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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'}
|
{'Arm - Disease - Biomarker': 'Exclude: PD-1, PD-L1, PD-L2, CTLA-4'}
|
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-
|
{'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'}
|
{'Arm - Disease - Biomarker': 'Exclude: PD-1, PD-L1, PD-L2, CTLA-4'}
|
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-
|
{'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'}
|
{'Arm - Disease - Biomarker': 'Exclude: PD-1, PD-L1, PD-L2, CTLA-4'}
|
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-
|
{'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'}
|
{'Arm - Disease - Biomarker': 'Exclude: PD-1, PD-L1, PD-L2, CTLA-4'}
|
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-
|
{'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'}
|
{'Arm - Disease - Biomarker': 'Exclude: PD-1, PD-L1, PD-L2, CTLA-4'}
|
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-
|
{'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.'}
|
{'Arm - Disease - Biomarker': 'Include: HR+, HER2- Exclude: HER2+'}
|
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-
|
{'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.'}
|
{'Arm - Disease - Biomarker': 'Include: HR+, HER2- Exclude: HER2+'}
|
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-
|
{'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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{'Arm - Disease - Biomarker': 'Include: EGFR mutation, specifically either DEL19 or L858R, confirmed acquired T790M mutation'}
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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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{'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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{'Arm - Disease - Biomarker': 'Include: EGFR mutation, specifically either DEL19 or L858R, confirmed acquired T790M mutation'}
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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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{'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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{'Arm - Disease - Biomarker': 'Include: Fibroblast growth factor receptor (FGFR) gene alterations '}
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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-
|
{'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'}
|
{'Arm - Disease - Biomarker': 'Include: Fibroblast growth factor receptor (FGFR) gene alterations '}
|
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-
|
{'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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{'Arm - Disease - Biomarker': 'Include: EGFR mutation (Exon 19 deletion, T790M, or L858R) on tumor samples'}
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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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{'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.'}
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{'Arm - Disease - Biomarker': 'Include: HR-Positive, HER2-Negative'}
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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-
|
{'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.'}
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{'Arm - Disease - Biomarker': 'Include: HR-Positive, HER2-Negative'}
|
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-
|
{'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."}
|
{'Arm - Disease - Biomarker': 'Include: HER2-Negative, HR-Positive Exclude: HER2-positive'}
|
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-
|
{'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."}
|
{'Arm - Disease - Biomarker': 'Include: HER2-Negative, HR-Positive, Regardless of HER3 expression Exclude: HER2-positive'}
|
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-
|
{'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."}
|
{'Arm - Disease - Biomarker': 'Include: HER2-Positive Exclude:HER2-Negative'}
|
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-
|
{'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'}
|
{'Arm - Disease - Biomarker': 'KRASG12C mutated'}
|
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-
|
{'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'}
|
{'Arm - Disease - Biomarker': 'KRASG12C mutated'}
|
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-
|
{'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'}
|
{'Arm - Disease - Biomarker': 'Include: PD-L1'}
|
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-
|
{'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'}
|
{'Arm - Disease - Biomarker': 'Include: PD-L1'}
|
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-
|
{'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'}
|
{'Arm - Disease - Biomarker': 'Include: PD-L1'}
|
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-
|
{'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'}
|
{'Arm - Disease - Biomarker': 'Include: PD-L1'}
|
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-
|
{'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'}
|
{'Arm - Disease - Biomarker': 'Include: PD-L1'}
|
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-
|
{'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'}
|
{'Arm - Disease - Biomarker': 'Include: PD-L1'}
|
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-
|
{'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'}
|
{'Arm - Disease - Biomarker': 'Include: PD-L1'}
|
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-
|
{'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'}
|
{'Arm - Disease - Biomarker': 'Include: PD-L1'}
|
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-
|
{'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'}
|
{'Arm - Disease - Biomarker': 'Include: KRAS G12C mutation'}
|
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-
|
{'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'}
|
{'Arm - Disease - Biomarker': 'Include: KRAS G12C mutation'}
|
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-
|
{'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'}
|
{'Arm - Disease - Biomarker': 'Include: KRAS G12C mutation'}
|
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-
|
{'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'}
|
{'Arm - Disease - Biomarker': 'Include: KRAS G12C mutation'}
|
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-
|
{'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'}
|
{'Arm - Disease - Biomarker': 'Include: KRAS G12C mutation'}
|
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-
|
{'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'}
|
{'Arm - Disease - Biomarker': 'Include: KRAS G12C mutation'}
|
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-
|
{'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'}
|
{'Arm - Disease - Biomarker': 'Include: KRAS G12C mutation'}
|
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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