneumonia HIV positive test, active hepatitis B or C, active tuberculosis. Uncontrolled cancer pain. previous live attenuated vaccine within 4 weeks prior to study entry or expected to be administered during or within 5 months of the end of the trial Prior treatment with PD-1/PD-L1 antibodies, CTLA-4 antibodies, or other therapies targeting PD-1/PD-L1 and/or VEGFR inhibitors or have not recovered from adverse events caused by dosing >4 weeks prior (i.e., have not returned to ≤ grade 1 or baseline levels)). Systemic application of glucocorticoids or immunosuppressants within 2 weeks prior to trial start (note: inhaled glucocorticoids and salicorticoids are permitted). Known presence of symptomatic CNS metastases and/or carcinomatous meningitis. Patients with a history of CNS metastases or spinal cord compression may be enrolled in the study if they are clearly treated and clinically stable after discontinuation of anticonvulsants and steroids for 4 weeks prior to the first dose of the study. Have a contraindication to hormone use. Have multiple factors that interfere with oral drug administration (e.g., inability to swallow, chronic diarrhea, and intestinal obstruction) peripheral neuropathy ≥ NCI CTCAE grade 2. Uncontrollable or symptomatic hypercalcemia. infections requiring antibiotics within 14 days prior to the start of the trial chronic enterocolitis. Patients with bone metastases at risk of paraplegia. Patients with any severe and/ or uncontrolled disease, including: Patients with suboptimal blood pressure control (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg) on antihypertensive medications; patients with class II or higher myocardial ischemia or myocardial infarction, arrhythmias (including QT interval ≥ 480 ms); class III-IV cardiac insufficiency by NYHA criteria, or cardiac ultrasound suggestive of left ventricular ejection fraction ( LVEF) <50% in patients. Active or uncontrolled severe infections. Liver disease such as cirrhosis, decompensated liver disease, chronic active hepatitis. Poorly controlled diabetes mellitus (fasting blood glucose (FBG) >10 mmol/L). Urine routine suggestive of urine protein ≥++ and confirmed 24-hour urine protein quantification >1.0 g. Long-term untreated wounds or fractures 23) Subjects who are unable to receive a trans-peripheral central venous placement (PICC) Subjects with abnormal coagulation (INR > 1.5 or APTT > 1.5 × ULN), with bleeding tendency or on thrombolytic or anticoagulant therapy. Known hereditary or acquired bleeding and thrombotic tendencies such as: hemophilia, impaired coagulation skills, thrombocytopenia, hypersplenism, etc. Active bleeding within 14 prior to study entry. Major surgical procedure (craniotomy, open-heart or open-heart surgery) within 4 weeks prior to the first dose of study, or anticipated need for major surgery during study treatment, or non-diagnostic surgery within 4 weeks prior to the start of the trial. history of gastrointestinal perforation and/or fistula within 3 months prior to enrollment in treatment; or arterial/venous thrombotic events such as cerebrovascular accidents (except stable cerebral infarction as assessed by the investigator), deep vein thrombosis, and pulmonary embolism (except if cured) Clinically significant thoracoabdominal fluid, including any thoracoabdominal fluid that is detectable on physical examination, previously treated or currently still requiring treatment Those with only a small amount of thoracic ascites on imaging but asymptomatic, which the investigator assesses does not require treatment may be enrolled. Interstitial lung disease requiring steroid hormone therapy. uncontrolled metabolic disorders or other non-malignant organ or systemic diseases or secondary reactions to cancer that can lead to higher medical risk and/or uncertainty in survival evaluation Patients with significant malnutrition. Patients with a history of psychotropic substance abuse and inability to abstain or with psychiatric disorders those with a history of immunodeficiency, including testing positive for HIV or having other acquired, congenital immunodeficiency disorders, or a history of organ transplantation History of other primary malignancies, except for 1) malignancies in complete remission for at least 2 years prior to enrollment and requiring no other treatment during the study period; 2) non-melanoma skin cancers or malignant freckled nevi that have been adequately treated and have no evidence of disease recurrence; and 3) carcinomas in situ that have been adequately treated and have no evidence of disease recurrence. Female patients who are pregnant or breastfeeding. those who, in the judgment of the investigator, have a serious concomitant disease that jeopardizes patient safety or interferes with the patient's ability to complete the study Participating in another trial within 30 days prior to the start of the trial, or planning to participate in another trial while the trial is ongoing. Inclusion in the row with the most stringent conditions, if there is duplication."}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
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{'Arm - Disease - Biomarker': 'Include: HER2 positive, Claudin 18.2 positive, HER2 negative, Claudin 18.2 negative'}
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{'Official Title': 'Single-center, Multi-cohort Exploratory Phase Ib/II Clinical Study of First-line Treatment of Unresectable Locally Advanced/Advanced Adenocarcinoma of the Stomach or Gastroesophageal Junction Based on Different Genotypes', 'Brief Summary': 'Abstract Study title: Single-center, Multi-cohort Exploratory Phase Ib/II Clinical Study of First-line Treatment of Unresectable Locally Advanced/Advanced Adenocarcinoma of the Stomach or Gastroesophageal Junction Based on Different Genotypes Protocol No: GC-MATCH Initiator: Henan Cancer Hospital Nature of study Investigator-initiated exploratory study Subjects Advanced first-line gastric cancer or adenocarcinoma of the gastroesophageal junction Objective: To evaluate the efficacy and safety of different first-line treatment options for unresectable locally advanced/advanced gastric or combined gastroesophageal adenocarcinoma with different gene/protein types. Evaluation criteria: To evaluate the adverse effects of drugs using the NCI CTCAE V5.0 criteria. RECIST1.1 criteria were used to evaluate drug efficacy Study endpoints: Primary indicators Objective Response Rate (ORR) Secondary indicators 1. drug safety. 2. disease control rate DCR (CR+PR+SD). 3. duration of remission DoR. 4. disease-free survival (PFS) and overall survival time (OS). 5. R0/R1 surgical resection rate Study design: Single-center umbrella clinical trial Planned number of enrollment: Total 39-45 cases Sample size estimation: This is an exploratory study and sample size was not calculated Statistical methods: Selection of data for statistical analysis Full Analysis Set (FAS): The efficacy analysis was performed on all patients who were enrolled and used the drug at least once, according to the principle of intentional analysis (ITT). Per-protocol Set: Cases with at least one oncologic efficacy assessment, compliance with the trial protocol, good compliance, no prohibited drugs during the trial, and completion of the case report form. Safety Analysis Set: All patients who had used the trial drug at least once and had a safety record after the drug was administered were enrolled in the Safety Analysis Set. Statistical analysis plan Validity analysis: for the efficacy index PFS, the Kaplan-Meier method will be used to estimate its median time and column Statistical methods: Out of two-sided 95% confidence intervals. Disease control rate (DCR = CR+PR+SD) and objective remission rate (ORR = CR+PR) were calculated using Fisher exact probability and bilateral 95% confidence intervals were presented. Safety analysis: descriptive statistical analysis was used to tabulate the AEs that occurred in this trial. laboratory test results were described as normal before the trial but abnormal after treatment and in relation to the trial drug when abnormal changes occurred. Treatment protocol: All subjects in this study were first tested for genes/proteins (HER2 protein, HER2FISH, PD-L1 protein 22C3, Claudin18.2, MMR) and received treatment in different groups according to gene/protein expression. Group 1 HER protein positive 3+ or FISH amplification or HER protein 2+ but FISH amplification Initial treatment (4-6 cycles): IBI315 injection, oxaliplatin, capecitabine Group 2 Claudin18.2 protein-positive Initial treatment (4-6 cycles): PD-L1 monoclonal antibody, TST001 injection, oxaliplatin, capecitabine Group 3 Her protein and Claudin18.2 protein were negative Initial treatment (4-6 cycles): TQB2450 injection, Anrotinib, Oxaliplatin, Capecitabine Patients can undergo radical gastric cancer surgery or radical gastric cancer surgery + local treatment during the maintenance treatment phase if their condition is stable and after in-hospital MDT consultation. The duration of maintenance treatment was 2 years from the time of enrollment. Principal Investigator: Luo Suxia, Li Ning Group leader unit: Henan Cancer Hospital', 'Condition': 'Gastric Cancer Gastroesophageal-junction Cancer', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Voluntarily sign the informed consent form for this study. Male or female patients aged 18-75 years. unresectable advanced or metastatic gastric cancer or adenocarcinoma of the gastroesophageal junction (including indolent cell carcinoma, mucinous adenocarcinoma, hepatoid adenocarcinoma) confirmed by pathological (histological or cytological) examination. >6 months from the end of prior (neo)adjuvant chemotherapy/adjuvant radiotherapy to the time of disease recurrence at least one measurable lesion or evaluable lesion according to RECIST version 1.1; measurable lesions should not have received local treatment such as radiotherapy (lesions located within the area of previous radiotherapy may also be optional targets if progression is confirmed and they meet RECIST 1.1 criteria) ECOG score: 0 to 1. Life expectancy ≥ 3 months. Adequate organ function, with the following laboratory test values required at screening. Routine blood test criteria to be met. Hemoglobin level (HB) ≥ 90 g/L (no blood transfusion within 14 days). Absolute neutrophil count (ANC) ≥ 1.5 x 109/L. Platelet count (PLT) ≥100×109/L (no interleukin 11 or TPO within 14 days). White blood cell count (WBC) ≥4.0×109/L (no granulocyte stimulating factor within 14 days). Biochemical tests are required to meet the following criteria. Serum total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN). ALT and AST ≤ 2.5 ULN. Cr ≤ 1.5 ULN or creatinine clearance (CCr) ≥ 60 ml/min, (Cockcroft-Gault formula). Serum albumin ≥ 25 g/L (2.5 g/dL). For subjects with liver metastases, AST and ALT must be ≤ 5 x ULN, leukocytes ≥ 4 x 109/L, untransfused platelets ≥ 100 x 109/L, absolute neutrophil value (ANC) without granulocyte-stimulating factor treatment ≥ 1.5 x 109/L, hemoglobin ≥ 90 g/L Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ low limit of normal (50%). Adequate coagulation, defined as an international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN. Women of childbearing potential are required to use highly effective contraception for the duration of the study, and for the period after the last dose and for at least 180 days after chemotherapy. It is recommended that contraception be initiated at least 3 months prior to study drug administration; non-sterile men are required to use highly effective contraception for the duration of the study and for at least 180 days after both the last dose and chemotherapy. It is recommended that contraception be initiated at least 3 months prior to study drug administration. If local treatment of metastases, such as radiotherapy or ablation, is performed, they may also be enrolled after 14 days of washout as long as an assessable lesion is still present and the local treatment is not followed by anti-tumor therapy such as targeted, chemotherapy or immunotherapy.', 'Exclusion Criteria': "Exclusion Criteria: Hypersensitivity to any of the test drugs and their excipients, or a history of severe allergy, or a contraindication to the test drug. A history or active stage of autoimmune disease. symptomatic/asymptomatic brain metastases CT suggestive of definite ulcerative lesions or positive fecal occult blood (risk of bleeding and suitability for enrollment as determined by the investigator) History of abnormal bleeding (except epistaxis) complained of 14 days prior to enrollment previous allogeneic bone marrow transplantation or organ transplantation congenital pulmonary fibrosis, drug-induced pneumonia, mechanized pneumonia, or CT-confirmed active pneumonia HIV positive test, active hepatitis B or C, active tuberculosis. Uncontrolled cancer pain. previous live attenuated vaccine within 4 weeks prior to study entry or expected to be administered during or within 5 months of the end of the trial Prior treatment with PD-1/PD-L1 antibodies, CTLA-4 antibodies, or other therapies targeting PD-1/PD-L1 and/or VEGFR inhibitors or have not recovered from adverse events caused by dosing >4 weeks prior (i.e., have not returned to ≤ grade 1 or baseline levels)). Systemic application of glucocorticoids or immunosuppressants within 2 weeks prior to trial start (note: inhaled glucocorticoids and salicorticoids are permitted). Known presence of symptomatic CNS metastases and/or carcinomatous meningitis. Patients with a history of CNS metastases or spinal cord compression may be enrolled in the study if they are clearly treated and clinically stable after discontinuation of anticonvulsants and steroids for 4 weeks prior to the first dose of the study. Have a contraindication to hormone use. Have multiple factors that interfere with oral drug administration (e.g., inability to swallow, chronic diarrhea, and intestinal obstruction) peripheral neuropathy ≥ NCI CTCAE grade 2. Uncontrollable or symptomatic hypercalcemia. infections requiring antibiotics within 14 days prior to the start of the trial chronic enterocolitis. Patients with bone metastases at risk of paraplegia. Patients with any severe and/ or uncontrolled disease, including: Patients with suboptimal blood pressure control (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg) on antihypertensive medications; patients with class II or higher myocardial ischemia or myocardial infarction, arrhythmias (including QT interval ≥ 480 ms); class III-IV cardiac insufficiency by NYHA criteria, or cardiac ultrasound suggestive of left ventricular ejection fraction ( LVEF) <50% in patients. Active or uncontrolled severe infections. Liver disease such as cirrhosis, decompensated liver disease, chronic active hepatitis. Poorly controlled diabetes mellitus (fasting blood glucose (FBG) >10 mmol/L). Urine routine suggestive of urine protein ≥++ and confirmed 24-hour urine protein quantification >1.0 g. Long-term untreated wounds or fractures 23) Subjects who are unable to receive a trans-peripheral central venous placement (PICC) Subjects with abnormal coagulation (INR > 1.5 or APTT > 1.5 × ULN), with bleeding tendency or on thrombolytic or anticoagulant therapy. Known hereditary or acquired bleeding and thrombotic tendencies such as: hemophilia, impaired coagulation skills, thrombocytopenia, hypersplenism, etc. Active bleeding within 14 prior to study entry. Major surgical procedure (craniotomy, open-heart or open-heart surgery) within 4 weeks prior to the first dose of study, or anticipated need for major surgery during study treatment, or non-diagnostic surgery within 4 weeks prior to the start of the trial. history of gastrointestinal perforation and/or fistula within 3 months prior to enrollment in treatment; or arterial/venous thrombotic events such as cerebrovascular accidents (except stable cerebral infarction as assessed by the investigator), deep vein thrombosis, and pulmonary embolism (except if cured) Clinically significant thoracoabdominal fluid, including any thoracoabdominal fluid that is detectable on physical examination, previously treated or currently still requiring treatment Those with only a small amount of thoracic ascites on imaging but asymptomatic, which the investigator assesses does not require treatment may be enrolled. Interstitial lung disease requiring steroid hormone therapy. uncontrolled metabolic disorders or other non-malignant organ or systemic diseases or secondary reactions to cancer that can lead to higher medical risk and/or uncertainty in survival evaluation Patients with significant malnutrition. Patients with a history of psychotropic substance abuse and inability to abstain or with psychiatric disorders those with a history of immunodeficiency, including testing positive for HIV or having other acquired, congenital immunodeficiency disorders, or a history of organ transplantation History of other primary malignancies, except for 1) malignancies in complete remission for at least 2 years prior to enrollment and requiring no other treatment during the study period; 2) non-melanoma skin cancers or malignant freckled nevi that have been adequately treated and have no evidence of disease recurrence; and 3) carcinomas in situ that have been adequately treated and have no evidence of disease recurrence. Female patients who are pregnant or breastfeeding. those who, in the judgment of the investigator, have a serious concomitant disease that jeopardizes patient safety or interferes with the patient's ability to complete the study Participating in another trial within 30 days prior to the start of the trial, or planning to participate in another trial while the trial is ongoing. Inclusion in the row with the most stringent conditions, if there is duplication."}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
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{'Arm - Disease - Biomarker': 'Include: HER2 positive, Claudin 18.2 positive, HER2 negative, Claudin 18.2 negative'}
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{'Official Title': 'Single-center, Multi-cohort Exploratory Phase Ib/II Clinical Study of First-line Treatment of Unresectable Locally Advanced/Advanced Adenocarcinoma of the Stomach or Gastroesophageal Junction Based on Different Genotypes', 'Brief Summary': 'Abstract Study title: Single-center, Multi-cohort Exploratory Phase Ib/II Clinical Study of First-line Treatment of Unresectable Locally Advanced/Advanced Adenocarcinoma of the Stomach or Gastroesophageal Junction Based on Different Genotypes Protocol No: GC-MATCH Initiator: Henan Cancer Hospital Nature of study Investigator-initiated exploratory study Subjects Advanced first-line gastric cancer or adenocarcinoma of the gastroesophageal junction Objective: To evaluate the efficacy and safety of different first-line treatment options for unresectable locally advanced/advanced gastric or combined gastroesophageal adenocarcinoma with different gene/protein types. Evaluation criteria: To evaluate the adverse effects of drugs using the NCI CTCAE V5.0 criteria. RECIST1.1 criteria were used to evaluate drug efficacy Study endpoints: Primary indicators Objective Response Rate (ORR) Secondary indicators 1. drug safety. 2. disease control rate DCR (CR+PR+SD). 3. duration of remission DoR. 4. disease-free survival (PFS) and overall survival time (OS). 5. R0/R1 surgical resection rate Study design: Single-center umbrella clinical trial Planned number of enrollment: Total 39-45 cases Sample size estimation: This is an exploratory study and sample size was not calculated Statistical methods: Selection of data for statistical analysis Full Analysis Set (FAS): The efficacy analysis was performed on all patients who were enrolled and used the drug at least once, according to the principle of intentional analysis (ITT). Per-protocol Set: Cases with at least one oncologic efficacy assessment, compliance with the trial protocol, good compliance, no prohibited drugs during the trial, and completion of the case report form. Safety Analysis Set: All patients who had used the trial drug at least once and had a safety record after the drug was administered were enrolled in the Safety Analysis Set. Statistical analysis plan Validity analysis: for the efficacy index PFS, the Kaplan-Meier method will be used to estimate its median time and column Statistical methods: Out of two-sided 95% confidence intervals. Disease control rate (DCR = CR+PR+SD) and objective remission rate (ORR = CR+PR) were calculated using Fisher exact probability and bilateral 95% confidence intervals were presented. Safety analysis: descriptive statistical analysis was used to tabulate the AEs that occurred in this trial. laboratory test results were described as normal before the trial but abnormal after treatment and in relation to the trial drug when abnormal changes occurred. Treatment protocol: All subjects in this study were first tested for genes/proteins (HER2 protein, HER2FISH, PD-L1 protein 22C3, Claudin18.2, MMR) and received treatment in different groups according to gene/protein expression. Group 1 HER protein positive 3+ or FISH amplification or HER protein 2+ but FISH amplification Initial treatment (4-6 cycles): IBI315 injection, oxaliplatin, capecitabine Group 2 Claudin18.2 protein-positive Initial treatment (4-6 cycles): PD-L1 monoclonal antibody, TST001 injection, oxaliplatin, capecitabine Group 3 Her protein and Claudin18.2 protein were negative Initial treatment (4-6 cycles): TQB2450 injection, Anrotinib, Oxaliplatin, Capecitabine Patients can undergo radical gastric cancer surgery or radical gastric cancer surgery + local treatment during the maintenance treatment phase if their condition is stable and after in-hospital MDT consultation. The duration of maintenance treatment was 2 years from the time of enrollment. Principal Investigator: Luo Suxia, Li Ning Group leader unit: Henan Cancer Hospital', 'Condition': 'Gastric Cancer Gastroesophageal-junction Cancer', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Voluntarily sign the informed consent form for this study. Male or female patients aged 18-75 years. unresectable advanced or metastatic gastric cancer or adenocarcinoma of the gastroesophageal junction (including indolent cell carcinoma, mucinous adenocarcinoma, hepatoid adenocarcinoma) confirmed by pathological (histological or cytological) examination. >6 months from the end of prior (neo)adjuvant chemotherapy/adjuvant radiotherapy to the time of disease recurrence at least one measurable lesion or evaluable lesion according to RECIST version 1.1; measurable lesions should not have received local treatment such as radiotherapy (lesions located within the area of previous radiotherapy may also be optional targets if progression is confirmed and they meet RECIST 1.1 criteria) ECOG score: 0 to 1. Life expectancy ≥ 3 months. Adequate organ function, with the following laboratory test values required at screening. Routine blood test criteria to be met. Hemoglobin level (HB) ≥ 90 g/L (no blood transfusion within 14 days). Absolute neutrophil count (ANC) ≥ 1.5 x 109/L. Platelet count (PLT) ≥100×109/L (no interleukin 11 or TPO within 14 days). White blood cell count (WBC) ≥4.0×109/L (no granulocyte stimulating factor within 14 days). Biochemical tests are required to meet the following criteria. Serum total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN). ALT and AST ≤ 2.5 ULN. Cr ≤ 1.5 ULN or creatinine clearance (CCr) ≥ 60 ml/min, (Cockcroft-Gault formula). Serum albumin ≥ 25 g/L (2.5 g/dL). For subjects with liver metastases, AST and ALT must be ≤ 5 x ULN, leukocytes ≥ 4 x 109/L, untransfused platelets ≥ 100 x 109/L, absolute neutrophil value (ANC) without granulocyte-stimulating factor treatment ≥ 1.5 x 109/L, hemoglobin ≥ 90 g/L Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ low limit of normal (50%). Adequate coagulation, defined as an international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN. Women of childbearing potential are required to use highly effective contraception for the duration of the study, and for the period after the last dose and for at least 180 days after chemotherapy. It is recommended that contraception be initiated at least 3 months prior to study drug administration; non-sterile men are required to use highly effective contraception for the duration of the study and for at least 180 days after both the last dose and chemotherapy. It is recommended that contraception be initiated at least 3 months prior to study drug administration. If local treatment of metastases, such as radiotherapy or ablation, is performed, they may also be enrolled after 14 days of washout as long as an assessable lesion is still present and the local treatment is not followed by anti-tumor therapy such as targeted, chemotherapy or immunotherapy.', 'Exclusion Criteria': "Exclusion Criteria: Hypersensitivity to any of the test drugs and their excipients, or a history of severe allergy, or a contraindication to the test drug. A history or active stage of autoimmune disease. symptomatic/asymptomatic brain metastases CT suggestive of definite ulcerative lesions or positive fecal occult blood (risk of bleeding and suitability for enrollment as determined by the investigator) History of abnormal bleeding (except epistaxis) complained of 14 days prior to enrollment previous allogeneic bone marrow transplantation or organ transplantation congenital pulmonary fibrosis, drug-induced pneumonia, mechanized pneumonia, or CT-confirmed active pneumonia HIV positive test, active hepatitis B or C, active tuberculosis. Uncontrolled cancer pain. previous live attenuated vaccine within 4 weeks prior to study entry or expected to be administered during or within 5 months of the end of the trial Prior treatment with PD-1/PD-L1 antibodies, CTLA-4 antibodies, or other therapies targeting PD-1/PD-L1 and/or VEGFR inhibitors or have not recovered from adverse events caused by dosing >4 weeks prior (i.e., have not returned to ≤ grade 1 or baseline levels)). Systemic application of glucocorticoids or immunosuppressants within 2 weeks prior to trial start (note: inhaled glucocorticoids and salicorticoids are permitted). Known presence of symptomatic CNS metastases and/or carcinomatous meningitis. Patients with a history of CNS metastases or spinal cord compression may be enrolled in the study if they are clearly treated and clinically stable after discontinuation of anticonvulsants and steroids for 4 weeks prior to the first dose of the study. Have a contraindication to hormone use. Have multiple factors that interfere with oral drug administration (e.g., inability to swallow, chronic diarrhea, and intestinal obstruction) peripheral neuropathy ≥ NCI CTCAE grade 2. Uncontrollable or symptomatic hypercalcemia. infections requiring antibiotics within 14 days prior to the start of the trial chronic enterocolitis. Patients with bone metastases at risk of paraplegia. Patients with any severe and/ or uncontrolled disease, including: Patients with suboptimal blood pressure control (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg) on antihypertensive medications; patients with class II or higher myocardial ischemia or myocardial infarction, arrhythmias (including QT interval ≥ 480 ms); class III-IV cardiac insufficiency by NYHA criteria, or cardiac ultrasound suggestive of left ventricular ejection fraction ( LVEF) <50% in patients. Active or uncontrolled severe infections. Liver disease such as cirrhosis, decompensated liver disease, chronic active hepatitis. Poorly controlled diabetes mellitus (fasting blood glucose (FBG) >10 mmol/L). Urine routine suggestive of urine protein ≥++ and confirmed 24-hour urine protein quantification >1.0 g. Long-term untreated wounds or fractures 23) Subjects who are unable to receive a trans-peripheral central venous placement (PICC) Subjects with abnormal coagulation (INR > 1.5 or APTT > 1.5 × ULN), with bleeding tendency or on thrombolytic or anticoagulant therapy. Known hereditary or acquired bleeding and thrombotic tendencies such as: hemophilia, impaired coagulation skills, thrombocytopenia, hypersplenism, etc. Active bleeding within 14 prior to study entry. Major surgical procedure (craniotomy, open-heart or open-heart surgery) within 4 weeks prior to the first dose of study, or anticipated need for major surgery during study treatment, or non-diagnostic surgery within 4 weeks prior to the start of the trial. history of gastrointestinal perforation and/or fistula within 3 months prior to enrollment in treatment; or arterial/venous thrombotic events such as cerebrovascular accidents (except stable cerebral infarction as assessed by the investigator), deep vein thrombosis, and pulmonary embolism (except if cured) Clinically significant thoracoabdominal fluid, including any thoracoabdominal fluid that is detectable on physical examination, previously treated or currently still requiring treatment Those with only a small amount of thoracic ascites on imaging but asymptomatic, which the investigator assesses does not require treatment may be enrolled. Interstitial lung disease requiring steroid hormone therapy. uncontrolled metabolic disorders or other non-malignant organ or systemic diseases or secondary reactions to cancer that can lead to higher medical risk and/or uncertainty in survival evaluation Patients with significant malnutrition. Patients with a history of psychotropic substance abuse and inability to abstain or with psychiatric disorders those with a history of immunodeficiency, including testing positive for HIV or having other acquired, congenital immunodeficiency disorders, or a history of organ transplantation History of other primary malignancies, except for 1) malignancies in complete remission for at least 2 years prior to enrollment and requiring no other treatment during the study period; 2) non-melanoma skin cancers or malignant freckled nevi that have been adequately treated and have no evidence of disease recurrence; and 3) carcinomas in situ that have been adequately treated and have no evidence of disease recurrence. Female patients who are pregnant or breastfeeding. those who, in the judgment of the investigator, have a serious concomitant disease that jeopardizes patient safety or interferes with the patient's ability to complete the study Participating in another trial within 30 days prior to the start of the trial, or planning to participate in another trial while the trial is ongoing. Inclusion in the row with the most stringent conditions, if there is duplication."}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: HER2 positive, Claudin 18.2 positive, HER2 negative, Claudin 18.2 negative'}
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{'Official Title': 'A Phase 2 Open Label Study of Oral Lorlatinib in Patients With Relapsed ALK Positive Lymphoma Previously Treated With ALK Inhibitors (CRU3)', 'Brief Summary': 'The purpose of this study is to define the objective response rates (ORR) of Lorlatinib in subjects with ALK+ lymphomas resistant or refractory to ALK inhibitors.', 'Condition': 'Anaplastic Large Cell Lymphoma, ALK-Positive', 'Detailed Description': 'Lorlatinib is a selective and potent tyrosine kinase inhibitor of ALK and ROS1 that pre-clinically demonstrated dose-dependent inhibition of mutations that confer resistance to other ALK inhibitors; it is also a brain-penetrant thus it might be active in patients with CNS metastases. Study Objectives Primary Define the objective response rates (ORR) of PF-06463922 in subjects with ALK+ lymphomas resistant or refractory to ALK inhibitors. Secondary Define the Progression Free Survival (PFS) in subjects with ALK+ lymphomas resistant or refractory to ALK inhibitors. Define the overall survival (OS) in ALK+ lymphoma patients treated with Lorlatinib, that are resistant or refractory to ALK inhibitors. Determine the toxicity profile of Lorlatinib in ALK+ lymphoma patients resistant or refractory to ALK inhibitors. Determine the Quality of Life (QoL) in this population of patients using the EORTC-C30 Quality of Life questionnaire. Study the mutational status of ALK pre/post Lorlatinib treatment through next-generation sequencing (NGS). Study design This is a phase 2 study open to 12 eligible patients with lymphoma with a confirmed ALK rearrangement. All patients must have been pretreated with at least one line of standard cytotoxic chemotherapy and at least one ALK inhibitor and they must have demonstrated progression (regardless of initial response) or resistance on the last treatment. The study begins with a screening period to assess eligibility, up to and including 28 days prior to the first dose of Lorlatinib. Treatment will continue until patient experiences unacceptable toxicity or progressive disease (PD), starts a new anti-cancer therapy or dies. The study will remain open until all patients have completed 3 years from the enrollment. Study treatment Patients will receive an oral administration of Lorlatinib at a dose of 100mg QD. In case of toxicity, it is possible to proceed to a dose reduction (75mg or 50mg QD) or a temporary interruption of Lorlatinib.', 'Inclusion Criteria': "Inclusion Criteria: Signed and dated Informed Consent approved by Local Ethical Committee before any protocol-specific screening procedures. ALK+ Lymphoma diagnosed by IHC or FISH. Refractory disease or relapse after at least one prior chemotherapy regimen (typically a minimum of 6 cycles of CHOP) and at least one ALK inhibitor; presence of measurable disease by physical examination, CT or CT-PET scan. Any prior antitumor medical treatment or major surgeries must have been completed at least 14 days prior to initiation of study medication. This could not be respected if there is clear evidence of disease progression, manifested as growing pain attributable to the tumour, fever, growing tumour lesions, increasing LDH values. Systemic anti-cancer therapy completed within a minimum of 5 half-lives of study entry. Able to take oral therapy. Female or male, 18 years of age or older. ECOG performance status 0-3. Adequate organ function as defined by the following criteria: Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN) or AST and ALT ≤ 5 x ULN if liver function abnormalities are due to underlying malignancy Total serum bilirubin 1.5 x ULN (except patients with documented Gilbert's syndrome Creatinine ≤ 1.5 x ULN. Adequate bone marrow function: Absolute neutrophil count (ANC) ≥ 1000/µL Platelets ≥ 50.000/µL Hemoglobin ≥ 9.0 g/dL The hematological values will not be considered in case of bone marrow involvement. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. Female and male patients who are of childbearing potential must agree to use an effective form of contraception (2 forms of contraception) with their partners throughout participation in this study and for at least 90 days after the last dose of treatment.", 'Exclusion Criteria': 'Exclusion Criteria: Current treatment on another therapeutic clinical trial. Clinically significant cardiovascular disease (that is, active or <3 months prior to enrollment): cerebral vascular accident/stroke, myocardial infarction, unstable angina, congestive heart failure (New York Heart Association Classification Class ≥ II) Ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥2: second-degree or third-degree AV block (unless paced) or any AV block with PR >220 msec, uncontrolled atrial fibrillation of any grade, bradycardia defined as <50 bpm (unless patient is otherwise healthy such as long-distance runners, etc.), machine-read ECG with QTc >470 msec, or congenital long QT syndrome. Pregnancy or breastfeeding. Use of drugs or foods that are known strong or moderate CYP3A4 inhibitors, inducers and substrates; drugs that are CYP2C9 substrates; drugs that are strong CYP2C19 inhibitors; drugs that are strong CYP2C8 inhibitors; and drugs that are P-gp substrates. Prior malignancy other than basal cell carcinoma , if original diagnosis happened in the last 5 years. Patients with predisposing characteristics for acute pancreatitis according to investigator judgment (e.g. uncontrolled hyperglycemia, current gallstone disease, alcoholism). Hypertriglyceridemia ≥ grade 1. Active and clinically significant bacterial, fungal, or viral infection including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS) related illness. Other severe acute or chronic medical or psychiatric conditions, or laboratory abnormalities that would impart, in the judgment of the investigator and/or sponsor, excess risk associated with study participation or study drug administration.'}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: ALK positive'}
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{'Official Title': 'A Randomised, Double-blind, Placebo-controlled, Multicentre Phase Ш Clinical Study to Evaluate the Efficacy and Safety of First-line Treatment With SG001 Plus Chemotherapy±Bevacizumab Versus Placebo Plus Chemotherapy±Bevacizumab for PD-L1 Positive (CPS≥1) Women With Recurrent, or Metastatic Cervical Cancer', 'Brief Summary': 'This study is a randomised, double-blind, placebo-controlled, multicentre phase 3 clinical study to evaluate the efficacy and safety of SG001 plus chemotherapy±bevacizumab versus placebo plus chemotherapy±bevacizumab, as first-line treatment, in patients with PD-L1 positive (CPS≥1), Recurrent or Metastatic Cervical Cancer. The study contains a Safety Lead-in Phase in which the safety and tolerability of SG001＋Chemotherapy±Bevacizumab will be assessed prior to the Phase 3 portion of the study.', 'Condition': 'Recurrent, or Metastatic Cervical Cancer With PD-L1 Positive (CPS≥1)', 'Detailed Description': 'The purpose of this study is to assess the efficacy and safety of SG001 plus one of four platinum-based chemotherapy regimens compared to the placebo plus one of four platinum-based chemotherapy regimens in the treatment of adult PD-L1 positive (CPS≥1) women with recurrent, or metastatic cervical cancer. Possible chemotherapy regimens include paclitaxel plus cisplatin with or without bevacizumab and paclitaxel plus carboplatin with or without bevacizumab. The study include two stages: the safety run-in phase and phase Ⅲ trail. Upon completion of the first stage study, the Safety Monitoring Committee (SMC) will decide whether to proceed directly to Phase Ⅲ study. The primary study hypotheses are that the combination of SG001 plus chemotherapy is superior to placebo plus chemotherapy with respect to: 1) Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1), 2) Overall Survival (OS).', 'Inclusion Criteria': "Inclusion Criteria: Age ≥ 18 and ≤ 70 on the day of signing informed consent and volunteered to participated in this study. Has histologically documented recurrent, or metastatic squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix which has not been treated with systemic chemotherapy and is not amenable to curative treatment (such as with surgery and/or radiation). (Safety Lead-in)Has a measurable lesion per RECIST 1.1 via CT or MRI. (Phase 3) Has a assessable lesion per RECIST 1.1 via CT or MRI. Has provided enough archival tumor tissue sample or willing to provide newly obtained core or excisional biopsy of a tumor lesion not previously irradiated for prospective determination of Programmed Cell Death-Ligand 1 (PD-L1) status prior to first dose. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 14 days prior to first dose. Has a predicted survival period ≥ 3 months assessed by investigators. Adverse reactions from the previous anti-tumor treatment have not yet recovered to ≤ level 1 based on CTCAE 5.0. Adequate organ function as defined below: Blood routine tests (No blood transfusions and hematopoietic stimulators have been used, and no drugs have been used to correct blood cell counts ): Absolute neutrophil count (ANC) ≥1.5×10^9/L; Platelets ≥100 ×10^9/L; Hemoglobin (HGB)≥9 g/dL; Serum biochemical indexs: Serum creatinine ≤1.5 × ULN or >1.5 × ULN with creatinine clearance (CCr) ≥ 60 mL/min; Serum total bilirubin (TBIL) ≤ 1.5 × ULN (Patients with Gilbert's syndrome can be up to 3 × ULN); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN or ≤5 X ULN for patients with liver metastases; Coagulation function: Activated partial thromboplastin time (APPT) and International Normalized Ratio (INR)≤1.5 × ULN (No anticoagulants or other drugs affecting clotting function have been used within 14 days prior to the first dose, except for patients requiring long-term anticoagulant therapy).", 'Exclusion Criteria': 'Exclusion Criteria: Active malignancy within 2 years prior to first dose of the investigational drug, except for cervical cancer studied in this trial and any locally curable tumor that has received radical therapy (e.g., resected basal or squamous cell skin cancer, superficial bladder cancer, cervical cancer in situ, breast cancer in situ, etc). History of primary immunodeficiency. History of active tuberculosis. Patients with any active autoimmune disease, except for patients with well-controlled type I diabetes, well-controlled hypothyroidism with hormone replacement therapy, skin diseases (such as vitiligo, psoriasis, or hair loss) without systemic treatment, or those who are not expected to relapse without external triggers. Serious cardiovascular disease within 6 months prior to the first dose, including but not limited to: stable angina with functional class III-IV; unstable angina or myocardial infarction; NYHA grade III-IV congestive heart failure; severe arrhythmias requiring drug therapy (congestive heart failure allowed if ventricular rate can be controlled; severe arrhythmias requiring drug therapy (congestive heart failure is allowed if the ventricular rate can be controlled). History of interstitial lung disease, or non-infectious pneumonitis requiring glucocorticoid therapy. Patients with active soft meningeal disease or poorly controlled brain metastasis. Prior therapy with any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways including anti-PD-1, anti-PD-L1, anti-PD-L2, anti CTLA-4, OX40 agonist, and anti-CD137, etc. Has received prior radiotherapy within 14 days prior to the first dose. Has received prior chemosensitizer within 14 days prior to the first dose. Presence of clinically significant hydronephros which cannot be relieved by ventriculostomy or ureteral stent placement assessed by investigator. Patients with un-controlled pleural effusion, pericardial effusion or seroperitoneum requiring repeated drainage. Has any active infection requiring systemic treatment by intravenous infusion within 14 days prior to the first dose. Has received systemic corticosteroids (at doses equivalent to or greater than 10 mg/day of prednisone) or other immunosuppressive drugs within 14 days prior to the first dose. Have received major surgery, open biopsy or traumatism within 28 days before the first dose, or planned to receive elective major surgery during the study period. planned to receive during the study period. Have received Chinese herbal medicine or Chinese patent medicine with anti-tumor activity within14 days prior to the first dose. History of organ transplant or allogenic haemopoietic stem cell transplantation. Patients should be excluded if they have a positive test for human immunodeficiency virus antibody (HIV-Ab) or treponema pallidum antibody (TP-Ab). Patients with positive Hepatitis B virus surface antigen (HBsAg) and/or hepatitis B virus core antibody (HBcAb) as well quantitative HBV-DNA above upper limit of normal value, and patients with positive hepatitis C virus antibody (HCV-Ab) as well quantitative HCV-RNA above upper limit of normal value, should also be excluded. Pregnant or lactating women; Or the blood pregnancy test of women at child-bearing age is positive during screening. History of severe allergic reactions and uncontrolled allergic asthma to all components of the monoclonal antibody formulation. Has a contraindication or hypersensitivity to any component of cisplatin, carboplatin, paclitaxel, or bevacizumab. Have participated other clinical trials and received related investigated drugs within 28 days prior to the first dose (counted from the date of the last treatment in the previous clinical trial, patients participated in the overall survival follow-up of the previous clinical trial can be accepted). Women of child-bearing potential (WOCBP) refuse to take reliable contraceptive methods from signing the informed consent form to 6 months after last dose of investigational drug. Not suitable for this study as determined by the investigator due to other reasons.'}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
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{'Arm - Disease - Biomarker': 'Include: PD-L1 positive'}
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{'Official Title': 'A Randomised, Double-blind, Placebo-controlled, Multicentre Phase Ш Clinical Study to Evaluate the Efficacy and Safety of First-line Treatment With SG001 Plus Chemotherapy±Bevacizumab Versus Placebo Plus Chemotherapy±Bevacizumab for PD-L1 Positive (CPS≥1) Women With Recurrent, or Metastatic Cervical Cancer', 'Brief Summary': 'This study is a randomised, double-blind, placebo-controlled, multicentre phase 3 clinical study to evaluate the efficacy and safety of SG001 plus chemotherapy±bevacizumab versus placebo plus chemotherapy±bevacizumab, as first-line treatment, in patients with PD-L1 positive (CPS≥1), Recurrent or Metastatic Cervical Cancer. The study contains a Safety Lead-in Phase in which the safety and tolerability of SG001＋Chemotherapy±Bevacizumab will be assessed prior to the Phase 3 portion of the study.', 'Condition': 'Recurrent, or Metastatic Cervical Cancer With PD-L1 Positive (CPS≥1)', 'Detailed Description': 'The purpose of this study is to assess the efficacy and safety of SG001 plus one of four platinum-based chemotherapy regimens compared to the placebo plus one of four platinum-based chemotherapy regimens in the treatment of adult PD-L1 positive (CPS≥1) women with recurrent, or metastatic cervical cancer. Possible chemotherapy regimens include paclitaxel plus cisplatin with or without bevacizumab and paclitaxel plus carboplatin with or without bevacizumab. The study include two stages: the safety run-in phase and phase Ⅲ trail. Upon completion of the first stage study, the Safety Monitoring Committee (SMC) will decide whether to proceed directly to Phase Ⅲ study. The primary study hypotheses are that the combination of SG001 plus chemotherapy is superior to placebo plus chemotherapy with respect to: 1) Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1), 2) Overall Survival (OS).', 'Inclusion Criteria': "Inclusion Criteria: Age ≥ 18 and ≤ 70 on the day of signing informed consent and volunteered to participated in this study. Has histologically documented recurrent, or metastatic squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix which has not been treated with systemic chemotherapy and is not amenable to curative treatment (such as with surgery and/or radiation). (Safety Lead-in)Has a measurable lesion per RECIST 1.1 via CT or MRI. (Phase 3) Has a assessable lesion per RECIST 1.1 via CT or MRI. Has provided enough archival tumor tissue sample or willing to provide newly obtained core or excisional biopsy of a tumor lesion not previously irradiated for prospective determination of Programmed Cell Death-Ligand 1 (PD-L1) status prior to first dose. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 14 days prior to first dose. Has a predicted survival period ≥ 3 months assessed by investigators. Adverse reactions from the previous anti-tumor treatment have not yet recovered to ≤ level 1 based on CTCAE 5.0. Adequate organ function as defined below: Blood routine tests (No blood transfusions and hematopoietic stimulators have been used, and no drugs have been used to correct blood cell counts ): Absolute neutrophil count (ANC) ≥1.5×10^9/L; Platelets ≥100 ×10^9/L; Hemoglobin (HGB)≥9 g/dL; Serum biochemical indexs: Serum creatinine ≤1.5 × ULN or >1.5 × ULN with creatinine clearance (CCr) ≥ 60 mL/min; Serum total bilirubin (TBIL) ≤ 1.5 × ULN (Patients with Gilbert's syndrome can be up to 3 × ULN); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN or ≤5 X ULN for patients with liver metastases; Coagulation function: Activated partial thromboplastin time (APPT) and International Normalized Ratio (INR)≤1.5 × ULN (No anticoagulants or other drugs affecting clotting function have been used within 14 days prior to the first dose, except for patients requiring long-term anticoagulant therapy).", 'Exclusion Criteria': 'Exclusion Criteria: Active malignancy within 2 years prior to first dose of the investigational drug, except for cervical cancer studied in this trial and any locally curable tumor that has received radical therapy (e.g., resected basal or squamous cell skin cancer, superficial bladder cancer, cervical cancer in situ, breast cancer in situ, etc). History of primary immunodeficiency. History of active tuberculosis. Patients with any active autoimmune disease, except for patients with well-controlled type I diabetes, well-controlled hypothyroidism with hormone replacement therapy, skin diseases (such as vitiligo, psoriasis, or hair loss) without systemic treatment, or those who are not expected to relapse without external triggers. Serious cardiovascular disease within 6 months prior to the first dose, including but not limited to: stable angina with functional class III-IV; unstable angina or myocardial infarction; NYHA grade III-IV congestive heart failure; severe arrhythmias requiring drug therapy (congestive heart failure allowed if ventricular rate can be controlled; severe arrhythmias requiring drug therapy (congestive heart failure is allowed if the ventricular rate can be controlled). History of interstitial lung disease, or non-infectious pneumonitis requiring glucocorticoid therapy. Patients with active soft meningeal disease or poorly controlled brain metastasis. Prior therapy with any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways including anti-PD-1, anti-PD-L1, anti-PD-L2, anti CTLA-4, OX40 agonist, and anti-CD137, etc. Has received prior radiotherapy within 14 days prior to the first dose. Has received prior chemosensitizer within 14 days prior to the first dose. Presence of clinically significant hydronephros which cannot be relieved by ventriculostomy or ureteral stent placement assessed by investigator. Patients with un-controlled pleural effusion, pericardial effusion or seroperitoneum requiring repeated drainage. Has any active infection requiring systemic treatment by intravenous infusion within 14 days prior to the first dose. Has received systemic corticosteroids (at doses equivalent to or greater than 10 mg/day of prednisone) or other immunosuppressive drugs within 14 days prior to the first dose. Have received major surgery, open biopsy or traumatism within 28 days before the first dose, or planned to receive elective major surgery during the study period. planned to receive during the study period. Have received Chinese herbal medicine or Chinese patent medicine with anti-tumor activity within14 days prior to the first dose. History of organ transplant or allogenic haemopoietic stem cell transplantation. Patients should be excluded if they have a positive test for human immunodeficiency virus antibody (HIV-Ab) or treponema pallidum antibody (TP-Ab). Patients with positive Hepatitis B virus surface antigen (HBsAg) and/or hepatitis B virus core antibody (HBcAb) as well quantitative HBV-DNA above upper limit of normal value, and patients with positive hepatitis C virus antibody (HCV-Ab) as well quantitative HCV-RNA above upper limit of normal value, should also be excluded. Pregnant or lactating women; Or the blood pregnancy test of women at child-bearing age is positive during screening. History of severe allergic reactions and uncontrolled allergic asthma to all components of the monoclonal antibody formulation. Has a contraindication or hypersensitivity to any component of cisplatin, carboplatin, paclitaxel, or bevacizumab. Have participated other clinical trials and received related investigated drugs within 28 days prior to the first dose (counted from the date of the last treatment in the previous clinical trial, patients participated in the overall survival follow-up of the previous clinical trial can be accepted). Women of child-bearing potential (WOCBP) refuse to take reliable contraceptive methods from signing the informed consent form to 6 months after last dose of investigational drug. Not suitable for this study as determined by the investigator due to other reasons.'}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
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{'Arm - Disease - Biomarker': 'Include: PD-L1 positive'}
|
{'Official Title': 'An Open Label, Single-Arm, Multi-center Phase Ib/II Study to Evaluate the Safety and Efficacy of INCB054828 in Combination With Paclitaxel as a Second Line Treatment in Recurrent/Advanced Gastric Cancer With FGFs/FGFRs Genetic Aberration.', 'Brief Summary': 'This study was conducted as a second-line treatment of recurrent / progressive gastric cancer patients with FGFs / FGFRs genetic mutations in the Ib / II clinical trial. The maximum maximal tolerated dose (MTD) and 2-phase recommended dose in combination with INCB054828 and paclitaxel (recommended phase II dose, RP2D), and evaluate the safety and clinical efficacy of this combination therapy. This study consists of two steps: Phase 1 is a dose escalation study to determine the maximum tolerated dose and 2-phase recommended dose of weekly paclitaxel and INCB054828 combination therapy, and Phase 2 is the dose escalation study in combination with INCB054828 and paclitaxel Assess safety and tolerability and identify antitumor effects in stomach cancer with FGFs / FGFRs genetic mutations.', 'Condition': 'Fibroblast Growth Factors (FGFs)/Fibroblast Growth Factor Receptors (FGFRs) Genetic Aberration Gastric Cancer, INCB054828, Paclitaxel', 'Detailed Description': 'phase> - Approximately 3-12 patients will be enrolled. The dose escalation will be three patients registered for each cohort until the first dose-limiting toxicity appears during the four weeks of treatment and observation. 13.5mg, once a day begins to take. The paclitaxel is administered once a week for three consecutive weeks and then for one week, followed by a total of four weeks in one cycle. phase> Phase 2 studies will be extended to a total of 30 patients with a two-phase recommended dose. Patients will be treated until the time of disease progression, intolerable toxicity, rejection of the patient, or withdrawal of consent. In its pre-screening phase, its next generation sequencing (NGS) is performed. Patients with FGFs / FGFRs genetic abnormalities may be enrolled in this study. If a patient has multiple genetic abnormalities, he or she will first be enrolled in a treatment group that targets a rare genetic abnormality. Registered patients will be treated on a continuous basis every four weeks.', 'Inclusion Criteria': 'Inclusion Criteria: Patients who agreed in writing to the clinical study consent Histologically or cytologically confirmed advanced gastric adenocarcinoma. Patients must have experienced objective radiological or disease progress with evidence during or after primary therapy with fluoropyrimidine and platinum. FGFs / FGFRs have genetic variation on NGS. Patients whose life expectancy is at least 3 months If the Eastern Cooperative Oncology Group (ECOG) is 0 or 1 Measurable or assessable lesion based on RECIST 1.1 scale Must be swallowed, should be able to take oral medication Possible long-term function to receive chemotherapy. Patients receiving anti-HER2 therapy for HER2 negative or HER2-positive primary treatment', 'Exclusion Criteria': 'Exclusion Criteria: When chemotherapy exceeded the first treatment Patients with multiple cancers Severe hypersensitivity reactions to anti-FGFR2 agents either now or in the past Patients with endocrine metabolic syndrome or history of calcium-phosphate homeostasis Patients with ectopic neoplasm or history of soft tissue, kidney, large intestine, heart, or abdomen Corneal lesions such as bullous keratopathy, corneal erosion, corneal erosion, corneal ulcer, corneal inflammation and keratoconjunctivitis were confirmed by ophthalmic examination Patients with metastasis to the brain or meninges. However, patients who do not have symptoms and do not need treatment can register. Clinically significant digestive system problems that can cause abnormalities in taking or absorbing clinical drugs Patients with uncontrollable or significant cardiovascular disease Patients with systemic infections requiring treatment Patients who were exposed to paclitaxel at or before the taxane If you undergo major surgery within 28 days before enrollment for this trial Patients who received radiotherapy for gastric cancer within 28 days prior to enrollment for this trial. However, the investigation of bone turnover was conducted within 14 days before the registration for this trial If you received general chemotherapy within 14 days of enrollment for this trial Patients who are positive for human immunodeficiency virus (HIV-1) antibody test, HBsAg results positive, HBV viral load greater than 2000 IU / ml (104 copies / ml), or HCV antibody test positive Patients who are pregnant, lactating, or are likely to be pregnant Anemia and hair loss are excluded if previous chemotherapy treatment has toxicity that is not recovered below grade 2. Patients who are judged to have lost their ability to cope with dementia or other comorbid conditions Other Patients who the examiner or the examiner deemed inappropriate for the clinical trial.'}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: FGFs/FGFRs Genetic Aberration'}
|
{'Official Title': 'A Randomised, Multicentre, Double-blind, Placebo-controlled, Phase III Study of First-line Carboplatin and Paclitaxel in Combination With Durvalumab, Followed by Maintenance Durvalumab With or Without Olaparib in Patients With Newly Diagnosed Advanced or Recurrent Endometrial Cancer (DUO-E)', 'Brief Summary': 'A study to assess the efficacy and safety of durvalumab in combination with platinum-based chemotherapy (paclitaxel + carboplatin) followed by maintenance durvalumab with or without olaparib for patients with newly diagnosed advanced or recurrent endometrial cancer.', 'Condition': 'Endometrial Neoplasms', 'Detailed Description': 'This Phase III study will assess the efficacy and safety of durvalumab in combination with platinum-based chemotherapy (paclitaxel + carboplatin) followed by maintenance durvalumab with or without olaparib for patients with newly diagnosed advanced or recurrent endometrial cancer. Target patient population: Adult female patients with histologically confirmed diagnosis of epithelial endometrial carcinoma (excluding sarcomas): newly diagnosed Stage III, newly diagnosed Stage IV, or recurrent endometrial cancer', 'Inclusion Criteria': 'Inclusion Criteria: Age ≥18 years at the time of screening and female. Histologically confirmed diagnosis of epithelial endometrial carcinoma. All histologies, including carcinosarcomas, will be allowed. Sarcomas will not be allowed. Patient must have endometrial cancer in one of the following categories: Newly diagnosed Stage III disease (measurable disease per RECIST 1.1 following surgery or diagnostic biopsy), Newly diagnosed Stage IV disease (with or without disease following surgery or diagnostic biopsy) Recurrence of disease (measurable or non-measurable disease per RECIST 1.1) where the potential for cure by surgery alone or in combination is poor. Naïve to first line systemic anti-cancer treatment. For patients with recurrent disease only, prior systemic anti-cancer treatment is allowed only if it was administered in the adjuvant setting and there is at least 12 months from date of last dose of systemic anti-cancer treatment administered to date of subsequent relapse FPPE tumor sample must be available for MMR evaluation. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days of starting study treatment.', 'Exclusion Criteria': 'Exclusion Criteria: History of leptomeningeal carcinomatosis. Brain metastases or spinal cord compression. Prior treatment with PARP inhibitors. Any prior exposure to immune-mediated therapy, including (but not limited to) other anti CTLA-4, anti-PD-1, anti-PD-L1, or anti-programmed-cell-death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines.'}
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Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: MMR evaluation.'}
|
{'Official Title': 'A Randomised, Multicentre, Double-blind, Placebo-controlled, Phase III Study of First-line Carboplatin and Paclitaxel in Combination With Durvalumab, Followed by Maintenance Durvalumab With or Without Olaparib in Patients With Newly Diagnosed Advanced or Recurrent Endometrial Cancer (DUO-E)', 'Brief Summary': 'A study to assess the efficacy and safety of durvalumab in combination with platinum-based chemotherapy (paclitaxel + carboplatin) followed by maintenance durvalumab with or without olaparib for patients with newly diagnosed advanced or recurrent endometrial cancer.', 'Condition': 'Endometrial Neoplasms', 'Detailed Description': 'This Phase III study will assess the efficacy and safety of durvalumab in combination with platinum-based chemotherapy (paclitaxel + carboplatin) followed by maintenance durvalumab with or without olaparib for patients with newly diagnosed advanced or recurrent endometrial cancer. Target patient population: Adult female patients with histologically confirmed diagnosis of epithelial endometrial carcinoma (excluding sarcomas): newly diagnosed Stage III, newly diagnosed Stage IV, or recurrent endometrial cancer', 'Inclusion Criteria': 'Inclusion Criteria: Age ≥18 years at the time of screening and female. Histologically confirmed diagnosis of epithelial endometrial carcinoma. All histologies, including carcinosarcomas, will be allowed. Sarcomas will not be allowed. Patient must have endometrial cancer in one of the following categories: Newly diagnosed Stage III disease (measurable disease per RECIST 1.1 following surgery or diagnostic biopsy), Newly diagnosed Stage IV disease (with or without disease following surgery or diagnostic biopsy) Recurrence of disease (measurable or non-measurable disease per RECIST 1.1) where the potential for cure by surgery alone or in combination is poor. Naïve to first line systemic anti-cancer treatment. For patients with recurrent disease only, prior systemic anti-cancer treatment is allowed only if it was administered in the adjuvant setting and there is at least 12 months from date of last dose of systemic anti-cancer treatment administered to date of subsequent relapse FPPE tumor sample must be available for MMR evaluation. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days of starting study treatment.', 'Exclusion Criteria': 'Exclusion Criteria: History of leptomeningeal carcinomatosis. Brain metastases or spinal cord compression. Prior treatment with PARP inhibitors. Any prior exposure to immune-mediated therapy, including (but not limited to) other anti CTLA-4, anti-PD-1, anti-PD-L1, or anti-programmed-cell-death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines.'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: MMR evaluation.'}
|
{'Official Title': 'A Randomised, Multicentre, Double-blind, Placebo-controlled, Phase III Study of First-line Carboplatin and Paclitaxel in Combination With Durvalumab, Followed by Maintenance Durvalumab With or Without Olaparib in Patients With Newly Diagnosed Advanced or Recurrent Endometrial Cancer (DUO-E)', 'Brief Summary': 'A study to assess the efficacy and safety of durvalumab in combination with platinum-based chemotherapy (paclitaxel + carboplatin) followed by maintenance durvalumab with or without olaparib for patients with newly diagnosed advanced or recurrent endometrial cancer.', 'Condition': 'Endometrial Neoplasms', 'Detailed Description': 'This Phase III study will assess the efficacy and safety of durvalumab in combination with platinum-based chemotherapy (paclitaxel + carboplatin) followed by maintenance durvalumab with or without olaparib for patients with newly diagnosed advanced or recurrent endometrial cancer. Target patient population: Adult female patients with histologically confirmed diagnosis of epithelial endometrial carcinoma (excluding sarcomas): newly diagnosed Stage III, newly diagnosed Stage IV, or recurrent endometrial cancer', 'Inclusion Criteria': 'Inclusion Criteria: Age ≥18 years at the time of screening and female. Histologically confirmed diagnosis of epithelial endometrial carcinoma. All histologies, including carcinosarcomas, will be allowed. Sarcomas will not be allowed. Patient must have endometrial cancer in one of the following categories: Newly diagnosed Stage III disease (measurable disease per RECIST 1.1 following surgery or diagnostic biopsy), Newly diagnosed Stage IV disease (with or without disease following surgery or diagnostic biopsy) Recurrence of disease (measurable or non-measurable disease per RECIST 1.1) where the potential for cure by surgery alone or in combination is poor. Naïve to first line systemic anti-cancer treatment. For patients with recurrent disease only, prior systemic anti-cancer treatment is allowed only if it was administered in the adjuvant setting and there is at least 12 months from date of last dose of systemic anti-cancer treatment administered to date of subsequent relapse FPPE tumor sample must be available for MMR evaluation. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days of starting study treatment.', 'Exclusion Criteria': 'Exclusion Criteria: History of leptomeningeal carcinomatosis. Brain metastases or spinal cord compression. Prior treatment with PARP inhibitors. Any prior exposure to immune-mediated therapy, including (but not limited to) other anti CTLA-4, anti-PD-1, anti-PD-L1, or anti-programmed-cell-death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines.'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: MMR evaluation.'}
|
{'Official Title': 'A Phase 2/3, Multicenter Randomized Study of Rituximab-Gemcitabine-Dexamethasone-Platinum (R-GDP) With or Without Selinexor in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma (RR DLBCL)', 'Brief Summary': 'The purpose of this Phase 2/3 study is to evaluate efficacy and safety of the combination of selinexor and R-GDP (SR-GDP) in patients with RR DLBCL who are not intended to receive hematopoetic stem cell transplantation (HSCT) or chimeric antigen receptor T cell (CAR-T) therapy. This study consists of 3 arms each in Phase 2 and 3. Phase 2 portion of the study will assess the two doses of selinexor (40 milligram [mg] or 60 mg) in combination with R-GDP, for up to 6 cycles (21-day per cycle), followed by 60 mg selinexor single agent continuous therapy for those who have reached a partial or complete response. Phase 3 portion of the study will evaluate the selected dose of SR-GDP (identified in Phase 2) versus standard R-GDP + matching placebo, for up to 6 cycles (21-day per cycle), followed by placebo or 60 mg selinexor single agent continuous therapy for those who have reached partial or complete response.', 'Condition': 'Relapsed/Refractory Diffuse Large B-cell Lymphoma', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Have pathologically confirmed de novo DLBCL or DLBCL transformed from previously diagnosed indolent lymphoma (e.g., follicular lymphoma). Patient with high-grade lymphoma with c-MYC, Bcl2 and/or Bcl6 rearrangements are eligible (only for Phase 2). (Documentation to be provided). Have received at least 1 but no more than 3 prior lines of systemic therapy for the treatment of DLBCL with relapsed or refractory disease following their most recent regimen. Salvage chemoimmunotherapy followed by stem cell transplantation will be considered as 1 line of systemic therapy. Maintenance therapy will not be counted as a separate line of systemic therapy. Radiation with curative intent for localized DLBCL will not be counted as 1 line of systemic therapy. Positron emission tomography (PET) positive measurable disease with at least 1 node having the longest diameter (LDi) greater than (>) 1.5 centimeter (cm) or 1 extranodal lesion with LDi >1 cm (per the Lugano Criteria 2014). The Deauville 5-point scale (D5PS) score assessed on the FDG PET/CT should be between 3 to 5. Not intended for HSCT or CAR-T cell therapy based on objective clinical criteria determined by the treating physician. Patients who cannot receive HSCT due to active disease are allowed on study (up to approximately 15 percent [%] of patients enrolled in each Phase). Documentation on lack of intention to proceed to receive HSCT or CAR-T therapy must be provided by the treating physician. Adequate bone marrow function at screening, defined as: Absolute neutrophil count (ANC) ≥1*10^9 per liter (/L). Platelet count ≥100*10^9/L (without platelet transfusion less than [<] 14 days prior to Cycle 1 Day 1 [C1D1]). Hemoglobin ≥8.5 gram per deciliter (g/dL) (without red blood cell transfusion <14 days prior to C1D1). Circulating lymphocytes less than or equal to (≤) 50*10^9/L. Adequate liver and kidney function, defined as: Aspartate transaminase (AST) or alanine transaminase (ALT) ≤2.5*upper limit of normal (ULN), or ≤5*ULN in cases with known lymphoma involvement in the liver. Serum total bilirubin ≤2*ULN, or ≤5*ULN if due to Gilbert syndrome or in cases with known lymphoma involvement in the liver. Calculated creatinine clearance (CrCl) ≥30 milliliter per minute (mL/min) based on Cockcroft-Gault formula. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2. An estimated life expectancy of >3 months at Screening. Patients with primary refractory DLBCL defined as no response or relapse within 6 months after ending first-line treatment, will be allowed in the study. Agree to highly effective contraception during the duration of the study with contraception use continuing for 12 months after the last dose of study treatment Female patients of childbearing potential must have a negative serum pregnancy test at Screening and agree to use highly effective methods of contraception throughout the study and for 12 months following the last dose of study treatment (except patients with Non-Childbearing potential: Age >50 years and naturally amenorrhoeic for >1 year, or previous bilateral salpingo-oophorectomy, or hysterectomy). Male patients who are sexually active must use highly effective methods of contraception throughout the study and for 12 months following the last dose of study treatment. Male patients must agree not to donate sperm during the study treatment period and for 12 months following the last dose of study treatment.', 'Exclusion Criteria': "Exclusion Criteria: DLBCL with mucosa-associated lymphoid tissue (MALT) lymphoma, composite lymphoma (Hodgkin's lymphoma + non-Hodgkin's lymphoma [NHL]), DLBCL transformed from diseases other than indolent NHL; primary mediastinal (thymic) large B-cell lymphoma (PMBL); T-cell rich large B-cell lymphoma. Previous treatment with selinexor or other XPO1 inhibitors. Contraindication to any drug contained in the combination therapy regimen (SR-GDP). Known active central nervous system or meningeal involvement by DLBCL at time of Screening. Use of any standard or experimental anti-DLBCL therapy (including nonpalliative radiation, chemotherapy, immunotherapy, radio-immunotherapy, or any other anticancer therapy) <21 days prior to C1D1 (prednisone <30 mg or equivalent is permitted; palliative radiation is permitted only if on non-target lesions). Any AE, by C1D1, which has not recovered to Grade ≤1 (Common Terminology Criteria for Adverse Events [CTCAE], v.5.0), or returned to baseline, related to the previous DLBCL therapy, except hematological abnormalities (as specified in the inclusion criteria) and alopecia. Major surgery <14 days of Cycle 1 Day 1. Hematopoietic stem cell transplantation/CAR-T therapy as follows: Autologous stem cell transplant (SCT) <100 days or allogeneic-SCT <180 days prior to C1D1 Active graft-versus-host disease (GVHD) after allogeneic SCT (or cannot discontinue GVHD treatment or prophylaxis) CAR-T cell infusion <90 days prior to Cycle 1 Neuropathy Grade ≥2 (CTCAE, v.5.0). Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the patient's safety, or being compliant with the study procedures. Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within 7 days prior to first dose of study treatment; however, prophylactic use of these agents is acceptable (including parenteral). Patient with active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infections: Patient with active HBV are allowed if antiviral therapy for hepatitis B has been given for >8 weeks and viral load is <100 International units (IU)/mL prior to first dose of study treatment. Patients with known history of HCV or found to be HCV antibody positive on screening, are allowed if there is documentation of negative viral load per institutional standard. Patients with HIV are allowed if they have a negative viral load per institutional standard, and no history of acquired immune deficiency syndrome (AIDS)-defining opportunistic infections in the last year. Inability to swallow tablets, malabsorption syndrome, or any other gastrointestinal (GI) disease or dysfunction that could interfere with absorption of study treatment. Breastfeeding or pregnant women. Inability or unwillingness to sign an informed consent form (ICF). In the opinion of the Investigator, patient who are significantly below their ideal body weight. Patients who received a live attenuated vaccine within prior 28 days of the first dose of study treatment."}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: c-MYC, Bcl2 and/or Bcl6 rearrangements'}
|
{'Official Title': 'A Phase 2/3, Multicenter Randomized Study of Rituximab-Gemcitabine-Dexamethasone-Platinum (R-GDP) With or Without Selinexor in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma (RR DLBCL)', 'Brief Summary': 'The purpose of this Phase 2/3 study is to evaluate efficacy and safety of the combination of selinexor and R-GDP (SR-GDP) in patients with RR DLBCL who are not intended to receive hematopoetic stem cell transplantation (HSCT) or chimeric antigen receptor T cell (CAR-T) therapy. This study consists of 3 arms each in Phase 2 and 3. Phase 2 portion of the study will assess the two doses of selinexor (40 milligram [mg] or 60 mg) in combination with R-GDP, for up to 6 cycles (21-day per cycle), followed by 60 mg selinexor single agent continuous therapy for those who have reached a partial or complete response. Phase 3 portion of the study will evaluate the selected dose of SR-GDP (identified in Phase 2) versus standard R-GDP + matching placebo, for up to 6 cycles (21-day per cycle), followed by placebo or 60 mg selinexor single agent continuous therapy for those who have reached partial or complete response.', 'Condition': 'Relapsed/Refractory Diffuse Large B-cell Lymphoma', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Have pathologically confirmed de novo DLBCL or DLBCL transformed from previously diagnosed indolent lymphoma (e.g., follicular lymphoma). Patient with high-grade lymphoma with c-MYC, Bcl2 and/or Bcl6 rearrangements are eligible (only for Phase 2). (Documentation to be provided). Have received at least 1 but no more than 3 prior lines of systemic therapy for the treatment of DLBCL with relapsed or refractory disease following their most recent regimen. Salvage chemoimmunotherapy followed by stem cell transplantation will be considered as 1 line of systemic therapy. Maintenance therapy will not be counted as a separate line of systemic therapy. Radiation with curative intent for localized DLBCL will not be counted as 1 line of systemic therapy. Positron emission tomography (PET) positive measurable disease with at least 1 node having the longest diameter (LDi) greater than (>) 1.5 centimeter (cm) or 1 extranodal lesion with LDi >1 cm (per the Lugano Criteria 2014). The Deauville 5-point scale (D5PS) score assessed on the FDG PET/CT should be between 3 to 5. Not intended for HSCT or CAR-T cell therapy based on objective clinical criteria determined by the treating physician. Patients who cannot receive HSCT due to active disease are allowed on study (up to approximately 15 percent [%] of patients enrolled in each Phase). Documentation on lack of intention to proceed to receive HSCT or CAR-T therapy must be provided by the treating physician. Adequate bone marrow function at screening, defined as: Absolute neutrophil count (ANC) ≥1*10^9 per liter (/L). Platelet count ≥100*10^9/L (without platelet transfusion less than [<] 14 days prior to Cycle 1 Day 1 [C1D1]). Hemoglobin ≥8.5 gram per deciliter (g/dL) (without red blood cell transfusion <14 days prior to C1D1). Circulating lymphocytes less than or equal to (≤) 50*10^9/L. Adequate liver and kidney function, defined as: Aspartate transaminase (AST) or alanine transaminase (ALT) ≤2.5*upper limit of normal (ULN), or ≤5*ULN in cases with known lymphoma involvement in the liver. Serum total bilirubin ≤2*ULN, or ≤5*ULN if due to Gilbert syndrome or in cases with known lymphoma involvement in the liver. Calculated creatinine clearance (CrCl) ≥30 milliliter per minute (mL/min) based on Cockcroft-Gault formula. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2. An estimated life expectancy of >3 months at Screening. Patients with primary refractory DLBCL defined as no response or relapse within 6 months after ending first-line treatment, will be allowed in the study. Agree to highly effective contraception during the duration of the study with contraception use continuing for 12 months after the last dose of study treatment Female patients of childbearing potential must have a negative serum pregnancy test at Screening and agree to use highly effective methods of contraception throughout the study and for 12 months following the last dose of study treatment (except patients with Non-Childbearing potential: Age >50 years and naturally amenorrhoeic for >1 year, or previous bilateral salpingo-oophorectomy, or hysterectomy). Male patients who are sexually active must use highly effective methods of contraception throughout the study and for 12 months following the last dose of study treatment. Male patients must agree not to donate sperm during the study treatment period and for 12 months following the last dose of study treatment.', 'Exclusion Criteria': "Exclusion Criteria: DLBCL with mucosa-associated lymphoid tissue (MALT) lymphoma, composite lymphoma (Hodgkin's lymphoma + non-Hodgkin's lymphoma [NHL]), DLBCL transformed from diseases other than indolent NHL; primary mediastinal (thymic) large B-cell lymphoma (PMBL); T-cell rich large B-cell lymphoma. Previous treatment with selinexor or other XPO1 inhibitors. Contraindication to any drug contained in the combination therapy regimen (SR-GDP). Known active central nervous system or meningeal involvement by DLBCL at time of Screening. Use of any standard or experimental anti-DLBCL therapy (including nonpalliative radiation, chemotherapy, immunotherapy, radio-immunotherapy, or any other anticancer therapy) <21 days prior to C1D1 (prednisone <30 mg or equivalent is permitted; palliative radiation is permitted only if on non-target lesions). Any AE, by C1D1, which has not recovered to Grade ≤1 (Common Terminology Criteria for Adverse Events [CTCAE], v.5.0), or returned to baseline, related to the previous DLBCL therapy, except hematological abnormalities (as specified in the inclusion criteria) and alopecia. Major surgery <14 days of Cycle 1 Day 1. Hematopoietic stem cell transplantation/CAR-T therapy as follows: Autologous stem cell transplant (SCT) <100 days or allogeneic-SCT <180 days prior to C1D1 Active graft-versus-host disease (GVHD) after allogeneic SCT (or cannot discontinue GVHD treatment or prophylaxis) CAR-T cell infusion <90 days prior to Cycle 1 Neuropathy Grade ≥2 (CTCAE, v.5.0). Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the patient's safety, or being compliant with the study procedures. Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within 7 days prior to first dose of study treatment; however, prophylactic use of these agents is acceptable (including parenteral). Patient with active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infections: Patient with active HBV are allowed if antiviral therapy for hepatitis B has been given for >8 weeks and viral load is <100 International units (IU)/mL prior to first dose of study treatment. Patients with known history of HCV or found to be HCV antibody positive on screening, are allowed if there is documentation of negative viral load per institutional standard. Patients with HIV are allowed if they have a negative viral load per institutional standard, and no history of acquired immune deficiency syndrome (AIDS)-defining opportunistic infections in the last year. Inability to swallow tablets, malabsorption syndrome, or any other gastrointestinal (GI) disease or dysfunction that could interfere with absorption of study treatment. Breastfeeding or pregnant women. Inability or unwillingness to sign an informed consent form (ICF). In the opinion of the Investigator, patient who are significantly below their ideal body weight. Patients who received a live attenuated vaccine within prior 28 days of the first dose of study treatment."}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: c-MYC, Bcl2 and/or Bcl6 rearrangements'}
|
{'Official Title': 'A Phase 2/3, Multicenter Randomized Study of Rituximab-Gemcitabine-Dexamethasone-Platinum (R-GDP) With or Without Selinexor in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma (RR DLBCL)', 'Brief Summary': 'The purpose of this Phase 2/3 study is to evaluate efficacy and safety of the combination of selinexor and R-GDP (SR-GDP) in patients with RR DLBCL who are not intended to receive hematopoetic stem cell transplantation (HSCT) or chimeric antigen receptor T cell (CAR-T) therapy. This study consists of 3 arms each in Phase 2 and 3. Phase 2 portion of the study will assess the two doses of selinexor (40 milligram [mg] or 60 mg) in combination with R-GDP, for up to 6 cycles (21-day per cycle), followed by 60 mg selinexor single agent continuous therapy for those who have reached a partial or complete response. Phase 3 portion of the study will evaluate the selected dose of SR-GDP (identified in Phase 2) versus standard R-GDP + matching placebo, for up to 6 cycles (21-day per cycle), followed by placebo or 60 mg selinexor single agent continuous therapy for those who have reached partial or complete response.', 'Condition': 'Relapsed/Refractory Diffuse Large B-cell Lymphoma', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Have pathologically confirmed de novo DLBCL or DLBCL transformed from previously diagnosed indolent lymphoma (e.g., follicular lymphoma). Patient with high-grade lymphoma with c-MYC, Bcl2 and/or Bcl6 rearrangements are eligible (only for Phase 2). (Documentation to be provided). Have received at least 1 but no more than 3 prior lines of systemic therapy for the treatment of DLBCL with relapsed or refractory disease following their most recent regimen. Salvage chemoimmunotherapy followed by stem cell transplantation will be considered as 1 line of systemic therapy. Maintenance therapy will not be counted as a separate line of systemic therapy. Radiation with curative intent for localized DLBCL will not be counted as 1 line of systemic therapy. Positron emission tomography (PET) positive measurable disease with at least 1 node having the longest diameter (LDi) greater than (>) 1.5 centimeter (cm) or 1 extranodal lesion with LDi >1 cm (per the Lugano Criteria 2014). The Deauville 5-point scale (D5PS) score assessed on the FDG PET/CT should be between 3 to 5. Not intended for HSCT or CAR-T cell therapy based on objective clinical criteria determined by the treating physician. Patients who cannot receive HSCT due to active disease are allowed on study (up to approximately 15 percent [%] of patients enrolled in each Phase). Documentation on lack of intention to proceed to receive HSCT or CAR-T therapy must be provided by the treating physician. Adequate bone marrow function at screening, defined as: Absolute neutrophil count (ANC) ≥1*10^9 per liter (/L). Platelet count ≥100*10^9/L (without platelet transfusion less than [<] 14 days prior to Cycle 1 Day 1 [C1D1]). Hemoglobin ≥8.5 gram per deciliter (g/dL) (without red blood cell transfusion <14 days prior to C1D1). Circulating lymphocytes less than or equal to (≤) 50*10^9/L. Adequate liver and kidney function, defined as: Aspartate transaminase (AST) or alanine transaminase (ALT) ≤2.5*upper limit of normal (ULN), or ≤5*ULN in cases with known lymphoma involvement in the liver. Serum total bilirubin ≤2*ULN, or ≤5*ULN if due to Gilbert syndrome or in cases with known lymphoma involvement in the liver. Calculated creatinine clearance (CrCl) ≥30 milliliter per minute (mL/min) based on Cockcroft-Gault formula. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2. An estimated life expectancy of >3 months at Screening. Patients with primary refractory DLBCL defined as no response or relapse within 6 months after ending first-line treatment, will be allowed in the study. Agree to highly effective contraception during the duration of the study with contraception use continuing for 12 months after the last dose of study treatment Female patients of childbearing potential must have a negative serum pregnancy test at Screening and agree to use highly effective methods of contraception throughout the study and for 12 months following the last dose of study treatment (except patients with Non-Childbearing potential: Age >50 years and naturally amenorrhoeic for >1 year, or previous bilateral salpingo-oophorectomy, or hysterectomy). Male patients who are sexually active must use highly effective methods of contraception throughout the study and for 12 months following the last dose of study treatment. Male patients must agree not to donate sperm during the study treatment period and for 12 months following the last dose of study treatment.', 'Exclusion Criteria': "Exclusion Criteria: DLBCL with mucosa-associated lymphoid tissue (MALT) lymphoma, composite lymphoma (Hodgkin's lymphoma + non-Hodgkin's lymphoma [NHL]), DLBCL transformed from diseases other than indolent NHL; primary mediastinal (thymic) large B-cell lymphoma (PMBL); T-cell rich large B-cell lymphoma. Previous treatment with selinexor or other XPO1 inhibitors. Contraindication to any drug contained in the combination therapy regimen (SR-GDP). Known active central nervous system or meningeal involvement by DLBCL at time of Screening. Use of any standard or experimental anti-DLBCL therapy (including nonpalliative radiation, chemotherapy, immunotherapy, radio-immunotherapy, or any other anticancer therapy) <21 days prior to C1D1 (prednisone <30 mg or equivalent is permitted; palliative radiation is permitted only if on non-target lesions). Any AE, by C1D1, which has not recovered to Grade ≤1 (Common Terminology Criteria for Adverse Events [CTCAE], v.5.0), or returned to baseline, related to the previous DLBCL therapy, except hematological abnormalities (as specified in the inclusion criteria) and alopecia. Major surgery <14 days of Cycle 1 Day 1. Hematopoietic stem cell transplantation/CAR-T therapy as follows: Autologous stem cell transplant (SCT) <100 days or allogeneic-SCT <180 days prior to C1D1 Active graft-versus-host disease (GVHD) after allogeneic SCT (or cannot discontinue GVHD treatment or prophylaxis) CAR-T cell infusion <90 days prior to Cycle 1 Neuropathy Grade ≥2 (CTCAE, v.5.0). Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the patient's safety, or being compliant with the study procedures. Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within 7 days prior to first dose of study treatment; however, prophylactic use of these agents is acceptable (including parenteral). Patient with active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infections: Patient with active HBV are allowed if antiviral therapy for hepatitis B has been given for >8 weeks and viral load is <100 International units (IU)/mL prior to first dose of study treatment. Patients with known history of HCV or found to be HCV antibody positive on screening, are allowed if there is documentation of negative viral load per institutional standard. Patients with HIV are allowed if they have a negative viral load per institutional standard, and no history of acquired immune deficiency syndrome (AIDS)-defining opportunistic infections in the last year. Inability to swallow tablets, malabsorption syndrome, or any other gastrointestinal (GI) disease or dysfunction that could interfere with absorption of study treatment. Breastfeeding or pregnant women. Inability or unwillingness to sign an informed consent form (ICF). In the opinion of the Investigator, patient who are significantly below their ideal body weight. Patients who received a live attenuated vaccine within prior 28 days of the first dose of study treatment."}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: c-MYC, Bcl2 and/or Bcl6 rearrangements'}
|
{'Official Title': 'A Phase 2/3, Multicenter Randomized Study of Rituximab-Gemcitabine-Dexamethasone-Platinum (R-GDP) With or Without Selinexor in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma (RR DLBCL)', 'Brief Summary': 'The purpose of this Phase 2/3 study is to evaluate efficacy and safety of the combination of selinexor and R-GDP (SR-GDP) in patients with RR DLBCL who are not intended to receive hematopoetic stem cell transplantation (HSCT) or chimeric antigen receptor T cell (CAR-T) therapy. This study consists of 3 arms each in Phase 2 and 3. Phase 2 portion of the study will assess the two doses of selinexor (40 milligram [mg] or 60 mg) in combination with R-GDP, for up to 6 cycles (21-day per cycle), followed by 60 mg selinexor single agent continuous therapy for those who have reached a partial or complete response. Phase 3 portion of the study will evaluate the selected dose of SR-GDP (identified in Phase 2) versus standard R-GDP + matching placebo, for up to 6 cycles (21-day per cycle), followed by placebo or 60 mg selinexor single agent continuous therapy for those who have reached partial or complete response.', 'Condition': 'Relapsed/Refractory Diffuse Large B-cell Lymphoma', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Have pathologically confirmed de novo DLBCL or DLBCL transformed from previously diagnosed indolent lymphoma (e.g., follicular lymphoma). Patient with high-grade lymphoma with c-MYC, Bcl2 and/or Bcl6 rearrangements are eligible (only for Phase 2). (Documentation to be provided). Have received at least 1 but no more than 3 prior lines of systemic therapy for the treatment of DLBCL with relapsed or refractory disease following their most recent regimen. Salvage chemoimmunotherapy followed by stem cell transplantation will be considered as 1 line of systemic therapy. Maintenance therapy will not be counted as a separate line of systemic therapy. Radiation with curative intent for localized DLBCL will not be counted as 1 line of systemic therapy. Positron emission tomography (PET) positive measurable disease with at least 1 node having the longest diameter (LDi) greater than (>) 1.5 centimeter (cm) or 1 extranodal lesion with LDi >1 cm (per the Lugano Criteria 2014). The Deauville 5-point scale (D5PS) score assessed on the FDG PET/CT should be between 3 to 5. Not intended for HSCT or CAR-T cell therapy based on objective clinical criteria determined by the treating physician. Patients who cannot receive HSCT due to active disease are allowed on study (up to approximately 15 percent [%] of patients enrolled in each Phase). Documentation on lack of intention to proceed to receive HSCT or CAR-T therapy must be provided by the treating physician. Adequate bone marrow function at screening, defined as: Absolute neutrophil count (ANC) ≥1*10^9 per liter (/L). Platelet count ≥100*10^9/L (without platelet transfusion less than [<] 14 days prior to Cycle 1 Day 1 [C1D1]). Hemoglobin ≥8.5 gram per deciliter (g/dL) (without red blood cell transfusion <14 days prior to C1D1). Circulating lymphocytes less than or equal to (≤) 50*10^9/L. Adequate liver and kidney function, defined as: Aspartate transaminase (AST) or alanine transaminase (ALT) ≤2.5*upper limit of normal (ULN), or ≤5*ULN in cases with known lymphoma involvement in the liver. Serum total bilirubin ≤2*ULN, or ≤5*ULN if due to Gilbert syndrome or in cases with known lymphoma involvement in the liver. Calculated creatinine clearance (CrCl) ≥30 milliliter per minute (mL/min) based on Cockcroft-Gault formula. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2. An estimated life expectancy of >3 months at Screening. Patients with primary refractory DLBCL defined as no response or relapse within 6 months after ending first-line treatment, will be allowed in the study. Agree to highly effective contraception during the duration of the study with contraception use continuing for 12 months after the last dose of study treatment Female patients of childbearing potential must have a negative serum pregnancy test at Screening and agree to use highly effective methods of contraception throughout the study and for 12 months following the last dose of study treatment (except patients with Non-Childbearing potential: Age >50 years and naturally amenorrhoeic for >1 year, or previous bilateral salpingo-oophorectomy, or hysterectomy). Male patients who are sexually active must use highly effective methods of contraception throughout the study and for 12 months following the last dose of study treatment. Male patients must agree not to donate sperm during the study treatment period and for 12 months following the last dose of study treatment.', 'Exclusion Criteria': "Exclusion Criteria: DLBCL with mucosa-associated lymphoid tissue (MALT) lymphoma, composite lymphoma (Hodgkin's lymphoma + non-Hodgkin's lymphoma [NHL]), DLBCL transformed from diseases other than indolent NHL; primary mediastinal (thymic) large B-cell lymphoma (PMBL); T-cell rich large B-cell lymphoma. Previous treatment with selinexor or other XPO1 inhibitors. Contraindication to any drug contained in the combination therapy regimen (SR-GDP). Known active central nervous system or meningeal involvement by DLBCL at time of Screening. Use of any standard or experimental anti-DLBCL therapy (including nonpalliative radiation, chemotherapy, immunotherapy, radio-immunotherapy, or any other anticancer therapy) <21 days prior to C1D1 (prednisone <30 mg or equivalent is permitted; palliative radiation is permitted only if on non-target lesions). Any AE, by C1D1, which has not recovered to Grade ≤1 (Common Terminology Criteria for Adverse Events [CTCAE], v.5.0), or returned to baseline, related to the previous DLBCL therapy, except hematological abnormalities (as specified in the inclusion criteria) and alopecia. Major surgery <14 days of Cycle 1 Day 1. Hematopoietic stem cell transplantation/CAR-T therapy as follows: Autologous stem cell transplant (SCT) <100 days or allogeneic-SCT <180 days prior to C1D1 Active graft-versus-host disease (GVHD) after allogeneic SCT (or cannot discontinue GVHD treatment or prophylaxis) CAR-T cell infusion <90 days prior to Cycle 1 Neuropathy Grade ≥2 (CTCAE, v.5.0). Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the patient's safety, or being compliant with the study procedures. Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within 7 days prior to first dose of study treatment; however, prophylactic use of these agents is acceptable (including parenteral). Patient with active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infections: Patient with active HBV are allowed if antiviral therapy for hepatitis B has been given for >8 weeks and viral load is <100 International units (IU)/mL prior to first dose of study treatment. Patients with known history of HCV or found to be HCV antibody positive on screening, are allowed if there is documentation of negative viral load per institutional standard. Patients with HIV are allowed if they have a negative viral load per institutional standard, and no history of acquired immune deficiency syndrome (AIDS)-defining opportunistic infections in the last year. Inability to swallow tablets, malabsorption syndrome, or any other gastrointestinal (GI) disease or dysfunction that could interfere with absorption of study treatment. Breastfeeding or pregnant women. Inability or unwillingness to sign an informed consent form (ICF). In the opinion of the Investigator, patient who are significantly below their ideal body weight. Patients who received a live attenuated vaccine within prior 28 days of the first dose of study treatment."}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: c-MYC, Bcl2 and/or Bcl6 rearrangements'}
|
{'Official Title': 'A Phase 2/3, Multicenter Randomized Study of Rituximab-Gemcitabine-Dexamethasone-Platinum (R-GDP) With or Without Selinexor in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma (RR DLBCL)', 'Brief Summary': 'The purpose of this Phase 2/3 study is to evaluate efficacy and safety of the combination of selinexor and R-GDP (SR-GDP) in patients with RR DLBCL who are not intended to receive hematopoetic stem cell transplantation (HSCT) or chimeric antigen receptor T cell (CAR-T) therapy. This study consists of 3 arms each in Phase 2 and 3. Phase 2 portion of the study will assess the two doses of selinexor (40 milligram [mg] or 60 mg) in combination with R-GDP, for up to 6 cycles (21-day per cycle), followed by 60 mg selinexor single agent continuous therapy for those who have reached a partial or complete response. Phase 3 portion of the study will evaluate the selected dose of SR-GDP (identified in Phase 2) versus standard R-GDP + matching placebo, for up to 6 cycles (21-day per cycle), followed by placebo or 60 mg selinexor single agent continuous therapy for those who have reached partial or complete response.', 'Condition': 'Relapsed/Refractory Diffuse Large B-cell Lymphoma', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Have pathologically confirmed de novo DLBCL or DLBCL transformed from previously diagnosed indolent lymphoma (e.g., follicular lymphoma). Patient with high-grade lymphoma with c-MYC, Bcl2 and/or Bcl6 rearrangements are eligible (only for Phase 2). (Documentation to be provided). Have received at least 1 but no more than 3 prior lines of systemic therapy for the treatment of DLBCL with relapsed or refractory disease following their most recent regimen. Salvage chemoimmunotherapy followed by stem cell transplantation will be considered as 1 line of systemic therapy. Maintenance therapy will not be counted as a separate line of systemic therapy. Radiation with curative intent for localized DLBCL will not be counted as 1 line of systemic therapy. Positron emission tomography (PET) positive measurable disease with at least 1 node having the longest diameter (LDi) greater than (>) 1.5 centimeter (cm) or 1 extranodal lesion with LDi >1 cm (per the Lugano Criteria 2014). The Deauville 5-point scale (D5PS) score assessed on the FDG PET/CT should be between 3 to 5. Not intended for HSCT or CAR-T cell therapy based on objective clinical criteria determined by the treating physician. Patients who cannot receive HSCT due to active disease are allowed on study (up to approximately 15 percent [%] of patients enrolled in each Phase). Documentation on lack of intention to proceed to receive HSCT or CAR-T therapy must be provided by the treating physician. Adequate bone marrow function at screening, defined as: Absolute neutrophil count (ANC) ≥1*10^9 per liter (/L). Platelet count ≥100*10^9/L (without platelet transfusion less than [<] 14 days prior to Cycle 1 Day 1 [C1D1]). Hemoglobin ≥8.5 gram per deciliter (g/dL) (without red blood cell transfusion <14 days prior to C1D1). Circulating lymphocytes less than or equal to (≤) 50*10^9/L. Adequate liver and kidney function, defined as: Aspartate transaminase (AST) or alanine transaminase (ALT) ≤2.5*upper limit of normal (ULN), or ≤5*ULN in cases with known lymphoma involvement in the liver. Serum total bilirubin ≤2*ULN, or ≤5*ULN if due to Gilbert syndrome or in cases with known lymphoma involvement in the liver. Calculated creatinine clearance (CrCl) ≥30 milliliter per minute (mL/min) based on Cockcroft-Gault formula. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2. An estimated life expectancy of >3 months at Screening. Patients with primary refractory DLBCL defined as no response or relapse within 6 months after ending first-line treatment, will be allowed in the study. Agree to highly effective contraception during the duration of the study with contraception use continuing for 12 months after the last dose of study treatment Female patients of childbearing potential must have a negative serum pregnancy test at Screening and agree to use highly effective methods of contraception throughout the study and for 12 months following the last dose of study treatment (except patients with Non-Childbearing potential: Age >50 years and naturally amenorrhoeic for >1 year, or previous bilateral salpingo-oophorectomy, or hysterectomy). Male patients who are sexually active must use highly effective methods of contraception throughout the study and for 12 months following the last dose of study treatment. Male patients must agree not to donate sperm during the study treatment period and for 12 months following the last dose of study treatment.', 'Exclusion Criteria': "Exclusion Criteria: DLBCL with mucosa-associated lymphoid tissue (MALT) lymphoma, composite lymphoma (Hodgkin's lymphoma + non-Hodgkin's lymphoma [NHL]), DLBCL transformed from diseases other than indolent NHL; primary mediastinal (thymic) large B-cell lymphoma (PMBL); T-cell rich large B-cell lymphoma. Previous treatment with selinexor or other XPO1 inhibitors. Contraindication to any drug contained in the combination therapy regimen (SR-GDP). Known active central nervous system or meningeal involvement by DLBCL at time of Screening. Use of any standard or experimental anti-DLBCL therapy (including nonpalliative radiation, chemotherapy, immunotherapy, radio-immunotherapy, or any other anticancer therapy) <21 days prior to C1D1 (prednisone <30 mg or equivalent is permitted; palliative radiation is permitted only if on non-target lesions). Any AE, by C1D1, which has not recovered to Grade ≤1 (Common Terminology Criteria for Adverse Events [CTCAE], v.5.0), or returned to baseline, related to the previous DLBCL therapy, except hematological abnormalities (as specified in the inclusion criteria) and alopecia. Major surgery <14 days of Cycle 1 Day 1. Hematopoietic stem cell transplantation/CAR-T therapy as follows: Autologous stem cell transplant (SCT) <100 days or allogeneic-SCT <180 days prior to C1D1 Active graft-versus-host disease (GVHD) after allogeneic SCT (or cannot discontinue GVHD treatment or prophylaxis) CAR-T cell infusion <90 days prior to Cycle 1 Neuropathy Grade ≥2 (CTCAE, v.5.0). Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the patient's safety, or being compliant with the study procedures. Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within 7 days prior to first dose of study treatment; however, prophylactic use of these agents is acceptable (including parenteral). Patient with active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infections: Patient with active HBV are allowed if antiviral therapy for hepatitis B has been given for >8 weeks and viral load is <100 International units (IU)/mL prior to first dose of study treatment. Patients with known history of HCV or found to be HCV antibody positive on screening, are allowed if there is documentation of negative viral load per institutional standard. Patients with HIV are allowed if they have a negative viral load per institutional standard, and no history of acquired immune deficiency syndrome (AIDS)-defining opportunistic infections in the last year. Inability to swallow tablets, malabsorption syndrome, or any other gastrointestinal (GI) disease or dysfunction that could interfere with absorption of study treatment. Breastfeeding or pregnant women. Inability or unwillingness to sign an informed consent form (ICF). In the opinion of the Investigator, patient who are significantly below their ideal body weight. Patients who received a live attenuated vaccine within prior 28 days of the first dose of study treatment."}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: c-MYC, Bcl2 and/or Bcl6 rearrangements'}
|
{'Official Title': 'A Phase 2/3, Multicenter Randomized Study of Rituximab-Gemcitabine-Dexamethasone-Platinum (R-GDP) With or Without Selinexor in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma (RR DLBCL)', 'Brief Summary': 'The purpose of this Phase 2/3 study is to evaluate efficacy and safety of the combination of selinexor and R-GDP (SR-GDP) in patients with RR DLBCL who are not intended to receive hematopoetic stem cell transplantation (HSCT) or chimeric antigen receptor T cell (CAR-T) therapy. This study consists of 3 arms each in Phase 2 and 3. Phase 2 portion of the study will assess the two doses of selinexor (40 milligram [mg] or 60 mg) in combination with R-GDP, for up to 6 cycles (21-day per cycle), followed by 60 mg selinexor single agent continuous therapy for those who have reached a partial or complete response. Phase 3 portion of the study will evaluate the selected dose of SR-GDP (identified in Phase 2) versus standard R-GDP + matching placebo, for up to 6 cycles (21-day per cycle), followed by placebo or 60 mg selinexor single agent continuous therapy for those who have reached partial or complete response.', 'Condition': 'Relapsed/Refractory Diffuse Large B-cell Lymphoma', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: Have pathologically confirmed de novo DLBCL or DLBCL transformed from previously diagnosed indolent lymphoma (e.g., follicular lymphoma). Patient with high-grade lymphoma with c-MYC, Bcl2 and/or Bcl6 rearrangements are eligible (only for Phase 2). (Documentation to be provided). Have received at least 1 but no more than 3 prior lines of systemic therapy for the treatment of DLBCL with relapsed or refractory disease following their most recent regimen. Salvage chemoimmunotherapy followed by stem cell transplantation will be considered as 1 line of systemic therapy. Maintenance therapy will not be counted as a separate line of systemic therapy. Radiation with curative intent for localized DLBCL will not be counted as 1 line of systemic therapy. Positron emission tomography (PET) positive measurable disease with at least 1 node having the longest diameter (LDi) greater than (>) 1.5 centimeter (cm) or 1 extranodal lesion with LDi >1 cm (per the Lugano Criteria 2014). The Deauville 5-point scale (D5PS) score assessed on the FDG PET/CT should be between 3 to 5. Not intended for HSCT or CAR-T cell therapy based on objective clinical criteria determined by the treating physician. Patients who cannot receive HSCT due to active disease are allowed on study (up to approximately 15 percent [%] of patients enrolled in each Phase). Documentation on lack of intention to proceed to receive HSCT or CAR-T therapy must be provided by the treating physician. Adequate bone marrow function at screening, defined as: Absolute neutrophil count (ANC) ≥1*10^9 per liter (/L). Platelet count ≥100*10^9/L (without platelet transfusion less than [<] 14 days prior to Cycle 1 Day 1 [C1D1]). Hemoglobin ≥8.5 gram per deciliter (g/dL) (without red blood cell transfusion <14 days prior to C1D1). Circulating lymphocytes less than or equal to (≤) 50*10^9/L. Adequate liver and kidney function, defined as: Aspartate transaminase (AST) or alanine transaminase (ALT) ≤2.5*upper limit of normal (ULN), or ≤5*ULN in cases with known lymphoma involvement in the liver. Serum total bilirubin ≤2*ULN, or ≤5*ULN if due to Gilbert syndrome or in cases with known lymphoma involvement in the liver. Calculated creatinine clearance (CrCl) ≥30 milliliter per minute (mL/min) based on Cockcroft-Gault formula. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2. An estimated life expectancy of >3 months at Screening. Patients with primary refractory DLBCL defined as no response or relapse within 6 months after ending first-line treatment, will be allowed in the study. Agree to highly effective contraception during the duration of the study with contraception use continuing for 12 months after the last dose of study treatment Female patients of childbearing potential must have a negative serum pregnancy test at Screening and agree to use highly effective methods of contraception throughout the study and for 12 months following the last dose of study treatment (except patients with Non-Childbearing potential: Age >50 years and naturally amenorrhoeic for >1 year, or previous bilateral salpingo-oophorectomy, or hysterectomy). Male patients who are sexually active must use highly effective methods of contraception throughout the study and for 12 months following the last dose of study treatment. Male patients must agree not to donate sperm during the study treatment period and for 12 months following the last dose of study treatment.', 'Exclusion Criteria': "Exclusion Criteria: DLBCL with mucosa-associated lymphoid tissue (MALT) lymphoma, composite lymphoma (Hodgkin's lymphoma + non-Hodgkin's lymphoma [NHL]), DLBCL transformed from diseases other than indolent NHL; primary mediastinal (thymic) large B-cell lymphoma (PMBL); T-cell rich large B-cell lymphoma. Previous treatment with selinexor or other XPO1 inhibitors. Contraindication to any drug contained in the combination therapy regimen (SR-GDP). Known active central nervous system or meningeal involvement by DLBCL at time of Screening. Use of any standard or experimental anti-DLBCL therapy (including nonpalliative radiation, chemotherapy, immunotherapy, radio-immunotherapy, or any other anticancer therapy) <21 days prior to C1D1 (prednisone <30 mg or equivalent is permitted; palliative radiation is permitted only if on non-target lesions). Any AE, by C1D1, which has not recovered to Grade ≤1 (Common Terminology Criteria for Adverse Events [CTCAE], v.5.0), or returned to baseline, related to the previous DLBCL therapy, except hematological abnormalities (as specified in the inclusion criteria) and alopecia. Major surgery <14 days of Cycle 1 Day 1. Hematopoietic stem cell transplantation/CAR-T therapy as follows: Autologous stem cell transplant (SCT) <100 days or allogeneic-SCT <180 days prior to C1D1 Active graft-versus-host disease (GVHD) after allogeneic SCT (or cannot discontinue GVHD treatment or prophylaxis) CAR-T cell infusion <90 days prior to Cycle 1 Neuropathy Grade ≥2 (CTCAE, v.5.0). Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the patient's safety, or being compliant with the study procedures. Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within 7 days prior to first dose of study treatment; however, prophylactic use of these agents is acceptable (including parenteral). Patient with active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infections: Patient with active HBV are allowed if antiviral therapy for hepatitis B has been given for >8 weeks and viral load is <100 International units (IU)/mL prior to first dose of study treatment. Patients with known history of HCV or found to be HCV antibody positive on screening, are allowed if there is documentation of negative viral load per institutional standard. Patients with HIV are allowed if they have a negative viral load per institutional standard, and no history of acquired immune deficiency syndrome (AIDS)-defining opportunistic infections in the last year. Inability to swallow tablets, malabsorption syndrome, or any other gastrointestinal (GI) disease or dysfunction that could interfere with absorption of study treatment. Breastfeeding or pregnant women. Inability or unwillingness to sign an informed consent form (ICF). In the opinion of the Investigator, patient who are significantly below their ideal body weight. Patients who received a live attenuated vaccine within prior 28 days of the first dose of study treatment."}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: c-MYC, Bcl2 and/or Bcl6 rearrangements'}
|
{'Official Title': 'Multicentric Randomized Phase I/II Study to Evaluate Efficacy of Trifluridine/Tipiracil Plus XB2001 (Anti-IL-1α True Human Antibody) Versus Trifluridine/Tipiracil Plus Placebo in Metastatic Colorectal Cancer Patients After Failure of Oxaliplatin, Irinotecan, Fluoropyrimidine', 'Brief Summary': 'Unresectable metastatic colorectal cancer (mCRC) remains an incurable disease. After failure of conventional treatments involving fluoropyrimidines, oxaliplatin and irinotecan in combination or not with biotherapies targeting EGFR and VEGF; regorafenib shows a modest improvement in overall survival. Recently, trifluridine/tipiracil has also shown efficacy in phase 3 with an overall survival of around 7 months. Trifluridine/tipiracil has become the standard of care for advanced mCRC in most western countries. However, the objective response rate remains very low and the survival gain remains moderate (+2 months). Therefore, new strategies are needed to ensure that mCRC patients who have received multiple lines of therapy can receive more effective treatments. Based on previous clinical trials on IL-1 inhibition and our preclinical data, IL-1 inhibition may increase the efficacy of trifluridine/tipiracil. The goal is to test whether the addition of XB2001 to trifluridine/tipiracil could be synergistic.', 'Condition': 'Metastatic Colorectal Cancer', 'Detailed Description': 'This project proposes to evaluate trifluridine/tipiracil plus XB2001 in patients with metastatic colorectal cancer previously treated with oxaliplatin, fluoropyrimidine and irinotecan in combination or not with an anti-angiogenic and an anti-EGFR for RAS Wild type tumor. The project will consist of a randomized (1:1 ratio), double-blind, non-comparative, multi-center Phase II study with two treatment arms: Experimental arm: trifluridine/tipiracil + XB2001 Control arm: trifluridine/tipiracil + placebo', 'Inclusion Criteria': "Inclusion Criteria: Male or female that must have signed a written informed consent prior to any study specific procedures Aged ≥ 18 years at randomization Patient with histologically proven metastatic colorectal cancer previously treated for metastatic disease by chemotherapy treatment including oxaliplatin, irinotecan, fluoropyrimidine, antiangiogenic (anti-VEGF: bevacizumab or aflibercept) and anti-EGFR (cetuximab or panitumumab) if indicated (MSI tumor could be included if previously pretreated with anti PD1/PDL1 therapy) Have a performance status of 0 or 1 according to the WHO Easter Cooperative Oncology Group (ECOG) Knowledge of RAS, BRAF, Microsatellite status Baseline tumoral evaluation (thoraco-abdomino-pelvic computed tomography) perfromed within 21 days before randomization with at least one measurable lesion according to RECIST 1.1 criteria. Patient willing and able to comply with protocol for the duration of the study including: scheduled visits and exams, visits during the follow-up and treatment compliance. Adequat hepatic, renal and bone marrow function within the following limits: Total bilirubin ≤ 1,5 times the upper limit of normal (ULN) (unless documented Gilbert's syndrome); ASAT et ALAT ≤ 5 times ULN; Measured Creatinine clearance (Cockcroft and Gault) > 30 ml / min Absolute Neutrophil Count (ANC) > 1,5. 109 / L; Platelet count ≥ 150. 109 / L; Haemoglobin ≥ 9 g / dL (patients can be included even if they have been transfused) Albuminemia ≥ 30 g / L; Negative Hepatitis B, C and HIV serologies, or absence of active B or C hepatitis Urea protein, urine dipstick should be less than 2 crossese or <1g/kg Availability of tumor material dated less than 2 years with sufficient quantity (15 to 20 whithe slides) Patient must be affiliated to a social health insurance Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients (urine within 72h or serum pregnancy within 14 days prior to inclusion). Women of childbearing potential willing to use adequate contraception method (including the use of a mechanical method of contraception in the event of hormonal contraceptive treatment) during the treatment period and 6 months following the end of treatment. Male patients with a partner of childbearing potential should use effective contraception during treatment and for up to 6 months after stopping treatment. Normal ECG or ECG without clinically significant findings with QTc < 470 ms.", 'Exclusion Criteria': 'Exclusion Criteria: Other concurrent malignancies the last 3 years, except adequately treated cone-biopsied in situ carcinoma of the cervix, basal cell, squamous cell carcinoma of the skin or low risk prostate cancer. Patient who have had potentially curative therapy for a prior malignancy are eligible provided there has been no evidence of disease for ≥ 5 years and the risk of recurrence is considered low. Symptomatic brain metastases Estimated prognosis <3 months. Mutational status BRAF mutant Participation in progress, or in the 30 days preceding the first scheduled day of dosing in this study, in another therapeutic trial with an experimental molecule or within a time interval less than at least 5 half-lives of the investigational agent, whichever is longer. Severe unbalanced illness, underlying infection that may prevent the patient from receiving treatment. Patients with a clinically important and unresolved Grade 3 or 4 non-haematologic adverse reaction related to previous therapies. Also participant with any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted > 4 weeks and was related to the most recent treatment. Bowel obstruction or sub-obstruction or a history of inflammatory bowel disease or significant gasto intestinal disorder History of autoimmune or inflammatory disease or interstitial lung disease. Patient with congenital galactosemia, total lactase deficiency (lactose intolerance) or glucose-galactose malabsorption syndrome Severe arterial thromboembolic events less than 6 months before randomization New York Heart Association (NYHA) Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure (defined as ≥ 160/100 mm Hg) Clinically significant decrease in performance status (medical records) within 2 weeks of intended first dose administration. -Contraindication to receive a treatment with trifluridine/tipiracil or an anti-IL-1α (XB2001 True Human antibody) Concomitant systemic treatment with immunotherapy, immunosuppressants, corticosteroid therapy ≥ 10 mg equivalent prednisone/prednisolone or hormone therapy: corticosteroid therapy administered chronically, immunosuppressive treatment, biotherapy administered as part of the management of an inflammatory disease (anti-TNF, anti-IL6, anti-IL1, anti PD-1, anti EGFR etc.) and live virus vaccines administered up to 14 days prior the first scheduled dose of treatement administration. Current pregnancy (mandatory pregnancy test at baseline for female of childbearing potential) or breastfeeding. Patient with any psychiatric, psychological, sociological, geographical problem or other severe concomitant disease, disorder or condition that potentially compromising the understanding of the information, the safety of the patient, the interpretation of study results or the conduct of the study compliance with the study protocol and follow-up schedule. Patient deprived of their liberty or under guardianship, curatorship or safeguard of justice. Known or suspected history of immunosuppression, including history of invasive opportunistic infections (e.g tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution. Presence or suspicion of active bacterial, fungal or viral infections, or uncontrolled fever. Major surgery within 2 weeks prior to randomization or have an unhealed operation wounds.'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Exclude: Mutational status BRAF mutant'}
|
{'Official Title': 'Multicentric Randomized Phase I/II Study to Evaluate Efficacy of Trifluridine/Tipiracil Plus XB2001 (Anti-IL-1α True Human Antibody) Versus Trifluridine/Tipiracil Plus Placebo in Metastatic Colorectal Cancer Patients After Failure of Oxaliplatin, Irinotecan, Fluoropyrimidine', 'Brief Summary': 'Unresectable metastatic colorectal cancer (mCRC) remains an incurable disease. After failure of conventional treatments involving fluoropyrimidines, oxaliplatin and irinotecan in combination or not with biotherapies targeting EGFR and VEGF; regorafenib shows a modest improvement in overall survival. Recently, trifluridine/tipiracil has also shown efficacy in phase 3 with an overall survival of around 7 months. Trifluridine/tipiracil has become the standard of care for advanced mCRC in most western countries. However, the objective response rate remains very low and the survival gain remains moderate (+2 months). Therefore, new strategies are needed to ensure that mCRC patients who have received multiple lines of therapy can receive more effective treatments. Based on previous clinical trials on IL-1 inhibition and our preclinical data, IL-1 inhibition may increase the efficacy of trifluridine/tipiracil. The goal is to test whether the addition of XB2001 to trifluridine/tipiracil could be synergistic.', 'Condition': 'Metastatic Colorectal Cancer', 'Detailed Description': 'This project proposes to evaluate trifluridine/tipiracil plus XB2001 in patients with metastatic colorectal cancer previously treated with oxaliplatin, fluoropyrimidine and irinotecan in combination or not with an anti-angiogenic and an anti-EGFR for RAS Wild type tumor. The project will consist of a randomized (1:1 ratio), double-blind, non-comparative, multi-center Phase II study with two treatment arms: Experimental arm: trifluridine/tipiracil + XB2001 Control arm: trifluridine/tipiracil + placebo', 'Inclusion Criteria': "Inclusion Criteria: Male or female that must have signed a written informed consent prior to any study specific procedures Aged ≥ 18 years at randomization Patient with histologically proven metastatic colorectal cancer previously treated for metastatic disease by chemotherapy treatment including oxaliplatin, irinotecan, fluoropyrimidine, antiangiogenic (anti-VEGF: bevacizumab or aflibercept) and anti-EGFR (cetuximab or panitumumab) if indicated (MSI tumor could be included if previously pretreated with anti PD1/PDL1 therapy) Have a performance status of 0 or 1 according to the WHO Easter Cooperative Oncology Group (ECOG) Knowledge of RAS, BRAF, Microsatellite status Baseline tumoral evaluation (thoraco-abdomino-pelvic computed tomography) perfromed within 21 days before randomization with at least one measurable lesion according to RECIST 1.1 criteria. Patient willing and able to comply with protocol for the duration of the study including: scheduled visits and exams, visits during the follow-up and treatment compliance. Adequat hepatic, renal and bone marrow function within the following limits: Total bilirubin ≤ 1,5 times the upper limit of normal (ULN) (unless documented Gilbert's syndrome); ASAT et ALAT ≤ 5 times ULN; Measured Creatinine clearance (Cockcroft and Gault) > 30 ml / min Absolute Neutrophil Count (ANC) > 1,5. 109 / L; Platelet count ≥ 150. 109 / L; Haemoglobin ≥ 9 g / dL (patients can be included even if they have been transfused) Albuminemia ≥ 30 g / L; Negative Hepatitis B, C and HIV serologies, or absence of active B or C hepatitis Urea protein, urine dipstick should be less than 2 crossese or <1g/kg Availability of tumor material dated less than 2 years with sufficient quantity (15 to 20 whithe slides) Patient must be affiliated to a social health insurance Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients (urine within 72h or serum pregnancy within 14 days prior to inclusion). Women of childbearing potential willing to use adequate contraception method (including the use of a mechanical method of contraception in the event of hormonal contraceptive treatment) during the treatment period and 6 months following the end of treatment. Male patients with a partner of childbearing potential should use effective contraception during treatment and for up to 6 months after stopping treatment. Normal ECG or ECG without clinically significant findings with QTc < 470 ms.", 'Exclusion Criteria': 'Exclusion Criteria: Other concurrent malignancies the last 3 years, except adequately treated cone-biopsied in situ carcinoma of the cervix, basal cell, squamous cell carcinoma of the skin or low risk prostate cancer. Patient who have had potentially curative therapy for a prior malignancy are eligible provided there has been no evidence of disease for ≥ 5 years and the risk of recurrence is considered low. Symptomatic brain metastases Estimated prognosis <3 months. Mutational status BRAF mutant Participation in progress, or in the 30 days preceding the first scheduled day of dosing in this study, in another therapeutic trial with an experimental molecule or within a time interval less than at least 5 half-lives of the investigational agent, whichever is longer. Severe unbalanced illness, underlying infection that may prevent the patient from receiving treatment. Patients with a clinically important and unresolved Grade 3 or 4 non-haematologic adverse reaction related to previous therapies. Also participant with any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted > 4 weeks and was related to the most recent treatment. Bowel obstruction or sub-obstruction or a history of inflammatory bowel disease or significant gasto intestinal disorder History of autoimmune or inflammatory disease or interstitial lung disease. Patient with congenital galactosemia, total lactase deficiency (lactose intolerance) or glucose-galactose malabsorption syndrome Severe arterial thromboembolic events less than 6 months before randomization New York Heart Association (NYHA) Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure (defined as ≥ 160/100 mm Hg) Clinically significant decrease in performance status (medical records) within 2 weeks of intended first dose administration. -Contraindication to receive a treatment with trifluridine/tipiracil or an anti-IL-1α (XB2001 True Human antibody) Concomitant systemic treatment with immunotherapy, immunosuppressants, corticosteroid therapy ≥ 10 mg equivalent prednisone/prednisolone or hormone therapy: corticosteroid therapy administered chronically, immunosuppressive treatment, biotherapy administered as part of the management of an inflammatory disease (anti-TNF, anti-IL6, anti-IL1, anti PD-1, anti EGFR etc.) and live virus vaccines administered up to 14 days prior the first scheduled dose of treatement administration. Current pregnancy (mandatory pregnancy test at baseline for female of childbearing potential) or breastfeeding. Patient with any psychiatric, psychological, sociological, geographical problem or other severe concomitant disease, disorder or condition that potentially compromising the understanding of the information, the safety of the patient, the interpretation of study results or the conduct of the study compliance with the study protocol and follow-up schedule. Patient deprived of their liberty or under guardianship, curatorship or safeguard of justice. Known or suspected history of immunosuppression, including history of invasive opportunistic infections (e.g tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution. Presence or suspicion of active bacterial, fungal or viral infections, or uncontrolled fever. Major surgery within 2 weeks prior to randomization or have an unhealed operation wounds.'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Exclude: Mutational status BRAF mutant'}
|
{'Official Title': 'A Phase 2/3 Study of Navtemadlin as Maintenance Therapy in Subjects With TP53WT Advanced or Recurrent Endometrial Cancer Who Responded to Chemotherapy', 'Brief Summary': 'This study evaluates navtemadlin as maintenance treatment for patients with advanced or recurrent endometrial cancer (EC) who have achieved complete response or partial response on chemotherapy. The study will be conducted in 2 parts. Part 1 will evaluate safety and efficacy of two different doses of navtemadlin alongside an observational control arm to determine the Phase 3 navtemadlin dose. Part 2 will evaluate the efficacy and safety of navtemadlin Phase 3 dose compared to placebo.', 'Condition': 'Endometrial Cancer', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: ECOG 0-1 Histologically or cytologically confirmed diagnosis of endometrial cancer documented as TP53WT Subjects with advanced or recurrent disease must have completed a single line of up to 6 cycles of taxane-platinum based chemo and achieved a CR or PR per RECIST V1.1 Adequate hematologic, hepatic and renal function (within 14 days)', 'Exclusion Criteria': 'Exclusion Criteria: Has any sarcomas or small-cell carcinomas with neuroendocrine differentiation Prior immune therapy, cytokine therapy, or any investigational therapy (within 28 days) Indwelling surgical drains Grade 2 or higher QTc prolongation History of major organ transplant History of bleeding diathesis; major hemorrhage or intracranial hemorrhage (within 24 weeks)'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: TP53WT'}
|
{'Official Title': 'A Phase 2/3 Study of Navtemadlin as Maintenance Therapy in Subjects With TP53WT Advanced or Recurrent Endometrial Cancer Who Responded to Chemotherapy', 'Brief Summary': 'This study evaluates navtemadlin as maintenance treatment for patients with advanced or recurrent endometrial cancer (EC) who have achieved complete response or partial response on chemotherapy. The study will be conducted in 2 parts. Part 1 will evaluate safety and efficacy of two different doses of navtemadlin alongside an observational control arm to determine the Phase 3 navtemadlin dose. Part 2 will evaluate the efficacy and safety of navtemadlin Phase 3 dose compared to placebo.', 'Condition': 'Endometrial Cancer', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: ECOG 0-1 Histologically or cytologically confirmed diagnosis of endometrial cancer documented as TP53WT Subjects with advanced or recurrent disease must have completed a single line of up to 6 cycles of taxane-platinum based chemo and achieved a CR or PR per RECIST V1.1 Adequate hematologic, hepatic and renal function (within 14 days)', 'Exclusion Criteria': 'Exclusion Criteria: Has any sarcomas or small-cell carcinomas with neuroendocrine differentiation Prior immune therapy, cytokine therapy, or any investigational therapy (within 28 days) Indwelling surgical drains Grade 2 or higher QTc prolongation History of major organ transplant History of bleeding diathesis; major hemorrhage or intracranial hemorrhage (within 24 weeks)'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: TP53WT'}
|
{'Official Title': 'A Phase 2/3 Study of Navtemadlin as Maintenance Therapy in Subjects With TP53WT Advanced or Recurrent Endometrial Cancer Who Responded to Chemotherapy', 'Brief Summary': 'This study evaluates navtemadlin as maintenance treatment for patients with advanced or recurrent endometrial cancer (EC) who have achieved complete response or partial response on chemotherapy. The study will be conducted in 2 parts. Part 1 will evaluate safety and efficacy of two different doses of navtemadlin alongside an observational control arm to determine the Phase 3 navtemadlin dose. Part 2 will evaluate the efficacy and safety of navtemadlin Phase 3 dose compared to placebo.', 'Condition': 'Endometrial Cancer', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: ECOG 0-1 Histologically or cytologically confirmed diagnosis of endometrial cancer documented as TP53WT Subjects with advanced or recurrent disease must have completed a single line of up to 6 cycles of taxane-platinum based chemo and achieved a CR or PR per RECIST V1.1 Adequate hematologic, hepatic and renal function (within 14 days)', 'Exclusion Criteria': 'Exclusion Criteria: Has any sarcomas or small-cell carcinomas with neuroendocrine differentiation Prior immune therapy, cytokine therapy, or any investigational therapy (within 28 days) Indwelling surgical drains Grade 2 or higher QTc prolongation History of major organ transplant History of bleeding diathesis; major hemorrhage or intracranial hemorrhage (within 24 weeks)'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: TP53WT'}
|
{'Official Title': 'A Phase 2/3 Study of Navtemadlin as Maintenance Therapy in Subjects With TP53WT Advanced or Recurrent Endometrial Cancer Who Responded to Chemotherapy', 'Brief Summary': 'This study evaluates navtemadlin as maintenance treatment for patients with advanced or recurrent endometrial cancer (EC) who have achieved complete response or partial response on chemotherapy. The study will be conducted in 2 parts. Part 1 will evaluate safety and efficacy of two different doses of navtemadlin alongside an observational control arm to determine the Phase 3 navtemadlin dose. Part 2 will evaluate the efficacy and safety of navtemadlin Phase 3 dose compared to placebo.', 'Condition': 'Endometrial Cancer', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: ECOG 0-1 Histologically or cytologically confirmed diagnosis of endometrial cancer documented as TP53WT Subjects with advanced or recurrent disease must have completed a single line of up to 6 cycles of taxane-platinum based chemo and achieved a CR or PR per RECIST V1.1 Adequate hematologic, hepatic and renal function (within 14 days)', 'Exclusion Criteria': 'Exclusion Criteria: Has any sarcomas or small-cell carcinomas with neuroendocrine differentiation Prior immune therapy, cytokine therapy, or any investigational therapy (within 28 days) Indwelling surgical drains Grade 2 or higher QTc prolongation History of major organ transplant History of bleeding diathesis; major hemorrhage or intracranial hemorrhage (within 24 weeks)'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: TP53WT'}
|
{'Official Title': 'A Phase 2/3 Study of Navtemadlin as Maintenance Therapy in Subjects With TP53WT Advanced or Recurrent Endometrial Cancer Who Responded to Chemotherapy', 'Brief Summary': 'This study evaluates navtemadlin as maintenance treatment for patients with advanced or recurrent endometrial cancer (EC) who have achieved complete response or partial response on chemotherapy. The study will be conducted in 2 parts. Part 1 will evaluate safety and efficacy of two different doses of navtemadlin alongside an observational control arm to determine the Phase 3 navtemadlin dose. Part 2 will evaluate the efficacy and safety of navtemadlin Phase 3 dose compared to placebo.', 'Condition': 'Endometrial Cancer', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: ECOG 0-1 Histologically or cytologically confirmed diagnosis of endometrial cancer documented as TP53WT Subjects with advanced or recurrent disease must have completed a single line of up to 6 cycles of taxane-platinum based chemo and achieved a CR or PR per RECIST V1.1 Adequate hematologic, hepatic and renal function (within 14 days)', 'Exclusion Criteria': 'Exclusion Criteria: Has any sarcomas or small-cell carcinomas with neuroendocrine differentiation Prior immune therapy, cytokine therapy, or any investigational therapy (within 28 days) Indwelling surgical drains Grade 2 or higher QTc prolongation History of major organ transplant History of bleeding diathesis; major hemorrhage or intracranial hemorrhage (within 24 weeks)'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: TP53WT'}
|
{'Official Title': 'A Phase 2/3 Study of Navtemadlin as Maintenance Therapy in Subjects With TP53WT Advanced or Recurrent Endometrial Cancer Who Responded to Chemotherapy', 'Brief Summary': 'This study evaluates navtemadlin as maintenance treatment for patients with advanced or recurrent endometrial cancer (EC) who have achieved complete response or partial response on chemotherapy. The study will be conducted in 2 parts. Part 1 will evaluate safety and efficacy of two different doses of navtemadlin alongside an observational control arm to determine the Phase 3 navtemadlin dose. Part 2 will evaluate the efficacy and safety of navtemadlin Phase 3 dose compared to placebo.', 'Condition': 'Endometrial Cancer', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: ECOG 0-1 Histologically or cytologically confirmed diagnosis of endometrial cancer documented as TP53WT Subjects with advanced or recurrent disease must have completed a single line of up to 6 cycles of taxane-platinum based chemo and achieved a CR or PR per RECIST V1.1 Adequate hematologic, hepatic and renal function (within 14 days)', 'Exclusion Criteria': 'Exclusion Criteria: Has any sarcomas or small-cell carcinomas with neuroendocrine differentiation Prior immune therapy, cytokine therapy, or any investigational therapy (within 28 days) Indwelling surgical drains Grade 2 or higher QTc prolongation History of major organ transplant History of bleeding diathesis; major hemorrhage or intracranial hemorrhage (within 24 weeks)'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: TP53WT'}
|
{'Official Title': 'A Phase 2/3 Study of Navtemadlin as Maintenance Therapy in Subjects With TP53WT Advanced or Recurrent Endometrial Cancer Who Responded to Chemotherapy', 'Brief Summary': 'This study evaluates navtemadlin as maintenance treatment for patients with advanced or recurrent endometrial cancer (EC) who have achieved complete response or partial response on chemotherapy. The study will be conducted in 2 parts. Part 1 will evaluate safety and efficacy of two different doses of navtemadlin alongside an observational control arm to determine the Phase 3 navtemadlin dose. Part 2 will evaluate the efficacy and safety of navtemadlin Phase 3 dose compared to placebo.', 'Condition': 'Endometrial Cancer', 'Detailed Description': '-', 'Inclusion Criteria': 'Inclusion Criteria: ECOG 0-1 Histologically or cytologically confirmed diagnosis of endometrial cancer documented as TP53WT Subjects with advanced or recurrent disease must have completed a single line of up to 6 cycles of taxane-platinum based chemo and achieved a CR or PR per RECIST V1.1 Adequate hematologic, hepatic and renal function (within 14 days)', 'Exclusion Criteria': 'Exclusion Criteria: Has any sarcomas or small-cell carcinomas with neuroendocrine differentiation Prior immune therapy, cytokine therapy, or any investigational therapy (within 28 days) Indwelling surgical drains Grade 2 or higher QTc prolongation History of major organ transplant History of bleeding diathesis; major hemorrhage or intracranial hemorrhage (within 24 weeks)'}
|
Biomarker Extraction Guideline
1. Review the “arms data” and identify the biomarker from the clinical trial arm.
2. Rely only on "arms data" to identify the biomarker. The "arms data" may be incomplete or irrelevant. You should not make assumptions about the "arms data" beyond what is mentioned.
3. Make sure to extract only the biomarker information.
4. Avoid any other additional context.
5. Return just the biomarker. Do not write a para.
6. Refer to these examples for formatting: Return Biomarker - HR+, HER2-
|
{'Arm - Disease - Biomarker': 'Include: TP53WT'}
|
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