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--- "a/ft_train.jsonl"
+++ "b/ft_train.jsonl"
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-{"input": "Product: PSB202 is a novel biological entity consisting of two engineered monoclonal\n antibodies, an Fc-enhanced humanized type II anti-CD20 IgG1 (PSB102) and a humanized\n anti-CD37 IgG1 (PSB107), that target B-cells. PSB202 is manufactured to work as a single\n product with the two components of PSB202 enabling a distinct dual target-specific antibody\n directed cell killing of B-cells.\n Study: Multi-center-, International Phase 1a/1b (Escalation/Expansion) study in patients with\n indolent-, relapsed-, B-cell malignancies. The Phase 1a (Dose Escalation) part of study\n follows a 3+3 design.\n ;\n ;\n Inclusion Criteria:\n Phase 1a (dose escalation):\n 1. Histologically confirmed CD20+ expressing indolent NHL (defined below), CLL or WM,\n failed or intolerant to standard of care therapies;\n 2. Relapsed/refractory following at least 2 prior lines of standard of care treatment.\n Prior treatments received must be documented on the enrollment request form. For FL,\n prior treatment must have included at least 1 rituximab containing regimen.\n 3. First three dose levels: in the opinion of the investigator, able to tolerate\n potentially subtherapeutic doses of PSB202 for the duration of a 28-day DLT\n observation window.\n Phase 1b - Dose Expansion:\n 4. Histologically confirmed CD20+ expression. For CD37+, if unavailable from the chart at\n screening, CD37+ expression may be documented from a new or archived blood specimen\n after enrollment.\n 5. Relapsed indolent NHL: histologies that may be included are CLL/SLL, MZL,\n MALT-lymphoma, follicular NHL, MCL or WM failed, relapsed/refractory or intolerant to\n at least 2 standard of care therapies. (APPENDIX B). For FL, prior treatment must have\n included rituximab. MCL must have received a prior alkylating agent.\n 6. Patients must have documented disease progression after at least two prior\n standard-of-care regimens.\n 7. Patients must have measurable disease.\n All Patients:\n 8. Signed Informed Consent;\n 9. Eastern Cooperative Oncology Group (ECOG) 0-2\n 10. Last dose of any anti-CD20 antibody therapy must have been >4 weeks before the first\n dose of PSB202\n 11. Patients with a medical history of Covid-19 positivity at within 6 months prior to\n enrollment, must be retested within 7 days of enrollment and confirm Covid-19\n negativity by a PCR-test.\n 12. At least 18 years of age. There is no upper age restriction.\n 13. Four weeks wash-out from any other prior cancer therapy, including rituximab or\n BTK-inhibitors. However, some heavily pretreated patients are at risk for significant\n morbidity from accelerated disease progression or \"flare\" when treatment is\n discontinued prior to the initiation of subsequent effective therapy. Absent residual\n toxicity and with documented Medical Monitor approval, such patients may receive study\n drug after five drug half-lives have passed following discontinuation of the immediate\n pre-study therapy.\n 14. Adequate hematologic and coagulation status, defined as the following on C1D1 before\n treatment:\n 1. Absolute neutrophil count (ANC) \u2265 0.75 billion/L; not requiring growth factors;\n after the DLT period, growth factor support is allowed and considered supportive\n care.\n 2. Platelet count \u226575 billion/L not requiring transfusion support; if there is\n documented bone marrow involvement, platelet transfusions may be used up to 7\n days prior to C1D1 to achieve this threshold.\n 3. Hemoglobin (Hb) \u22659 mg/dL not requiring transfusion support or growth factors.\n After the DLT period, growth factor support is allowed and considered supportive\n care.\n 4. Adequate coagulation, defined as aPTT and PT (INR) not greater than 1.5 \u00d7 upper\n limit of normal (ULN) (patients appropriately anticoagulated for a preexisting\n medical condition [e.g., atrial fibrillation] may be eligible with documented\n Sponsor approval).\n 15. Adequate hepatic function, defined as:\n 1. ALT or AST \u22642.5 X the ULN or \u22645 X ULN with documented liver involvement.\n 2. Total bilirubin \u22641.5 X ULN or \u22643 X ULN with documented liver involvement and/or\n Gilbert's Disease\n 3. Adequate renal function, with estimated glomerular filtration rate (eGFR) \u226550\n mL/minute.\n 16. Ability to comply with outpatient treatment, laboratory monitoring, and required\n clinic visits for the duration of study participation.\n 17. Willingness of men and women of reproductive potential to observe conventional and\n effective birth control for the duration of treatment and for 3 months following the\n last dose of study treatment; this may include barrier methods such as condom or\n diaphragm with spermicidal gel.\n Exclusion Criteria\n Phase 1a (dose escalation) only:\n 18. NHL with bulky disease defined as a mass \u226510 cm in longest diameter\n 19. Transformation (e.g., Richter's transformation, prolymphocytic leukemia, transformed\n NHL, blastoid lymphoma) prior to planned start of PSB202. In addition, no concurrent\n investigational therapy is permitted.\n All patients: Phase 1a (dose escalation) and Phase 1b (dose expansion):\n 20. Major surgery within 4 weeks prior to planned start of PSB202\n 21. Radiotherapy with a limited field of radiation for palliation within 7 days of the\n first dose of study treatment, except for patients receiving radiation to more than\n 30% of the bone marrow or receiving whole brain radiotherapy, which must be completed\n at least 4 weeks prior to the first dose of study treatment\n 22. Continuation of certain standard of care anticancer therapies, including hormonal\n therapy for breast and prostate cancer, and growth factor support after completion of\n the DLT-period, is allowed.\n 23. Therapeutic monoclonal antibody treatment must be discontinued a minimum of 4 weeks\n prior to the first dose of PSB202. PSB202 may be started sooner after prior\n investigational agent or anticancer therapy if considered by the Investigator to be\n safe and within the best interest of the patient (e.g., to avoid disease flare) and\n with documented Sponsor approval.\n 24. Any unresolved toxicities from prior therapy greater than CTCAE (version 5.0) Grade 2\n or greater at the time of starting study treatment except for alopecia.\n 25. History of autologous stem cell transplant (auto-SCT) or chimeric antigen\n receptor-modified T cell (CAR-T) therapy within the past 180 days with any of the\n following: cytopenias from incomplete blood cell count recovery post-transplant, need\n for anti-cytokine therapy, residual symptoms of neurotoxicity > Grade 1, or ongoing\n immunosuppressive therapy.\n 26. Active graft versus host disease (GVHD, including resultant from any prior solid organ\n transplants, if received), or ongoing immunosuppressive therapy.\n 27. History of allogeneic stem cell transplant (allo-SCT) or allogeneic CAR-T at any time\n in the patient's medical history\n 28. Known central nervous system (CNS) involvement by lymphoma. Patients with previous\n treatment for CNS involvement who are neurologically stable and without evidence of\n active CNS-disease may be eligible if a clinical rationale is provided by the\n Investigator and with documented Sponsor approval\n 29. Active auto-immune cytopenia (e.g., autoimmune hemolytic anemia [AIHA], idiopathic\n thrombocytopenic purpura [ITP])\n 30. Cerebrovascular accident (CVA), Transient ischemic attack (TIA), myocardial\n infarction, unstable angina, or New York Heart Association (NYHA) class III or IV\n heart failure < 6 months of study screening; mean ECG QT-interval corrected according\n to Fridericia's formula (QTcF) > 450 milliseconds (ms) (males) or > 470 ms (females)\n obtained from three ECGs; uncontrolled arrhythmia < 3 months of study screening.\n Patients with rate-controlled arrhythmias may be eligible for study entry at\n discretion of the Investigator.\n 31. Active uncontrolled systemic bacterial, viral, fungal or parasitic infection (except\n for fungal nail infection), or other clinically significant active disease process\n which in the opinion of the Investigator and the Sponsor makes it undesirable for the\n patient to participate in the trial. Screening for chronic conditions is not required.\n 32. Tested positive for Human Immunodeficiency Virus (HIV) is excluded (due to potential\n drug-drug interactions between anti-retroviral medications and PSB202 and risk of\n opportunistic infections). For patients with unknown HIV status, HIV testing will be\n performed at Screening\n 33. Active viral hepatitis (B or C, HBsAg, anti-HBs/HBcAb and anti-HCV Ab tests) as\n demonstrated by positive serology or requiring treatment. Subjects who are\n anti-HBs/HBcAb (+) without detectable HBV-DNA are eligible. Subjects with a history of\n Hepatitis C and have received successful curative treatment are eligible.\n 34. Pregnancy or lactation.\n 35. Active autoimmune disease or history of autoimmune disease requiring systemic therapy\n < 2 years prior to screening except hypothyroidism, vitiligo, Grave's disease,\n Hashimoto's disease, or Type I diabetes. Patients with childhood asthma or atopy that\n has not been active in the 2 years prior to study screening are eligible.\n 36. History of drug-induced liver injury or cirrhosis\n 37. History of pneumonitis or interstitial lung disease\n 38. Patients with significant medical diseases or conditions, as assessed by the\n Investigator and Sponsor, that would substantially increase the risk-benefit ratio of\n participating in the study.\n -", "output": {"inclusion_biomarker": [["CD20 positive"], ["CD20 positive", "CD37 positive"]], "exclusion_biomarker": []}}
+{"input": "Product: PSB202 is a novel biological entity consisting of two engineered monoclonal\n antibodies, an Fc-enhanced humanized type II anti-CD20 IgG1 (PSB102) and a humanized\n anti-CD37 IgG1 (PSB107), that target B-cells. PSB202 is manufactured to work as a single\n product with the two components of PSB202 enabling a distinct dual target-specific antibody\n directed cell killing of B-cells.\n Study: Multi-center-, International Phase 1a/1b (Escalation/Expansion) study in patients with\n indolent-, relapsed-, B-cell malignancies. The Phase 1a (Dose Escalation) part of study\n follows a 3+3 design.\n ;\n ;\n Inclusion Criteria:\n Phase 1a (dose escalation):\n 1. Histologically confirmed CD20+ expressing indolent NHL (defined below), CLL or WM,\n failed or intolerant to standard of care therapies;\n 2. Relapsed/refractory following at least 2 prior lines of standard of care treatment.\n Prior treatments received must be documented on the enrollment request form. For FL,\n prior treatment must have included at least 1 rituximab containing regimen.\n 3. First three dose levels: in the opinion of the investigator, able to tolerate\n potentially subtherapeutic doses of PSB202 for the duration of a 28-day DLT\n observation window.\n Phase 1b - Dose Expansion:\n 4. Histologically confirmed CD20+ expression. For CD37+, if unavailable from the chart at\n screening, CD37+ expression may be documented from a new or archived blood specimen\n after enrollment.\n 5. Relapsed indolent NHL: histologies that may be included are CLL/SLL, MZL,\n MALT-lymphoma, follicular NHL, MCL or WM failed, relapsed/refractory or intolerant to\n at least 2 standard of care therapies. (APPENDIX B). For FL, prior treatment must have\n included rituximab. MCL must have received a prior alkylating agent.\n 6. Patients must have documented disease progression after at least two prior\n standard-of-care regimens.\n 7. Patients must have measurable disease.\n All Patients:\n 8. Signed Informed Consent;\n 9. Eastern Cooperative Oncology Group (ECOG) 0-2\n 10. Last dose of any anti-CD20 antibody therapy must have been >4 weeks before the first\n dose of PSB202\n 11. Patients with a medical history of Covid-19 positivity at within 6 months prior to\n enrollment, must be retested within 7 days of enrollment and confirm Covid-19\n negativity by a PCR-test.\n 12. At least 18 years of age. There is no upper age restriction.\n 13. Four weeks wash-out from any other prior cancer therapy, including rituximab or\n BTK-inhibitors. However, some heavily pretreated patients are at risk for significant\n morbidity from accelerated disease progression or \"flare\" when treatment is\n discontinued prior to the initiation of subsequent effective therapy. Absent residual\n toxicity and with documented Medical Monitor approval, such patients may receive study\n drug after five drug half-lives have passed following discontinuation of the immediate\n pre-study therapy.\n 14. Adequate hematologic and coagulation status, defined as the following on C1D1 before\n treatment:\n 1. Absolute neutrophil count (ANC) \u2265 0.75 billion/L; not requiring growth factors;\n after the DLT period, growth factor support is allowed and considered supportive\n care.\n 2. Platelet count \u226575 billion/L not requiring transfusion support; if there is\n documented bone marrow involvement, platelet transfusions may be used up to 7\n days prior to C1D1 to achieve this threshold.\n 3. Hemoglobin (Hb) \u22659 mg/dL not requiring transfusion support or growth factors.\n After the DLT period, growth factor support is allowed and considered supportive\n care.\n 4. Adequate coagulation, defined as aPTT and PT (INR) not greater than 1.5 \u00d7 upper\n limit of normal (ULN) (patients appropriately anticoagulated for a preexisting\n medical condition [e.g., atrial fibrillation] may be eligible with documented\n Sponsor approval).\n 15. Adequate hepatic function, defined as:\n 1. ALT or AST \u22642.5 X the ULN or \u22645 X ULN with documented liver involvement.\n 2. Total bilirubin \u22641.5 X ULN or \u22643 X ULN with documented liver involvement and/or\n Gilbert's Disease\n 3. Adequate renal function, with estimated glomerular filtration rate (eGFR) \u226550\n mL/minute.\n 16. Ability to comply with outpatient treatment, laboratory monitoring, and required\n clinic visits for the duration of study participation.\n 17. Willingness of men and women of reproductive potential to observe conventional and\n effective birth control for the duration of treatment and for 3 months following the\n last dose of study treatment; this may include barrier methods such as condom or\n diaphragm with spermicidal gel.\n Exclusion Criteria\n Phase 1a (dose escalation) only:\n 18. NHL with bulky disease defined as a mass \u226510 cm in longest diameter\n 19. Transformation (e.g., Richter's transformation, prolymphocytic leukemia, transformed\n NHL, blastoid lymphoma) prior to planned start of PSB202. In addition, no concurrent\n investigational therapy is permitted.\n All patients: Phase 1a (dose escalation) and Phase 1b (dose expansion):\n 20. Major surgery within 4 weeks prior to planned start of PSB202\n 21. Radiotherapy with a limited field of radiation for palliation within 7 days of the\n first dose of study treatment, except for patients receiving radiation to more than\n 30% of the bone marrow or receiving whole brain radiotherapy, which must be completed\n at least 4 weeks prior to the first dose of study treatment\n 22. Continuation of certain standard of care anticancer therapies, including hormonal\n therapy for breast and prostate cancer, and growth factor support after completion of\n the DLT-period, is allowed.\n 23. Therapeutic monoclonal antibody treatment must be discontinued a minimum of 4 weeks\n prior to the first dose of PSB202. PSB202 may be started sooner after prior\n investigational agent or anticancer therapy if considered by the Investigator to be\n safe and within the best interest of the patient (e.g., to avoid disease flare) and\n with documented Sponsor approval.\n 24. Any unresolved toxicities from prior therapy greater than CTCAE (version 5.0) Grade 2\n or greater at the time of starting study treatment except for alopecia.\n 25. History of autologous stem cell transplant (auto-SCT) or chimeric antigen\n receptor-modified T cell (CAR-T) therapy within the past 180 days with any of the\n following: cytopenias from incomplete blood cell count recovery post-transplant, need\n for anti-cytokine therapy, residual symptoms of neurotoxicity > Grade 1, or ongoing\n immunosuppressive therapy.\n 26. Active graft versus host disease (GVHD, including resultant from any prior solid organ\n transplants, if received), or ongoing immunosuppressive therapy.\n 27. History of allogeneic stem cell transplant (allo-SCT) or allogeneic CAR-T at any time\n in the patient's medical history\n 28. Known central nervous system (CNS) involvement by lymphoma. Patients with previous\n treatment for CNS involvement who are neurologically stable and without evidence of\n active CNS-disease may be eligible if a clinical rationale is provided by the\n Investigator and with documented Sponsor approval\n 29. Active auto-immune cytopenia (e.g., autoimmune hemolytic anemia [AIHA], idiopathic\n thrombocytopenic purpura [ITP])\n 30. Cerebrovascular accident (CVA), Transient ischemic attack (TIA), myocardial\n infarction, unstable angina, or New York Heart Association (NYHA) class III or IV\n heart failure < 6 months of study screening; mean ECG QT-interval corrected according\n to Fridericia's formula (QTcF) > 450 milliseconds (ms) (males) or > 470 ms (females)\n obtained from three ECGs; uncontrolled arrhythmia < 3 months of study screening.\n Patients with rate-controlled arrhythmias may be eligible for study entry at\n discretion of the Investigator.\n 31. Active uncontrolled systemic bacterial, viral, fungal or parasitic infection (except\n for fungal nail infection), or other clinically significant active disease process\n which in the opinion of the Investigator and the Sponsor makes it undesirable for the\n patient to participate in the trial. Screening for chronic conditions is not required.\n 32. Tested positive for Human Immunodeficiency Virus (HIV) is excluded (due to potential\n drug-drug interactions between anti-retroviral medications and PSB202 and risk of\n opportunistic infections). For patients with unknown HIV status, HIV testing will be\n performed at Screening\n 33. Active viral hepatitis (B or C, HBsAg, anti-HBs/HBcAb and anti-HCV Ab tests) as\n demonstrated by positive serology or requiring treatment. Subjects who are\n anti-HBs/HBcAb (+) without detectable HBV-DNA are eligible. Subjects with a history of\n Hepatitis C and have received successful curative treatment are eligible.\n 34. Pregnancy or lactation.\n 35. Active autoimmune disease or history of autoimmune disease requiring systemic therapy\n < 2 years prior to screening except hypothyroidism, vitiligo, Grave's disease,\n Hashimoto's disease, or Type I diabetes. Patients with childhood asthma or atopy that\n has not been active in the 2 years prior to study screening are eligible.\n 36. History of drug-induced liver injury or cirrhosis\n 37. History of pneumonitis or interstitial lung disease\n 38. Patients with significant medical diseases or conditions, as assessed by the\n Investigator and Sponsor, that would substantially increase the risk-benefit ratio of\n participating in the study.\n -", "output": {"inclusion_biomarker": [["CD20 expression"], ["CD37 expression"]], "exclusion_biomarker": []}}
 {"input": "Multiple Myeloma (MM) is a cancer of the blood's plasma cells ( blood cell). The cancer is\n typically found in the bones and bone marrow (the spongy tissue inside of the bones) and can\n cause bone pain, fractures, infections, weaker bones, and kidney failure. Treatments are\n available, but MM can come back (relapsed) or may not get better (refractory) with treatment.\n This is a study to determine adverse events and change in disease symptoms of ABBV-383 in\n adult participants with relapsed/refractory (R/R) MM.\n ABBV-383 is an investigational drug being developed for the treatment of R/R Multiple Myeloma\n (MM). This study includes 2 parts; step-up dose optimization (Part 1) and dose expansion\n (Part 2). In Part 1, different level of step-up doses are tested followed by the target dose\n of ABBV-383. In Part 2, the step-up dose identified in Part 1 will be used followed by the\n target dose of ABBV-383. Around 80 adult participants with relapsed/refractory multiple\n myeloma will be enrolled at approximately 30 sites across the world.\n Participants will receive ABBV-383 as an infusion into the vein in 28 day cycles for\n approximately 3 years.\n There may be higher treatment burden for participants in this trial compared to their\n standard of care. Participants will attend regular visits during the study at a hospital or\n clinic. The effect of the treatment will be checked by medical assessments, blood tests,\n checking for side effects and questionnaires.\n ;NA;\n Inclusion Criteria:\n - Must have measurable disease as outlined in the protocol.\n - Eastern Cooperative Oncology Group (ECOG) performance of <= 2.\n - Relapsed/refractory (R/R) multiple myeloma (MM) with documented evidence of\n progression during or after the participant's last treatment regimen based on the\n investigator's determination of the International Myeloma Working Group (IMWG) 2016\n criteria.\n - Must be na\u00efve to treatment with ABBV-383.\n - Must have received at least 3 or more lines of therapy, including a proteasome\n inhibitor (PI), an immunomodulatory imide drug (IMiD), and an anti-CD38 monoclonal\n antibody.\n Exclusion Criteria:\n - Received B-cell maturation antigen (BCMA)-targeted therapy.", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
 {"input": "This is a phase 1/2, open label study of D-1553 single agent and combination treatment to\n assess the safety and tolerability, identify the MTD and RP2D, evaluate the PK properties and\n antitumor activities in subjects with advanced or metastatic solid tumor with KRasG12C\n mutation.\n ;NA;\n Inclusion criteria\n - Subject with histologically proven, locally advanced, unresectable and/or metastatic\n solid tumor, for which no standard treatment is available or the subject is refractory\n to or intolerant of existing standard treatment.\n - Subject has KRasG12C mutation in tumor tissue or other biospecimens containing cancer\n cells or DNA. Historical, local laboratory result (up to 5 years prior to this study)\n can be used for Phase 1 subjects. Phase 2 subjects must be tested for KRasG12C\n mutation by a central laboratory.\n - Subject has tumor type requirement as follows: advanced or metastatic solid tumors\n including NSCLC and CRC.\n - Subject has measurable disease according to RECIST, v1.1.\n Exclusion Criteria:\n - Subject with unstable or progressive central nervous system (CNS) metastases.\n - Subject with acute myocardial infarction, severe/unstable angina; or with cardiac\n insufficiency of New York Heart Association Functional Classification Grade 2 or\n above.\n - Subject has corrected QT interval using Fridericia's formula (QTcF) prolongation at\n rest, where the mean QTc interval is > 480 msec based on triplicate measurements of\n electrocardiogram (ECG).\n - Subject with stroke or other severe cerebrovascular diseases within 12 months before\n enrollment;\n - Subject with interstitial lung disease or acute lung infection not yet recovered\n including but not limited to severe acute respiratory syndrome coronavirus 2\n (SARS-CoV-2) infection;\n - Subject has any history or evidence of substance abuse or medical, psychological or\n social conditions that may, in the opinion of the investigator, interfere with\n participation in the study or evaluation of the study results.\n - Subject has impaired gastrointestinal (GI) function or GI diseases that may\n significantly alter the absorption or metabolism of oral medications.\n - Subject has unresolved toxicities from prior anticancer therapy, defined as toxicities\n (other than alopecia) not yet resolved to NCI CTCAE, v5.0, Grade \u2264 1 (Grade \u2264 2 for\n peripheral neuropathy).\n - Subject had major surgery within 4 weeks prior to study intervention administration or\n last dose of palliative radiation therapy within 2 weeks prior to study intervention\n administration.\n - Subject is pregnant or lactating.", "output": {"inclusion_biomarker": [["KRas G12C"]], "exclusion_biomarker": []}}
-{"input": "This will be a Phase 1 Open-Label, dose escalation and expansion study of MT-0169 (an\n Engineered toxin body (ETB) in patients with relapsed or refractory multiple myeloma or\n non-Hodgkin lymphoma. MT-0169 is an investigational drug that recognizes and binds to the\n CD38 receptor, which may be found on the surface of multiple myeloma and non-Hodgkin lymphoma\n cancer cells. It delivers a dose of a modified toxin that kills these cells.\n ;\n ;\n Inclusion Criteria Part 1 (RRMM patients only)\n 1. Confirmed diagnosis of MM per revised IMWG diagnostic criteria\n 2. Patients with RRMM who have failed treatment with, are intolerant to, or are not\n candidates for available therapies that are known to confer clinical benefit\n 3. Must meet all of the following criteria for prior therapy:\n 1. Must be refractory to \u22651 proteasome inhibitor (PI), \u22651 immunomodulatory drug\n (IMiD), and \u22651 steroid\n 2. Must either have received \u22653 prior lines of therapy or \u22652 prior lines of therapy\n if 1 line included a combination of PI and IMiD (prior treatment with anti-CD38\n therapy is permitted).\n 4. With measurable disease, defined as \u22651 of the following:\n 1. Serum M-protein \u2265500 mg/dL (\u22655 g/L) on serum protein electrophoresis (SPEP).\n 2. Urine M-protein \u2265200 mg/24 h on urine protein electrophoresis (UPEP).\n 3. Serum FLC assay result with an involved FLC level \u226510 mg/dL (\u2265100 mg/L) if serum\n FLC ratio is abnormal.\n 5. Patients with serum M-protein, urine M-protein, or involved immunoglobulin FLC not\n meeting the measurable disease criteria above will be eligible if they have \u22651 of the\n following:\n 1. Bone marrow (BM) aspirate/biopsy with plasma cell percentage \u226530%\n 2. PET imaging with \u22651 plasmacytoma lesion with a single diameter of \u22652cm.\n 6. With Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1.\n 7. With normal QT interval corrected by the Fridericia method (QTcF) on screening\n electrocardiogram (ECG)[ QTcF of \u2264450 millisecond (ms) in males or \u2264470 ms in females]\n 8. Must meet the following clinical laboratory criteria at entry:\n 1. Total bilirubin \u22641.5*the upper limit of the normal range (ULN), except for\n Gilbert's syndrome (direct bilirubin must be <2.0*ULN)\n 2. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) \u22642.5*ULN.\n 3. Estimated glomerular filtration rate (eGFR) \u226530 (mL/min/1.73 square meter [m2]),\n using the modification of diet in renal disease (MDRD) equation\n 4. Absolute neutrophil count (ANC) \u22651000 per cubic millimeter (/mm3) (\u22651.0*109 per\n liter [/L]); \u2265750/mm3 (\u22650.75*109/L) may be acceptable for participants with >50%\n of plasma cells in BM\n 5. Platelet count \u226575,000/ mm3 (\u226575*109/L); \u226550,000/ mm3 (\u226550*109/L) may be\n acceptable for participants with >50% of plasma cells in BM\n 6. Hemoglobin \u22657.5 g/dL without transfusion within 7 days before the lab test.\n 7. Serum albumin \u22652.5 g/dL.\n 9. Female patients who:\n 1. are postmenopausal for at least 1 year prior to screening OR\n 2. are surgically sterile OR\n 3. If they are of childbearing potential, agree to practice 1 highly effective\n method of contraception and 1 additional effective barrier method at the same\n time from study entry through 30 days after the last dose of study drug OR\n 4. agree to practice true abstinence if in line with the preferred, usual lifestyle\n [periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation\n methods), withdrawal, spermicides only, and lactational amenorrhea are not\n acceptable. Female and male condoms should not be used together]\n 10. Male patients, even if surgically sterilized (postvasectomy) who:\n 1. Agree to practice effective barrier contraception during the entire study and\n through 90 days after last dose of study drug OR\n 2. Agree to practice true abstinence if in line with the preferred, usual lifestyle\n [periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation\n methods), withdrawal, spermicides only, and lactational amenorrhea are not\n acceptable. Female and male condoms should not be used together]\n Inclusion criteria Part 2 (both RRMM and RRNHL patients)\n 1. ECOG performance score of 0 or 1.\n 2. Normal QTcF on screening ECG, defined as QTcF of \u2264450 ms in males or \u2264470 ms in\n females\n 3. Must meet the following clinical laboratory criteria at study entry:\n 1. Total bilirubin \u22641.5*the ULN, except for Gilbert's syndrome (direct bilirubin\n must be <2.0*ULN)\n 2. Serum ALT and AST \u22642.5*ULN\n 3. eGFR \u226530 mL/min/1.73 m2(MDRD equation)\n 4. ANC \u22651000 mm3 (\u22651.0*109 /L); a count of \u2265750/mm3 (\u22650.75*109/L) may be acceptable\n for participant with >50% of plasma cells in BM\n 5. Platelet count \u226575,000/ mm3 (\u226575*109/L); a value of \u226550,000/ mm3(\u226550*109/L) may\n be acceptable for participants with >50% of plasma cells in BM\n 6. Hemoglobin \u22657.5 g/dL without transfusion within 7 days before the lab test\n 7. Serum albumin \u22652.5 g/dL\n 4. Female patients who:\n 1. are postmenopausal for at least 1 year prior to screening OR\n 2. are surgically sterile OR\n 3. If they are of childbearing potential, agree to practice 1 highly effective\n method of contraception and 1 additional effective barrier method at the same\n time from study entry through 30 days after last dose of study drug OR\n 4. agree to practice true abstinence if in line with the preferred, usual lifestyle\n [periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation\n methods), withdrawal, spermicides only, and lactational amenorrhea are not\n acceptable. Female and male condoms should not be used together]\n 5. Male patients, even if surgically sterilized (postvasectomy) who:\n 1. Agree to practice effective barrier contraception during the entire study and\n through 90 days after the last dose of study drug OR\n 2. Agree to practice true abstinence if in line with the preferred and usual\n lifestyle [periodic abstinence (e.g., calendar, ovulation, symptothermal,\n postovulation methods), withdrawal, spermicides only, and lactational amenorrhea\n are not acceptable. Female and male condoms should not be used together]\n Inclusion Criteria Part 2 for RRNHL patients\n 6. Pathologically confirmed diagnosis of the following NHL subtype based on local\n pathology report:\n 1. Mantle cell lymphoma (MCL) i. Nodal MCL\n 2. Diffuse large B-cell lymphoma (DLBCL) i. DLBCL-NOS ii. Plasmablastic lymphoma\n (PbL) iii. Primary effusion lymphoma (PEL). iv. Primary effusion lymphoma (PMBL)\n 3. Follicular lymphoma\n 4. Burkitt lymphoma (BL)\n 5. Peripheral T-cell lymphoma (PTCL) i. PTCL-NOS (eligible at MTD/RPTD if biopsy\n evidence of CD38 positivity) ii. Angioimmunoblastic T-cell lymphoma (AITL)\n 6. Extranodal NK/T-cell lymphoma (ENKTL)-nasal type\n 7. RRNHL, having failed treatment with, is intolerant to, or is determined not to be a\n candidate for available therapies considered standard of care (SOC) or are known to\n confer clinical benefit.\n 8. At least 1 measurable site of disease according to the Lugano classification for\n lymphoma.\n 1. A measurable nodal lesion with longest diameter (LDi) greater than 1.5cm OR\n 2. A measurable extranodal lesion with LDi greater than 1.0cm\n 9. Evidence of a CD38 positive tumor. Any of the following are acceptable:\n 1. Evidence of CD38 expression from most recent biopsy or blood sample [either flow\n cytometry (FCM) or immunohistochemistry (IHC)] OR\n 2. The most recently archived tissue assessed for CD38 expression by IHC OR\n 3. Fresh biopsy for CD38 expression assessment by IHC within 35 days of Cycle 1 Day\n 1 OR\n 4. Fresh blood sample with circulating NHL cells assessed by FCM within 35 days of\n Cycle 1 Day 1 (BM biopsy excisional lymph node biopsy, core biopsy of any\n involved organ are all acceptable methods, find needle aspirate is not. Any level\n of positive CD38 expression is eligible). Fine needle aspirate may be accepted on\n a case-by-case basis after discussion with the medical monitor of the sponsor.\n Inclusion Criteria Part 2 for RRMM patients\n 1. Confirmed diagnosis of MM per IMWG diagnosis criteria:\n 2. RRMM, having failed treatment with, is intolerant to, or is determined not to be a\n candidate for available therapies considered SOC or are known to confer clinical\n benefit.\n 3. Must meet the following criteria for prior therapy:\n 1. Refractory or intolerant to \u22651 PI and \u22651 IMiD\n 2. Receipt of \u22653 prior lines of therapy or \u22652 prior lines of therapy if 1 of those\n lines included a combination of a PI or IMiD (prior treatment with anti-CD38\n therapy is permitted except for patients enrolled in the anti-CD38 therapy na\u00efve\n cohort)\n 3. Daratumumab RR cohorts: RR to daratumumab at any time during treatment. Patients\n RR to other anti-CD38 therapies are excluded.\n 4. Anti-CD38 therapy na\u00efve cohort: must not have received any prior anti CD-38\n therapy.\n 4. Measurable disease, defined as \u22651 of the following\n 1. Serum M-protein \u226550 mg/dL (\u22655 g/L) on SPEP.\n 2. Urine M-protein \u2265200 mg/24 hours on UPEP.\n 3. Serum FLC assay result with and involved FLC level \u226510 mg/dL (\u2265100mg/L), provided\n the serum FLC ratio is abnormal.\n 5. Serum M-protein, urine M-protein or involved immunoglobulin FLC not meeting measurable\n disease criteria if at least 1 of the following criteria is met:\n 1. BM aspirate/biopsy showing plasma cell percentage \u226530%\n 2. PET imaging showing at least 1 plasmacytoma lesion with a single diameter \u22652 cm.\n Exclusion Criteria for Part 1 (RRMM patients only):\n 1. With polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin\n changes (POEMS) syndrome, monoclonal gammopathy of unknown significance, smoldering\n myeloma, solitary plasmacytoma, amyloidosis, Waldenstr\u00f6m macroglobulinemia, or\n Immunoglobulin M (IgM) myeloma.\n 2. With sensory or motor neuropathy of NCI CTCAE V5 Grade \u22653.\n 3. Have received final dose of any of the following treatments/procedures within the\n following interval before the first dose of MT-0169:\n - Myeloma-specific therapy, including PIs and IMiDs: 14 days\n - Anti-CD38 (a) therapy: Isatuximab 90 days; daratumumab 60 days\n - Corticosteroid therapy for myeloma: 7 days\n - Radiation therapy for localized bone lesions: 14 days\n - Major surgery:30 days\n - Autologous stem cell transplant: 90 days\n - Investigational therapy: 30 days\n 4. Have received an allogeneic stem cell transplant or organ transplantation.\n 5. Have not recovered to Grade \u22641 or baseline, from adverse reactions to prior myeloma\n treatment or procedures (chemotherapy, immunotherapy, radiation therapy) excluding\n alopecia and Grade 2 neuropathy.\n 6. With clinical signs of central nervous system (CNS) involvement of MM.\n 7. With a history of myelodysplastic syndrome or another malignancy other than MM except\n for the following: any malignancy in complete remission for 3 years, adequately\n treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in\n situ, superficial bladder cancer, or asymptomatic prostate cancer without known\n metastatic disease and not requiring therapy or requiring only hormonal therapy and\n with normal prostate-specific antigen level for \u22651 year before the start of study\n therapy.\n 8. With known or suspected light chain amyloidosis of any organ (amyloid on the BM biopsy\n without other evidence of amyloidosis is acceptable).\n 9. With any of the following cardiovascular conditions:\n 1. Congestive heart failure (NYHA) class \u2265II or left ventricular ejection fraction\n (LVEF <40%, cardiac myopathy, active ischemia, or any other uncontrolled cardiac\n condition or myocardial infarction or clinically significant arrhythmia requiring\n therapy including anticoagulants within the past 6 months or at screening\n 2. Resting tachycardia (heart rate of > 100 bpm) at screening\n 3. Clinically significant uncontrolled hypertension at screening\n 4. Cardiac MRI at screening demonstrates evidence of infiltrative disease of the\n myocardium\n 10. With a history of document significant pleural or pericardial effusions within 3\n months before the start of treatment, including:\n 1. Pericarditis (any Grade)\n 2. Pericardial effusion (Grade \u22652)\n 3. Non-malignant pleural effusion (Grade \u22652)\n 4. Malignant pleural effusion (Grade \u22652)\n 11. Patients with a history of noncardiogenic pulmonary edema associated with diffuse\n peripheral edema and history of intravascular hypovolemia associated with systemic\n antineoplastic therapy.\n 12. With chronic or active infection requiring systemic therapy, history of symptomatic\n viral infection that has not been fully cured.\n 1. With HIV and an undetectable viral load and CD4+ T-cell (CD4+) counts \u2265350\n cells/mL may be allowed but patient must be taking appropriate opportunistic\n infection prophylaxis if clinically relevant\n 2. With positive HBV serology may be allowed if undetectable viral load, receiving\n antiviral prophylaxis for potential HBV reactivation per institutional guidelines\n 3. With positive HCV serology may be allowed if quantitative PCR for plasma HCV RNA\n is below the lower limit of detection. Concurrent antiviral HCV treatment per\n institutional guidelines is allowed.\n 13. Have received a live attenuated vaccine within 28 days of first dose of MT-0169.\n 14. With a history of \u2265 Grade 2 systemic inflammatory response syndrome (SIRS)/ cytokine\n release syndrome (CRS) reactions following infusion with any monoclonal antibodies or\n Chimeric Antigen Receptor (CAR) T therapy\n 15. With a chronic condition requiring systemic corticosteroids at >10 mg/day of\n prednisone or equivalent.\n 16. Are lactating and breastfeeding or have a positive serum pregnancy test during the\n screening period or patients of reproductive potential who are not employing an\n effective birth control\n 17. With a concurrent medical or psychiatric illness that would preclude study conduct and\n assessment including, but not limited to, uncontrolled medical conditions, active\n infection, risk of bleeding, diabetes mellitus, pulmonary disease, alcoholic liver\n disease, or primary biliary cirrhosis.\n 18. With known allergy or intolerance to any of the drugs used in the study or excipients\n in MT-0169\n 19. With a history of hypersensitivity or serious toxic reaction to kanamycin or another\n aminoglycoside.\n Exclusion Criteria for Part 2 NHL patients only:\n 1. With known CNS lymphoma (exception if history of CNS disease and evidence of SD on\n neuroimaging separated by at least 4 weeks and within 4 weeks of Cycle 1 Day 1)\n 2. Have received a final dose of any of the following treatments/procedures within the\n following minimum interval before the first dose of MT-0169:\n - Nitrosoureas: 6 weeks\n - Chemotherapy: 4 weeks\n - Small molecules (<0.9 kDa): 5 half-lives or at least 2 weeks\n - Therapeutic antibodies: 4 weeks\n - Radio/toxin -immunoconjugates: 12 weeks\n - Radiation therapy - target lesion (measurable disease): 4 weeks\n - Radiation therapy - nontarget lesion: 2 weeks\n - Investigational chemotherapeutic agents or antibodies: 4 weeks\n - Daratumumab: 60 days\n - Isatuximab: 90 days\n - (MCL) Bruton's tyrosine kinase inhibitors: 2 weeks or 5 half-lives, whichever is\n longer\n - Major surgery (determined by the principal investigator and Sponsor): 4 weeks\n - Autologous stem cell transplant: 100 days\n - Allogenic stem cell transplant: 180 days (patients with graft vs host disease >\n Grade 1 will be excluded)\n 3. With a history of myelodysplastic syndrome or malignancy (other than NHL) except for\n the following: any malignancy in complete remission for 3 years, adequately treated\n local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ,\n superficial bladder cancer, or asymptomatic prostate cancer without known metastatic\n disease and not requiring therapy or requiring only hormonal therapy and with normal\n prostate-specific antigen level for \u22651 year before the start of study therapy\n Exclusion Criteria for Part 2 RRMM patients only:\n 4. With POEMS syndrome, monoclonal gammopathy of unknown significance, smoldering\n myeloma, solitary plasmacytoma, amyloidosis, Waldenstr\u00f6m macroglobulinemia, IgM\n myeloma.\n 5. Have received a final dose of any of the following treatments/procedures within the\n following interval before the first dose of MT-0169:\n - Myeloma-specific therapy, including PIs and IMiDs: 14 days\n - Anti-CD38 therapy - Isatuximab: 90 days\n - Anti-CD38 therapy - Daratumumab: 60 days\n - Corticosteroid therapy for myeloma: 7 days\n - Radiation therapy for localized bone lesions: 14 days\n - Major surgery: 30 days\n - Autologous stem cell transplant: 90 days\n - Investigational therapy: 30 days\n 6. Have received an allogenic stem cell or organ transplant.\n 7. With clinical signs of CNS involvement of MM.\n 8. With a history of myelodysplastic syndrome or another malignancy other than MM except\n or any malignancy in complete remission for 3 years, adequately treated local basal\n cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial\n bladder cancer, or asymptomatic prostate cancer without known metastatic disease and\n not requiring therapy or requiring only hormonal therapy and with normal\n prostate-specific antigen level for >1 year before the start of study therapy.\n 9. With known or suspected light chain amyloidosis of any organ (amyloid on BM biopsy\n without other evidence of amyloidosis is acceptable).\n Exclusion Criteria for Part 2 (both RRMM and NHL patients):\n 10. Failed to recover to Grade \u22641 or baseline from adverse reactions to prior treatment or\n procedures (chemotherapy, immunotherapy, radiation therapy) excluding alopecia and\n stable Grade 2 neuropathy.\n 11. With any of the following cardiovascular conditions:\n 1. Congestive heart failure (NYHA) class \u2265II LVEF <40%, cardiac myopathy, active\n ischemia, or any other uncontrolled cardiac condition such as angina pectoris or\n myocardial infarction or clinically significant arrhythmia requiring therapy\n including anticoagulants within the past 6 months or at screening\n 2. Resting tachycardia (heart rate of >100 bpm) at screening\n 3. Clinically significant uncontrolled hypertension at screening\n 4. Cardiac MRI at screening demonstrating infiltrative disease of the myocardium\n 12. With a history of documented significant pleural or pericardial effusions,\n specifically any of the following within 3 months before the start of study treatment:\n 1. Pericarditis (any grade)\n 2. Pericardial effusion (Grade \u22652)\n 3. Non-malignant pleural effusion (Grade \u22652) OR\n 4. Malignant pleural effusion (Grade \u22653)\n 13. With a history of noncardiogenic pulmonary edema associated with peripheral edema and\n a history of intravascular hypovolemia associated with antineoplastic therapy.\n 14. With chronic or active infection requiring systemic therapy and a history of\n symptomatic viral infection that is not fully controlled or cured. The following\n exceptions apply for those with positive serologies of HIV, HBV, or HCV:\n 1. With HIV and undetectable viral load and CD4+ T-cell (CD4+) counts \u2265350 cells/mL\n may be enrolled, but must be taking appropriate opportunistic infection\n prophylaxis, if clinically relevant.\n 2. With positive HBV serology are eligible if they have an undetectable viral load\n and the patient will receive antiviral prophylaxis for potential HBV reactivation\n per institutional guidelines.\n 3. With positive HCV serology are eligible if qPCR for plasma HCV RNA is below the\n lower limit of detection. Concurrent antiviral HCV treatment per institutional\n guidelines is allowed.\n 15. Have received a live attenuated vaccine within 28 days of the first dose of MT-0169\n 16. With a history of Grade \u22652 SIRS/CRS reactions following infusion with any mAbs or CAR\n T therapy.\n 17. With a chronic condition requiring systemic corticosteroids \u226510 mg/day of prednisone\n or equivalent.\n 18. With a known allergy or intolerance to any of the drugs in the study or excipients in\n the MT-0169 formulation.\n 19. Are lactating and breastfeeding or have a positive serum pregnancy test during the\n screening period or male or female patients of reproductive potential who are not\n employing effective birth control.\n 20. With a concurrent medical or psychiatric illness that would preclude study conduct and\n assessment including, but not limited to, uncontrolled medical conditions,\n uncontrolled and active infection, uncontrolled risk of bleeding, uncontrolled\n diabetes mellitus, pulmonary disease, alcoholic liver disease, or primary biliary\n cirrhosis.\n 21. With a history of hypersensitivity or serious toxic reactions to kanamycin or another\n aminoglycoside", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
+{"input": "This will be a Phase 1 Open-Label, dose escalation and expansion study of MT-0169 (an\n Engineered toxin body (ETB) in patients with relapsed or refractory multiple myeloma or\n non-Hodgkin lymphoma. MT-0169 is an investigational drug that recognizes and binds to the\n CD38 receptor, which may be found on the surface of multiple myeloma and non-Hodgkin lymphoma\n cancer cells. It delivers a dose of a modified toxin that kills these cells.\n ;\n ;\n Inclusion Criteria Part 1 (RRMM patients only)\n 1. Confirmed diagnosis of MM per revised IMWG diagnostic criteria\n 2. Patients with RRMM who have failed treatment with, are intolerant to, or are not\n candidates for available therapies that are known to confer clinical benefit\n 3. Must meet all of the following criteria for prior therapy:\n 1. Must be refractory to \u22651 proteasome inhibitor (PI), \u22651 immunomodulatory drug\n (IMiD), and \u22651 steroid\n 2. Must either have received \u22653 prior lines of therapy or \u22652 prior lines of therapy\n if 1 line included a combination of PI and IMiD (prior treatment with anti-CD38\n therapy is permitted).\n 4. With measurable disease, defined as \u22651 of the following:\n 1. Serum M-protein \u2265500 mg/dL (\u22655 g/L) on serum protein electrophoresis (SPEP).\n 2. Urine M-protein \u2265200 mg/24 h on urine protein electrophoresis (UPEP).\n 3. Serum FLC assay result with an involved FLC level \u226510 mg/dL (\u2265100 mg/L) if serum\n FLC ratio is abnormal.\n 5. Patients with serum M-protein, urine M-protein, or involved immunoglobulin FLC not\n meeting the measurable disease criteria above will be eligible if they have \u22651 of the\n following:\n 1. Bone marrow (BM) aspirate/biopsy with plasma cell percentage \u226530%\n 2. PET imaging with \u22651 plasmacytoma lesion with a single diameter of \u22652cm.\n 6. With Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1.\n 7. With normal QT interval corrected by the Fridericia method (QTcF) on screening\n electrocardiogram (ECG)[ QTcF of \u2264450 millisecond (ms) in males or \u2264470 ms in females]\n 8. Must meet the following clinical laboratory criteria at entry:\n 1. Total bilirubin \u22641.5*the upper limit of the normal range (ULN), except for\n Gilbert's syndrome (direct bilirubin must be <2.0*ULN)\n 2. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) \u22642.5*ULN.\n 3. Estimated glomerular filtration rate (eGFR) \u226530 (mL/min/1.73 square meter [m2]),\n using the modification of diet in renal disease (MDRD) equation\n 4. Absolute neutrophil count (ANC) \u22651000 per cubic millimeter (/mm3) (\u22651.0*109 per\n liter [/L]); \u2265750/mm3 (\u22650.75*109/L) may be acceptable for participants with >50%\n of plasma cells in BM\n 5. Platelet count \u226575,000/ mm3 (\u226575*109/L); \u226550,000/ mm3 (\u226550*109/L) may be\n acceptable for participants with >50% of plasma cells in BM\n 6. Hemoglobin \u22657.5 g/dL without transfusion within 7 days before the lab test.\n 7. Serum albumin \u22652.5 g/dL.\n 9. Female patients who:\n 1. are postmenopausal for at least 1 year prior to screening OR\n 2. are surgically sterile OR\n 3. If they are of childbearing potential, agree to practice 1 highly effective\n method of contraception and 1 additional effective barrier method at the same\n time from study entry through 30 days after the last dose of study drug OR\n 4. agree to practice true abstinence if in line with the preferred, usual lifestyle\n [periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation\n methods), withdrawal, spermicides only, and lactational amenorrhea are not\n acceptable. Female and male condoms should not be used together]\n 10. Male patients, even if surgically sterilized (postvasectomy) who:\n 1. Agree to practice effective barrier contraception during the entire study and\n through 90 days after last dose of study drug OR\n 2. Agree to practice true abstinence if in line with the preferred, usual lifestyle\n [periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation\n methods), withdrawal, spermicides only, and lactational amenorrhea are not\n acceptable. Female and male condoms should not be used together]\n Inclusion criteria Part 2 (both RRMM and RRNHL patients)\n 1. ECOG performance score of 0 or 1.\n 2. Normal QTcF on screening ECG, defined as QTcF of \u2264450 ms in males or \u2264470 ms in\n females\n 3. Must meet the following clinical laboratory criteria at study entry:\n 1. Total bilirubin \u22641.5*the ULN, except for Gilbert's syndrome (direct bilirubin\n must be <2.0*ULN)\n 2. Serum ALT and AST \u22642.5*ULN\n 3. eGFR \u226530 mL/min/1.73 m2(MDRD equation)\n 4. ANC \u22651000 mm3 (\u22651.0*109 /L); a count of \u2265750/mm3 (\u22650.75*109/L) may be acceptable\n for participant with >50% of plasma cells in BM\n 5. Platelet count \u226575,000/ mm3 (\u226575*109/L); a value of \u226550,000/ mm3(\u226550*109/L) may\n be acceptable for participants with >50% of plasma cells in BM\n 6. Hemoglobin \u22657.5 g/dL without transfusion within 7 days before the lab test\n 7. Serum albumin \u22652.5 g/dL\n 4. Female patients who:\n 1. are postmenopausal for at least 1 year prior to screening OR\n 2. are surgically sterile OR\n 3. If they are of childbearing potential, agree to practice 1 highly effective\n method of contraception and 1 additional effective barrier method at the same\n time from study entry through 30 days after last dose of study drug OR\n 4. agree to practice true abstinence if in line with the preferred, usual lifestyle\n [periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation\n methods), withdrawal, spermicides only, and lactational amenorrhea are not\n acceptable. Female and male condoms should not be used together]\n 5. Male patients, even if surgically sterilized (postvasectomy) who:\n 1. Agree to practice effective barrier contraception during the entire study and\n through 90 days after the last dose of study drug OR\n 2. Agree to practice true abstinence if in line with the preferred and usual\n lifestyle [periodic abstinence (e.g., calendar, ovulation, symptothermal,\n postovulation methods), withdrawal, spermicides only, and lactational amenorrhea\n are not acceptable. Female and male condoms should not be used together]\n Inclusion Criteria Part 2 for RRNHL patients\n 6. Pathologically confirmed diagnosis of the following NHL subtype based on local\n pathology report:\n 1. Mantle cell lymphoma (MCL) i. Nodal MCL\n 2. Diffuse large B-cell lymphoma (DLBCL) i. DLBCL-NOS ii. Plasmablastic lymphoma\n (PbL) iii. Primary effusion lymphoma (PEL). iv. Primary effusion lymphoma (PMBL)\n 3. Follicular lymphoma\n 4. Burkitt lymphoma (BL)\n 5. Peripheral T-cell lymphoma (PTCL) i. PTCL-NOS (eligible at MTD/RPTD if biopsy\n evidence of CD38 positivity) ii. Angioimmunoblastic T-cell lymphoma (AITL)\n 6. Extranodal NK/T-cell lymphoma (ENKTL)-nasal type\n 7. RRNHL, having failed treatment with, is intolerant to, or is determined not to be a\n candidate for available therapies considered standard of care (SOC) or are known to\n confer clinical benefit.\n 8. At least 1 measurable site of disease according to the Lugano classification for\n lymphoma.\n 1. A measurable nodal lesion with longest diameter (LDi) greater than 1.5cm OR\n 2. A measurable extranodal lesion with LDi greater than 1.0cm\n 9. Evidence of a CD38 positive tumor. Any of the following are acceptable:\n 1. Evidence of CD38 expression from most recent biopsy or blood sample [either flow\n cytometry (FCM) or immunohistochemistry (IHC)] OR\n 2. The most recently archived tissue assessed for CD38 expression by IHC OR\n 3. Fresh biopsy for CD38 expression assessment by IHC within 35 days of Cycle 1 Day\n 1 OR\n 4. Fresh blood sample with circulating NHL cells assessed by FCM within 35 days of\n Cycle 1 Day 1 (BM biopsy excisional lymph node biopsy, core biopsy of any\n involved organ are all acceptable methods, find needle aspirate is not. Any level\n of positive CD38 expression is eligible). Fine needle aspirate may be accepted on\n a case-by-case basis after discussion with the medical monitor of the sponsor.\n Inclusion Criteria Part 2 for RRMM patients\n 1. Confirmed diagnosis of MM per IMWG diagnosis criteria:\n 2. RRMM, having failed treatment with, is intolerant to, or is determined not to be a\n candidate for available therapies considered SOC or are known to confer clinical\n benefit.\n 3. Must meet the following criteria for prior therapy:\n 1. Refractory or intolerant to \u22651 PI and \u22651 IMiD\n 2. Receipt of \u22653 prior lines of therapy or \u22652 prior lines of therapy if 1 of those\n lines included a combination of a PI or IMiD (prior treatment with anti-CD38\n therapy is permitted except for patients enrolled in the anti-CD38 therapy na\u00efve\n cohort)\n 3. Daratumumab RR cohorts: RR to daratumumab at any time during treatment. Patients\n RR to other anti-CD38 therapies are excluded.\n 4. Anti-CD38 therapy na\u00efve cohort: must not have received any prior anti CD-38\n therapy.\n 4. Measurable disease, defined as \u22651 of the following\n 1. Serum M-protein \u226550 mg/dL (\u22655 g/L) on SPEP.\n 2. Urine M-protein \u2265200 mg/24 hours on UPEP.\n 3. Serum FLC assay result with and involved FLC level \u226510 mg/dL (\u2265100mg/L), provided\n the serum FLC ratio is abnormal.\n 5. Serum M-protein, urine M-protein or involved immunoglobulin FLC not meeting measurable\n disease criteria if at least 1 of the following criteria is met:\n 1. BM aspirate/biopsy showing plasma cell percentage \u226530%\n 2. PET imaging showing at least 1 plasmacytoma lesion with a single diameter \u22652 cm.\n Exclusion Criteria for Part 1 (RRMM patients only):\n 1. With polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin\n changes (POEMS) syndrome, monoclonal gammopathy of unknown significance, smoldering\n myeloma, solitary plasmacytoma, amyloidosis, Waldenstr\u00f6m macroglobulinemia, or\n Immunoglobulin M (IgM) myeloma.\n 2. With sensory or motor neuropathy of NCI CTCAE V5 Grade \u22653.\n 3. Have received final dose of any of the following treatments/procedures within the\n following interval before the first dose of MT-0169:\n - Myeloma-specific therapy, including PIs and IMiDs: 14 days\n - Anti-CD38 (a) therapy: Isatuximab 90 days; daratumumab 60 days\n - Corticosteroid therapy for myeloma: 7 days\n - Radiation therapy for localized bone lesions: 14 days\n - Major surgery:30 days\n - Autologous stem cell transplant: 90 days\n - Investigational therapy: 30 days\n 4. Have received an allogeneic stem cell transplant or organ transplantation.\n 5. Have not recovered to Grade \u22641 or baseline, from adverse reactions to prior myeloma\n treatment or procedures (chemotherapy, immunotherapy, radiation therapy) excluding\n alopecia and Grade 2 neuropathy.\n 6. With clinical signs of central nervous system (CNS) involvement of MM.\n 7. With a history of myelodysplastic syndrome or another malignancy other than MM except\n for the following: any malignancy in complete remission for 3 years, adequately\n treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in\n situ, superficial bladder cancer, or asymptomatic prostate cancer without known\n metastatic disease and not requiring therapy or requiring only hormonal therapy and\n with normal prostate-specific antigen level for \u22651 year before the start of study\n therapy.\n 8. With known or suspected light chain amyloidosis of any organ (amyloid on the BM biopsy\n without other evidence of amyloidosis is acceptable).\n 9. With any of the following cardiovascular conditions:\n 1. Congestive heart failure (NYHA) class \u2265II or left ventricular ejection fraction\n (LVEF <40%, cardiac myopathy, active ischemia, or any other uncontrolled cardiac\n condition or myocardial infarction or clinically significant arrhythmia requiring\n therapy including anticoagulants within the past 6 months or at screening\n 2. Resting tachycardia (heart rate of > 100 bpm) at screening\n 3. Clinically significant uncontrolled hypertension at screening\n 4. Cardiac MRI at screening demonstrates evidence of infiltrative disease of the\n myocardium\n 10. With a history of document significant pleural or pericardial effusions within 3\n months before the start of treatment, including:\n 1. Pericarditis (any Grade)\n 2. Pericardial effusion (Grade \u22652)\n 3. Non-malignant pleural effusion (Grade \u22652)\n 4. Malignant pleural effusion (Grade \u22652)\n 11. Patients with a history of noncardiogenic pulmonary edema associated with diffuse\n peripheral edema and history of intravascular hypovolemia associated with systemic\n antineoplastic therapy.\n 12. With chronic or active infection requiring systemic therapy, history of symptomatic\n viral infection that has not been fully cured.\n 1. With HIV and an undetectable viral load and CD4+ T-cell (CD4+) counts \u2265350\n cells/mL may be allowed but patient must be taking appropriate opportunistic\n infection prophylaxis if clinically relevant\n 2. With positive HBV serology may be allowed if undetectable viral load, receiving\n antiviral prophylaxis for potential HBV reactivation per institutional guidelines\n 3. With positive HCV serology may be allowed if quantitative PCR for plasma HCV RNA\n is below the lower limit of detection. Concurrent antiviral HCV treatment per\n institutional guidelines is allowed.\n 13. Have received a live attenuated vaccine within 28 days of first dose of MT-0169.\n 14. With a history of \u2265 Grade 2 systemic inflammatory response syndrome (SIRS)/ cytokine\n release syndrome (CRS) reactions following infusion with any monoclonal antibodies or\n Chimeric Antigen Receptor (CAR) T therapy\n 15. With a chronic condition requiring systemic corticosteroids at >10 mg/day of\n prednisone or equivalent.\n 16. Are lactating and breastfeeding or have a positive serum pregnancy test during the\n screening period or patients of reproductive potential who are not employing an\n effective birth control\n 17. With a concurrent medical or psychiatric illness that would preclude study conduct and\n assessment including, but not limited to, uncontrolled medical conditions, active\n infection, risk of bleeding, diabetes mellitus, pulmonary disease, alcoholic liver\n disease, or primary biliary cirrhosis.\n 18. With known allergy or intolerance to any of the drugs used in the study or excipients\n in MT-0169\n 19. With a history of hypersensitivity or serious toxic reaction to kanamycin or another\n aminoglycoside.\n Exclusion Criteria for Part 2 NHL patients only:\n 1. With known CNS lymphoma (exception if history of CNS disease and evidence of SD on\n neuroimaging separated by at least 4 weeks and within 4 weeks of Cycle 1 Day 1)\n 2. Have received a final dose of any of the following treatments/procedures within the\n following minimum interval before the first dose of MT-0169:\n - Nitrosoureas: 6 weeks\n - Chemotherapy: 4 weeks\n - Small molecules (<0.9 kDa): 5 half-lives or at least 2 weeks\n - Therapeutic antibodies: 4 weeks\n - Radio/toxin -immunoconjugates: 12 weeks\n - Radiation therapy - target lesion (measurable disease): 4 weeks\n - Radiation therapy - nontarget lesion: 2 weeks\n - Investigational chemotherapeutic agents or antibodies: 4 weeks\n - Daratumumab: 60 days\n - Isatuximab: 90 days\n - (MCL) Bruton's tyrosine kinase inhibitors: 2 weeks or 5 half-lives, whichever is\n longer\n - Major surgery (determined by the principal investigator and Sponsor): 4 weeks\n - Autologous stem cell transplant: 100 days\n - Allogenic stem cell transplant: 180 days (patients with graft vs host disease >\n Grade 1 will be excluded)\n 3. With a history of myelodysplastic syndrome or malignancy (other than NHL) except for\n the following: any malignancy in complete remission for 3 years, adequately treated\n local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ,\n superficial bladder cancer, or asymptomatic prostate cancer without known metastatic\n disease and not requiring therapy or requiring only hormonal therapy and with normal\n prostate-specific antigen level for \u22651 year before the start of study therapy\n Exclusion Criteria for Part 2 RRMM patients only:\n 4. With POEMS syndrome, monoclonal gammopathy of unknown significance, smoldering\n myeloma, solitary plasmacytoma, amyloidosis, Waldenstr\u00f6m macroglobulinemia, IgM\n myeloma.\n 5. Have received a final dose of any of the following treatments/procedures within the\n following interval before the first dose of MT-0169:\n - Myeloma-specific therapy, including PIs and IMiDs: 14 days\n - Anti-CD38 therapy - Isatuximab: 90 days\n - Anti-CD38 therapy - Daratumumab: 60 days\n - Corticosteroid therapy for myeloma: 7 days\n - Radiation therapy for localized bone lesions: 14 days\n - Major surgery: 30 days\n - Autologous stem cell transplant: 90 days\n - Investigational therapy: 30 days\n 6. Have received an allogenic stem cell or organ transplant.\n 7. With clinical signs of CNS involvement of MM.\n 8. With a history of myelodysplastic syndrome or another malignancy other than MM except\n or any malignancy in complete remission for 3 years, adequately treated local basal\n cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial\n bladder cancer, or asymptomatic prostate cancer without known metastatic disease and\n not requiring therapy or requiring only hormonal therapy and with normal\n prostate-specific antigen level for >1 year before the start of study therapy.\n 9. With known or suspected light chain amyloidosis of any organ (amyloid on BM biopsy\n without other evidence of amyloidosis is acceptable).\n Exclusion Criteria for Part 2 (both RRMM and NHL patients):\n 10. Failed to recover to Grade \u22641 or baseline from adverse reactions to prior treatment or\n procedures (chemotherapy, immunotherapy, radiation therapy) excluding alopecia and\n stable Grade 2 neuropathy.\n 11. With any of the following cardiovascular conditions:\n 1. Congestive heart failure (NYHA) class \u2265II LVEF <40%, cardiac myopathy, active\n ischemia, or any other uncontrolled cardiac condition such as angina pectoris or\n myocardial infarction or clinically significant arrhythmia requiring therapy\n including anticoagulants within the past 6 months or at screening\n 2. Resting tachycardia (heart rate of >100 bpm) at screening\n 3. Clinically significant uncontrolled hypertension at screening\n 4. Cardiac MRI at screening demonstrating infiltrative disease of the myocardium\n 12. With a history of documented significant pleural or pericardial effusions,\n specifically any of the following within 3 months before the start of study treatment:\n 1. Pericarditis (any grade)\n 2. Pericardial effusion (Grade \u22652)\n 3. Non-malignant pleural effusion (Grade \u22652) OR\n 4. Malignant pleural effusion (Grade \u22653)\n 13. With a history of noncardiogenic pulmonary edema associated with peripheral edema and\n a history of intravascular hypovolemia associated with antineoplastic therapy.\n 14. With chronic or active infection requiring systemic therapy and a history of\n symptomatic viral infection that is not fully controlled or cured. The following\n exceptions apply for those with positive serologies of HIV, HBV, or HCV:\n 1. With HIV and undetectable viral load and CD4+ T-cell (CD4+) counts \u2265350 cells/mL\n may be enrolled, but must be taking appropriate opportunistic infection\n prophylaxis, if clinically relevant.\n 2. With positive HBV serology are eligible if they have an undetectable viral load\n and the patient will receive antiviral prophylaxis for potential HBV reactivation\n per institutional guidelines.\n 3. With positive HCV serology are eligible if qPCR for plasma HCV RNA is below the\n lower limit of detection. Concurrent antiviral HCV treatment per institutional\n guidelines is allowed.\n 15. Have received a live attenuated vaccine within 28 days of the first dose of MT-0169\n 16. With a history of Grade \u22652 SIRS/CRS reactions following infusion with any mAbs or CAR\n T therapy.\n 17. With a chronic condition requiring systemic corticosteroids \u226510 mg/day of prednisone\n or equivalent.\n 18. With a known allergy or intolerance to any of the drugs in the study or excipients in\n the MT-0169 formulation.\n 19. Are lactating and breastfeeding or have a positive serum pregnancy test during the\n screening period or male or female patients of reproductive potential who are not\n employing effective birth control.\n 20. With a concurrent medical or psychiatric illness that would preclude study conduct and\n assessment including, but not limited to, uncontrolled medical conditions,\n uncontrolled and active infection, uncontrolled risk of bleeding, uncontrolled\n diabetes mellitus, pulmonary disease, alcoholic liver disease, or primary biliary\n cirrhosis.\n 21. With a history of hypersensitivity or serious toxic reactions to kanamycin or another\n aminoglycoside", "output": {"inclusion_biomarker": [["CD38 expression"]], "exclusion_biomarker": []}}
 {"input": "To evaluate the safety and tolerability of sotorasib administered in investigational regimens\n in adult participants with KRAS p.G12C mutant advanced solid tumors.\n ;NA;\n Inclusion Criteria:\n - Men or women greater than or equal to 18 years old.\n - Pathologically documented, locally-advanced or metastatic malignancy with, KRAS p.G12C\n mutation identified through molecular testing performed according to in-country\n requirements. In the United States, this test must be performed in a Clinical\n Laboratory Improvement Amendments (CLIA)-certified laboratory.\n Exclusion Criteria:\n - Primary brain tumor.\n - Spinal cord compression, or untreated, or symptomatic, or active brain metastases, or\n leptomeningeal disease from non-brain tumors.\n - Myocardial infarction within 6 months of study day 1.\n - Gastrointestinal (GI) tract disease causing the inability to take oral medication.", "output": {"inclusion_biomarker": [["KRAS p.G12C"]], "exclusion_biomarker": []}}
 {"input": "This is a phase 2 study to evaluate the safety and efficacy of the combination of INCMGA00012\n and pelareorep and to see how well they work in treating patients with triple negative breast\n cancer that has spread to other parts of the body (metastatic).\n INCMGA00012 is a monoclonal antibody that works by attaching to the programmed cell death\n protein 1 (PD-1) and blocking this pathway, allowing the immune system to recognize and\n attack the cancer cells. Pelareorep is a type of virus called reovirus which occurs naturally\n and may break down cancer cells. Giving INCMGA00012 and pelareorep may slow the growth and\n spread of the cancer to another part of the body.\n ;\n ;\n Inclusion Criteria:\n - Metastatic or inoperable locally advanced, histologically documented triple negative\n breast cancer (TNBC) (negative expression of estrogen receptor [ER], progesterone\n receptor [PR] and human epidermal growth factor receptor 2 [HER2] immunohistochemistry\n [IHC] 0 or 1+, HER2 fluorescence in situ hybridization [FISH] negative if IHC 2+, per\n American Society of Clinical Oncology [ASCO] College of American Pathologists [CAP]\n guidelines)\n - Pre-menopausal and post-menopausal women who have received 1-2 prior lines of systemic\n therapy for metastatic triple negative breast cancer. Patients must have received at\n least one prior line of chemotherapy\n - Patients who have received adjuvant therapy for locally advanced triple negative\n breast cancer may be eligible for the study if they relapse with metastatic disease\n within 6 months since completion of neo-adjuvant/adjuvant systemic therapy. The\n adjuvant/neoadjuvant therapy will be considered as 1 line of therapy\n - Availability of tumor specimen for determination of PD-L1 and additional biomarker\n studies. Patient should be willing to undergo a pre-treatment biopsy as well as a\n biopsy after cycle 2 to evaluate the tumor microenvironment\n - Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2\n - Patients who have received prior treatment with anti-PD-1 or anti-PD-L1 inhibitors are\n eligible for the study\n - Absolute neutrophil count >= 1,000/uL\n - Platelet count >= 100,000/uL\n - Hemoglobin >= 9.0 g/dL\n - Total bilirubin =< 2 x upper limit of normal (ULN) or =< 3 x ULN for subjects with\n Gilbert's disease or liver metastases\n - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN (=< 5 x\n ULN if evidence of hepatic involvement by malignant disease)\n - Estimated glomerular filtration rate (eGFR) >= 40 mL/min/1.73m^2\n - Lactate dehydrogenase (LDH) < 2 x ULN\n - Provision of signed and dated informed consent form\n - Life expectancy >= 3 months, as determined by the investigator\n - Patients must have clinically and/or radiographically documented measurable disease.\n At least one site of disease must be uni-dimensionally measurable as per Response\n Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1\n - For patients receiving therapeutic anticoagulation: stable anticoagulant regimen\n during the 14 days prior to initiation of study treatment\n - Subjects with central nervous system (CNS) metastases treated with radiation therapy\n (whole-brain radiation therapy [WBXRT] or stereotactic radiosurgery [SRS]) are\n eligible if, > 28 days following completion of radiation therapy (XRT), they show\n stable disease on post-treatment magnetic resonance imaging (MRI)/computed tomography\n (CT), are off corticosteroids, and are neurologically stable\n - Female patients of childbearing potential have a negative pregnancy test at baseline.\n Females of childbearing potential are defined as sexually mature women without prior\n hysterectomy or who have had any evidence of menses in the past 12 months. However,\n women who have been amenorrheic for 12 or more months are still considered to be of\n childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anti\n estrogens, or ovarian suppression\n - Patients who are not postmenopausal (>= 12 months of non-therapy-induced\n amenorrhea) or surgically sterile must have a negative urine pregnancy test\n (positive urine tests are to be confirmed by serum test) documented within 14\n days of treatment initiation\n - Sexually active women of childbearing potential enrolled in the study must agree\n to use 2 forms of accepted methods of contraception during the course of the\n study and for 12 weeks after their last dose of study drug. Effective birth\n control includes (a) intrauterine device plus 1 barrier method; (b) on stable\n doses of hormonal contraception for at least 3 months (e.g., oral, injectable,\n implant, transdermal) plus one barrier method; (c) 2 barrier methods. Effective\n barrier methods are male or female condoms, diaphragms, and spermicides (creams\n or gels that contain a chemical to kill sperm); or (d) a vasectomized partner\n Exclusion Criteria:\n - Subjects who have received 4 or more lines prior treatment in the metastatic setting\n - Has active autoimmune disease that has required systemic treatment in the past 2 years\n (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive\n drugs) or a documented history of clinically severe autoimmune disease, or a syndrome\n that requires systemic steroids or immunosuppressive agents. Vitiligo, alopecia,\n hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic\n treatment, celiac disease controlled by diet alone or conditions not expected to recur\n in the absence of an external trigger are permitted\n - History of psychiatric illness or social situations that would limit compliance with\n study requirements. Has a history or current evidence of any condition, therapy, or\n laboratory abnormality that might confound the results of the trial, interfere with\n the subject's participation for the full duration of the trial, or is not in the best\n interest of the subject to participate, in the opinion of the treating investigator\n - Known active, untreated central nervous system (CNS) metastases and/or carcinomatous\n meningitis except for patients with =< 3 small (< 0.6 cm) asymptomatic brain lesions\n where treatment is not indicated. Patients with neurological symptoms must undergo a\n head computed tomography (CT) scan or brain magnetic resonance imaging (MRI) to\n exclude brain metastasis\n - Subjects previously treated with pelareorep\n - Evidence of interstitial lung disease, history of interstitial lung disease, or\n active, noninfectious pneumonitis\n - Prior allogeneic stem cell or solid organ transplantation\n - Patients may not have non-oncology vaccine therapies for prevention of infectious\n disease (for example, seasonal live influenza vaccine, human papilloma virus vaccine)\n within 4 weeks of study drug administration. Vaccination while on study is also\n prohibited except for administration of the inactivated influenza vaccine\n - Known history of human immunodeficiency virus (HIV) or other serious immunocompromised\n state\n - Known positive hepatitis B surface antigen undergoing anti-viral treatment and/or\n active hepatitis C indicated by positive quantitative hepatitis C virus (HCV)\n ribonucleic acid (RNA)\n - Patient is pregnant or breastfeeding\n - Receipt of any investigational treatment or anti-cancer therapy within 14 days of\n enrollment into the study\n - Known hypersensitivity to the study drugs or their components\n - Documented history of a cerebral vascular event (stroke or transient ischemic attack),\n unstable angina, myocardial infarction, or cardiac symptoms consistent with New York\n Heart Association (NYHA) class III-IV within 6 months prior to their first dose of\n study drugs\n - Prior malignancies (except non-melanoma skin cancers, and the following in situ\n cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or\n breast) unless a complete remission was achieved at least 1 year prior to study entry\n - Active alcohol or drug abuse per treating physician\n - Patients may not participate in any other therapeutic clinical trials, including those\n with other investigational agents not included in this trial, throughout the duration\n of this study\n - Toxicity of prior therapy that has not recovered to =< grade 1 or baseline (with the\n exception of any grade of alopecia and anemia not requiring transfusion support)\n - For patients who have received prior immune-checkpoint therapy: Immune-related\n toxicity during prior checkpoint inhibitor therapy for which permanent discontinuation\n of therapy was recommended (per product label or consensus guidelines), OR any\n immune-related toxicity that required intensive or prolonged immunosuppression. (With\n the exception of endocrinopathy that is well controlled on replacement hormones)", "output": {"inclusion_biomarker": [["ER negative", "PR negative", "HER2 negative"]], "exclusion_biomarker": []}}
 {"input": "This is a Phase 1/2, open-label, first-in-human (FIH) study designed to evaluate the safety,\n tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and anticancer activity of\n BLU-222, a selective inhibitor of CDK2.\n ;\n ;\n Inclusion Criteria:\n 1. Advanced solid tumors that has progressed beyond standard of care OR\n 2. ER+ HER2- BC that has progressed following treatment with a CDK4/6 inhibitor OR\n 3. Endometrial and gastric cancer that has progressed after at least 2 prior therapies\n (including one prior platinum therapy) OR\n 4. Platinum refractory or platinum resistant ovarian cancer CCNE1 amplified tumors that\n have progressed beyond standard of care\n Exclusion Criteria:\n 1. Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis.\n 2. Have received the following anticancer therapy:\n a. Previous therapy with CDK2i, PKMYT1i, or WEE1i, except in Part 1A where up to 10\n patients who previously received PKMYT1i, or WEE1 inhibitor will be permitted.\n 3. Have central nervous system (CNS) metastases or spinal cord compression that is\n associated with progressive neurological symptoms or requires increasing doses of\n corticosteroids to control the CNS disease.\n 4. Have known intracranial hemorrhage and/or bleeding diatheses.\n 5. Have clinically active ongoing ILD of any etiology, including drug-induced ILD, and\n radiation pneumonitis within 28 days prior to initiation of study treatment.\n 6. Have any unresolved toxicities from prior therapy greater than CTCAE Grade 1 or that\n have not resolved to baseline at the time of starting the study.\n 7. Have mean resting QTcF > 450 msec, a history of prolonged QT syndrome or Torsades de\n pointes, or a familial history of prolonged QT syndrome.\n 8. Have clinically significant, uncontrolled, cardiovascular disease including congestive\n heart failure Grade III or IV according to the New York Heart Association\n classification; myocardial infarction or unstable angina within the previous 6 months,\n uncontrolled hypertension, or clinically significant, uncontrolled arrhythmias,\n including bradyarrhythmia that may cause QT prolongation (eg, Type II second degree\n heart block or third-degree heart block).\n 9. Have a history of another primary malignancy other than completely resected carcinomas\n in situ) that has been diagnosed or required therapy within 2 years prior to\n initiation of study treatment.\n 10. Have active, uncontrolled infection (viral, bacterial, or fungal), including\n tuberculosis, hepatitis B virus (HBV), hepatitis C virus, AIDS-related illness, or\n COVID-19 infection (symptoms and a positive test result).\n 11. Requires treatment with a prohibited medication or herbal remedy that cannot be\n discontinued at least 2 weeks before the start of study drug administration.\n 12. Have planned major surgical procedure within 14 days of the first dose of study drug\n (procedures such as central venous catheter placement, tumor needle biopsy, and\n feeding tube placement are not considered major surgical procedures).\n 13. Unwilling or unable to comply with scheduled visits, study drug administration plan,\n laboratory tests, or other study procedures and study restrictions.\n 14. Patient is a woman who is not postmenopausal or surgically sterile, and is unwilling\n to abstain from sexual intercourse or employ highly effective contraception OR is a\n man who is not surgically sterile, and is unwilling to abstain from sexual intercourse\n or employ highly effective contraception\n 15. Patient is a pregnant female", "output": {"inclusion_biomarker": [["HR positive", "HER2 positive"], ["CCNE1 amplification"]], "exclusion_biomarker": []}}
-{"input": "Vorasidenib in combination with pembrolizumab in participants with recurrent or progressive\n enhancing isocitrate dehydrogenase-1 (IDH-1) mutant astrocytomas.\n ;\n ;\n Inclusion Criteria:\n 1. Have Karnofsky Performance Status (KPS) of \u2265 70%.\n 2. Have expected survival of \u2265 3 months.\n 3. Have histologically confirmed Grade 2 or Grade 3 astrocytoma (per the 2016 World\n Health Organization [WHO] Classification of Tumors of the central nervous system)\n 4. Have documented IDH1-R132H gene mutation and absence of 1p19q co-deletion (i.e.,\n non-co-deleted, or intact) by local testing.\n 5. Have measurable, magnetic resonance imaging (MRI)-evaluable, unequivocal contrast\n enhancing disease as determined by institution radiologist/Investigator at Screening\n on either 2D T1 post-contrast weighted images or 3D T1 post-contrast weighted images.\n Per mRANO criteria, measurable lesion is defined as at least 1 enhancing lesion\n measuring \u2265 1 cm x \u2265 1 cm.\n 6. Have recurrent or progressive disease and received prior treatment with chemotherapy,\n radiation, or both.\n 7. Surgical resection is indicated for treatment, but surgery is not urgently indicated\n (e.g., for whom surgery within the next 6-9 weeks is appropriate). (NOTE: This\n criterion only applies to participants enrolled in the perioperative phase of the\n study. Participants in the Safety Lead-In should not require surgery).\n Exclusion Criteria:\n 1. Have received prior systemic anti-cancer therapy within 1 month of the first dose of\n IMP, radiation within 12 months of the first dose of IMP, or an investigational agent\n < 14 days prior to the first dose of IMP. In addition, the first dose of IMP should\n not occur before a period of \u2265 5 half-lives of the investigational agent has elapsed.\n 2. Have received 2 or more courses of radiation.\n 3. Have received any prior treatment with an isocitrate dehydrogenase (IDH) inhibitor;\n anti-programmed cell death 1 (PD1), anti-programmed cell death ligand 1 (PD-L1), or\n anti-PD-ligand 2 (L2) agent, or with an agent directed to another stimulatory or\n co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137); any other checkpoint\n inhibitor; bevacizumab; or any prior vaccine therapy.\n Note: Other inclusion and exclusion criteria may apply.", "output": {"inclusion_biomarker": [["IDH1 R132H"], ["ATRX loss of nuclear expression"], ["ATRX mutation"]], "exclusion_biomarker": [["1p19q co-deletion"]]}}
+{"input": "Vorasidenib in combination with pembrolizumab in participants with recurrent or progressive\n enhancing isocitrate dehydrogenase-1 (IDH-1) mutant astrocytomas.\n ;\n ;\n Inclusion Criteria:\n 1. Have Karnofsky Performance Status (KPS) of \u2265 70%.\n 2. Have expected survival of \u2265 3 months.\n 3. Have histologically confirmed Grade 2 or Grade 3 astrocytoma (per the 2016 World\n Health Organization [WHO] Classification of Tumors of the central nervous system)\n 4. Have documented IDH1-R132H gene mutation and absence of 1p19q co-deletion (i.e.,\n non-co-deleted, or intact) by local testing.\n 5. Have measurable, magnetic resonance imaging (MRI)-evaluable, unequivocal contrast\n enhancing disease as determined by institution radiologist/Investigator at Screening\n on either 2D T1 post-contrast weighted images or 3D T1 post-contrast weighted images.\n Per mRANO criteria, measurable lesion is defined as at least 1 enhancing lesion\n measuring \u2265 1 cm x \u2265 1 cm.\n 6. Have recurrent or progressive disease and received prior treatment with chemotherapy,\n radiation, or both.\n 7. Surgical resection is indicated for treatment, but surgery is not urgently indicated\n (e.g., for whom surgery within the next 6-9 weeks is appropriate). (NOTE: This\n criterion only applies to participants enrolled in the perioperative phase of the\n study. Participants in the Safety Lead-In should not require surgery).\n Exclusion Criteria:\n 1. Have received prior systemic anti-cancer therapy within 1 month of the first dose of\n IMP, radiation within 12 months of the first dose of IMP, or an investigational agent\n < 14 days prior to the first dose of IMP. In addition, the first dose of IMP should\n not occur before a period of \u2265 5 half-lives of the investigational agent has elapsed.\n 2. Have received 2 or more courses of radiation.\n 3. Have received any prior treatment with an isocitrate dehydrogenase (IDH) inhibitor;\n anti-programmed cell death 1 (PD1), anti-programmed cell death ligand 1 (PD-L1), or\n anti-PD-ligand 2 (L2) agent, or with an agent directed to another stimulatory or\n co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137); any other checkpoint\n inhibitor; bevacizumab; or any prior vaccine therapy.\n Note: Other inclusion and exclusion criteria may apply.", "output": {"inclusion_biomarker": [["IDH1 R132H"]], "exclusion_biomarker": [["1p19q co-deletion"]]}}
 {"input": "To study the radioactive uptake of [68Ga]P137 in the lesion sites of PCa patients and\n evaluate the ability of [68Ga]P137 to detect PSMA overexpression in PCa patients (especially\n those with recurrent or advanced PCa).\n ;\n ;\n Inclusion Criteria:\n - Men over 18 years of age need to undergo [68Ga]P137 PET/CT examination for suspected\n prostate cancer.\n - The patients can fully understand and voluntarily participate in this experiment, and\n sign the informed consent.\n Exclusion Criteria:\n - Significant hepatic or renal dysfunction;\n - Patients with malignant tumors other than prostate cancer within 2 years;\n - Ready to pregnant;\n - The patient can not tolerate all clinical tests.", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
-{"input": "The ATR (ataxia-telangiectasia and Rad3 related protein) inhibitor BAY1895344 is developed\n for the treatment of patients with advanced solid tumors and lymphomas. The purpose of the\n proposed trial is to evaluate the safety and tolerability of BAY1895344, and to identify the\n maximum tolerated dose of BAY1895344 that could be safely given to cancer patients. Further,\n the response of the cancer to the treatment will be determined.\n ;NA;\n Inclusion Criteria:\n Part A - single-agent dose-escalation:\n - Patients with histologically confirmed solid tumors or NHL. Patients with tumors known to\n be positive for deoxyribonucleic acid damage repair (DDR) defects (such as\n ataxia-telangiectasia mutated [ATM] deleterious mutation or low ATM expression) can be\n included.\n J-arm of Part A - single-agent dose-escalation in Japanese:\n - Japanese patients with histologically confirmed solid tumors. Patients with tumors known\n to be positive for DDR defects (such as ATM deleterious mutation or low ATM expression) can\n be included.\n Part A.1 - single-agent dose-escalation with alternative dosing schedule:\n - Patients with histologically confirmed solid tumors or NHL known to be positive for ATM\n loss and/or ATM deleterious mutations will be included. The biomarker status of patients in\n Part A.1 will be evaluated before general screening and only patients with the presence of\n the putative biomarkers of DDR deficiency will be recruited into general screening.\n Part B - single-agent expansion:\n - Patients with DDR deficiency biomarker-positive advanced solid tumors of the following\n histologies: i) CRPC; ii) HER2-negative BC that is hormone-receptor positive\n (estrogen-receptor positive, progesterone-receptor positive, or both) or TNBC; iii)\n CRC, and iv) gynecological tumors (ovarian, primary peritoneal, and fallopian tube\n cancers, endometrial cancer, or cervical cancer).\n - Patients with histologically confirmed advanced solid cancer, regardless of the cancer\n type, or NHL and loss of ATM protein by IHC.\n - The biomarker status of patients in Part B will be evaluated before general screening\n and only patients with the presence of the putative biomarkers of DDR deficiency will\n be recruited into general screening.\n Part A.1 And Part B:\n - Patients must be able to provide either samples of archival tumor tissue not older than 6\n months or a fresh tumor biopsy during general screening.\n Part B.1 - single-agent expansion with alternative dosing schedule:\n - Patients with histologically confirmed R/R MCL. These patients do not undergo biomarker\n testing to determine eligibility. The provision of baseline tumor tissue (archival or\n fresh) is strongly encouraged. If archival tissue \u2264 6 months old is unavailable, a fresh\n baseline biopsy may be obtained if safe and feasible.\n The following inclusion criteria apply to ALL (dose-escalation and expansion) patients:\n - Patients with tumors resistant or refractory to standard treatment and in which, in\n the opinion of the investigator, experimental treatment with BAY1895344 may be of\n benefit. Furthermore, no standard therapy would confer clinical benefit to the\n patient. Patients in the MCL cohort of Part B.1 are to be relapsed or refractory to\n standard treatments.\n - Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. For MCL\n patients: ECOG of 0 to 2.\n - Patients must have adequate bone marrow function as assessed by the following\n laboratory tests to be conducted within 7 (+2) days before the first dose of study\n drug. Note that the below values are to be independent of red blood cell transfusions\n or granulocytes colony-stimulating factor (G-CSF) (i.e., no red blood cell or\n platelets transfusion within 28 days prior to the screening complete blood count [CBC]\n result, or administration of G-CSF is to occur within 14 days prior to the CBC\n result). Requirements for MCL patients are indicated below.\n - a. Hemoglobin \u2265 9 g/dL. Patients with chronic erythropoietin treatment consistent\n with institutional guidelines can be included. For MCL patients: \u2265 8 g/dL; red\n blood cell transfusions during the screening period are allowed, and patients\n with chronic erythropoietin treatment consistent with institutional guidelines\n can be included\n - b. Absolute neutrophil count (ANC) \u2265 1.5 X 10^9/L (\u2265 1500/mm^3). For MCL\n patients: ANC \u2265 1.0 X 10^9/L. Patients with ANC \u2264 1.0 X 10^9/L due to marrow\n infiltration may receive G-CSF during screening to bring pretreatment ANC levels\n to \u2265 1.0 X 10^9/L\n - c. Platelet count \u2265 100 X 10^9/L (\u2265100,000/mm^3). For MCL patients: \u2265 75 X 10^9/L\n Exclusion Criteria:\n - Known hypersensitivity to the study drugs or excipients of the preparations or any\n agent given in association with this study\n - History of cardiac disease: congestive heart failure New York Heart Association (NYHA)\n class >II, unstable angina (angina symptoms at rest), new-onset angina (within the\n past 6 months before study entry), myocardial infarction within the past 6 months\n before study entry, or cardiac arrhythmias requiring anti-arrhythmic therapy (beta\n blockers, calcium channel blockers, and digoxin are permitted)\n - Moderate or severe hepatic impairment, i.e. Child-Pugh class B or C\n - Known human immunodeficiency virus (HIV)-infected persons are not eligible if any of\n the following criteria apply\uff1a\n - CD4+ T-cell count less than 350 cells/\u03bcL\n - History of AIDS-defining opportunistic infection within the past 12 months\n - On established antiretroviral therapy (ART) for less than 4 weeks or presenting\n with a viral load of more than 400 copies/mL prior to enrollment\n - On ART or prophylactic antimicrobials that are expected to cause significant\n drug-drug interactions or overlapping toxicities with study intervention\n - Patients who have an active hepatitis B virus (HBV) or hepatitis C virus (HCV)\n infection requiring treatment. Patients with chronic HBV or HCV infection are eligible\n at the investigator's discretion provided that the disease is stable and sufficiently\n controlled under treatment.\n - Infections of Common Terminology Criteria for Adverse Events Version (CTCAE) Grade 2\n not responding to therapy or active clinically serious infections of CTCAE Grade > 2\n - Metastatic solid brain, spinal, or meningeal tumors or central nervous system (CNS)\n lymphoma manifestations (including meningeosis lymphomatosa and parenchymal lymphoma\n lesions) unless the patient is > 3 months from definitive therapy, has a stable\n imaging study within 4 weeks prior to the first dose of study drug and is clinically\n stable with respect to the tumor at the time of study entry. Patients with\n asymptomatic brain metastases must not be on steroid therapy. Patients with\n neurological symptoms should undergo a CT / MRI scan of the brain or spinal column to\n exclude new or progressive brain, meningeal, or spinal metastases or CNS lymphoma\n manifestations.\n - History of organ allograft transplantation. For MCL patients: Those who received an\n allogeneic stem cell transplant may participate provided that engraftment has\n occurred, there is no evidence of GVHD, and the patient is not taking immune\n suppressants. MCL patients who received an autologous stem cell transplant may\n participate once they have recovered from the procedure.\n - Treatment with anticancer chemotherapy or immunotherapy during the study or within 3\n weeks before the first dose of study drug. For small-molecule drugs, a period of at\n least 3 half-lives before the first dose of study drug is acceptable. Mitomycin C or\n nitrosoureas should not be given within 6 weeks before the first dose of study drug.\n - Treatment with systemic steroids (methylprednisolone dose \u226510 mg/day or equivalent\n dose). For MCL patients: Treatment with systemic corticosteroids > 20 mg/day\n prednisone equivalent (unless patient has been taking a stable dose for >3 weeks and\n has shown tumor progression).", "output": {"inclusion_biomarker": [["DDR positive"], ["ATM mutation"], ["ATM low expression"], ["ATM loss"], ["DDR positive", "HER2 negative", "HR positive"], ["ATM loss"]], "exclusion_biomarker": []}}
+{"input": "The ATR (ataxia-telangiectasia and Rad3 related protein) inhibitor BAY1895344 is developed\n for the treatment of patients with advanced solid tumors and lymphomas. The purpose of the\n proposed trial is to evaluate the safety and tolerability of BAY1895344, and to identify the\n maximum tolerated dose of BAY1895344 that could be safely given to cancer patients. Further,\n the response of the cancer to the treatment will be determined.\n ;NA;\n Inclusion Criteria:\n Part A - single-agent dose-escalation:\n - Patients with histologically confirmed solid tumors or NHL. Patients with tumors known to\n be positive for deoxyribonucleic acid damage repair (DDR) defects (such as\n ataxia-telangiectasia mutated [ATM] deleterious mutation or low ATM expression) can be\n included.\n J-arm of Part A - single-agent dose-escalation in Japanese:\n - Japanese patients with histologically confirmed solid tumors. Patients with tumors known\n to be positive for DDR defects (such as ATM deleterious mutation or low ATM expression) can\n be included.\n Part A.1 - single-agent dose-escalation with alternative dosing schedule:\n - Patients with histologically confirmed solid tumors or NHL known to be positive for ATM\n loss and/or ATM deleterious mutations will be included. The biomarker status of patients in\n Part A.1 will be evaluated before general screening and only patients with the presence of\n the putative biomarkers of DDR deficiency will be recruited into general screening.\n Part B - single-agent expansion:\n - Patients with DDR deficiency biomarker-positive advanced solid tumors of the following\n histologies: i) CRPC; ii) HER2-negative BC that is hormone-receptor positive\n (estrogen-receptor positive, progesterone-receptor positive, or both) or TNBC; iii)\n CRC, and iv) gynecological tumors (ovarian, primary peritoneal, and fallopian tube\n cancers, endometrial cancer, or cervical cancer).\n - Patients with histologically confirmed advanced solid cancer, regardless of the cancer\n type, or NHL and loss of ATM protein by IHC.\n - The biomarker status of patients in Part B will be evaluated before general screening\n and only patients with the presence of the putative biomarkers of DDR deficiency will\n be recruited into general screening.\n Part A.1 And Part B:\n - Patients must be able to provide either samples of archival tumor tissue not older than 6\n months or a fresh tumor biopsy during general screening.\n Part B.1 - single-agent expansion with alternative dosing schedule:\n - Patients with histologically confirmed R/R MCL. These patients do not undergo biomarker\n testing to determine eligibility. The provision of baseline tumor tissue (archival or\n fresh) is strongly encouraged. If archival tissue \u2264 6 months old is unavailable, a fresh\n baseline biopsy may be obtained if safe and feasible.\n The following inclusion criteria apply to ALL (dose-escalation and expansion) patients:\n - Patients with tumors resistant or refractory to standard treatment and in which, in\n the opinion of the investigator, experimental treatment with BAY1895344 may be of\n benefit. Furthermore, no standard therapy would confer clinical benefit to the\n patient. Patients in the MCL cohort of Part B.1 are to be relapsed or refractory to\n standard treatments.\n - Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. For MCL\n patients: ECOG of 0 to 2.\n - Patients must have adequate bone marrow function as assessed by the following\n laboratory tests to be conducted within 7 (+2) days before the first dose of study\n drug. Note that the below values are to be independent of red blood cell transfusions\n or granulocytes colony-stimulating factor (G-CSF) (i.e., no red blood cell or\n platelets transfusion within 28 days prior to the screening complete blood count [CBC]\n result, or administration of G-CSF is to occur within 14 days prior to the CBC\n result). Requirements for MCL patients are indicated below.\n - a. Hemoglobin \u2265 9 g/dL. Patients with chronic erythropoietin treatment consistent\n with institutional guidelines can be included. For MCL patients: \u2265 8 g/dL; red\n blood cell transfusions during the screening period are allowed, and patients\n with chronic erythropoietin treatment consistent with institutional guidelines\n can be included\n - b. Absolute neutrophil count (ANC) \u2265 1.5 X 10^9/L (\u2265 1500/mm^3). For MCL\n patients: ANC \u2265 1.0 X 10^9/L. Patients with ANC \u2264 1.0 X 10^9/L due to marrow\n infiltration may receive G-CSF during screening to bring pretreatment ANC levels\n to \u2265 1.0 X 10^9/L\n - c. Platelet count \u2265 100 X 10^9/L (\u2265100,000/mm^3). For MCL patients: \u2265 75 X 10^9/L\n Exclusion Criteria:\n - Known hypersensitivity to the study drugs or excipients of the preparations or any\n agent given in association with this study\n - History of cardiac disease: congestive heart failure New York Heart Association (NYHA)\n class >II, unstable angina (angina symptoms at rest), new-onset angina (within the\n past 6 months before study entry), myocardial infarction within the past 6 months\n before study entry, or cardiac arrhythmias requiring anti-arrhythmic therapy (beta\n blockers, calcium channel blockers, and digoxin are permitted)\n - Moderate or severe hepatic impairment, i.e. Child-Pugh class B or C\n - Known human immunodeficiency virus (HIV)-infected persons are not eligible if any of\n the following criteria apply\uff1a\n - CD4+ T-cell count less than 350 cells/\u03bcL\n - History of AIDS-defining opportunistic infection within the past 12 months\n - On established antiretroviral therapy (ART) for less than 4 weeks or presenting\n with a viral load of more than 400 copies/mL prior to enrollment\n - On ART or prophylactic antimicrobials that are expected to cause significant\n drug-drug interactions or overlapping toxicities with study intervention\n - Patients who have an active hepatitis B virus (HBV) or hepatitis C virus (HCV)\n infection requiring treatment. Patients with chronic HBV or HCV infection are eligible\n at the investigator's discretion provided that the disease is stable and sufficiently\n controlled under treatment.\n - Infections of Common Terminology Criteria for Adverse Events Version (CTCAE) Grade 2\n not responding to therapy or active clinically serious infections of CTCAE Grade > 2\n - Metastatic solid brain, spinal, or meningeal tumors or central nervous system (CNS)\n lymphoma manifestations (including meningeosis lymphomatosa and parenchymal lymphoma\n lesions) unless the patient is > 3 months from definitive therapy, has a stable\n imaging study within 4 weeks prior to the first dose of study drug and is clinically\n stable with respect to the tumor at the time of study entry. Patients with\n asymptomatic brain metastases must not be on steroid therapy. Patients with\n neurological symptoms should undergo a CT / MRI scan of the brain or spinal column to\n exclude new or progressive brain, meningeal, or spinal metastases or CNS lymphoma\n manifestations.\n - History of organ allograft transplantation. For MCL patients: Those who received an\n allogeneic stem cell transplant may participate provided that engraftment has\n occurred, there is no evidence of GVHD, and the patient is not taking immune\n suppressants. MCL patients who received an autologous stem cell transplant may\n participate once they have recovered from the procedure.\n - Treatment with anticancer chemotherapy or immunotherapy during the study or within 3\n weeks before the first dose of study drug. For small-molecule drugs, a period of at\n least 3 half-lives before the first dose of study drug is acceptable. Mitomycin C or\n nitrosoureas should not be given within 6 weeks before the first dose of study drug.\n - Treatment with systemic steroids (methylprednisolone dose \u226510 mg/day or equivalent\n dose). For MCL patients: Treatment with systemic corticosteroids > 20 mg/day\n prednisone equivalent (unless patient has been taking a stable dose for >3 weeks and\n has shown tumor progression).", "output": {"inclusion_biomarker": [["ATM deleterious mutation"], ["ATM low expression"], ["ATM loss"], ["DDR deficiency", "estrogen-receptor positive"], ["DDR deficiency", "progesterone-receptor positive"], ["DDR deficiency", "estrogen-receptor positive", "progesterone-receptor positive"]], "exclusion_biomarker": []}}
 {"input": "This is a phase II, prospective, open label, one-center study for evaluation of the addition\n of nivolumab to the chemotherapy phase of the neoadjuvant treatment for locally advanced\n rectal cancer patients. Subjects must have received no prior treatment for rectal cancer\n (chemotherapy, radiotherapy or surgery) and no prior treatment with checkpoint inhibitors.\n Eligible subjects will receive chemoradiation for a period of 5 weeks, 6 cycles of\n chemo-immunotherapy (mFOLFOX6 + nivolumab) for a period of 12 weeks, once every 2 weeks, and\n will undergo surgery after 4 weeks.\n ;NA;\n Inclusion Criteria:\n - Signed written IRB approved informed consent\n - Age \u2265 18 years\n - ECOG PS 0-1\n - Subjects with histologically confirmed primary (non-recurrent) locally advanced rectal\n adenocarcinoma\n - Stage T3-4 N0 or TX N+ according to baseline rectal EUS and PET-CT\n - Patients who are planned for neoadjuvant chemoradiation and are surgical candidates\n - No prior chemotherapy, radiotherapy or surgery for rectal cancer\n - No prior radiotherapy to the pelvis, for any reason\n - Presence of adequate contraception in fertile patients\n - Women of childbearing potential must have a negative serum or urine pregnancy test\n within 24 hours prior to the start of study drug\n - Women must not be breastfeeding\n - Ability to swallow tablets\n - No previous (within the last 5 years) or concurrent malignancies, with the exception\n of adequately treated cone-biopsied in situ carcinoma of the cervix or basal cell\n carcinoma of the skin\n Exclusion Criteria:\n - Active autoimmune disease. [Subjects with type I diabetes mellitus, hypothyroidism\n only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or\n alopecia) not requiring systemic treatment, or conditions not expected to recur in the\n absence of an external trigger are permitted to enroll]\n - Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4\n antibody, or any other antibody or drug specifically targeting T-cell co-stimulation\n or checkpoint pathways\n - Known history of positive test for human immunodeficiency virus (HIV) or known\n acquired immunodeficiency syndrome (AIDS)\n - Pregnancy or breastfeeding", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
 {"input": "The Safety and Effectiveness of Four Courses of R-CHOP Plus Four Courses of Rituximab Versus\n Six Courses of R-CHOP Plus Two Courses of Rituximab in the Treatment of Naive, Low-risk,\n Non-mass Diffuse Large B-cell Lymphoma: a Multi-center, Prospective, Randomized Controlled\n Study\n ;\n ;\n Inclusion Criteria:\n - Pathologically confirmed CD20 positive DLBCL based on 2016 WHO classification who\n achieved CR after 4 cycles of RCHOP therapy (examined by PET-CT, Deauville score 1-2)\n - Treatment na\u00efve\n - IPI=0,1\n - Age \u2265 14 or \u226475 years\n - non-mass (The length of the lesion<7.5cm)\n - ECOG=0,1\n - Life expectancy>6 months\n - Informed consented\n Exclusion Criteria:\n - Have received systemic or local treatment including chemotherapy in the past\n - Have received autologous stem cell transplantation in the past\n - Past medical history of other malignant tumors, except basal cell carcinoma of the\n skin and cervical cancer in situ\n - Accompanied by uncontrolled cardiovascular and cerebrovascular diseases, coagulopathy,\n connective tissue diseases, severe infectious diseases and other diseases\n - Primary skin, primary central nervous system lymphoma\n - Left ventricular ejection fraction \u226650%\n - Other concurrent and uncontrolled situation which will affect the patient's medical\n status based on researchers decision\n - Laboratory test value during screening: (unless it is caused by lymphoma) Neutrophils\n <1.5*109/L Platelet<80*109/L Hemoglobin <100g/L ALT or AST is 2 times higher than the\n upper limit of normal, AKP and bilirubin are 1.5 times higher than the upper limit of\n normal E. Creatinine level is higher than 1.5 times the upper limit of normal\n - Psychiatric patients or other patients who are known or suspected to be unable to\n fully accomplish with the research protocol\n - Pregnant or lactating women\n - Patients with positive HbsAg test results need to undergo HBV-DNA test and can be\n admitted to the group after turning negative. In addition, if the HBsAg test result is\n negative, but the HBcAb test is positive (regardless of the HBsAb status), HBV-DNA is\n also required\uff1bif the result is positive, patients also need to be treated to become\n negative before entering the group\n - Patients living with HIV\n - Patients with TP53 mutations or those who have not undergone DLBCL hot spot gene\n screening", "output": {"inclusion_biomarker": [["CD20 positive"]], "exclusion_biomarker": [["TP53 mutation"]]}}
-{"input": "This is a first-in-human, Phase I, open-label, dose-escalation and expansion study designed\n to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary\n efficacy of PT199 (an Anti-CD73 mAb) alone and in combination with a PD-1 inhibitor, in\n patients with locally advanced or metastatic solid tumors that have progressed after all\n available standard therapy or for which standard therapy has proven to be ineffective,\n intolerable, or is considered inappropriate.\n ;\n ;\n Inclusion Criteria:\n 1. 18 years or older and able to sign informed consent and comply with the protocol\n 2. At least one measurable lesion as defined by RECIST V1.1 criteria for solid tumors\n 3. Histologically or cytologically confirmed unresectable advanced or metastatic solid\n tumors previously treated with all available systemic standard therapy or for which\n treatment is not available or not tolerated, or for subjects enrolling in parts B and\n C (combination therapy groups) only anti PD-1 therapy is indicated as standard of care\n therapy.\n 4. Able to provide a formalin fixed, paraffin embedded (FFPE) tumor tissue sample\n (archival tissue or fresh biopsy). To be assessed for CD73 and other biomarkers\n (PD-L1) expression.\n - Biopsy must be excisional, incisional, or core. Needle aspiration is\n insufficient.\n - Archival tissue is acceptable if biopsy was completed within 6 months.\n - Biopsy is optional in part A (monotherapy dose escalation).\n 5. ECOG performance status of 0 or 1\n 6. Adequate organ function confirmed at screening and within 7 days of initiating\n treatment, as evidenced by:\n - Absolute neutrophil count (ANC) \u2265 1.5 \u00d7 109/L\n - Hemoglobin (Hgb) \u2265 9 g/dl (RBC and Platelets transfusion are not allowed within 2\n weeks of C1D1).\n - Platelets (plt) \u2265 75 \u00d7 109/L\n - AST/SGOT and ALT/SGPT \u2264 2.5 \u00d7 Upper Limit of Normal (ULN) or \u2264 5.0 \u00d7 ULN if liver\n metastases are present\n - Total bilirubin \u2264 1.5 \u00d7 ULN\n - Calculated creatinine clearance \u2265 50 mL/min (Cockcroft Gault formula)\n 7. Resolution of all acute adverse events resulting from prior cancer therapies to\n National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE\n V5.0) Grade \u2264 1 or baseline (except alopecia or neuropathy)\n 8. Negative serum pregnancy test within 72 hours before starting study treatment in all\n pre-menopausal women and women < 24 months after the onset of menopause (had a\n menstrual period in past 24 months) and are of childbearing potential (women who\n underwent hysterectomy or bilateral oophorectomy do not need a pregnancy test)\n 9. Must agree to use effective contraceptive methods to avoid pregnancy (including male\n and female participants and partners of study subjects) during the study and until at\n least 6 months after ceasing study treatment. Examples of contraceptive methods with a\n failure rate of < 1% per year include bilateral tubal ligation, male sterilization,\n established, proper use of hormonal contraceptives that inhibit ovulation,\n hormone-releasing intrauterine devices, and copper intrauterine devices. The\n reliability of sexual abstinence should be evaluated in relation to the duration of\n the clinical trial and the preferred and usual lifestyle of the patient. Periodic\n abstinence (e.g., calendar, ovulation, sympto-thermal, or post-ovulation methods) and\n withdrawal are not acceptable methods of contraception\n Exclusion Criteria:\n 1. Women who are pregnant or lactating\n 2. Women of child-bearing potential (WOCBP) who do not use adequate birth control\n 3. Autoimmune disease requiring systemic treatment within the past twelve months\n 4. Condition requiring systemic treatment with either corticosteroids or other\n immunosuppressive medications within 14 days prior to study treatment. Corticosteroids\n doses equivalent to Prednisone 10mg per day or less are allowed.\n 5. Patients with a history of (non-infectious) pneumonitis that required steroids,\n current pneumonitis, or has a history of interstitial lung disease.\n 6. Patients with untreated brain or central nervous system (CNS) metastases or brain/CNS\n metastases that have progressed (e.g., evidence of new or enlarging brain metastasis\n or new neurological symptoms attributable to brain/CNS metastases) Note: Patients with\n treated brain metastases that are off corticosteroids and have been clinically stable\n for 28 days are eligible for enrollment.\n 7. Patients with a known concurrent malignancy that is progressing or requires active\n treatment. Exceptions include basal cell carcinoma of the skin, carcinoma in situ of\n the cervix or other noninvasive or indolent malignancy that has previously undergone\n potentially curative therapy.\n 8. Patients who have received an investigational product, < 5 half-lives duration.\n 9. Patients who have previously received immune checkpoint inhibitor therapy and\n discontinued treatment because of immune-related adverse events\n 10. Patients who have allergies or hypersensitivity reactions to immune checkpoint\n inhibitor therapy or any of the inactive ingredients\n 11. Prior T-cell, NK cell, or CD73 inhibitor therapy (Prior Checkpoint inhibitor anti PD-1\n and anti PD-L1 therapies are allowed)\n 12. Patients that have received a live-virus vaccination within 30 days of planned\n treatment start (exception Janssen JNJ-78436735 COVID-19 vaccine).\n 13. Impaired cardiac function or significant diseases, including but not limited to any of\n the following:\n - LVEF < 45% as determined by MUGA scan or ECHO\n - Congenital long QT syndrome\n - QTcF \u2265 480 msec on screening ECG\n - Unstable angina pectoris \u2264 3 months prior to starting study drug\n - Acute myocardial infarction \u2264 3 months prior to starting study drug\n 14. Patients with uncontrolled hypertension or blood pressure of \u2265 150 mmHg systolic\n and/or \u2265 90 mmHg diastolic at Screening.\n 15. Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g.,\n uncontrolled hypertriglyceridemia [triglycerides > 500 mg/dL], or active or\n uncontrolled infection) that could cause unacceptable safety risks or compromise\n compliance with the protocol\n 16. Patients who have received chemotherapy, \u2264 5 half-lives or 3 weeks, whichever is\n shorter (6 weeks for nitrosourea or mitomycin-C), targeted therapy, or immunotherapy\n within 4 weeks prior to starting study drug\n 17. Patients who have \u2265 Grade 3 neuropathy\n 18. Patients who have received wide field radiotherapy \u2264 4 weeks or limited field\n radiation for palliation \u2264 2 weeks prior to starting study drug or who have not\n recovered from adverse events of prior therapy\n 19. Patients who have undergone major surgery \u2264 4 weeks prior to starting study drug or\n who have not recovered from adverse events of prior therapy\n 20. Patients who are currently receiving treatment with therapeutic doses of warfarin\n sodium (Coumadin\u00ae) or any other coumarin-derivative anticoagulants (Other\n anticoagulants such as anti-thrombin or factor X are allowed).\n 21. Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not\n mandatory; patients with well controlled HIV might be enrolled per investigator's\n discretion and Sponsor approval\n 22. Evidence of active infection with Hepatitis B or Hepatitis C that is not adequately\n controlled. (For patients with known prior history of Hepatitis B or Hepatitis C,\n enrollment may be allowed per investigator's discretion and Sponsor approval.)\n 23. Has a history or current evidence of any medical or psychiatric condition, therapy, or\n laboratory abnormality that, in the opinion of the investigator, might confound the\n results of the trial, interfere with the patient's safe participation and compliance\n in the trial. For example, conditions that depend on the establishment of collateral\n circulation, such as peripheral arterial vascular disease, myocardial infraction\n recovery period, etc", "output": {"inclusion_biomarker": [["CD73 expression", "PD-L1 expression"]], "exclusion_biomarker": []}}
+{"input": "This is a first-in-human, Phase I, open-label, dose-escalation and expansion study designed\n to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary\n efficacy of PT199 (an Anti-CD73 mAb) alone and in combination with a PD-1 inhibitor, in\n patients with locally advanced or metastatic solid tumors that have progressed after all\n available standard therapy or for which standard therapy has proven to be ineffective,\n intolerable, or is considered inappropriate.\n ;\n ;\n Inclusion Criteria:\n 1. 18 years or older and able to sign informed consent and comply with the protocol\n 2. At least one measurable lesion as defined by RECIST V1.1 criteria for solid tumors\n 3. Histologically or cytologically confirmed unresectable advanced or metastatic solid\n tumors previously treated with all available systemic standard therapy or for which\n treatment is not available or not tolerated, or for subjects enrolling in parts B and\n C (combination therapy groups) only anti PD-1 therapy is indicated as standard of care\n therapy.\n 4. Able to provide a formalin fixed, paraffin embedded (FFPE) tumor tissue sample\n (archival tissue or fresh biopsy). To be assessed for CD73 and other biomarkers\n (PD-L1) expression.\n - Biopsy must be excisional, incisional, or core. Needle aspiration is\n insufficient.\n - Archival tissue is acceptable if biopsy was completed within 6 months.\n - Biopsy is optional in part A (monotherapy dose escalation).\n 5. ECOG performance status of 0 or 1\n 6. Adequate organ function confirmed at screening and within 7 days of initiating\n treatment, as evidenced by:\n - Absolute neutrophil count (ANC) \u2265 1.5 \u00d7 109/L\n - Hemoglobin (Hgb) \u2265 9 g/dl (RBC and Platelets transfusion are not allowed within 2\n weeks of C1D1).\n - Platelets (plt) \u2265 75 \u00d7 109/L\n - AST/SGOT and ALT/SGPT \u2264 2.5 \u00d7 Upper Limit of Normal (ULN) or \u2264 5.0 \u00d7 ULN if liver\n metastases are present\n - Total bilirubin \u2264 1.5 \u00d7 ULN\n - Calculated creatinine clearance \u2265 50 mL/min (Cockcroft Gault formula)\n 7. Resolution of all acute adverse events resulting from prior cancer therapies to\n National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE\n V5.0) Grade \u2264 1 or baseline (except alopecia or neuropathy)\n 8. Negative serum pregnancy test within 72 hours before starting study treatment in all\n pre-menopausal women and women < 24 months after the onset of menopause (had a\n menstrual period in past 24 months) and are of childbearing potential (women who\n underwent hysterectomy or bilateral oophorectomy do not need a pregnancy test)\n 9. Must agree to use effective contraceptive methods to avoid pregnancy (including male\n and female participants and partners of study subjects) during the study and until at\n least 6 months after ceasing study treatment. Examples of contraceptive methods with a\n failure rate of < 1% per year include bilateral tubal ligation, male sterilization,\n established, proper use of hormonal contraceptives that inhibit ovulation,\n hormone-releasing intrauterine devices, and copper intrauterine devices. The\n reliability of sexual abstinence should be evaluated in relation to the duration of\n the clinical trial and the preferred and usual lifestyle of the patient. Periodic\n abstinence (e.g., calendar, ovulation, sympto-thermal, or post-ovulation methods) and\n withdrawal are not acceptable methods of contraception\n Exclusion Criteria:\n 1. Women who are pregnant or lactating\n 2. Women of child-bearing potential (WOCBP) who do not use adequate birth control\n 3. Autoimmune disease requiring systemic treatment within the past twelve months\n 4. Condition requiring systemic treatment with either corticosteroids or other\n immunosuppressive medications within 14 days prior to study treatment. Corticosteroids\n doses equivalent to Prednisone 10mg per day or less are allowed.\n 5. Patients with a history of (non-infectious) pneumonitis that required steroids,\n current pneumonitis, or has a history of interstitial lung disease.\n 6. Patients with untreated brain or central nervous system (CNS) metastases or brain/CNS\n metastases that have progressed (e.g., evidence of new or enlarging brain metastasis\n or new neurological symptoms attributable to brain/CNS metastases) Note: Patients with\n treated brain metastases that are off corticosteroids and have been clinically stable\n for 28 days are eligible for enrollment.\n 7. Patients with a known concurrent malignancy that is progressing or requires active\n treatment. Exceptions include basal cell carcinoma of the skin, carcinoma in situ of\n the cervix or other noninvasive or indolent malignancy that has previously undergone\n potentially curative therapy.\n 8. Patients who have received an investigational product, < 5 half-lives duration.\n 9. Patients who have previously received immune checkpoint inhibitor therapy and\n discontinued treatment because of immune-related adverse events\n 10. Patients who have allergies or hypersensitivity reactions to immune checkpoint\n inhibitor therapy or any of the inactive ingredients\n 11. Prior T-cell, NK cell, or CD73 inhibitor therapy (Prior Checkpoint inhibitor anti PD-1\n and anti PD-L1 therapies are allowed)\n 12. Patients that have received a live-virus vaccination within 30 days of planned\n treatment start (exception Janssen JNJ-78436735 COVID-19 vaccine).\n 13. Impaired cardiac function or significant diseases, including but not limited to any of\n the following:\n - LVEF < 45% as determined by MUGA scan or ECHO\n - Congenital long QT syndrome\n - QTcF \u2265 480 msec on screening ECG\n - Unstable angina pectoris \u2264 3 months prior to starting study drug\n - Acute myocardial infarction \u2264 3 months prior to starting study drug\n 14. Patients with uncontrolled hypertension or blood pressure of \u2265 150 mmHg systolic\n and/or \u2265 90 mmHg diastolic at Screening.\n 15. Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g.,\n uncontrolled hypertriglyceridemia [triglycerides > 500 mg/dL], or active or\n uncontrolled infection) that could cause unacceptable safety risks or compromise\n compliance with the protocol\n 16. Patients who have received chemotherapy, \u2264 5 half-lives or 3 weeks, whichever is\n shorter (6 weeks for nitrosourea or mitomycin-C), targeted therapy, or immunotherapy\n within 4 weeks prior to starting study drug\n 17. Patients who have \u2265 Grade 3 neuropathy\n 18. Patients who have received wide field radiotherapy \u2264 4 weeks or limited field\n radiation for palliation \u2264 2 weeks prior to starting study drug or who have not\n recovered from adverse events of prior therapy\n 19. Patients who have undergone major surgery \u2264 4 weeks prior to starting study drug or\n who have not recovered from adverse events of prior therapy\n 20. Patients who are currently receiving treatment with therapeutic doses of warfarin\n sodium (Coumadin\u00ae) or any other coumarin-derivative anticoagulants (Other\n anticoagulants such as anti-thrombin or factor X are allowed).\n 21. Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not\n mandatory; patients with well controlled HIV might be enrolled per investigator's\n discretion and Sponsor approval\n 22. Evidence of active infection with Hepatitis B or Hepatitis C that is not adequately\n controlled. (For patients with known prior history of Hepatitis B or Hepatitis C,\n enrollment may be allowed per investigator's discretion and Sponsor approval.)\n 23. Has a history or current evidence of any medical or psychiatric condition, therapy, or\n laboratory abnormality that, in the opinion of the investigator, might confound the\n results of the trial, interfere with the patient's safe participation and compliance\n in the trial. For example, conditions that depend on the establishment of collateral\n circulation, such as peripheral arterial vascular disease, myocardial infraction\n recovery period, etc", "output": {"inclusion_biomarker": [["CD73 expression"], ["PD-L1 expression"]], "exclusion_biomarker": []}}
 {"input": "Quizartinib is an experimental drug. It is not approved for regular use. It can only be used\n in medical research.\n Children or young adults with a certain kind of blood cancer (FLT3-ITD AML) might be able to\n join this study if it has come back after remission or is not responding to treatment.\n ;\n ;\n Inclusion Criteria:\n - Has diagnosis of AML according to the World Health Organization (WHO) 2008\n classification with \u22655% blasts in bone marrow, with or without extramedullary disease\n - Is in first relapse or refractory to first-line high-dose chemotherapy with no more\n than 1 attempt (1 to 2 cycles of induction chemotherapy) at remission induction -\n prior HSCT is permitted\n - Has presence of the FLT3-ITD activating mutation in bone marrow or peripheral blood as\n defined in the protocol\n - Is between 1 month and 21 years of age at the time the Informed Consent/Assent form is\n signed\n - Has protocol-defined adequate performance status score\n - Has fully recovered from the acute clinically significant toxicity effects of all\n prior chemotherapy, immunotherapy, or radiotherapy, per protocol guidelines\n - Has protocol-defined adequate renal, hepatic and cardiac functions\n - If of reproductive potential, is permanently sterile or agrees to use highly effective\n birth control upon enrollment, during the period of therapy, and for 6 months\n following the last dose of study drug or cytarabine, whichever is later\n - If female of child-bearing potential, tests negative for pregnancy and agrees not to\n breast feed\n - Participant/legal representative is capable of understanding the investigational\n nature of the study, potential risks, and benefits, and the patient (and/or legal\n representative) signs a written assent/informed consent\n - Meets protocol-specified guidelines before inclusion in the continuation therapy phase\n Exclusion Criteria:\n - Has been diagnosed with isolated central nervous system relapse, certain kinds of\n leukemia, or with myeloid proliferations related to Down syndrome\n - Has uncontrolled or pre-defined significant cardiovascular disease as detailed in the\n protocol\n - Has systemic fungal, bacterial, viral or other infection that is exhibiting ongoing\n signs/symptoms related to the infection without improvement despite appropriate\n antibiotics or other treatment. The patient must be off vasopressors and have negative\n blood cultures for at least 48 hours prior to the start of systematic protocol\n therapy.\n - Has known active clinically relevant liver disease (e.g., active hepatitis B or active\n hepatitis C)\n - Has known history of human immunodeficiency virus (HIV)\n - Has history of hypersensitivity to any of the study medications or their excipients\n - Is receiving or is anticipated to receive concomitant chemotherapy, radiation, or\n immunotherapy other than as specified in the protocol\n - Has any significant concurrent disease, illness, psychiatric disorder or social issue\n that would compromise subject safety or compliance, interfere with consent/assent,\n study participation, follow up, or interpretation of study results\n - Is currently participating in another investigative interventional procedure\n (observational or long-term interventional follow-up is allowed)\n - Is otherwise considered inappropriate for the study by the Investigator", "output": {"inclusion_biomarker": [["FLT3 ITD"]], "exclusion_biomarker": []}}
 {"input": "This study will assess the safety, tolerability, and efficacy of multiple dose levels of\n PC14586 in participants with advanced solid tumors containing a TP53 Y220C mutation.\n ;\n ;\n Inclusion Criteria:\n - At least 18 years of age or 12 to 17 years of age after adequate adult safety data\n become available\n - Advanced solid malignancy with a TP53 Y220C mutation\n - Eastern Cooperative Oncology Group (ECOG) status of 0 or 1\n - Previously treated with one or more lines of anticancer therapy and progressive\n disease\n - Adequate organ function\n Exclusion Criteria:\n - Anti-cancer therapy within 21 days (or 5 half-lives) of receiving the study drug\n - Radiotherapy within 28 days of receiving the study drug\n - Primary CNS tumor (Phase 1, Phase 2 Cohort A)\n - History of leptomeningeal disease or spinal cord compression\n - Brain metastases, unless neurologically stable and do not require steroids to treat\n associated neurological symptom\n - Stroke or transient ischemic attack within 6 months prior to screening\n - Heart conditions such as unstable angina, uncontrolled hypertension, a heart attack\n within 6 months prior to screening, congestive heart failure, prolongation of QT\n interval, or other rhythm abnormalities\n - Strong CYP3A4 inhibitors or inducers, medications with a known risk of QT/QTc\n prolongation, or proton pump inhibitors\n - History of gastrointestinal (GI) disease that may interfere with absorption of study\n drug or patients unable to take oral medication\n - History of prior organ transplant\n - Known, active malignancy, except for treated cervical intraepithelial neoplasia, or\n non-melanoma skin cancer\n - Known, active uncontrolled Hepatitis B, Hepatitis C, or human immunodeficiency virus\n infection", "output": {"inclusion_biomarker": [["TP53 Y220C"]], "exclusion_biomarker": []}}
 {"input": "Despite improvements in outcomes for patients with localized Ewing sarcoma, patients with\n relapsed metastatic Ewing sarcoma continue to have poor outcomes with current chemotherapy\n options. A large body of preclinical data supports a role for IGF-1R inhibition in the\n treatment of Ewing sarcoma.\n More recently, clinical trials of IGF-1R monoclonal antibodies have demonstrated single-\n agent activity in patients with relapsed Ewing sarcoma. Ganitumab (AMG 479) is a fully human\n monoclonal antibody directed against IGF-1R. We are proposing this single-agent expanded\n access IND to provide our patient the opportunity to benefit from this treatment after having\n developed progressive disease after multiple lines of prior therapy.\n ;\n ;\n Inclusion Criteria:\n Diagnosis: Confirmed translocation-positive Ewing sarcoma\n Organ Function Requirements:\n Serum creatinine < 1.4 Adequate liver function\n - Total bilitubin <1.5x upper limit of normal for age\n - SGPT (ALT) < 5x upper limit of normal for age Adequate cardiac function > 50% by\n echocardiogram Bone Marrow\n - Absolute neutrophil count > 750\n - Platelet count > 75\n Exclusion Criteria:\n - Female patients of childbearing potential are not eligible unless a negative pregnancy\n test result has been obtained. Lactating females are not eligible unless they have\n agreed not to breastfeed their infants for the duration of protocol therapy. Sexually\n active patients of reproductive potential are not eligible unless they have agreed to\n use an effective contraceptive method for the duration of protocol therapy.\n - Patients with known pre-existing diabetes mellitus will be excluded from study.", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
@@ -24,39 +24,39 @@
 {"input": "This is a phase I, first in human, single arm, open label study that will assess safety,\n tolerability and clinical activity of FHND6091 when taken orally on a weekly dosing schedule\n by patients with relapsed and refractory multiple myeloma (RRMM).The study will consist of\n two parts: dose escalation (Part 1) and dose expansion (Part 2).The dose escalation (Part 1)\n of the study will evaluate the safety and tolerability of FHND6091 using a dose escalation\n scheme to establish a maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D).\n And the dose expansion (Part B) of the study will further evaluate the safety,\n pharmacokinetics (PK)/ pharmacodynamics (PD), and efficacy of FHND6091 at two selected dose\n levels to characterize the safety, tolerability and efficacy of FHND6091.\n A total of 40 evaluable participants will be enrolled in the study. The participants\n receiving treatment in part 1 and part 2 may continue combination treatment for a total of up\n to 12 cycles. After 12 cycles of therapy, the participants will continue treatment until the\n occurrence of PD, intolerable AEs, consent withdrawal, death or end of study based on the\n judgement of investigator's assessment.\n ;NA;\n Inclusion Criteria:\n - Patients must give written informed consent.\n - Male or female patients 18 years or older.\n - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2.\n - Life expectancy of at least 12 weeks.\n - Patients with multiple myeloma who have relapsed or refractory, intolerance or refuse\n treatment following at least 3 regimens or lines of therapy that must include an IMID\n (lenalidomide or thalidomide), a proteasome inhibitor (bortezomib) , a CD38-targeted\n mAbs and corticosteroids. Patients must have received transplant therapy or are not\n suitable for transplant.\n - For Patients With Relapsed Refractory Multiple Myeloma must have measurable disease\n defined by at least 1 of the following 2 measurements: Serum M-protein \u2265 5 g/L, or\n Urine M-protein \u2265 200 mg/24 hours. For patients with serum free light chain as\n measurable disease: Serum immunoglobulin free light chain \u226510 mg/dL and abnormal serum\n immunoglobulin kappa to lambda free light chain ratio.\n - Clinical laboratory values as specified below within 14 days before the first dose of\n study drug:\n 1. Hemoglobin \u2265 75 g/L, Absolute neutrophil count \u2265 1.0 x 10E9/L and Platelet count\n \u2265 75 x 10E9/L without blood transfusion, EPO or G-CSF and other medical support\n for at least 14 days prior to receiving screening.\n 2. Total bilirubin levels \u2264 2 x ULN, AST (SGOT) and ALT (SGPT) \u2264 2 x ULN.\n 3. Calculated or measured creatinine clearance (CrCl) of \u2265 30 mL/minute as\n calculated by Cockcroft-Gault method.\n 4. Corrected Serum Calcium \u2264 ULN.\n - For man and women of childbearing potential: agreement to remain abstinent or use\n contraception, during the treatment period (including treatment interruptions) and for\n at least 180 days after the last dose of FHND6091 was administered. Women of\n childbearing potential should be negative by serum pregnancy test within 7 days prior\n dosing.\n Exclusion Criteria:\n - Documented allergy to proteasome inhibitor or \uff1b\n - Patients with peripheral neuropathy \u2265 Grade 2 or Grade 1 peripheral neuropathy with\n pain.\n - Patients with diarrhea > Grade 1 (Increase of <4 stools per day over baseline; mild\n increase in ostomy output compared to baseline).\n - Patients received chemotherapy, radiation therapy, targeted therapy, immunotherapy or\n other systemic anticancer therapy within 14 days prior FHND6091 treatment.\n - Patients received ixazomib treatment within 5 elimination half-life prior first dose\n of FHND6091 treatment.\n - Patients received allogeneic stem cell transplantation or autologous stem cell\n transplant with 12 weeks before screening.\n - Patients with symptomatic brain metastases, leptomeningeal metastases or, spinal cord\n compression or central nervous system (CNS) injuries/abnormalities based on\n investigator judgement.\n - Evidence of severe or uncontrolled systemic diseases (eg, unstable or uncompensated\n respiratory, hepatic or renal disease), or receive major surgery.\n - Patients with unstable hypertension after drug treatment (SBP \u2265140 mmHg, DBP \u226590 mmHg\n ) or heart failure, myocardial ischemia or myocardial infarction, unstable angina,\n arrhythmia (The corrected QT interval (Fridericia formula) interval (QTcF) > 470 msec\n for females and > 450 msec for men in electrocardiogram (ECG)).\n - Patients with active, or a history of immunodeficiency, including HIV positive or\n other acquired and congenital immunodeficiency diseases, or a history of solid organ\n transplant.\n - Patients with a history of other serious underlying diseases, such as: a, history of a\n clear neurological or psychiatric disorder, including epilepsy or dementia. b, HBV\n surface antigen positivity (subjects with documented laboratory evidence of HBV\n clearance may be enrolled) or positive HCV antibody. c, presence of infection\n requiring systemic treatment.\n - Systemic treatment with strong inhibitors of of CYP3A4 or strong CYP3A4 inducers\n within 5 elimination half-life prior first dose of FHND6091 treatment.\n - Patients have not recovered (ie, \u2264 Grade 1 toxicity by CTCAE 5.0) from the reversible\n effects of prior antineoplastic therapy (except for alopecia )\n - Patients with other malignancy\uff1b\n - Treatment with any investigational products within 28 days before the first dose of\n study treatment", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
 {"input": "Numerous evidences verified that erlotinib could dramatically improve the PFS and OS of\n non-small cell lung cancers who harbor EGFR sensitive mutations, however, primary or\n secondary resistance will be developed after TKI treatment, doctors do plenty of researches\n to overcome TKI resistance. FAST ACT-2 study present that, first line erlotinib combined with\n chemotherapy could improved mOS to more than 30 months in NSCLCs who harbor EGFR sensitive\n mutations, several study shows that sensitive mutations still exist after TKI resistance,\n because of the next generation TKIs(such as BIBW2992) are not avaliable at present, agents\n for met amplification(such as Crizotinib) are so expensive that many Chinese patients could\n not support. Thus, the investigators hypothesis that, after first line TKI treatment, the\n patients who developed TKI resistance could still benefit from second line TKI combined with\n chemotherapy.\n ;\n ;\n Inclusion Criteria:\n - advanced non-small cell lung cancer, stage IIIB/IV\n - non-squamous\n - EGFR sensitive mutations, such as exon 19 del, or exon 21 L858R\n - received first line TKIs treatment and developed TKI resistance\n - ECOG 0-2\n Exclusion Criteria:\n - squamous non-small cell lung cancer\n - patients have unstable brain metastasis, predict survival less than 8 weeks\n - spinal-cord compression without evidence of stabilisation or treatment\n - women who were pregnant or lactating; women with a positive or no available pregnancy\n test result at baseline\n - patients have any unstable illness that could not receive further treatment", "output": {"inclusion_biomarker": [["EGFR exon 19 del"], ["EGFR exon 21 L858R"]], "exclusion_biomarker": []}}
 {"input": "RAD-18-001 is a First-In-Man, Dose Escalation study conducted at 2 sites. The dose escalation\n will be performed based on a 3 + 3 design. Increasing dose levels starting at 1 MBq will be\n followed by 2, 4 and 7 MBq. If the highest dose level of 7 MBq is reached without Dose\n Limiting Toxicicities (which will stop the dose escalation), this will be the recommended\n dose for further exploration. Each subject will be followed until disease progression (in the\n abdominal cavity), or for 24 months after the administration of Radspherin\u00ae (whichever comes\n first).\n In the expansion cohort the subject will receive the recommended dose. The expansion cohort\n will be conducted at 4 sites. Each subject will be followed until disease progression (in the\n abdominal cavity), or for 24 months after the administration of Radspherin\u00ae (whichever comes\n first).\n ;\n ;\n Inclusion Criteria:\n 1. Able and willing to provide written informed consent and to comply with the clinical\n study protocol\n 2. Age \u2265 18 years\n 3. Histologically confirmed epithelial ovarian, fallopian tube and primary peritoneal\n carcinoma\n 4. Platinum sensitive recurrences of ovarian carcinoma who are eligible for debulking\n surgery to R0.\n 5. AEs recovered to at least grade 1 from the effects (excluding alopecia) of any prior\n medical therapy for malignancy at time of first administration of Radspherin\u00ae\n 6. ECOG Performance Status Score of 0 - 1\n 7. Adequate renal function\n - Creatinine \u2264 1.8 mg/dl (159 \u03bcmol/l) and\n - calculated creatinine clearance using the Cockcroft-Gault formula \u2265 45 ml/min, or\n - measured creatinine clearance \u2265 45 ml/min\n 8. Adequate hepatic function\n - Serum bilirubin <1.5 x upper limit of normal (ULN)\n - Aspartate transaminase (AST) and alanine transaminase (ALT) \u2264 3 x ULN\n 9. Adequate bone marrow function:\n - Absolute neutrophil count (ANC) \u2265 1.5 x 10^9/l\n - Platelets \u2265 100 x 10^9/l\n - Haemoglobin \u2265 9 g/dL\n 10. Adequate coagulation tests: INR \u2264 1.5 x ULN\n 11. For females of childbearing potential, a negative pregnancy test must be documented\n prior to enrolment\n 12. For females of childbearing potential who have a male partner: agreement to use two\n adequate methods of contraception (e.g. barrier, intrauterine device, hormonal\n implants, combined oral contraceptives or vasectomized partner), during the treatment\n period and for at least 3 months after the last dose of IMP.\n Exclusion Criteria:\n 1. Neuroendocrine tumors, or non-epithelial ovarian cancers (e.g. germ cell tumors,\n Sex-cord tumors)\n 2. Tumors of borderline malignancy\n 3. Other synchronous visceral metastatic lesions, symptomatic CNS metastases. Metastatic\n lymph nodes are acceptable, except thoracic lymph nodes.\n 4. Pregnant or lactating (nursing) women\n 5. Active infections requiring antibiotics, and/or physician monitoring or recurrent\n fever >38.0 \u2070C associated with a clinical diagnosis of active infection\n 6. Active liver disease with positive serology for active hepatitis B, hepatitis C or\n known HIV\n 7. Administration of an investigational medicinal product within 28 days, or at least 5\n times the half-life, prior to enrolment\n 8. Concurrent administration of any cancer therapy other than planned study treatment\n within 4 weeks prior to, and up to 4 weeks after the last study treatment\n 9. Another primary malignancy within the past 3 years (except for non-melanoma skin\n cancer, cervical cancer in situ or in situ stage 1 synchronous endometrial cancer)\n 10. Concurrent congestive heart failure or prior history of New York Heart Association\n (NYHA) class III/IV cardiac disease\n 11. Any condition or illness that, in the opinion of the Investigator or the medical\n monitor, would compromise the safety of the subjects or interfere with the evaluation\n of the safety of the IMP\n 12. In the Investigator's opinion not able to comply with study procedures. Any medical or\n psychological condition that would preclude participation in the study or compromise\n the ability to give informed consent\n 13. Treatment with bevacizumab (Avastin\u00ae) within 5 weeks prior to CRS\n 14. Known hypersensitivity to any of the excipients in the study drug\n 15. Persons who have been placed in an institution under an official or judicial order\n 16. Persons who are dependent on the sponsor financially must be excluded from\n participation\n 17. Persons with active SARS-CoV-2 infection must be excluded from participation", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
-{"input": "This is a Phase 1 study of JSI-1187 as monotherapy and in combination with dabrafenib for the\n treatment of advanced solid tumors with MAPK pathway mutations, including mutations that\n cause MAPK pathway hyperactivation.\n ;\n ;\n Inclusion Criteria:\n - Males and females \u2265 18 years of age\n - Have locally advanced or metastatic solid tumor malignancy with measurable disease and\n be an appropriate candidate for experimental therapy\n - Part A (JSI-1187 Monotherapy Dose Escalation): Histologically or cytologically\n confirmed MAPK pathway mutation, including hyperactivating pathway mutations or gene\n fusions, e.g., BRAF (Class I, II or III), RAS (H/K/N), MEK (MAP2K1), RAS-GAP (NF1\n loss, RASA1), RAS-GEF, refractory to or relapsed on prior therapy, and have received\n all available therapy known to confer clinical benefit\n - Part B (JSI-1187 Plus Dabrafenib Combination Dose Escalation): Histologically or\n cytologically confirmed BRAF V600E/K-mutated unresectable or metastatic melanoma, BRAF\n V600E-mutated metastatic NSCLC, BRAF V600E-mutated locally advanced or metastatic\n anaplastic thyroid cancer, or other BRAF V600E-mutated unresectable or metastatic\n solid tumors, excluding colorectal cancer, refractory to, or relapsed on, prior\n therapy, and have received all available therapy known to confer clinical benefit\n - Part C (JSI-1187 Plus Dabrafenib Expansion Cohorts): Histologically or cytologically\n confirmed:\n - Cohort 1: BRAF V600E/K-mutated unresectable or metastatic melanoma after 1-3\n prior therapies for metastatic disease, including anti-PD1 therapy, with or\n without ipilimumab, and BRAF/MEK inhibitor treatment\n - Cohort 2: BRAF V600E/K-mutated unresectable or metastatic melanoma after BRAF/MEK\n inhibitor adjuvant therapy for Stage 3 disease followed by 1-2 prior therapies\n for metastatic disease, including anti-PD-1 therapy, with or without ipilimumab,\n and excluding BRAF/MEK inhibitor treatment\n - Cohort 3: BRAF V600E-mutated metastatic NSCLC after 1 or 2 prior therapies for\n metastatic disease\n - MAPK mutation tumor status will be established prior to entry based on previous MAPK\n pathway mutation reports from a CLIA qualified laboratory, or, if a report is not\n available, the mutation analysis will be performed at Screening on archival tissue or\n newly biopsied tumor tissue.\n - Have discontinued previous treatments for cancer and have resolution, except where\n otherwise stated in the inclusion criteria, of all clinically significant toxic\n effects of prior cancer treatment, surgery, or radiotherapy to Grade \u2264 1. Subjects\n with prior immune checkpoint inhibitor endocrinopathies must have resolution to \u2264\n Grade 2 and be stable on hormonal therapy (e.g., levothyroxine, hydrocortisone,\n insulin, etc.).\n - Adequate performance status: Eastern Cooperative Oncology Group (ECOG) \u2264 2\n - Life expectancy of \u2265 3 months\n - Subjects with asymptomatic stable, prior or currently treated brain metastases are\n allowed\n - Adequate hematologic parameters without ongoing transfusional support:\n - Hemoglobin (Hb) \u2265 9 g/dL\n - Absolute neutrophil count (ANC) \u2265 1.0 x 10^9 cells/L\n - Platelets \u2265 75 x 10^9 cells/L\n - Adequate renal and hepatic function:\n - Creatinine \u2264 1.5 times the upper limit of normal (ULN), or calculated creatinine\n clearance \u2265 50 mL/minute x 1.73 m^2 per the Cockcroft-Gault formula\n - Total bilirubin \u2264 1.5 times the (ULN) unless due to Gilbert's disease\n - ALT/AST \u2264 2 times the ULN, or < 3 times the ULN for subjects with liver\n metastases\n - Negative serum pregnancy test within 14 days prior to the first dose of study therapy\n for women of child-bearing potential (WCBP). Sexually active WCBP and male subjects\n must agree to use adequate methods to avoid pregnancy throughout the study and for 28\n days after the completion of study treatment.\n - Ability to provide written informed consent\n Exclusion Criteria:\n - Serious cardiac condition within the last 6 months, such as uncontrolled arrhythmia,\n myocardial infarction, unstable angina or heart disease defined by the New York Heart\n Association (NYHA) Class III or Class IV\n - QT interval corrected for rate (QTc) > 480 msec on the ECG obtained at Screening using\n Fridericia method for QTc calculation\n - Concomitant medication(s) that may cause QTc prolongation or induce Torsades de\n Pointes, with the exception of anti-microbials that are used as standard of care to\n prevent or treat infections and other such drugs that are considered by the\n Investigator to be essential for patient care.\n - Medications that are strong inhibitors of CYP3A4 are prohibited during study and for\n 14 days prior to the first dose of study drug(s).\n - Medications that are strong inducers of CYP3A4 are prohibited during study and for 14\n days prior to the first dose of study drug(s).\n - Medications that are strong inhibitors of BCRP are prohibited during study and for 14\n days prior to the first dose of study drugs(s).\n - Subjects on dabrafenib (Parts B and C) also are advised to avoid concurrent\n administration of strong inhibitors of CYP2C8 as these medications may increase the\n concentration of dabrafenib\n - History of or current evidence/risk of retinal vein occlusion or central serous\n retinopathy, or has medically relevant abnormalities identified on screening\n ophthalmologic examination\n - Symptomatic central nervous system malignancy or metastasis\n - Gastrointestinal conditions that could impair absorption of study drug(s)\n - Current hematologic malignancies\n - Second, active primary solid tumor malignancy that, in the judgement of the\n investigator or Sponsor medical monitor, may affect the interpretation of results\n - Prior malignancies, with the exception of carcinoma in situ of any origin, non-muscle\n invasive bladder cancer, Gleason 3+3 prostate cancer and prior malignancies in\n remission whose likelihood of recurrence is very low, as judged by the Sponsor medical\n monitor.\n - Active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or\n hepatitis C virus (HCV) requiring treatment within the last week prior to study\n treatment\n - Other active infection requiring IV antibiotic usage within the last week prior to\n study treatment\n - Any other medical intervention or other condition which, in the opinion of the\n Principal Investigator, could compromise adherence to study requirements or confound\n the interpretation of study results\n - Receipt of an investigational product on a clinical trial within 5 elimination\n half-lives or within 28 days, whichever is shorter, prior to C1D1 on this study, or\n currently enrolled in a clinical trial, involving an investigational product or any\n other type of medical research judged not to be scientifically or medically compatible\n with this study\n - Previously completed or withdrawn from this study or any other study investigating an\n ERK1/2 inhibitor.\n - If female, pregnant, breast-feeding, or planning to become pregnant", "output": {"inclusion_biomarker": [["BRAF (Class I, II or III)"], ["RAS (H/K/N)"], ["MEK (MAP2K1)"], ["RAS-GAP (NF1 loss, RASA1)"], ["RAS-GEF"], ["BRAF V600E/K"], ["BRAF V600E"]], "exclusion_biomarker": []}}
+{"input": "This is a Phase 1 study of JSI-1187 as monotherapy and in combination with dabrafenib for the\n treatment of advanced solid tumors with MAPK pathway mutations, including mutations that\n cause MAPK pathway hyperactivation.\n ;\n ;\n Inclusion Criteria:\n - Males and females \u2265 18 years of age\n - Have locally advanced or metastatic solid tumor malignancy with measurable disease and\n be an appropriate candidate for experimental therapy\n - Part A (JSI-1187 Monotherapy Dose Escalation): Histologically or cytologically\n confirmed MAPK pathway mutation, including hyperactivating pathway mutations or gene\n fusions, e.g., BRAF (Class I, II or III), RAS (H/K/N), MEK (MAP2K1), RAS-GAP (NF1\n loss, RASA1), RAS-GEF, refractory to or relapsed on prior therapy, and have received\n all available therapy known to confer clinical benefit\n - Part B (JSI-1187 Plus Dabrafenib Combination Dose Escalation): Histologically or\n cytologically confirmed BRAF V600E/K-mutated unresectable or metastatic melanoma, BRAF\n V600E-mutated metastatic NSCLC, BRAF V600E-mutated locally advanced or metastatic\n anaplastic thyroid cancer, or other BRAF V600E-mutated unresectable or metastatic\n solid tumors, excluding colorectal cancer, refractory to, or relapsed on, prior\n therapy, and have received all available therapy known to confer clinical benefit\n - Part C (JSI-1187 Plus Dabrafenib Expansion Cohorts): Histologically or cytologically\n confirmed:\n - Cohort 1: BRAF V600E/K-mutated unresectable or metastatic melanoma after 1-3\n prior therapies for metastatic disease, including anti-PD1 therapy, with or\n without ipilimumab, and BRAF/MEK inhibitor treatment\n - Cohort 2: BRAF V600E/K-mutated unresectable or metastatic melanoma after BRAF/MEK\n inhibitor adjuvant therapy for Stage 3 disease followed by 1-2 prior therapies\n for metastatic disease, including anti-PD-1 therapy, with or without ipilimumab,\n and excluding BRAF/MEK inhibitor treatment\n - Cohort 3: BRAF V600E-mutated metastatic NSCLC after 1 or 2 prior therapies for\n metastatic disease\n - MAPK mutation tumor status will be established prior to entry based on previous MAPK\n pathway mutation reports from a CLIA qualified laboratory, or, if a report is not\n available, the mutation analysis will be performed at Screening on archival tissue or\n newly biopsied tumor tissue.\n - Have discontinued previous treatments for cancer and have resolution, except where\n otherwise stated in the inclusion criteria, of all clinically significant toxic\n effects of prior cancer treatment, surgery, or radiotherapy to Grade \u2264 1. Subjects\n with prior immune checkpoint inhibitor endocrinopathies must have resolution to \u2264\n Grade 2 and be stable on hormonal therapy (e.g., levothyroxine, hydrocortisone,\n insulin, etc.).\n - Adequate performance status: Eastern Cooperative Oncology Group (ECOG) \u2264 2\n - Life expectancy of \u2265 3 months\n - Subjects with asymptomatic stable, prior or currently treated brain metastases are\n allowed\n - Adequate hematologic parameters without ongoing transfusional support:\n - Hemoglobin (Hb) \u2265 9 g/dL\n - Absolute neutrophil count (ANC) \u2265 1.0 x 10^9 cells/L\n - Platelets \u2265 75 x 10^9 cells/L\n - Adequate renal and hepatic function:\n - Creatinine \u2264 1.5 times the upper limit of normal (ULN), or calculated creatinine\n clearance \u2265 50 mL/minute x 1.73 m^2 per the Cockcroft-Gault formula\n - Total bilirubin \u2264 1.5 times the (ULN) unless due to Gilbert's disease\n - ALT/AST \u2264 2 times the ULN, or < 3 times the ULN for subjects with liver\n metastases\n - Negative serum pregnancy test within 14 days prior to the first dose of study therapy\n for women of child-bearing potential (WCBP). Sexually active WCBP and male subjects\n must agree to use adequate methods to avoid pregnancy throughout the study and for 28\n days after the completion of study treatment.\n - Ability to provide written informed consent\n Exclusion Criteria:\n - Serious cardiac condition within the last 6 months, such as uncontrolled arrhythmia,\n myocardial infarction, unstable angina or heart disease defined by the New York Heart\n Association (NYHA) Class III or Class IV\n - QT interval corrected for rate (QTc) > 480 msec on the ECG obtained at Screening using\n Fridericia method for QTc calculation\n - Concomitant medication(s) that may cause QTc prolongation or induce Torsades de\n Pointes, with the exception of anti-microbials that are used as standard of care to\n prevent or treat infections and other such drugs that are considered by the\n Investigator to be essential for patient care.\n - Medications that are strong inhibitors of CYP3A4 are prohibited during study and for\n 14 days prior to the first dose of study drug(s).\n - Medications that are strong inducers of CYP3A4 are prohibited during study and for 14\n days prior to the first dose of study drug(s).\n - Medications that are strong inhibitors of BCRP are prohibited during study and for 14\n days prior to the first dose of study drugs(s).\n - Subjects on dabrafenib (Parts B and C) also are advised to avoid concurrent\n administration of strong inhibitors of CYP2C8 as these medications may increase the\n concentration of dabrafenib\n - History of or current evidence/risk of retinal vein occlusion or central serous\n retinopathy, or has medically relevant abnormalities identified on screening\n ophthalmologic examination\n - Symptomatic central nervous system malignancy or metastasis\n - Gastrointestinal conditions that could impair absorption of study drug(s)\n - Current hematologic malignancies\n - Second, active primary solid tumor malignancy that, in the judgement of the\n investigator or Sponsor medical monitor, may affect the interpretation of results\n - Prior malignancies, with the exception of carcinoma in situ of any origin, non-muscle\n invasive bladder cancer, Gleason 3+3 prostate cancer and prior malignancies in\n remission whose likelihood of recurrence is very low, as judged by the Sponsor medical\n monitor.\n - Active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or\n hepatitis C virus (HCV) requiring treatment within the last week prior to study\n treatment\n - Other active infection requiring IV antibiotic usage within the last week prior to\n study treatment\n - Any other medical intervention or other condition which, in the opinion of the\n Principal Investigator, could compromise adherence to study requirements or confound\n the interpretation of study results\n - Receipt of an investigational product on a clinical trial within 5 elimination\n half-lives or within 28 days, whichever is shorter, prior to C1D1 on this study, or\n currently enrolled in a clinical trial, involving an investigational product or any\n other type of medical research judged not to be scientifically or medically compatible\n with this study\n - Previously completed or withdrawn from this study or any other study investigating an\n ERK1/2 inhibitor.\n - If female, pregnant, breast-feeding, or planning to become pregnant", "output": {"inclusion_biomarker": [["MAPK pathway mutation"], ["BRAF Class 1 mutation"], ["BRAF Class 2 mutation"], ["BRAF Class 3 mutation"], ["HRAS mutation"], ["KRAS mutation"], ["NRAS mutation"], ["MEK mutation"], ["NF1 loss"], ["RASA1 mutation"], ["RAS-GEF"], ["BRAF V600E"], ["BRAF V600K"]], "exclusion_biomarker": []}}
 {"input": "Study STML-901-0119 is a dose-escalation study evaluating multiple doses and schedules of\n orally administered SL-901 in patients with Advanced Solid Tumors.\n ;\n ;\n Inclusion Criteria:\n 1. 18 years old or older.\n 2. Population by study stage:\n 1. Part 1a: Patients with advanced, metastatic, and/or progressive solid tumors for\n whom there is no effective standard therapy available.\n 2. Part 1b: Patients with histologically confirmed, advanced, metastatic,\n unresectable, and/or progressive solid tumors for whom there is no effective\n standard therapy available and their PI3K or DNA-PK pathway is deregulated or\n their tumor genetic profile has been shown to correlate with sensitivity to PI3K\n and/or DNA-PK inhibition based on clinical and preclinical experience. Specific\n criteria will be determined based on ongoing experiments and will be introduced\n in a future protocol amendment.\n 3. Evaluable or measurable disease.\n 4. Eastern Cooperative Oncology Group (ECOG) performance status \u22642.\n 5. Able to take oral medications.\n 6. If a woman of childbearing potential (WOCBP), the patient has a negative serum or\n urine pregnancy test within 1 week before Cycle 1, Day 1 (C1D1). Refer to Section\n 8.1.3 for further practical information about contraception.\n 7. The patient (either male or female) agrees to use acceptable contraceptive methods for\n the duration of time in the study, and to continue to use acceptable contraceptive\n methods for 1 month after the last dose of SL-901. Refer to Section 8.1.3 for further\n practical information about contraception.\n 8. Able to provide written informed consent.\n 9. Willing to provide consent for biomarker analysis of existing paraffin-embedded tumor\n samples.\n Exclusion Criteria:\n 1. Received an investigational anticancer drug within 4 weeks of the first planned SL-901\n dose.\n 2. Received major surgery, radiotherapy, or immunotherapy within 4 weeks of C1D1.\n Localized palliative radiotherapy is permitted for symptom control.\n 3. Received chemotherapy regimens with delayed toxicity within 4 weeks (6 weeks for prior\n nitrosourea or mitomycin C) of C1D1.\n 4. Received chemotherapy regimens given continuously or on a weekly basis which have\n limited potential for delayed toxicity within 2 weeks of C1D1.\n 5. Clinically significant, unresolved toxicity from previous anticancer therapy \u2265Grade 2\n (except alopecia), as determined by the Investigator using the National Cancer\n Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.\n 6. Presence of active gastrointestinal disease or other condition that will interfere\n significantly with the absorption, distribution, metabolism, or excretion of drugs.\n 7. Left ventricular ejection fraction <50%.\n 8. Corrected QT interval (based on Fridericia's formula) >450 msec.\n 9. Type 1 or 2 diabetes mellitus requiring medication. (In Part 1b, patients with type 2\n diabetes mellitus controlled by medication, as indicated by a glycated hemoglobin of\n \u22647.5% are eligible.)\n 10. Known active human immunodeficiency virus, hepatitis B, or hepatitis C infection.\n 11. Ongoing systemic bacterial, fungal, or viral infection.\n 12. History of interstitial pneumonitis.\n 13. Absolute neutrophil count (ANC) 1.5\u00d710\u2079/L.\n 14. Hemoglobin <10 g/dL.\n 15. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5x the upper\n limit of normal (ULN).\n 16. Known hypersensitivity or allergy to the active ingredient or excipients of SL-901.\n 17. Breast-feeding females.", "output": {"inclusion_biomarker": [["PI3K pathway deregulation"], ["DNA-PK pathway deregulation"]], "exclusion_biomarker": []}}
 {"input": "The incidence of breast reconstruction failure after conventional photon radiotherapy for\n breast cancer is about 18.7%. At present, there is limited data on proton radiotherapy for\n post operative breast cancer with implantation reconstruction. Proton radiotherapy for breast\n cancer can significantly reduce the radiation dose of the ipsilateral heart and lung, thereby\n reducing the incidence of cardiac events and radiation pneumonia. This study is aimed at the\n study of adjuvant hypofractionated intensity-modulated proton radiotherapy for post operative\n breast cancer with implantation reconstruction. It can provide an ideal treatment option for\n such patients to effectively protect the heart and lungs without increasing the failure rate\n of breast reconstruction after adjuvant radiotherapy.\n ;NA;\n Inclusion Criteria:\n - 1: Patients with pathologically confirmed breast cancer\n 2: Indications: patients who need adjuvant radiotherapy after mastectomy and implant\n reconstruction\n 3: No distant metastasis\n 4: Had no chest and breast radiotherapy history\n 5: Between the ages of 18 and 80\n 6: ECOG general status score is 0-2,There are no serious pulmonary hypertension,\n cardiovascular disease, peripheral vascular disease, serious chronic heart disease and\n other complications that may affect the radiotherapy\n 7: Non pregnancy (confirmed by serum or urine \u03b2- HCG test) or lactating women\n 8: The patient must sign the informed consent form for receiving radiotherapy.\n Exclusion Criteria:\n - 1: No pathological confirmation\uff1b\n 2: Distant metastasis\uff1b\n 3: Had chest and breast radiotherapy history\n 4: Organs at risk could not achieve safe dose\n 5: Pregnancy (confirmed by serum or urine \u03b2- HCG test) or lactating women\n 6: Poor general health status, i.e. KPS<70, or ECOG>2\n 7: There are serious complications that may affect the radiotherapy, including: a)\n unstable angina, congestive heart failure and myocardial infarction requiring\n hospitalization in the past 6 months\uff1b b) Acute bacterial or systemic fungal\n infection\uff1bc) Chronic obstructive pulmonary disease exacerbation or other respiratory\n diseases need hospitalization\uff1b d) Patients with immunosuppression\uff1be) With connective\n tissue disease, such as active scleroderma or lupus and other contraindications to\n radiotherapy\uff1b\n 8: Unable to understand the purpose of treatment or unwilling/unable to sign informed\n consent.", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
 {"input": "To evaluate the anti cancer effect of VK 2019 in subjects with EBV related nasopharyngeal\n carcinoma (NPC) for whom there is no other standard treatment available\n ;\n ;\n Inclusion Criteria:\n - 1 Informed consent obtained prior to any protocol mandated study specific procedures\n in accordance with institutional policies.\n - 2 Either loco regionally recurrent or metastatic EBV positive RECIST evaluable\n nasopharyngeal carcinoma not amenable to curative treatment with no accepted effective\n standard of care therapeutic option.\n Addendum for phase 2 exploratory cohorts: subjects with PTLD or EBV lymphoma not amenable\n to curative treatment with no accepted effective standard of care therapeutic option.\n - 3 Not eligible for other approved or standard therapies\n - 4.Prior palliative radiation must have been completed at least 2 weeks prior to study\n Cycle 1 Day 0\n - 5.Prior anti cancer systemic treatment must have been completed greater than 4 weeks\n prior to the first dose of VK 2019 or subjects must have recovered from all acute\n prior treatment related AEs\n - 6.Toxicities related to prior anti cancer therapy must have returned to Grade 1 or\n less. Peripheral neuropathy must be Grade 2 or less. Chronic but stable toxicities\n Grade > 1 (eg, dysphasia, G tube dependence, etc.) are permissible.\n - 7.Age \u2265 18\n - 8.Absolute neutrophil count > 1500/\u00b5L (stable off any growth factor for at least 1\n week of study drug administration)\n - 9.Hemoglobin > 9g/dL (transfusion to achieve this level is permitted)\n - 10.Platelet count > 75 x 103/ \u00b5L (transfusion to achieve this level is NOT permitted)\n - 11.Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) \u2264 2.5 x\n upper limit of normal (ULN) .Total serum bilirubin \u2264 1.5 x ULN\n - 12.Serum creatinine \u2264 1.5 x ULN or creatinine clearance \u2265 50 mL/min as calculated per\n Cockcroft Gault equation\n - 13.Urinary protein < 2+ by dipstick. If dipstick \u2265 2+, then a 24 hour urine collection\n can be done and the subject may enter only if urinary protein is < 1 g/24 hour\n - 14.Sexually active subjects must agree to utilize birth control method during\n treatment and for 18 weeks after the last dose of VK 2019.\n - 15.Eastern Cooperative Oncology Group (ECOG) performance status 2 or less.\n - 16.Ability to understand and the willingness to personally sign the written IRB\n approved informed consent document.\n Exclusion Criteria:\n - 1.Prior therapy restrictions.\n - 2.Concurrent treatment with systemic cancer directed therapy including complementary,\n alternative, herbal or nutritional supplement based treatments whose purpose is for\n anti cancer effect\n - 3.Severe or active symptomatic cardiopulmonary diseases, including unstable angina,\n congestive heart failure, or peripheral vascular disease within 12 months prior to\n study drug administration; and/or chronic obstructive pulmonary disease exacerbation\n or other respiratory illness requiring hospitalization within 4 weeks prior to study\n drug administration. Subjects with effectively treated conditions (eg, stenting for\n coronary artery disease) are eligible if stable for at least 4 weeks prior to study\n drug administration\n - 4.Metastatic disease with active central nervous system (CNS) involvement, defined as\n parenchymal brain involvement. Subjects with cranial nerve or base of skull\n involvement without the above are eligible. Subjects with CNS metastases that are\n stable on imaging at least 1 month following focal treatment with radiation are\n eligible\n - 5.Known history of human immunodeficiency virus (HIV) unless the HIV positive subjects\n has:\n 1. A stable regimen of highly active anti retroviral therapy (HAART)\n 2. No requirement for concurrent antibiotics or antifungal agents for the prevention\n of opportunistic infections\n 3. A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard\n PCR based test\n - 6.Serious uncontrolled medical disorder or active infection which would, in the\n opinion of the Investigator, impair the ability of the subject to receive protocol\n therapy or whose control may be jeopardized by the complications of this therapy\n - 7.NPC subjects: Have received a prior organ allograft or allogeneic bone marrow\n transplant.\n - 8.Current non prescription drug or alcohol dependence\n - 9.For all female subjects: pregnancy or breastfeeding\n - 10.All female subjects with reproductive potential must have a negative pregnancy test\n (serum or urine) prior to enrollment\n - 11.Other severe acute or chronic medical or psychiatric condition or laboratory\n abnormality that may increase the risk associated with study participation or study\n drug administration, or may interfere with the interpretation of study results, or in\n the judgment of the investigator would make the subject inappropriate for entry into\n the study\n - 12.Corrected QT by Fridericia's formula (QTcF) of > 470 ms average (mean) on\n triplicate ECG performed during screening", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
-{"input": "AL2846 is a multi-target receptor tyrosine kinase inhibitor. The purpose of this study is to\n evaluate the safety and efficacy of AL2846 capsules in Chinese patients with type I\n neurofibromatosis (NF1) (neurofibromas and malignant peripheral nerve sheath tumors).\n ;NA;\n Inclusion Criteria:\n - Patients who voluntarily join the study and sign the informed consent form;\n - Aged 18 to 75 years (when signing informed consent); Eastern cooperative oncology\n group\uff08 ECOG\uff09 score: \u22642 ; patients with malignant peripheral nerve sheath tumors\n \uff08MPNST\uff09who are expected to survive \u226512 weeks;\n - NF1 patients (including patients with MPNST) who are judged by the investigator as\n incomplete surgical resection, require systemic treatment, and have measurable\n lesions;\n Note: NF1 diagnostic criteria meets at least one of the following:\n 1. Genetic examination confirmation: test positive for NF1 germline mutation in a\n Clinical Laboratory Improvement Amendments \uff08CLIA\uff09-certified laboratory (positive NF1\n germline mutation must be confirmed by the central laboratory of this project, or an\n NF1 mutation test report issued by a CLIA-certified laboratory;\n 2. Clinical and imaging examination confirmation: According to the clinical National\n Institute of Health (NIH) consensus criteria, at least two of the following NF1\n diagnostic criteria are met:\n 1. Six or more caf\u00e9-au-lait macules (\u22650.5cm in prepubertal patients or \u22651.5 cm in\n post pubertal patients)\n 2. Freckling in axilla or groin\n 3. \u22652 neurofibromas of any type, or \u22651 plexiform neurofibromas\n 4. Optic glioma\n 5. Two or more Lisch nodules\n 6. A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or\n thinning of long bone cortex)\n 7. A first-degree relative with NF1\n - Patients who are confirmed by direct measurement or according to the Response\n Evaluation Criteria in Solid Tumors\uff08RECIST\uff09 1.1 standard that there is at least\n one evaluable lesion, and the diameter of the lesion is greater than 3 cm, and\n the lesion can be seen in three consecutive sections;\n - The main organs function well and meet the following standards:\n 1. Blood routine examination standard (no blood transfusion and no hematopoietic\n stimulating factor drugs used for correction within 7 days before the examination):\n a. White blood cell count (WBC) \u22653.5\u00d7109/L b. Hemoglobin (HGB) \u226590 g/L; c. The\n absolute value of neutrophils (NEUT) \u2265 1.5\u00d7109/L; d. Platelet count (PLT) \u2265 100\u00d7109/L.\n 2. The biochemical inspection shall meet the following standards:\n a. Albumin (ALB) \u226535g/L; b. Total bilirubin (TBIL) \u2264 1.5\u00d7 the upper limit of normal\n (ULN), and patients with Gilbert syndrome are \u2264 2.5\u00d7 ULN; c. Alanine-based transferase\n (ALT) and aspartate-based transferase (AST) \u22642.5\u00d7ULN; d. Serum creatinine (CR)\n \u22641.5\u00d7ULN or creatinine clearance (CCR) \u226550ml/min (application of standard\n Cockcroft-Gault formula);\n 3. The coagulation function test shall meet the following standards:\n International normalized ratio (INR)\u22641.5\u00d7ULN (have not received anticoagulant\n therapy);\n 4. Thyroid function examination must meet the following standards:\n Thyroid-stimulating hormone (TSH)\u2264ULN; if abnormal, Triiodothyronine \uff08T3\uff09 and\n thyroxine\uff08T4\uff09levels should be examined, and T3 and T4 levels are normal.\n 5. Heart color Doppler ultrasound assessment: Left ventricular ejection fraction (LVEF)\n \u226550%.\n - Female patients of childbearing age should agree to use contraceptive measures (such as\n intrauterine devices, contraceptives or condoms) during the study period and within 6\n months after the end of the study; serum pregnancy test within 7 days before study entry\n Negative, and must be a non-lactating subject; male patients should agree to adopt\n avoidance measures during the study period and within 6 months after the end of the study\n period;\n - Patients enrolled in the second stage need to be pathologically confirmed to be enrolled\n in cohort 1, cohort 2 or cohort 3.\n Exclusion Criteria:\n - Combined diseases and medical history:\n 1. Patients who have other malignant tumors within 3 years before the first medication\n or are currently suffering from other malignancies. The following two situations can\n be enrolled: other malignant tumors treated by a single operation; achieving 5\n consecutive years of disease-free survival (DFS);\n 2. With factors that affect oral medications (such as dysphagia, chronic diarrhea and\n intestinal obstruction, etc.)\n 3. Unreliable toxic reactions higher than Common Terminology Criteria for Adverse\n Events(CTCAE) v5.0 level 1 caused by any previous treatment, excluding hair loss;\n 4. Received major surgical treatment or obvious traumatic injury within 28 days before\n the first medication;\n 5. Long-term unhealed wounds or fractures caused by surgery or trauma;\n 6. Arterial/venous thrombosis occurred within 6 months before the first medication,\n such as cerebrovascular accident (including temporary ischemic attack, cerebral\n hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism;\n 7. With a history of psychotropic drug abuse and cannot be quit or have mental\n disorders;\n 8. There are risk factors for prolonging the corrected QT interval\uff08QTc\uff09interval, such\n as uncorrectable hypokalemia, hereditary long QT syndrome, or taking drugs that\n prolong the QTc interval (mainly class Ia, Ic, and III antiarrhythmic drugs) \uff1b\n 9. Past or current retinal vein stenosis, retinal detachment, central retinal vein\n occlusion, glaucoma, grade 1 cataract, related symptoms caused by the disease are not\n considered as exclusion criteria;\n 10. Interstitial pneumonia, including clinically significant radiation pneumonia;\n 11. Patients with any severe and/or uncontrollable disease, including:\n 1. Unsatisfactory blood pressure control (systolic blood pressure \u2265150 mmHg or\n diastolic blood pressure \u2265100 mmHg);\n 2. Suffering from grade \u22652 myocardial ischemia or myocardial infarction, arrhythmia\n (including male QTc \u2265450 ms (male), QTc \u2265470 ms (female)) and grade \u22652 congestive\n heart failure (New York Heart Association ( NYHA) classification, appendix 2);\n 3. Active or uncontrolled serious infection (\u2265CTCAE v5.0 Grade 2 infection);\n 4. Active hepatitis: hepatitis B reference: HBsAg is positive, and the HBV DNA test\n value exceeds the upper limit of normal; hepatitis C reference: HCV antibody is\n positive, and the HCV virus titer test value exceeds the upper limit of normal;\n Note: Those who meet the criteria for entry, hepatitis B surface antigen-positive\n or core antibody-positive patients, and hepatitis C patients need to continue\n antiviral therapy to prevent virus activation;\n 5. Renal failure requiring hemodialysis or peritoneal dialysis;\n 6. A history of immunodeficiency, including HIV positive or other acquired or\n congenital immunodeficiency diseases, or a history of organ transplantation;\n 7. Poor diabetes control (fasting blood glucose (FBG)> 10 mmol/L);\n 8. Urine routines suggest that urine protein is \u2265++, and the 24-hour urine protein\n quantification is confirmed to be >1.0 g;\n 9. Those who suffer from epilepsy and need treatment;\n - Tumor-related symptoms and treatment:\n 1. Have received surgery, chemotherapy, radiotherapy or other anti-cancer therapies\n within 4 weeks before the first medication (the washout period will be calculated from\n the end of the last treatment); Note: Those who have received local radiotherapy in\n the past can be included in the group if the following conditions are met: the end of\n radiotherapy is more than 4 weeks from the beginning of the study treatment (brain\n radiotherapy is more than 2 weeks); and the target lesion selected for this study is\n not in the radiotherapy area; Or the target lesion is located in the radiotherapy\n area, but the progress has been confirmed.\n 2. Have received National Medical Products Administration(NMPA) approved Chinese\n patent medicines with anti-tumor indications (including compound cantharidin capsules,\n Kangai injections, Kanglaite capsules/injections, Aidi injections, Brucea javanica oil\n injections). /Capsules, Xiaoaiping Tablets/Injections, Huachansu Capsules, etc.)\n treatment;\n - Research and treatment related:\n 1. Patients who have previously received one of the following treatments:\n a. Patients who have received NF1 drug treatment within 3 months before\n enrollment, and the related side effects have not yet recovered to below grade 1\n (except for hair loss). Note: Patients who are receiving NF1 drug treatment must\n recover from the acute toxicity of the current NF1 treatment to less than or\n equal to Grade 1 (refer to CTCAE v5.0) before entering this study; b. Patients\n Received tipifarnib, pirfenidone, peg-interferon, sorafenib or other VEGFR\n inhibitor or biological treatments within 14 days before receiving study drug\n treatment ; c. Receiving strong Cytochrome P450 3A4 enzyme\uff08CYP3A4\uff09 inhibitors\n (amprenavir, atazanavir, boceprevir, clarithromycin, cornivatan, delavirdine,\n diltiazem, erythromycin) within 14 days before receiving study drug treatment ,\n Fursanavir, Indinavir, Itraconazole, Ketoconazole, Lopinavir, Mibefradil,\n Miconazole, Nefazodone, Nefinavir, Posaconazole, Ritonavir, saquinavir,\n tilarrevir, telithromycin, verapamil, voriconazole, etc.) or strong inducers\n (carbamazepine, felbamate, nevirapine, phenobarbital, phenytoin, Patients with\n primidone, rifabutin, rifampicin, rifapentin, etc.), except for external use on\n the skin;\n 2. Unable to perform Magnetic Resonance Imaging(MRI) examination and/or there are\n contraindications for MRI examination, such as prosthesis, orthotics or\n orthodontics, which will interfere with the volume analysis of the target\n Plexiform neurofibroma( PN) on MRI;\n - Patients who need to take more than the recommended dose of vitamin E daily;\n - Patients who have participated within 4 weeks before the first medication and used\n other anti-tumor clinical trial drugs or wihtin 5 half-lives;\n - According to the judgment of the investigator, there are situations that seriously\n endanger the safety of the patients or affect the completion of the study.", "output": {"inclusion_biomarker": [["NF1 mutation (germline)"], ["NF1 mutation"]], "exclusion_biomarker": []}}
+{"input": "AL2846 is a multi-target receptor tyrosine kinase inhibitor. The purpose of this study is to\n evaluate the safety and efficacy of AL2846 capsules in Chinese patients with type I\n neurofibromatosis (NF1) (neurofibromas and malignant peripheral nerve sheath tumors).\n ;NA;\n Inclusion Criteria:\n - Patients who voluntarily join the study and sign the informed consent form;\n - Aged 18 to 75 years (when signing informed consent); Eastern cooperative oncology\n group\uff08 ECOG\uff09 score: \u22642 ; patients with malignant peripheral nerve sheath tumors\n \uff08MPNST\uff09who are expected to survive \u226512 weeks;\n - NF1 patients (including patients with MPNST) who are judged by the investigator as\n incomplete surgical resection, require systemic treatment, and have measurable\n lesions;\n Note: NF1 diagnostic criteria meets at least one of the following:\n 1. Genetic examination confirmation: test positive for NF1 germline mutation in a\n Clinical Laboratory Improvement Amendments \uff08CLIA\uff09-certified laboratory (positive NF1\n germline mutation must be confirmed by the central laboratory of this project, or an\n NF1 mutation test report issued by a CLIA-certified laboratory;\n 2. Clinical and imaging examination confirmation: According to the clinical National\n Institute of Health (NIH) consensus criteria, at least two of the following NF1\n diagnostic criteria are met:\n 1. Six or more caf\u00e9-au-lait macules (\u22650.5cm in prepubertal patients or \u22651.5 cm in\n post pubertal patients)\n 2. Freckling in axilla or groin\n 3. \u22652 neurofibromas of any type, or \u22651 plexiform neurofibromas\n 4. Optic glioma\n 5. Two or more Lisch nodules\n 6. A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or\n thinning of long bone cortex)\n 7. A first-degree relative with NF1\n - Patients who are confirmed by direct measurement or according to the Response\n Evaluation Criteria in Solid Tumors\uff08RECIST\uff09 1.1 standard that there is at least\n one evaluable lesion, and the diameter of the lesion is greater than 3 cm, and\n the lesion can be seen in three consecutive sections;\n - The main organs function well and meet the following standards:\n 1. Blood routine examination standard (no blood transfusion and no hematopoietic\n stimulating factor drugs used for correction within 7 days before the examination):\n a. White blood cell count (WBC) \u22653.5\u00d7109/L b. Hemoglobin (HGB) \u226590 g/L; c. The\n absolute value of neutrophils (NEUT) \u2265 1.5\u00d7109/L; d. Platelet count (PLT) \u2265 100\u00d7109/L.\n 2. The biochemical inspection shall meet the following standards:\n a. Albumin (ALB) \u226535g/L; b. Total bilirubin (TBIL) \u2264 1.5\u00d7 the upper limit of normal\n (ULN), and patients with Gilbert syndrome are \u2264 2.5\u00d7 ULN; c. Alanine-based transferase\n (ALT) and aspartate-based transferase (AST) \u22642.5\u00d7ULN; d. Serum creatinine (CR)\n \u22641.5\u00d7ULN or creatinine clearance (CCR) \u226550ml/min (application of standard\n Cockcroft-Gault formula);\n 3. The coagulation function test shall meet the following standards:\n International normalized ratio (INR)\u22641.5\u00d7ULN (have not received anticoagulant\n therapy);\n 4. Thyroid function examination must meet the following standards:\n Thyroid-stimulating hormone (TSH)\u2264ULN; if abnormal, Triiodothyronine \uff08T3\uff09 and\n thyroxine\uff08T4\uff09levels should be examined, and T3 and T4 levels are normal.\n 5. Heart color Doppler ultrasound assessment: Left ventricular ejection fraction (LVEF)\n \u226550%.\n - Female patients of childbearing age should agree to use contraceptive measures (such as\n intrauterine devices, contraceptives or condoms) during the study period and within 6\n months after the end of the study; serum pregnancy test within 7 days before study entry\n Negative, and must be a non-lactating subject; male patients should agree to adopt\n avoidance measures during the study period and within 6 months after the end of the study\n period;\n - Patients enrolled in the second stage need to be pathologically confirmed to be enrolled\n in cohort 1, cohort 2 or cohort 3.\n Exclusion Criteria:\n - Combined diseases and medical history:\n 1. Patients who have other malignant tumors within 3 years before the first medication\n or are currently suffering from other malignancies. The following two situations can\n be enrolled: other malignant tumors treated by a single operation; achieving 5\n consecutive years of disease-free survival (DFS);\n 2. With factors that affect oral medications (such as dysphagia, chronic diarrhea and\n intestinal obstruction, etc.)\n 3. Unreliable toxic reactions higher than Common Terminology Criteria for Adverse\n Events(CTCAE) v5.0 level 1 caused by any previous treatment, excluding hair loss;\n 4. Received major surgical treatment or obvious traumatic injury within 28 days before\n the first medication;\n 5. Long-term unhealed wounds or fractures caused by surgery or trauma;\n 6. Arterial/venous thrombosis occurred within 6 months before the first medication,\n such as cerebrovascular accident (including temporary ischemic attack, cerebral\n hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism;\n 7. With a history of psychotropic drug abuse and cannot be quit or have mental\n disorders;\n 8. There are risk factors for prolonging the corrected QT interval\uff08QTc\uff09interval, such\n as uncorrectable hypokalemia, hereditary long QT syndrome, or taking drugs that\n prolong the QTc interval (mainly class Ia, Ic, and III antiarrhythmic drugs) \uff1b\n 9. Past or current retinal vein stenosis, retinal detachment, central retinal vein\n occlusion, glaucoma, grade 1 cataract, related symptoms caused by the disease are not\n considered as exclusion criteria;\n 10. Interstitial pneumonia, including clinically significant radiation pneumonia;\n 11. Patients with any severe and/or uncontrollable disease, including:\n 1. Unsatisfactory blood pressure control (systolic blood pressure \u2265150 mmHg or\n diastolic blood pressure \u2265100 mmHg);\n 2. Suffering from grade \u22652 myocardial ischemia or myocardial infarction, arrhythmia\n (including male QTc \u2265450 ms (male), QTc \u2265470 ms (female)) and grade \u22652 congestive\n heart failure (New York Heart Association ( NYHA) classification, appendix 2);\n 3. Active or uncontrolled serious infection (\u2265CTCAE v5.0 Grade 2 infection);\n 4. Active hepatitis: hepatitis B reference: HBsAg is positive, and the HBV DNA test\n value exceeds the upper limit of normal; hepatitis C reference: HCV antibody is\n positive, and the HCV virus titer test value exceeds the upper limit of normal;\n Note: Those who meet the criteria for entry, hepatitis B surface antigen-positive\n or core antibody-positive patients, and hepatitis C patients need to continue\n antiviral therapy to prevent virus activation;\n 5. Renal failure requiring hemodialysis or peritoneal dialysis;\n 6. A history of immunodeficiency, including HIV positive or other acquired or\n congenital immunodeficiency diseases, or a history of organ transplantation;\n 7. Poor diabetes control (fasting blood glucose (FBG)> 10 mmol/L);\n 8. Urine routines suggest that urine protein is \u2265++, and the 24-hour urine protein\n quantification is confirmed to be >1.0 g;\n 9. Those who suffer from epilepsy and need treatment;\n - Tumor-related symptoms and treatment:\n 1. Have received surgery, chemotherapy, radiotherapy or other anti-cancer therapies\n within 4 weeks before the first medication (the washout period will be calculated from\n the end of the last treatment); Note: Those who have received local radiotherapy in\n the past can be included in the group if the following conditions are met: the end of\n radiotherapy is more than 4 weeks from the beginning of the study treatment (brain\n radiotherapy is more than 2 weeks); and the target lesion selected for this study is\n not in the radiotherapy area; Or the target lesion is located in the radiotherapy\n area, but the progress has been confirmed.\n 2. Have received National Medical Products Administration(NMPA) approved Chinese\n patent medicines with anti-tumor indications (including compound cantharidin capsules,\n Kangai injections, Kanglaite capsules/injections, Aidi injections, Brucea javanica oil\n injections). /Capsules, Xiaoaiping Tablets/Injections, Huachansu Capsules, etc.)\n treatment;\n - Research and treatment related:\n 1. Patients who have previously received one of the following treatments:\n a. Patients who have received NF1 drug treatment within 3 months before\n enrollment, and the related side effects have not yet recovered to below grade 1\n (except for hair loss). Note: Patients who are receiving NF1 drug treatment must\n recover from the acute toxicity of the current NF1 treatment to less than or\n equal to Grade 1 (refer to CTCAE v5.0) before entering this study; b. Patients\n Received tipifarnib, pirfenidone, peg-interferon, sorafenib or other VEGFR\n inhibitor or biological treatments within 14 days before receiving study drug\n treatment ; c. Receiving strong Cytochrome P450 3A4 enzyme\uff08CYP3A4\uff09 inhibitors\n (amprenavir, atazanavir, boceprevir, clarithromycin, cornivatan, delavirdine,\n diltiazem, erythromycin) within 14 days before receiving study drug treatment ,\n Fursanavir, Indinavir, Itraconazole, Ketoconazole, Lopinavir, Mibefradil,\n Miconazole, Nefazodone, Nefinavir, Posaconazole, Ritonavir, saquinavir,\n tilarrevir, telithromycin, verapamil, voriconazole, etc.) or strong inducers\n (carbamazepine, felbamate, nevirapine, phenobarbital, phenytoin, Patients with\n primidone, rifabutin, rifampicin, rifapentin, etc.), except for external use on\n the skin;\n 2. Unable to perform Magnetic Resonance Imaging(MRI) examination and/or there are\n contraindications for MRI examination, such as prosthesis, orthotics or\n orthodontics, which will interfere with the volume analysis of the target\n Plexiform neurofibroma( PN) on MRI;\n - Patients who need to take more than the recommended dose of vitamin E daily;\n - Patients who have participated within 4 weeks before the first medication and used\n other anti-tumor clinical trial drugs or wihtin 5 half-lives;\n - According to the judgment of the investigator, there are situations that seriously\n endanger the safety of the patients or affect the completion of the study.", "output": {"inclusion_biomarker": [["NF1 mutation (germline)"]], "exclusion_biomarker": []}}
 {"input": "The main purpose of this first-in-human study of GEN1056, is to evaluate safety. In addition,\n the study will determine the recommended dose and frequency for subsequent clinical studies\n and will assess the preliminary anti-tumor activity of GEN1056. GEN1056 will be studied in\n patients with advanced or metastatic solid cancer, for whom standard of care (SOC) therapy is\n not an option. All participants will get GEN1056.\n ;\n ;\n Key Inclusion Criteria:\n - Subjects with histologically or cytologically confirmed non-CNS advanced or metastatic\n solid tumors which has progressed despite standard therapy, or subjects who are\n intolerant of standard therapy, or for which no standard therapy exists, and for whom,\n in the opinion of the investigator, experimental therapy with GEN1056 may be\n beneficial\n - Have personally (or in countries where permitted, their legally acceptable\n representative) signed an Informed Consent Form (ICF)\n - Are at least 18 years of age.\n - Have measurable disease according to the RECIST v1.1 criteria.\n - Have an ECOG PS of 0 to 1 at screening and on C1D1 pre-treatment.\n - Have acceptable laboratory test results during the screening period.\n - Must provide an archival (FFPE) tumor tissue sample or newly obtained core or\n excisional biopsy of a tumor lesion not previously irradiated.\n - A female subject with reproductive potential must agree to use adequate contraception\n during the trial, and for 4 months after receiving the last dose of trial drug\n GEN1056.\n Key Exclusion Criteria:\n - Subject is considered a poor medical risk due to a serious, uncontrolled inter-current\n illness\n - Prior therapy with a checkpoint inhibitor agent or with an agent directed to another\n stimulatory or co-inhibitory T-cell receptor.\n - Prior exposure to any of the following prior therapies within the specified\n timeframes:\n 1. Systemic cytotoxic chemotherapy or antineoplastic biological therapy within 28\n days or at least 5 elimination half-lives of the drug (whichever is shorter) of\n the first dose of trial treatment\n 2. Radiotherapy within 21 days of start of trial treatment. Note: palliative\n radiotherapy be allowed.\n 3. Prior treatment with live, attenuated vaccines within 28 days prior to initiation\n of GEN1056\n - Known active CNS metastases and/or carcinomatous meningitis, or spinal cord\n compression.\n - Positive for Human Immunodeficiency Virus (HIV), Hepatitis B (Hepatitis B Surface\n Antigen (HBsAg), HBV DNA), or Hepatitis C infection (Hepatitis C Virus Ribonucleic\n Acid (HCV RNA), HCV antibodies).\n - An active, known, or suspected autoimmune disease, requiring systemic steroid.\n - A condition requiring systemic treatment with either corticosteroids (>10 mg daily\n prednisone equivalent) or other immunosuppressive medications within 14 days of first\n treatment.\n - History of non-infectious pneumonitis/interstitial lung disease that required steroids\n or has current pneumonitis/interstitial lung disease requiring treatment with\n steroids.\n NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
 {"input": "Patients entered into the study will receive ASTX727 orally up to 3 to 8 days prior to\n receiving Lutathera treatment to determine whether pre-treatment with ASTX727 results in\n re-expression of somatostatin receptor-2 in patients with metastatic neuroendocrine tumours.\n The study will use [68Ga]-DOTA-TATE PET to image epigenetic modification of the receptor\n locus.\n ;\n ;\n Inclusion criteria\n 1. Be willing and able to provide written informed consent for the trial.\n 2. Be aged 18 or over at the day of signing consent\n 3. Histologic or cytologic confirmed diagnosis of neuroendocrine tumour\n 4. Have archival tissue block available or willing to have fresh tissue biopsy if blocks\n not available\n 5. Have disease that can be readily biopsied by ultrasound guidance (n=5)\n 6. Ki67 < 55% (only patients with well differentiated grade 1-3 NETs will be included in\n the study as patients with poorly differentiated grade 3 NETs have a prognosis of less\n than 6 months)\n 7. Progression or intolerance to first line therapy including somatostatin analogues\n 8. ECOG Performance status 0 - 2\n 9. No tumoural uptake on [68Ga]-DOTA-TATE or uptake less than background liver\n 10. Measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated\n area are considered measurable if progression has been demonstrated in such lesions\n 11. Adequate organ function as outlined in the protocol\n 12. Women of childbearing potential must be willing to use a highly effective method of\n contraception as outlined in the protocol for the course of the study through 6 months\n after the last dose of Investigational Medicinal Product (IMP).\n Note: Abstinence is acceptable if this is the usual lifestyle and preferred\n contraception for the subjects\n 13. Sexually active males must agree to use an adequate method of contraception as\n outlined in the protocol starting with the first dose of IMP through 6 months after\n the last dose of study therapy. Note: Abstinence is acceptable if this is the usual\n lifestyle and preferred contraception for the subject\n Exclusion criteria\n 1. Previous treatment with either study medication and/or known hypersensitivity to the\n study medication\n 2. Serious concurrent medical illness, including serious active infection\n 3. History of organ transplant\n 4. Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is\n required unless mandated by local health authority.\n 5. Has a known history of active Bacillus Tuberculosis (TB).\n 6. Has known active CNS metastases and/or carcinomatous meningitis. Participants with\n previously treated brain metastases may participate provided they are radiologically\n stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging\n (note that the repeat imaging should be performed during study screening), clinically\n stable and without requirement of steroid treatment for at least 14 days prior to\n first dose of study treatment.\n 7. Bleeding or thrombotic disorders or subjects at risk for severe haemorrhage\n 8. Is currently participating and receiving therapy or has participated or is\n participating in a study of an IMP or used an investigational device within 4 weeks of\n the first dose of IMP.\n 9. Has a known additional malignancy that is progressing or requires active treatment.\n Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the\n skin that has undergone potentially curative therapy or in situ cervical cancer.\n 10. Has a history or current evidence of any condition, therapy, or laboratory abnormality\n that might confound the results of the trial, interfere with the subject's\n participation for the full duration of the trial, or is not in the best interest of\n the subject to participate, in the opinion of the treating Principal Investigator\n (PI).\n 11. Has known psychiatric or substance abuse disorders that would interfere with\n cooperation with the requirements of the trial.\n 12. Is pregnant or breastfeeding, or expecting to conceive or father children within the\n projected duration of the trial, starting with the screening visit through to 6 months\n after the last dose of IMP.\n 13. Has received a live vaccine within 30 days of first dose of ASTX727 administration.\n Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines\n and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist\u00ae) are live\n attenuated vaccines, and are not allowed.\n 14. Has received prior radiotherapy within 2 weeks of start of study treatment.\n Participants must have recovered from all radiation-related toxicities, not require\n corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted\n for palliative radiation (\u22642 weeks of radiotherapy) to non-CNS disease and\n stereotactic radiotherapy to the CNS\n 15. Other clinically significant co-morbidities that could compromise the subject's\n participating in the study", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
-{"input": "This study is designed as a single arm open label Phase I, 3x3, multicenter study of\n CD4-directed chimeric antigen receptor engineered T-cells (CD4CAR) in patients with relapsed\n or refractory T-cell leukemia and lymphoma. Specifically, the study will evaluate the safety\n and tolerability of CD4CAR T-cells. Funding Source - FDA OOPD\n ;\n ;\n Inclusion Criteria\n In order to be eligible to participate in this study, an individual will be enrolled if\n they meet the following criteria:\n 1. Patients must voluntarily sign and date informed consent forms that state his or her\n willingness to comply with all study procedures and availability for the duration of\n the study.\n 2. Age 18 years old or older\n 3. T-cell \u2265 500\n 4. Subjects with documented CD4+ hematologic malignancies. Male and female subjects with\n CD4+ T-cell malignancies with either relapsed or refractory disease (including those\n patients who have undergone a prior transplant and patients with an inadequate\n response after 4-6 cycles of standard chemotherapy)\n 5. For patients who present with CD4+ Leukemia, either relapsed disease or minimal\n residual disease (MRD); any of the following are eligible:\n 1. Peripheral T-cell leukemia, NOS\n 2. T-cell prolymphocytic leukemia\n 3. Adult T-cell leukemia\n 4. T-cell large granular lymphocytic leukemia\n 5. T cell acute lymphoblastic leukemia T-ALL\n 6. For patients with CD4+ Lymphoma, either relapsed or refractory disease; any of the\n following are eligible:\n 1. Peripheral T-cell lymphoma, NOS\n 2. Sezary syndrome/cutaneous T-cell lymphoma\n 3. Angioimmunoblastic T-cell lymphoma\n 4. Adult T-cell lymphoma\n 5. Blastic plasmacytoid dendritic cell neoplasm (BPDCN)\n 7. Creatinine clearance of > 60 ml/min (or otherwise non clinically-significant, per\n study investigator)\n 8. ALT/AST < 3 x ULN\n 9. Bilirubin < 2 x ULN\n 10. Pulmonary Function Test (PFT) with a DLCO of \u2265 60%.\n 11. Adequate echocardiogram with EF of \u226550%\n 12. Adequate venous access for apheresis and no other contraindications for leukapheresis\n Exclusion Criteria\n 1. Pregnant or lactating women. The safety of this therapy on unborn children is not\n known. Female study participants of reproductive potential (see definition below) must\n have a negative serum or urine pregnancy test prior to initiation of conditioning\n chemotherapy, per research sites' clinical policy.\n 2. Uncontrolled active infection.\n 3. Active hepatitis B or hepatitis C infection.\n 4. Concurrent use of systemic glucocorticoids in greater than replacement doses or\n steroid dependency. Recent or current use of inhaled glucocorticoids is not\n exclusionary.\n \u2022 Note: The following doses of glucocorticoids are permitted:\n 1. Hydrocortisone 25mg/day or less\n 2. Prednisone 10mg/day or less\n 3. Dexamethasone 4mg or less\n 5. Any previous treatment with any gene therapy products.\n 6. Any uncontrolled active medical disorder that would preclude participation as outlined\n in the opinion of the treating investigator and/or study chair\n 7. HIV infection.\n 8. Patients declining to consent for treatment\n 9. Absolute lymphocyte count <500/mm3 (<0.5 x 109 /L) (can be repeated, if indicated and\n possible)\n Screen Failures\n First point screen failure: Apheresis Subject with an absolute lymphocyte count < 500/mm3\n at the time of apheresis will be considered a screenfailure.\n Note: This test may be repeated in 2-3 weeks or often as needed to meet eligibility for\n apheresis, as long as the subject otherwise continues to be eligible.\n Second point screen failure\n Subjects who fail to cytoreduce with conditioning chemotherapy with persistence of high\n disease burden will be considered a screenfail according to the guidelines below:\n 1. CD4+ Leukemias ( Liquid Blood and marrow disease):\n 1. Subjects at study entry with bone marrow malignant replacement estimated at > 80%\n of total cellularity and accompanied by significant peripheral pancytopenia, ANC\n <500, platelet count < 50,000 will need to have roughly 50% or greater reduction\n on the marrow malignant component to be considered eligible after cytoreductive\n chemotherapy and for CD4CAR infusion. This will be determined and approved by PI,\n treating physician and study team as applicable.\n 2. Subjects at study entry with bone marrow malignant replacement estimated at less\n than 80% of total cellularity will need to have stable disease or disease that is\n less than 80% in the marrow as determined and approved by the PI, treating\n physician and study team as applicable.\n Note: Bone marrow sampling is not an accurate reflection of disease burden because\n only a small biopsy is obtained to represent a patchy disease distributed all over the\n marrow. Hence these numbers and in the absence of severe cytopenias that are\n attributed to documented marrow replacement with malignant cells should not be\n formidable as is and borderline cases should be discussed and approved by the PI and\n the study team as applicable before moving forward.\n 2. Solid Mass Forming CD4+ lymphomas: (in lymph nodes or extra nodal sites)\n 1. Stage IV disease: Subjects with Stage IV disease that is deemed bulky by the\n standard definition of the presence of at least one site with a mass that is >\n 7.5 cm in largest diameter who have a 50% estimated reduction of total disease\n burden by imagining as read by radiology after conditioning chemotherapy are\n eligible to continue on study. In borderline cases, where they don't meet this\n criteria but are thought to have bulky disease by the treating investigator,\n clinical judgment will be required to determine eligibility of subjects who\n experience for example mixed responses; improved sites and progressed sites. In\n these cases, the PI, treating physician, and study team as applicable should\n agree and document that total disease burden has been reduced by about 50% when\n taking all sites involved into account as there is no objective method to make\n this estimated reduction if some areas improve and others don't, or even new\n sites arise.\n 2. Stage I-III disease: Subjects with stage I-III ( No extra nodal disease) who\n continue to have stable disease or better after conditioning chemotherapy are\n eligible to continue on study.\n 3. Skin Disease a. There will be no response or non-response criteria assessed that will\n be specific to skin disease since disease burden is almost never expected to be high\n without skin barrier violation and often involve infections that would make subjects\n ineligible at the time\n Eligibility for CD4CAR infusion:\n Inclusion\n 1. Afebrile and not receiving antipyretics, and no evidence of active infection\n 2. Specific organ function criteria for cardiac, renal, and liver function must be\n similar to initial inclusion values. Tests such as echocardiogram and PFTs need not be\n repeated if within 6 weeks of initial assessment.\n 3. Negative pregnancy testing (if applicable)\n 4. If previous history of corticosteroid chemotherapy, subject must be off all but\n adrenal replacement doses\n 5. Planned infusion dose was successfully manufactured and met release criteria.", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
-{"input": "This phase I/II trial studies the side effects and best dose of avelumab with M6620 in\n treating patients with deoxyribonucleic acid (DNA) damage repair (DDR) deficient solid tumors\n that have spread to other places in the body (metastatic) or cannot be removed by surgery\n (unresectable). DDR deficiency refers to a decrease in the ability of cells to respond to\n damaged DNA and to repair the damage, which can be caused by genetic mutations. Immunotherapy\n with monoclonal antibodies, such as avelumab, may help the body's immune system attack the\n cancer, and may interfere with the ability of tumor cells to grow and spread. M6620 may stop\n the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving\n avelumab together with M6620 may help to control DDR deficient metastatic or unresectable\n solid tumors.\n ;\n ;\n Inclusion Criteria:\n - Subjects must have histologically confirmed malignancy that is metastatic or\n unresectable and for which standard curative measures do not exist or are no longer\n effective\n - Subjects will be eligible for this study based on the presence of actionable\n aberrations in one or more of the following DNA damage response (DDR) genes: ARID1A,\n ATM, ATR, ATRX, BAP1, BARD1, BRCA1/2, BRIP1, CDK12, CHEK2, FANCA, FANCC, FANCD2,\n FANCE, FANCF, FANCM, MRE11A, MSH2, NBN (NBS1), PALB2, RAD51, RAD51C, RAD51D, SMARCB1,\n and VHL, or other related genes at the discretion of the principal investigator in\n consultation with the MD Anderson Cancer Center Institute for Personalized Cancer\n Therapy Precision Oncology Decision Support (PODS) group. Variant interpretation for\n actionability will be performed by PODS\n - Subjects with germline defects in DDR genes are eligible for this trial\n - The collection of archival tumor tissue (within 1 year prior to study enrollment) will\n be mandatory. Tumor biopsies on cycle 1 day 15 will be mandatory. Subjects will not be\n put at undue risk to obtain the biopsy at cycle 1 day 15 (C1D15). A biopsy at C1D15\n will not be required if it poses a serious/severe complication risk greater than 2%.\n All other biopsy time points are not mandatory but will be strongly encouraged where\n feasible. These include at baseline and at disease progression. Archival and fresh\n tissue requests can be waived in exceptional circumstances with principal investigator\n (PI) approval and only where rationale is documented\n - Subjects must have received at least 1 line of systemic therapy in the\n advanced/metastatic setting. Subjects with diseases without known effective options,\n and subjects who had declined standard of care therapy prior to study introduction are\n also eligible\n - Subjects enrolling in the dose escalation should have progressed on or be intolerant\n to all therapies known to confer a clinical benefit. Subjects must not have refused\n all available therapies\n - Subjects who have received prior therapy with immune checkpoint inhibitors (ICIs) are\n eligible for this trial. Subjects with a standard-of-care option for an immune\n checkpoint inhibitor are eligible\n - Subjects must have measurable disease per Response Evaluation Criteria in Solid Tumors\n (RECIST) version (v) 1.1, or patients may have bone metastatic disease evaluable by\n Prostate Cancer Working Group 3 (PCWG3) for subjects with metastatic\n castration-resistant prostate cancer (CRPC), or according to tumor evaluation criteria\n best suited and accepted for the tumor type to be evaluated\n - Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1\n - Subjects must have a life expectancy >= 12 weeks\n - Absolute neutrophil count >= 1.5 x 10^9/L\n - Platelets >= 100 x 10^9/L\n - Hemoglobin >= 9 g/dL or >= 5.6 mmol/L\n - Total bilirubin =< 1.5 X the institutional upper limit of normal (ULN)\n - Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)/\n alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT) =< 2.5 X\n institutional ULN or =< 5 X institutional ULN in the presence of liver metastases\n - Serum creatinine =< 2 X ULN or estimated creatinine clearance >= 30 mL/min according\n to the Cockcroft-Gault formula\n - Female patients of childbearing potential must have a negative serum or urine\n pregnancy test at screening (and again at baseline just prior to first administration\n of study drugs)\n - Female patients of non-childbearing potential must meet at least 1 of the following\n criteria:\n - Achieved postmenopausal status, defined as follows: cessation of regular menses\n for at least 12 consecutive months, with no alternative pathological or\n physiological cause;\n - Have undergone a documented hysterectomy and/or bilateral oophorectomy\n - Have medically confirmed ovarian failure All other female patients (including\n female patients with tubal ligation) are considered to be of childbearing\n potential\n - Women of childbearing potential and fertile men must agree to use adequate\n contraception when sexually active from signing of the informed consent form for the\n full study until at least 6 months after the last study drug administration. Patients\n must agree to utilize 2 reliable and acceptable methods of contraception\n simultaneously. A man is considered fertile after puberty unless permanently sterile\n by bilateral orchiectomy. Men taking part in this study are advised not to father a\n child during and up to 6 months after treatment; prior to treatment, advice should be\n sought for conserving sperm due to the chance of irreversible infertility as a\n consequence of treatment. Female partners of childbearing potential from male study\n patients have to use adequate contraception / birth control between signing of the\n informed consent and 6 months after the last administration of the study drug if the\n male study patient is not sterilized. The investigator or a designated associate is\n requested to advise the patient how to achieve highly effective birth control. Highly\n effective (failure rate of less than 1% per year) contraception methods, when used\n consistently and correctly, include:\n - Combined (estrogen and progestin containing: oral, intravaginal, transdermal) and\n progestin-only (oral, injectable, implantable) hormonal contraception associated\n with inhibition of ovulation\n - Intra-uterine device or intrauterine hormone-releasing system\n - Bilateral tubal occlusion or vasectomized partner (provided that partner is the\n sole sexual partner and has received medical assessment of the surgical success)\n - Sexual abstinence (reliability to be evaluated in relation to the duration of the\n clinical trial and the preferred and usual lifestyle of the patient) Male\n patients with a female partner of reproductive potential must use a condom and\n ensure that an additional form of contraception is also used during treatment and\n until 6 months after last study drug administration. Patients must agree to\n utilize 2 reliable and acceptable methods of contraception simultaneously\n - Evidence of a personally signed and dated informed consent document indicating that\n the patient has been informed of all pertinent aspects of the study\n - Willing and able to comply with scheduled visits, treatment plan, laboratory tests,\n and other procedures\n - Human immunodeficiency virus (HIV)-infected (HIV1/2 antibody-positive) patients may\n participate IF they meet all the following eligibility requirements:\n - They must be on an anti-retroviral regimen with evidence of at least two\n undetectable viral loads within the past 6 months on this same regimen; the most\n recent undetectable viral load must be within the past 12 weeks\n - They must have a CD4 count >= 250 cells/mcL over the past 6 months on this same\n anti-retroviral regimen and must not have had a CD4 count < 200 cells/ mcL over\n the past 2 years, unless it was deemed related to the cancer and/or\n chemotherapy-induced bone marrow suppression\n - For patients who have received chemotherapy in the past 6 months, a CD4\n count < 250 cells/mcL during chemotherapy is permitted as long as viral\n loads were undetectable during this same chemotherapy\n - They must have an undetectable viral load and a CD4 count >= 250 cells/mcL within\n 7 days of enrolment\n - They must not be currently receiving prophylactic therapy for an opportunistic\n infection and must not have had an opportunistic infection within the past 6\n months\n Exclusion Criteria:\n - Anticancer systemic therapy or radiotherapy within 4 weeks or 5 half-lives, whichever\n is shorter prior to starting the study agents. Prior palliative radiotherapy to\n metastatic lesion(s) is permitted, provided it has been completed 2 weeks prior to\n study enrollment, and no clinically significant toxicities are expected (e.g.,\n mucositis, esophagitis)\n - Known symptomatic brain metastases requiring steroids. Patients with previously\n treated diagnosed brain metastases are eligible if they have completed their treatment\n and have recovered from the acute effects of radiation therapy or surgery prior to\n study enrollment, have discontinued corticosteroid treatment for these metastases for\n at least 4 weeks and are neurologically stable\n - Current use of immunosuppressive medication at the time of study enrollment, EXCEPT\n for the following permitted steroids:\n - Intranasal, inhaled, topical steroids, eye drops, or local steroid injection\n (e.g., intra-articular injection)\n - Systemic corticosteroids at physiologic doses =< 10 mg/day of prednisone or\n equivalent\n - Steroids as premedication for hypersensitivity reactions (e.g. computed\n tomography [CT] scan premedication)\n - Subjects who had major surgery within 4 weeks prior to study enrollment\n - Known prior severe hypersensitivity to investigational products or any component in\n their formulations, including known severe hypersensitivity reactions to monoclonal\n antibodies (National Cancer Institute [NCI] Common Terminology Criteria for Adverse\n Events [CTCAE] version [v] 5 grade >= 3)\n - Active infection requiring systemic therapy\n - Known history of immune-mediated colitis, inflammatory bowel disease, pneumonitis, and\n pulmonary fibrosis\n - Active or prior autoimmune disease that may deteriorate when receiving an\n immunostimulatory agent. Patients with type I diabetes, vitiligo, psoriasis, or hypo-\n or hyperthyroid disease not requiring immunosuppressive treatment are eligible\n - Prior organ transplantation including allogenic stem cell transplantation\n - Diagnosis of myelodysplastic syndrome (MDS)\n - Vaccination within 4 weeks of study enrollment and while on trial is prohibited except\n for the administration of inactivated vaccines\n - Clinically significant (i.e., active) cardiovascular disease: cerebral vascular\n accident/stroke (< 6 month prior to enrollment), myocardial infarction (< 6 months\n prior to enrollment), unstable angina, congestive heart failure (>= New York Heart\n Association Classification class II) or a serious cardiac arrhythmia requiring\n medication\n - Other acute or chronic medical or psychiatric conditions including but not limited to\n recent (within the past year) or active suicidal ideation or behavior or laboratory\n abnormality that may increase the risk associated with study participation or\n investigational product administration or may interfere with the interpretation of\n study results, and in the judgement of the Investigator, would make the patient\n inappropriate for entry into this study\n - Pregnant female patients, breastfeeding female patients, fertile male patients, and\n female patients of childbearing potential who are unwilling or unable to use 2 highly\n effective methods of contraception as outlined in this protocol for the duration of\n the study, and for at least 6 months after the last dose of study drug administration\n - Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive\n HBV surface antigen or HCV ribonucleic acid (RNA) if anti-HCV antibody screening test\n is positive)\n - Known additional malignancy that is active and/or progressive requiring treatment;\n exceptions include basal cell or squamous cell skin cancer, in situ bladder cancer, or\n other cancer for which the patient has been disease-free for >= 2 years\n - Persisting toxicity related to prior therapy (NCI CTCAE v5 grade > 1); however,\n alopecia and sensory neuropathy grade =< 2, or other grade =< 2 AEs not constituting a\n safety risk, based on the investigator's judgement, are acceptable\n - Subjects receiving treatment with strong inhibitors or inducers of CYP3A4 that cannot\n be discontinued before start of investigational treatment and for the duration of\n study\n - Subjects with ongoing toxicity (any grade) and/or resolved ICI toxicity (grade 3 or\n higher only)", "output": {"inclusion_biomarker": [["ARID1A aberration"], ["ATM aberration"], ["ATR aberration"], ["ATRX aberration"], ["BAP1 aberration"], ["BARD1 aberration"], ["BRCA1 aberration"], ["BRCA2 aberration"], ["BRIP1 aberration"], ["CDK12 aberration"], ["CHEK2 aberration"], ["FANCA aberration"], ["FANCC aberration"], ["FANCD2 aberration"], ["FANCE aberration"], ["FANCF aberration"], ["FANCM aberration"], ["MRE11A aberration"], ["MSH2 aberration"], ["NBS1 aberration"], ["PALB2 aberration"], ["RAD51 aberration"], ["RAD51C aberration"], ["RAD51D aberration"], ["SMARCB1 aberration"], ["VHL aberration"], ["DDR genes defect (germline)"]], "exclusion_biomarker": []}}
+{"input": "This study is designed as a single arm open label Phase I, 3x3, multicenter study of\n CD4-directed chimeric antigen receptor engineered T-cells (CD4CAR) in patients with relapsed\n or refractory T-cell leukemia and lymphoma. Specifically, the study will evaluate the safety\n and tolerability of CD4CAR T-cells. Funding Source - FDA OOPD\n ;\n ;\n Inclusion Criteria\n In order to be eligible to participate in this study, an individual will be enrolled if\n they meet the following criteria:\n 1. Patients must voluntarily sign and date informed consent forms that state his or her\n willingness to comply with all study procedures and availability for the duration of\n the study.\n 2. Age 18 years old or older\n 3. T-cell \u2265 500\n 4. Subjects with documented CD4+ hematologic malignancies. Male and female subjects with\n CD4+ T-cell malignancies with either relapsed or refractory disease (including those\n patients who have undergone a prior transplant and patients with an inadequate\n response after 4-6 cycles of standard chemotherapy)\n 5. For patients who present with CD4+ Leukemia, either relapsed disease or minimal\n residual disease (MRD); any of the following are eligible:\n 1. Peripheral T-cell leukemia, NOS\n 2. T-cell prolymphocytic leukemia\n 3. Adult T-cell leukemia\n 4. T-cell large granular lymphocytic leukemia\n 5. T cell acute lymphoblastic leukemia T-ALL\n 6. For patients with CD4+ Lymphoma, either relapsed or refractory disease; any of the\n following are eligible:\n 1. Peripheral T-cell lymphoma, NOS\n 2. Sezary syndrome/cutaneous T-cell lymphoma\n 3. Angioimmunoblastic T-cell lymphoma\n 4. Adult T-cell lymphoma\n 5. Blastic plasmacytoid dendritic cell neoplasm (BPDCN)\n 7. Creatinine clearance of > 60 ml/min (or otherwise non clinically-significant, per\n study investigator)\n 8. ALT/AST < 3 x ULN\n 9. Bilirubin < 2 x ULN\n 10. Pulmonary Function Test (PFT) with a DLCO of \u2265 60%.\n 11. Adequate echocardiogram with EF of \u226550%\n 12. Adequate venous access for apheresis and no other contraindications for leukapheresis\n Exclusion Criteria\n 1. Pregnant or lactating women. The safety of this therapy on unborn children is not\n known. Female study participants of reproductive potential (see definition below) must\n have a negative serum or urine pregnancy test prior to initiation of conditioning\n chemotherapy, per research sites' clinical policy.\n 2. Uncontrolled active infection.\n 3. Active hepatitis B or hepatitis C infection.\n 4. Concurrent use of systemic glucocorticoids in greater than replacement doses or\n steroid dependency. Recent or current use of inhaled glucocorticoids is not\n exclusionary.\n \u2022 Note: The following doses of glucocorticoids are permitted:\n 1. Hydrocortisone 25mg/day or less\n 2. Prednisone 10mg/day or less\n 3. Dexamethasone 4mg or less\n 5. Any previous treatment with any gene therapy products.\n 6. Any uncontrolled active medical disorder that would preclude participation as outlined\n in the opinion of the treating investigator and/or study chair\n 7. HIV infection.\n 8. Patients declining to consent for treatment\n 9. Absolute lymphocyte count <500/mm3 (<0.5 x 109 /L) (can be repeated, if indicated and\n possible)\n Screen Failures\n First point screen failure: Apheresis Subject with an absolute lymphocyte count < 500/mm3\n at the time of apheresis will be considered a screenfailure.\n Note: This test may be repeated in 2-3 weeks or often as needed to meet eligibility for\n apheresis, as long as the subject otherwise continues to be eligible.\n Second point screen failure\n Subjects who fail to cytoreduce with conditioning chemotherapy with persistence of high\n disease burden will be considered a screenfail according to the guidelines below:\n 1. CD4+ Leukemias ( Liquid Blood and marrow disease):\n 1. Subjects at study entry with bone marrow malignant replacement estimated at > 80%\n of total cellularity and accompanied by significant peripheral pancytopenia, ANC\n <500, platelet count < 50,000 will need to have roughly 50% or greater reduction\n on the marrow malignant component to be considered eligible after cytoreductive\n chemotherapy and for CD4CAR infusion. This will be determined and approved by PI,\n treating physician and study team as applicable.\n 2. Subjects at study entry with bone marrow malignant replacement estimated at less\n than 80% of total cellularity will need to have stable disease or disease that is\n less than 80% in the marrow as determined and approved by the PI, treating\n physician and study team as applicable.\n Note: Bone marrow sampling is not an accurate reflection of disease burden because\n only a small biopsy is obtained to represent a patchy disease distributed all over the\n marrow. Hence these numbers and in the absence of severe cytopenias that are\n attributed to documented marrow replacement with malignant cells should not be\n formidable as is and borderline cases should be discussed and approved by the PI and\n the study team as applicable before moving forward.\n 2. Solid Mass Forming CD4+ lymphomas: (in lymph nodes or extra nodal sites)\n 1. Stage IV disease: Subjects with Stage IV disease that is deemed bulky by the\n standard definition of the presence of at least one site with a mass that is >\n 7.5 cm in largest diameter who have a 50% estimated reduction of total disease\n burden by imagining as read by radiology after conditioning chemotherapy are\n eligible to continue on study. In borderline cases, where they don't meet this\n criteria but are thought to have bulky disease by the treating investigator,\n clinical judgment will be required to determine eligibility of subjects who\n experience for example mixed responses; improved sites and progressed sites. In\n these cases, the PI, treating physician, and study team as applicable should\n agree and document that total disease burden has been reduced by about 50% when\n taking all sites involved into account as there is no objective method to make\n this estimated reduction if some areas improve and others don't, or even new\n sites arise.\n 2. Stage I-III disease: Subjects with stage I-III ( No extra nodal disease) who\n continue to have stable disease or better after conditioning chemotherapy are\n eligible to continue on study.\n 3. Skin Disease a. There will be no response or non-response criteria assessed that will\n be specific to skin disease since disease burden is almost never expected to be high\n without skin barrier violation and often involve infections that would make subjects\n ineligible at the time\n Eligibility for CD4CAR infusion:\n Inclusion\n 1. Afebrile and not receiving antipyretics, and no evidence of active infection\n 2. Specific organ function criteria for cardiac, renal, and liver function must be\n similar to initial inclusion values. Tests such as echocardiogram and PFTs need not be\n repeated if within 6 weeks of initial assessment.\n 3. Negative pregnancy testing (if applicable)\n 4. If previous history of corticosteroid chemotherapy, subject must be off all but\n adrenal replacement doses\n 5. Planned infusion dose was successfully manufactured and met release criteria.", "output": {"inclusion_biomarker": [["CD4 positive"]], "exclusion_biomarker": []}}
+{"input": "This phase I/II trial studies the side effects and best dose of avelumab with M6620 in\n treating patients with deoxyribonucleic acid (DNA) damage repair (DDR) deficient solid tumors\n that have spread to other places in the body (metastatic) or cannot be removed by surgery\n (unresectable). DDR deficiency refers to a decrease in the ability of cells to respond to\n damaged DNA and to repair the damage, which can be caused by genetic mutations. Immunotherapy\n with monoclonal antibodies, such as avelumab, may help the body's immune system attack the\n cancer, and may interfere with the ability of tumor cells to grow and spread. M6620 may stop\n the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving\n avelumab together with M6620 may help to control DDR deficient metastatic or unresectable\n solid tumors.\n ;\n ;\n Inclusion Criteria:\n - Subjects must have histologically confirmed malignancy that is metastatic or\n unresectable and for which standard curative measures do not exist or are no longer\n effective\n - Subjects will be eligible for this study based on the presence of actionable\n aberrations in one or more of the following DNA damage response (DDR) genes: ARID1A,\n ATM, ATR, ATRX, BAP1, BARD1, BRCA1/2, BRIP1, CDK12, CHEK2, FANCA, FANCC, FANCD2,\n FANCE, FANCF, FANCM, MRE11A, MSH2, NBN (NBS1), PALB2, RAD51, RAD51C, RAD51D, SMARCB1,\n and VHL, or other related genes at the discretion of the principal investigator in\n consultation with the MD Anderson Cancer Center Institute for Personalized Cancer\n Therapy Precision Oncology Decision Support (PODS) group. Variant interpretation for\n actionability will be performed by PODS\n - Subjects with germline defects in DDR genes are eligible for this trial\n - The collection of archival tumor tissue (within 1 year prior to study enrollment) will\n be mandatory. Tumor biopsies on cycle 1 day 15 will be mandatory. Subjects will not be\n put at undue risk to obtain the biopsy at cycle 1 day 15 (C1D15). A biopsy at C1D15\n will not be required if it poses a serious/severe complication risk greater than 2%.\n All other biopsy time points are not mandatory but will be strongly encouraged where\n feasible. These include at baseline and at disease progression. Archival and fresh\n tissue requests can be waived in exceptional circumstances with principal investigator\n (PI) approval and only where rationale is documented\n - Subjects must have received at least 1 line of systemic therapy in the\n advanced/metastatic setting. Subjects with diseases without known effective options,\n and subjects who had declined standard of care therapy prior to study introduction are\n also eligible\n - Subjects enrolling in the dose escalation should have progressed on or be intolerant\n to all therapies known to confer a clinical benefit. Subjects must not have refused\n all available therapies\n - Subjects who have received prior therapy with immune checkpoint inhibitors (ICIs) are\n eligible for this trial. Subjects with a standard-of-care option for an immune\n checkpoint inhibitor are eligible\n - Subjects must have measurable disease per Response Evaluation Criteria in Solid Tumors\n (RECIST) version (v) 1.1, or patients may have bone metastatic disease evaluable by\n Prostate Cancer Working Group 3 (PCWG3) for subjects with metastatic\n castration-resistant prostate cancer (CRPC), or according to tumor evaluation criteria\n best suited and accepted for the tumor type to be evaluated\n - Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1\n - Subjects must have a life expectancy >= 12 weeks\n - Absolute neutrophil count >= 1.5 x 10^9/L\n - Platelets >= 100 x 10^9/L\n - Hemoglobin >= 9 g/dL or >= 5.6 mmol/L\n - Total bilirubin =< 1.5 X the institutional upper limit of normal (ULN)\n - Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)/\n alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT) =< 2.5 X\n institutional ULN or =< 5 X institutional ULN in the presence of liver metastases\n - Serum creatinine =< 2 X ULN or estimated creatinine clearance >= 30 mL/min according\n to the Cockcroft-Gault formula\n - Female patients of childbearing potential must have a negative serum or urine\n pregnancy test at screening (and again at baseline just prior to first administration\n of study drugs)\n - Female patients of non-childbearing potential must meet at least 1 of the following\n criteria:\n - Achieved postmenopausal status, defined as follows: cessation of regular menses\n for at least 12 consecutive months, with no alternative pathological or\n physiological cause;\n - Have undergone a documented hysterectomy and/or bilateral oophorectomy\n - Have medically confirmed ovarian failure All other female patients (including\n female patients with tubal ligation) are considered to be of childbearing\n potential\n - Women of childbearing potential and fertile men must agree to use adequate\n contraception when sexually active from signing of the informed consent form for the\n full study until at least 6 months after the last study drug administration. Patients\n must agree to utilize 2 reliable and acceptable methods of contraception\n simultaneously. A man is considered fertile after puberty unless permanently sterile\n by bilateral orchiectomy. Men taking part in this study are advised not to father a\n child during and up to 6 months after treatment; prior to treatment, advice should be\n sought for conserving sperm due to the chance of irreversible infertility as a\n consequence of treatment. Female partners of childbearing potential from male study\n patients have to use adequate contraception / birth control between signing of the\n informed consent and 6 months after the last administration of the study drug if the\n male study patient is not sterilized. The investigator or a designated associate is\n requested to advise the patient how to achieve highly effective birth control. Highly\n effective (failure rate of less than 1% per year) contraception methods, when used\n consistently and correctly, include:\n - Combined (estrogen and progestin containing: oral, intravaginal, transdermal) and\n progestin-only (oral, injectable, implantable) hormonal contraception associated\n with inhibition of ovulation\n - Intra-uterine device or intrauterine hormone-releasing system\n - Bilateral tubal occlusion or vasectomized partner (provided that partner is the\n sole sexual partner and has received medical assessment of the surgical success)\n - Sexual abstinence (reliability to be evaluated in relation to the duration of the\n clinical trial and the preferred and usual lifestyle of the patient) Male\n patients with a female partner of reproductive potential must use a condom and\n ensure that an additional form of contraception is also used during treatment and\n until 6 months after last study drug administration. Patients must agree to\n utilize 2 reliable and acceptable methods of contraception simultaneously\n - Evidence of a personally signed and dated informed consent document indicating that\n the patient has been informed of all pertinent aspects of the study\n - Willing and able to comply with scheduled visits, treatment plan, laboratory tests,\n and other procedures\n - Human immunodeficiency virus (HIV)-infected (HIV1/2 antibody-positive) patients may\n participate IF they meet all the following eligibility requirements:\n - They must be on an anti-retroviral regimen with evidence of at least two\n undetectable viral loads within the past 6 months on this same regimen; the most\n recent undetectable viral load must be within the past 12 weeks\n - They must have a CD4 count >= 250 cells/mcL over the past 6 months on this same\n anti-retroviral regimen and must not have had a CD4 count < 200 cells/ mcL over\n the past 2 years, unless it was deemed related to the cancer and/or\n chemotherapy-induced bone marrow suppression\n - For patients who have received chemotherapy in the past 6 months, a CD4\n count < 250 cells/mcL during chemotherapy is permitted as long as viral\n loads were undetectable during this same chemotherapy\n - They must have an undetectable viral load and a CD4 count >= 250 cells/mcL within\n 7 days of enrolment\n - They must not be currently receiving prophylactic therapy for an opportunistic\n infection and must not have had an opportunistic infection within the past 6\n months\n Exclusion Criteria:\n - Anticancer systemic therapy or radiotherapy within 4 weeks or 5 half-lives, whichever\n is shorter prior to starting the study agents. Prior palliative radiotherapy to\n metastatic lesion(s) is permitted, provided it has been completed 2 weeks prior to\n study enrollment, and no clinically significant toxicities are expected (e.g.,\n mucositis, esophagitis)\n - Known symptomatic brain metastases requiring steroids. Patients with previously\n treated diagnosed brain metastases are eligible if they have completed their treatment\n and have recovered from the acute effects of radiation therapy or surgery prior to\n study enrollment, have discontinued corticosteroid treatment for these metastases for\n at least 4 weeks and are neurologically stable\n - Current use of immunosuppressive medication at the time of study enrollment, EXCEPT\n for the following permitted steroids:\n - Intranasal, inhaled, topical steroids, eye drops, or local steroid injection\n (e.g., intra-articular injection)\n - Systemic corticosteroids at physiologic doses =< 10 mg/day of prednisone or\n equivalent\n - Steroids as premedication for hypersensitivity reactions (e.g. computed\n tomography [CT] scan premedication)\n - Subjects who had major surgery within 4 weeks prior to study enrollment\n - Known prior severe hypersensitivity to investigational products or any component in\n their formulations, including known severe hypersensitivity reactions to monoclonal\n antibodies (National Cancer Institute [NCI] Common Terminology Criteria for Adverse\n Events [CTCAE] version [v] 5 grade >= 3)\n - Active infection requiring systemic therapy\n - Known history of immune-mediated colitis, inflammatory bowel disease, pneumonitis, and\n pulmonary fibrosis\n - Active or prior autoimmune disease that may deteriorate when receiving an\n immunostimulatory agent. Patients with type I diabetes, vitiligo, psoriasis, or hypo-\n or hyperthyroid disease not requiring immunosuppressive treatment are eligible\n - Prior organ transplantation including allogenic stem cell transplantation\n - Diagnosis of myelodysplastic syndrome (MDS)\n - Vaccination within 4 weeks of study enrollment and while on trial is prohibited except\n for the administration of inactivated vaccines\n - Clinically significant (i.e., active) cardiovascular disease: cerebral vascular\n accident/stroke (< 6 month prior to enrollment), myocardial infarction (< 6 months\n prior to enrollment), unstable angina, congestive heart failure (>= New York Heart\n Association Classification class II) or a serious cardiac arrhythmia requiring\n medication\n - Other acute or chronic medical or psychiatric conditions including but not limited to\n recent (within the past year) or active suicidal ideation or behavior or laboratory\n abnormality that may increase the risk associated with study participation or\n investigational product administration or may interfere with the interpretation of\n study results, and in the judgement of the Investigator, would make the patient\n inappropriate for entry into this study\n - Pregnant female patients, breastfeeding female patients, fertile male patients, and\n female patients of childbearing potential who are unwilling or unable to use 2 highly\n effective methods of contraception as outlined in this protocol for the duration of\n the study, and for at least 6 months after the last dose of study drug administration\n - Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive\n HBV surface antigen or HCV ribonucleic acid (RNA) if anti-HCV antibody screening test\n is positive)\n - Known additional malignancy that is active and/or progressive requiring treatment;\n exceptions include basal cell or squamous cell skin cancer, in situ bladder cancer, or\n other cancer for which the patient has been disease-free for >= 2 years\n - Persisting toxicity related to prior therapy (NCI CTCAE v5 grade > 1); however,\n alopecia and sensory neuropathy grade =< 2, or other grade =< 2 AEs not constituting a\n safety risk, based on the investigator's judgement, are acceptable\n - Subjects receiving treatment with strong inhibitors or inducers of CYP3A4 that cannot\n be discontinued before start of investigational treatment and for the duration of\n study\n - Subjects with ongoing toxicity (any grade) and/or resolved ICI toxicity (grade 3 or\n higher only)", "output": {"inclusion_biomarker": [["ARID1A aberration"], ["ATM aberration"], ["ATR aberration"], ["ATRX aberration"], ["BAP1 aberration"], ["BARD1 aberration"], ["BRCA1 aberration"], ["BRCA2 aberration"], ["BRIP1 aberration"], ["CDK12 aberration"], ["CHEK2 aberration"], ["FANCA aberration"], ["FANCC aberration"], ["FANCD2 aberration"], ["FANCE aberration"], ["FANCF aberration"], ["FANCM aberration"], ["MRE11A aberration"], ["MSH2 aberration"], ["NBS1 aberration"], ["PALB2 aberration"], ["RAD51 aberration"], ["RAD51C aberration"], ["RAD51D aberration"], ["SMARCB1 aberration"], ["VHL aberration"], ["ARID1A defect (germline)"], ["ATM defect (germline)"], ["ATR defect (germline)"], ["ATRX defect (germline)"], ["BAP1 defect (germline)"], ["BARD1 defect (germline)"], ["BRCA1 defect (germline)"], ["BRCA2 defect (germline)"], ["BRIP1 defect (germline)"], ["CDK12 defect (germline)"], ["CHEK2 defect (germline)"], ["FANCA defect (germline)"], ["FANCC defect (germline)"], ["FANCD2 defect (germline)"], ["FANCE defect (germline)"], ["FANCF defect (germline)"], ["FANCM defect (germline)"], ["MRE11A defect (germline)"], ["MSH2 defect (germline)"], ["NBS1 defect (germline)"], ["PALB2 defect (germline)"], ["RAD51 defect (germline)"], ["RAD51C defect (germline)"], ["RAD51D defect (germline)"], ["SMARCB1 defect (germline)"], ["VHL defect (germline)"]], "exclusion_biomarker": []}}
 {"input": "In this study, the purpose of this study is to investigate whether prophylactic medical\n compression therapy in breast cancer patients receiving docetaxel adjuvant chemotherapy could\n reduce the incidence and severity of lymphedema in the upper limbs that received axillary\n lymph node resection (sentinel lymph node biopsy or axillary lymph node dissection).\n ;NA;\n Inclusion Criteria:\n 1. Patients who underwent radical mastectomy and sentinel lymphctomy or axillary\n lymphectomy after diagnosis of unilateral breast cancer\n 2. Patients who are scheduled for adjuvant chemotherapy including Docetaxel after surgery\n 3. Patients aged 19 to 70\n 4. Patients who can understand the contents of this study and obtain consent\n Exclusion Criteria:\n 1. Patients with a history of breast-related surgery prior to this breast cancer surgery\n 2. Patients with metastases to other organs\n 3. Patients who have undergone neoadjuvant chemotherapy or have previously received\n radiation therapy\n 4. Patients with systemic diseases that may not be able to conduct clinical research\n 5. Patients with skin diseases who cannot receive medical compression treatment", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
 {"input": "Expanded access requests for IFx-Hu2.0 may be considered for the treatment of adult patients\n (greater than or equal to 18 years of age) with stage III through IV cutaneous melanoma,\n advanced Merkel cell carcinoma (MCC), or advanced cutaneous squamous cell carcinoma (cSCC)\n who have failed all available treatment options.\n To request access, use Responsible Party contact information provided in this record..\n ;NA;\n Inclusion Criteria:\n - To request more information use Responsible Party contact information provided in this\n record\n Exclusion Criteria:\n - To request more information use Responsible Party contact information provided in this\n record", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
 {"input": "This is a first in human, multicenter, open label, Phase 1a/b dose escalation and dose\n expansion study to establish the maximum tolerated dose (MTD), recommended Phase 2 dose\n (RP2D), and evaluate the safety and tolerability of QD oral dosing of HC 7366 in a dose\n escalating fashion in subjects with advanced solid tumors. Up to 36 subjects will be enrolled\n into the Phase 1a dose escalation part of the study. Every effort will be made to ensure\n approximately 50% of all subjects enrolled in this study will be subjects with the tumors of\n special interest such as squamous cell carcinoma of the head and neck (SCCHN), colorectal\n cancer (CRC), non-small cell lung cancer (NSCLC), and transitional cell carcinoma of the\n bladder (TCC). Subjects with other solid tumor types are also eligible provided study\n selection criteria are met and they do not exceed 50% of all enrolled subjects. The study\n will be conducted in the United States at approximately 3 to 5 sites. This Phase 1a/b study\n will follow a traditional 3+3 design. The starting dose level will be 10 mg QD, escalating to\n 20, 40, 75, 125, and 150 mg QD as safety allows. All doses are to be administered in the\n fasting state with water at least 1 hour before food or at least 2 hours after food. The\n Phase 1b dose expansion part will involve cohort expansion at up to 2 dose levels selected\n from the dose escalation data by the safety monitoring committee (SMC), to obtain additional\n safety and preliminary efficacy information. Each cohort in Phase 1b will enroll 15 subjects.\n The study will be expanded into a Phase 2 study via protocol amendment which will then assess\n the dose and tumor type(s) selected in Phase 1a/b as the most appropriate for further\n clinical development. Subjects will be dosed until unacceptable toxicity, disease progression\n per immune-related Response Evaluation Criteria in Solid Tumors (iRECIST), discontinuation of\n treatment for other protocol allowed reason (eg, subject refusal), any other administrative\n reasons, or after 2 years of treatment, whichever occurs first. For scheduling purposes,\n dosing will occur in 3 week cycles and computed tomography (CT) scans will be conducted once\n every 6 weeks with the first postbaseline scan after 6 weeks of dosing (precycle 3).\n ;\n ;\n Inclusion Criteria:\n 1. Have a signed an informed consent form prior to any study specific procedures or\n treatment\n 2. Be \u226518 years of age (male or female) at the time of consent\n 3. Have 1 of the following tumor types with qualifying characteristics, and have received\n at least 1 and no more than 5 prior lines of therapy:\n 1. SCCHN\n 2. CRC\n 3. NSCLC\n 4. TCC\n 5. Other solid tumors (eg, carcinoma of unknown primary) with the exception of\n rapidly progressing neoplasms (eg, pancreatic cancer, glioblastoma,\n hepatocellular carcinoma). Note: Subjects do not need to have progressed through\n all possible available therapies with known clinical benefit for their respective\n cancers to participate in this study. Note: Subjects with SCCHN, CRC, NSCLC, and\n TCC are a priority and should constitute as a whole, at least 50% of the enrolled\n population. Enrollment of all others will be capped when reaching a combined 50%,\n in order to maintain 18 slots for subjects with SCCHN, CRC, NSCLC, and TCC.\n 4. Have at least 1 radiologically measurable lesion as per Response Evaluation Criteria\n in Solid Tumors (RECIST) v 1.1 defined as a lesion that is at least 10 mm in longest\n diameter or lymph node that is at least 15 mm in short axis imaged by CT scan or\n magnetic resonance imaging and obtained by imaging within 28 days prior to study\n treatment. Tumor lesions situated in a previously irradiated area are considered\n measurable if progression has been demonstrated in such lesions\n 5. Have resolution of all previous treatment related toxicities to Grade 1 severity or\n lower, except for stable sensory neuropathy (\u2264Grade 2) and alopecia. If the subject\n received major surgery or radiation therapy of >30 Gy, they must have recovered from\n the toxicity and/or complications from the intervention\n 6. If subjects were previously treated with immune checkpoint inhibitors, at least 4\n weeks must have elapsed since the last dose, and toxicities resolved as above\n 7. Subjects must have at least one biopsiable lesion at baseline. Biopsies in this\n clinical study will conform to American Society of Clinical Oncology's Ethical\n Framework for Including Research Biopsies in Oncology Clinical Trials. Provided there\n are suitable and accessible lesions, no biopsy contraindications, minimal risk of\n complications and a positive informed decision, subjects are willing to provide fresh\n tissue for biomarker analysis, and, based on the adequacy of the tissue sample\n quality, for assessment of biomarker status. Two biopsies will be necessary: at\n baseline (within 15 days prior to study Day 1) and at the time of the first response\n assessment CT scan at Cycle 3/Day 1 (+7 days). Newly obtained biopsy specimens are\n preferred to archived samples and formalin fixed, paraffin embedded block specimens\n are preferred to slides\n 8. Have Eastern Cooperative Oncology Group performance status of 0 or 1 and sustained\n between screening and initiation of dosing on Day 1\n 9. Have no swallowing difficulties that would prevent compliance with oral dosing\n 10. Have not experienced >10% body weight loss in the previous 4 weeks\n 11. Have a serum albumin level >3 g/dL\n 12. Have life expectancy of 3 months or greater as determined by the treating physician\n 13. Have adequate organ function on Day 1, as defined by meeting all of the following\n criteria:\n 1. Total bilirubin \u22641.5 \u00d7 upper limit of normal (ULN) OR direct bilirubin \u2264ULN for\n subjects with total bilirubin levels >1.5 x ULN\n 2. Aspartate aminotransferase and alanine aminotransferase \u22642.5 \u00d7 ULN or \u22645 \u00d7 ULN\n for subjects with known hepatic metastases\n 14. Have adequate renal function on Day 1, as defined by creatinine \u22641.5 \u00d7 ULN and\n creatinine clearance \u226560 mL/min, as per the below Cockcroft Gault formula\n 15. Have adequate hematologic function on Day 1, as defined by meeting all of the\n following criteria:\n 1. Hemoglobin \u22659 g/dL (uncorrected by red blood cell transfusion or erythropoietin\n support)\n 2. Absolute neutrophil count \u22651.5 \u00d7 109/L\n 3. Platelet count \u2265100 \u00d7 109/L\n 16. Have adequate coagulation function on Day 1, as defined by either of the following\n criteria:\n 1. International normalized ratio (INR) <1.5 \u00d7 ULN OR for subjects receiving\n warfarin or low molecular weight heparin, the subject must, in the investigator's\n opinion, be clinically stable with no evidence of active bleeding while receiving\n anticoagulant therapy. The INR for these subjects may exceed 1.5 \u00d7 ULN if that is\n the goal of anticoagulant therapy\n 2. Activated partial thromboplastin time <1.5 \u00d7 ULN unless subject is receiving\n anticoagulant therapy, provided prothrombin time or partial thromboplastin time\n is within therapeutic range of intended use of anticoagulants\n 17. Have normal or adequately controlled pan-endocrine function (pituitary, adrenal,\n thyroid, pancreatic, gonadal). Subjects on hormonal supplementation must be stable at\n their treatment doses\n 18. Female subjects of childbearing potential must have a negative urine or serum\n pregnancy test within 72 hours prior to receiving the first dose of study medication.\n If the urine test is positive or cannot be confirmed as negative, a serum pregnancy\n test will be required\n 19. Female subjects of childbearing potential must be willing to use an adequate form of\n contraception from the signing of the ICF until 90 days after the last dose of study\n medication\n 20. Female subjects must agree not to breastfeed and not to donate ova starting at\n screening and throughout the study treatment, and for 90 days after the final\n administration of study drug\n 21. Male subjects with a pregnant or breastfeeding partner(s) must agree to remain\n abstinent or use a condom for the duration of the pregnancy or for the time their\n partner is breastfeeding throughout the study treatment and for 90 days after the\n final administration of study drug\n 22. Male subjects must not donate sperm during the treatment period and for at least 90\n days after the final administration of the study drug\n 23. Male subjects with female partner(s) of child bearing potential must agree to use a\n condom with spermicide during the treatment period and for at least 90 days after the\n final administration of the study drug\n 24. Be willing and have the ability to comply with scheduled visits (including\n geographical proximity), treatment plans, laboratory tests, and other study\n procedures.\n Exclusion Criteria:\n 1. Had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2\n weeks prior to the first dose of study treatment or who has not recovered from adverse\n reactions due to a previously administered agent or major surgery\n 2. Is currently participating and receiving study therapy or has participated in a study\n of an investigational agent and received study therapy or used an investigational\n device within 4 weeks of the first dose of treatment\n 3. Has a diagnosis of immunodeficiency or receiving systemic steroid therapy or any other\n form of immunosuppressive therapy within 7 days prior to the first dose of study\n treatment. The use of physiologic doses of corticosteroids may be approved after\n consultation with the sponsor\n 4. Has known history of active tuberculosis\n 5. Has known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)\n 6. Has known active hepatitis B (eg, hepatitis B surface antigen reactive) or hepatitis C\n (eg, hepatitis C virus ribonucleic acid [RNA] [qualitative]) infection\n 7. Has been diagnosed with severe acute respiratory syndrome coronavirus 2 infection\n confirmed by real time polymerase chain reaction (PCR) test as per the local\n guidelines at screening and positive by PCR within 7 days prior to the first dose of\n study treatment\n 8. Has a history of clinically severe autoimmune disease, or history of organ transplant\n 9. Has a history of retinitis or photosensitive skin disorders including (but not limited\n to) erythema multiforme, atopic eczema, psoriasis, viral exanthemata, pemphigus, and\n dermatitis herpetiformis\n 10. Has known additional malignancy that is progressing or required active treatment\n within the previous 5 years. Exceptions include basal cell carcinoma or squamous cell\n carcinoma of the skin that has undergone potentially curative therapy, superficial\n bladder cancer, or in situ cervical cancer. Subjects with other malignancies are\n eligible if they were cured by surgery alone or surgery plus radiotherapy and have\n been continuously disease free for at least 5 years\n 11. Has known active central nervous system metastases and/or carcinomatous meningitis.\n Subjects with previously treated brain metastases may participate provided they are\n stable (without evidence of disease progression by imaging for at least 4 weeks prior\n to the first dose of study treatment and any neurologic symptoms have returned to\n baseline), have no evidence of new or enlarging brain metastases, and are not using\n systemic steroids for at least 7 days prior to study treatment. This exception does\n not include carcinomatous meningitis which is excluded regardless of clinical\n stability\n 12. Has a history of interstitial lung disease, pneumonitis within 12 months prior to\n screening, or current pneumonitis\n 13. Has an active infection requiring systemic therapy\n 14. Has a history or current evidence of any condition, therapy, or laboratory abnormality\n that might confound the results of the study, interfere with the subject's\n participation for the full duration of the study, or is not in the best interest of\n the subject to participate, in the opinion of the treating investigator\n 15. Has a clinically significant cardiovascular disease such as unstable angina,\n myocardial infarction, or acute coronary syndrome, symptomatic or uncontrolled\n arrhythmia, congestive heart failure, baseline electrocardiogram (ECG) abnormalities,\n including, but not limited to, QTc prolongation to greater than 470 ms, or any Class\n III or IV cardiac disease as defined by the New York Heart Association Functional\n Classification\n 16. Has overt or latent disorders of the exocrine pancreas (such as acute or chronic\n pancreatitis of any etiology) or chronic (including autoimmune) gastrointestinal\n disorders such as Crohn's disease, ulcerative colitis, rheumatoid arthritis, lupus,\n scleroderma, Sjogren's syndrome, and polyarteritis nodosa\n 17. Has a known psychiatric or substance abuse disorder(s) that would interfere with\n informed consent or cooperation with the requirements of the study\n 18. Is pregnant or breastfeeding or expecting to conceive children within the projected\n duration of the study, starting with the screening visit through 90 days after the\n final administration of the study drug\n 19. Is a first degree relative of the investigator, staff, or study sponsor.", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
 {"input": "This is a surgical biospecimen collection study. The purpose of this study is to understand\n how much of two drugs (dabrafenib and trametinib) are able to penetrate brain tumors and turn\n off the RAF signaling pathway. This is important because these drugs are currently FDA\n approved for other tumors and may have efficacy in brain tumors with the BRAF V600E mutation.\n ;\n ;\n Inclusion Criteria:\n - Subjects must have a history of primary brain tumor (including but not limited to\n glioblastoma (GBM), anaplastic astrocytoma (AA), anaplastic ganglioglioma (AG), and\n anaplastic pleomorphic xanthoastrocytoma (PXA)).\n - Subjects must have a BRAF-V600 mutation identified in previous tissue analysis (may be\n IHC or PCR based). Allowable mutations include V600E, V600K, V600R, and V600D.\n - Subjects must be taking dabrafenib at a dose of at least 50mg twice daily (adults\n only) and / or trametinib at a dose of at least 1mg daily (adults only) for at least 7\n days prior to surgery as prescribed by their treating physician. Note: Pediatric\n patients may be taking any dose of dabrafenib and / or trametinib as prescribed by\n their treating physician for at least 7 days prior to surgery.\n - Subjects must be undergoing surgery for clinical purposes.\n - Written informed consent - a signed informed consent and/or assent (as age\n appropriate) for study participation will be obtained according to institutional\n guidelines.\n Exclusion Criteria:\n - Subjects who are receiving any other investigational agents or chemotherapeutic\n agents.\n - Subjects for whom collection of blood, spinal fluid, or tissue samples is unsafe or\n clinically inadvisable.", "output": {"inclusion_biomarker": [["BRAF V600E"], ["BRAF V600K"], ["BRAF V600R"], ["BRAF V600D"]], "exclusion_biomarker": []}}
-{"input": "The MyDRUG study is a type of Precision Medicine trial to treat patients with drugs targeted\n to affect specific genes that are mutated as part of the disease. Mutations in genes can lead\n to uncontrolled cell growth and cancer. Patients with a greater than 25% mutation to any of\n the following genes; CDKN2C, FGFR3, KRAS, NRAS, BRAF V600E, IDH2 or T(11;14) can be enrolled\n to one of the treatment arms. These arms have treatments specifically directed to the mutated\n genes. Patients that do not have a greater than 25% mutation to the genes listed can be\n enrolled to a non-actionable treatment arm.\n The genetic sequencing of the patient's tumor is required via enrollment to the MMRF002\n study: Clinical-grade Molecular Profiling of Patients with Multiple Myeloma and Related\n Plasma Cell Malignancies. (NCT02884102).\n ;\n ;\n Inclusion Criteria:\n - Willing to be registered into the pomalidomide (POMALYST\u00ae) Risk Evaluation and\n Mitigation Strategy (REMS\u00ae) program\n - Enrolled in the MMRF002 Molecular Profiling Protocol (NCT02884102) with report less\n than 120 days old\n - Disease free of prior malignancies for \u2265 3 years with exception of currently treated\n basal cell, squamous cell carcinoma of the skin, carcinoma \"in situ\" of the cervix or\n breast, or prostate cancer not requiring therapy\n - High risk patients with relapsed refractory multiple myeloma (RRMM), who have:\n - received at least one prior but no more than 3 prior therapies\n - exposed to both a PI and an IMiD\n - had early relapse after initial treatment Early relapse as defined by at least\n one of the following: (Relapse is defined as the IMWG uniform response)\n 1. Relapse within 3 years of initiation of induction chemo therapy for post\n autologous stem cell transplantation (ASCT) followed by maintenance, or 18\n months if unmaintained after ASCT\n 2. Within 18 months of initial non-ASCT based therapy\n - Patients must have progressed after their most recent treatment and require therapy\n for myeloma\n - Females of reproductive potential must have a negative pregnancy test at baseline, be\n non-lactating, and willing to adhere to scheduled pregnancy testing\n - Females of reproductive potential and males must practice and acceptable method of\n birth control\n - Laboratory values obtained \u2264 14 days prior to registration:\n - Absolute neutrophil count (ANC) \u2265 1000/ul\n - Hemoglobin (Hgb) \u2265 8 g/dl\n - Platelet (PLT) \u2265 75,000/ul\n - Total bilirubin <1.5 x upper limit of normal (ULN) or if total bilirubin is >1.5\n x ULN, the direct bilirubin must be \u2264 2.0 mg/dL\n - Aspartate aminotransferase (AST) <3 x ULN\n - Creatinine Clearance \u2265 30 mL/min\n Measurable disease of Multiple Myeloma (MM) as defined by at least one of the following:\n - Serum monoclonal protein \u2265 0.5 g by protein electrophoresis\n - \u2265200 mg of monoclonal protein in the urine on 24-hour electrophoresis\n - Serum immunoglobulin free light chain (FLC) \u226510 mg/dL AND abnormal serum\n immunoglobulin kappa to lambda FLC ratio\n - Monoclonal bone marrow plasmacytosis \u226530% (evaluable disease)\n - Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1, or 2\n - Ability to take aspirin, warfarin, or low molecular weight heparin\n Sub-Protocol Inclusion Criteria:\n Refer to each respective Sub Protocol for additional inclusion criteria.\n Exclusion Criteria:\n Patients will be ineligible for this study if they meet any one of the following criteria:\n - Aggressive multiple myeloma requiring immediate treatment as defined by:\n - Lactate dehydrogenase (LDH) > 2 times ULN\n - Presence of symptomatic extramedullary disease or central nervous system\n involvement\n - Hypercalcemia >11.5 mg/dl\n - Acute worsening of renal function (CrCl < 30 ml/min) directly related to myeloma\n relapse\n - Any neurological emergency related to myeloma\n - Clinical symptoms of hyperviscosity related to monoclonal protein\n - Involved serum free light chain > 100 mg/dL (1000 mg/L) in the setting of prior\n diagnosis of cast nephropathy\n - Infection requiring systemic antibiotic therapy or other serious infection within 14\n days of enrolment\n - Known hypersensitivity or development of erythema nodosum if characterized by a\n desquamating rash while taking thalidomide, lenalidomide, pomalidomide or similar\n drug. Known allergy to any of the study medications, their analogues, or excipients in\n the various formulations of the agents\n - Prior Ixazomib/Pomalidomide/Dexamethasone combination therapy\n - Pregnant or breast-feeding females\n - Serious medical or psychiatric illness, active alcoholism, or drug addiction that may\n hinder or confuse compliance, interfere in the completion of treatment per protocol,\n or follow-up evaluation\n - Active hepatitis A, B or C viral infection or known human immunodeficiency virus (HIV)\n infection\n - Concurrent symptomatic amyloidosis or plasma cell leukemia\n - POEMS syndrome [plasma cell dyscrasia with polyneuropathy, organomegaly,\n endocrinopathy, monoclonal protein (M-protein) and skin changes]\n - Residual side effects to previous therapy > Grade 1 prior to initiation of therapy\n (Alopecia any grade and/or neuropathy Grade 2 without pain are permitted)\n - Prior allogeneic or ASCT within 12 weeks of initiation of therapy. Prior allogeneic\n stem cell transplant with active graft-versus-host disease (GVHD)\n - Prior experimental therapy within 14 days of protocol treatment or 5 half-lives of the\n investigational drug, whichever is longer\n - Prior anticancer therapy within 14 days of initiation of protocol therapy\n (Dexamethasone/ 40mg/day) for a maximum of 4 days before screening is allowed\n - Prior major surgical procedure or radiation therapy within 4 weeks of the initiation\n of therapy (this does not include limited course of radiation used for management of\n bone pain within 7 days of initiation of therapy).\n - Known to have dysphagia, short-gut syndrome, gastroparesis, or other conditions that\n limit the ingestion or Gastro Intestinal (GI) absorption of drugs administered orally\n - Evidence of current uncontrolled cardiovascular conditions, including uncontrolled\n hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure,\n unstable angina, or myocardial infarction within the past 6 months\n - Other co-morbidity, which would interfere with patient's ability to participate in\n trial or that confounds the ability to interpret data from the study\n Sub-Protocol Exclusion Criteria:\n Refer to each respective Sub Protocol for additional exclusion criteria.", "output": {"inclusion_biomarker": [["CDKN2C mutation"], ["FGFR3 mutation"], ["KRAS mutation"], ["NRAS mutation"], ["BRAF V600E,"], ["IDH2 mutation"], ["T(11;14)"]], "exclusion_biomarker": []}}
+{"input": "The MyDRUG study is a type of Precision Medicine trial to treat patients with drugs targeted\n to affect specific genes that are mutated as part of the disease. Mutations in genes can lead\n to uncontrolled cell growth and cancer. Patients with a greater than 25% mutation to any of\n the following genes; CDKN2C, FGFR3, KRAS, NRAS, BRAF V600E, IDH2 or T(11;14) can be enrolled\n to one of the treatment arms. These arms have treatments specifically directed to the mutated\n genes. Patients that do not have a greater than 25% mutation to the genes listed can be\n enrolled to a non-actionable treatment arm.\n The genetic sequencing of the patient's tumor is required via enrollment to the MMRF002\n study: Clinical-grade Molecular Profiling of Patients with Multiple Myeloma and Related\n Plasma Cell Malignancies. (NCT02884102).\n ;\n ;\n Inclusion Criteria:\n - Willing to be registered into the pomalidomide (POMALYST\u00ae) Risk Evaluation and\n Mitigation Strategy (REMS\u00ae) program\n - Enrolled in the MMRF002 Molecular Profiling Protocol (NCT02884102) with report less\n than 120 days old\n - Disease free of prior malignancies for \u2265 3 years with exception of currently treated\n basal cell, squamous cell carcinoma of the skin, carcinoma \"in situ\" of the cervix or\n breast, or prostate cancer not requiring therapy\n - High risk patients with relapsed refractory multiple myeloma (RRMM), who have:\n - received at least one prior but no more than 3 prior therapies\n - exposed to both a PI and an IMiD\n - had early relapse after initial treatment Early relapse as defined by at least\n one of the following: (Relapse is defined as the IMWG uniform response)\n 1. Relapse within 3 years of initiation of induction chemo therapy for post\n autologous stem cell transplantation (ASCT) followed by maintenance, or 18\n months if unmaintained after ASCT\n 2. Within 18 months of initial non-ASCT based therapy\n - Patients must have progressed after their most recent treatment and require therapy\n for myeloma\n - Females of reproductive potential must have a negative pregnancy test at baseline, be\n non-lactating, and willing to adhere to scheduled pregnancy testing\n - Females of reproductive potential and males must practice and acceptable method of\n birth control\n - Laboratory values obtained \u2264 14 days prior to registration:\n - Absolute neutrophil count (ANC) \u2265 1000/ul\n - Hemoglobin (Hgb) \u2265 8 g/dl\n - Platelet (PLT) \u2265 75,000/ul\n - Total bilirubin <1.5 x upper limit of normal (ULN) or if total bilirubin is >1.5\n x ULN, the direct bilirubin must be \u2264 2.0 mg/dL\n - Aspartate aminotransferase (AST) <3 x ULN\n - Creatinine Clearance \u2265 30 mL/min\n Measurable disease of Multiple Myeloma (MM) as defined by at least one of the following:\n - Serum monoclonal protein \u2265 0.5 g by protein electrophoresis\n - \u2265200 mg of monoclonal protein in the urine on 24-hour electrophoresis\n - Serum immunoglobulin free light chain (FLC) \u226510 mg/dL AND abnormal serum\n immunoglobulin kappa to lambda FLC ratio\n - Monoclonal bone marrow plasmacytosis \u226530% (evaluable disease)\n - Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1, or 2\n - Ability to take aspirin, warfarin, or low molecular weight heparin\n Sub-Protocol Inclusion Criteria:\n Refer to each respective Sub Protocol for additional inclusion criteria.\n Exclusion Criteria:\n Patients will be ineligible for this study if they meet any one of the following criteria:\n - Aggressive multiple myeloma requiring immediate treatment as defined by:\n - Lactate dehydrogenase (LDH) > 2 times ULN\n - Presence of symptomatic extramedullary disease or central nervous system\n involvement\n - Hypercalcemia >11.5 mg/dl\n - Acute worsening of renal function (CrCl < 30 ml/min) directly related to myeloma\n relapse\n - Any neurological emergency related to myeloma\n - Clinical symptoms of hyperviscosity related to monoclonal protein\n - Involved serum free light chain > 100 mg/dL (1000 mg/L) in the setting of prior\n diagnosis of cast nephropathy\n - Infection requiring systemic antibiotic therapy or other serious infection within 14\n days of enrolment\n - Known hypersensitivity or development of erythema nodosum if characterized by a\n desquamating rash while taking thalidomide, lenalidomide, pomalidomide or similar\n drug. Known allergy to any of the study medications, their analogues, or excipients in\n the various formulations of the agents\n - Prior Ixazomib/Pomalidomide/Dexamethasone combination therapy\n - Pregnant or breast-feeding females\n - Serious medical or psychiatric illness, active alcoholism, or drug addiction that may\n hinder or confuse compliance, interfere in the completion of treatment per protocol,\n or follow-up evaluation\n - Active hepatitis A, B or C viral infection or known human immunodeficiency virus (HIV)\n infection\n - Concurrent symptomatic amyloidosis or plasma cell leukemia\n - POEMS syndrome [plasma cell dyscrasia with polyneuropathy, organomegaly,\n endocrinopathy, monoclonal protein (M-protein) and skin changes]\n - Residual side effects to previous therapy > Grade 1 prior to initiation of therapy\n (Alopecia any grade and/or neuropathy Grade 2 without pain are permitted)\n - Prior allogeneic or ASCT within 12 weeks of initiation of therapy. Prior allogeneic\n stem cell transplant with active graft-versus-host disease (GVHD)\n - Prior experimental therapy within 14 days of protocol treatment or 5 half-lives of the\n investigational drug, whichever is longer\n - Prior anticancer therapy within 14 days of initiation of protocol therapy\n (Dexamethasone/ 40mg/day) for a maximum of 4 days before screening is allowed\n - Prior major surgical procedure or radiation therapy within 4 weeks of the initiation\n of therapy (this does not include limited course of radiation used for management of\n bone pain within 7 days of initiation of therapy).\n - Known to have dysphagia, short-gut syndrome, gastroparesis, or other conditions that\n limit the ingestion or Gastro Intestinal (GI) absorption of drugs administered orally\n - Evidence of current uncontrolled cardiovascular conditions, including uncontrolled\n hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure,\n unstable angina, or myocardial infarction within the past 6 months\n - Other co-morbidity, which would interfere with patient's ability to participate in\n trial or that confounds the ability to interpret data from the study\n Sub-Protocol Exclusion Criteria:\n Refer to each respective Sub Protocol for additional exclusion criteria.", "output": {"inclusion_biomarker": [["CDKN2C mutation"], ["FGFR3 mutation"], ["KRAS mutation"], ["NRAS mutation"], ["BRAF V600E"], ["IDH2 mutation"], ["T(11;14)"]], "exclusion_biomarker": []}}
 {"input": "This phase II trial studies the effect of larotrectinib in treating patients with NTRK gene\n amplification positive solid tumors that have spread to nearby tissues or lymph nodes\n (locally advanced) or other places in the body (metastatic). Larotrectinib may stop the\n growth of tumor cells by blocking some of the enzymes needed for cell growth.\n ;\n ;\n Inclusion Criteria:\n - At least 16 years of age\n - Locally-advanced or metastatic malignancy with an NTRK1, NTRK2, or NTRK3 gene\n amplification identified through molecular assays (such as IHC and any next-generation\n sequencing [NGS] platform, reference lab NGS, or in house NGS platform) as routinely\n performed at The University of Texas MD Anderson Cancer Center or other\n similarly-certified laboratories. The minimum level of amplification is 7 copies. This\n rationale of amplification level is based on data from MOCLIA at The University of\n Texas MD Anderson Cancer Center\n - Must have received prior standard therapy appropriate for tumor type and stage of\n disease, or, in the opinion of the investigator, is unlikely to tolerate or derive\n clinically meaningful benefit from appropriate standard of care therapy\n - Must have at least one measurable lesion as defined by RECIST v1.1. Subjects with\n primary CNS tumors should meet the following criteria:\n - Must have received prior treatment including radiation and/or chemotherapy, with\n radiation completed > 12 weeks prior to cycle 1 day 1 (C1D1) of therapy, as\n recommended or appropriate for the tumor type\n - Must have >= 1 site of bi-dimensionally measurable disease (confirmed by magnetic\n resonance imaging [MRI] and evaluable by RANO), with the size of at least one of\n the measurable lesions >= 1 cm in each dimension\n - Must have imaging study within 28 days before enrollment. If on steroid therapy,\n the dose must be stable for at least five days immediately before and during the\n imaging study\n - Eastern Cooperative Oncology Group (ECOG) score =< 3. If enrolled with primary CNS\n tumor to be assessed by RANO, Karnofsky performance score (KPS) >= 70 %\n - Archived tumor tissue. If archival tissue is unavailable, an on-study tumor biopsy\n should be attempted if it can be safely performed\n - Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) < 2.5\n x upper limit of normal (ULN) or < 5 x ULN if liver function abnormalities are due to\n underlying malignancy\n - Total bilirubin < 2.5 x ULN, except in cases of biliary obstruction. Subjects with a\n known history of Gilberts disease and an isolated elevation of indirect bilirubin are\n eligible\n - Serum creatinine < 2.0 x ULN or estimated glomerular filtration rate >= 30 mL/minute\n using the Cockcroft-Gault formula\n - Ability to comply with outpatient treatment, laboratory monitoring, and required\n clinic visits for the duration of study participation\n - Willingness of men and women of reproductive potential to use two effective birth\n control methods, one used by the subject and another by his/her partner, for the\n duration of treatment and for 3 months following study completion\n Exclusion Criteria:\n - Investigational agent or anticancer therapy within 2 weeks prior to the planned start\n of larotrectinib or five half-lives, whichever is shorter, and without clinically\n significant toxicities from that therapy\n - Prior progression while receiving approved or investigational tyrosine kinase\n inhibitors targeting TRK. However, subjects who received less than 28 days of such\n treatment and discontinued because of intolerance or toxicity are eligible\n - Symptomatic or unstable brain metastases that needs corticosteroid usage. Subjects\n with asymptomatic brain metastases or primary CNS tumors are eligible\n - Uncontrolled concurrent malignancy that would limit assessment of efficacy. Allowed\n diseases may include, but are not limited to in situ cancers of cervix, breast, or\n skin, superficial bladder cancer, limited-stage prostate cancer, and basal or squamous\n cancers of the skin\n - Active uncontrolled systemic bacterial, viral, or fungal infection, unstable\n cardiovascular disease or other systemic disease that would limit compliance with\n study procedures. Unstable cardiovascular disease is defined as:\n - Persistently uncontrolled hypertension defined as systolic blood pressure (BP) >\n 150 mmHg and/or diastolic BP > 100 mmHg despite antihypertensive therapy\n - Myocardial infarction within 3 months of screening\n - Stroke within 3 months of screening\n - Inability to discontinue treatment with a strong cytochrome P450 (CYP450), 3A4\n (CYP3A4) inhibitor or inducer prior to start of treatment\n - Pregnancy or lactation", "output": {"inclusion_biomarker": [["NTRK1 amplification"], ["NTRK2 amplification"], ["NTRK3 amplification"]], "exclusion_biomarker": []}}
 {"input": "This is a prospective single arm, multi-center, phase II clinical trial to observe the\n efficacy and safety of VR-CAP (Bortezomib and Rituximab-Cyclophosphamide, Epirubicin and\n Prednisone) in the first-line treatment for patients with marginal zone lymphoma.\n ;\n ;\n Inclusion Criteria:\n 1. Age between 18 to 70 years old (including 18 and 70)\n 2. Diagnosed as marginal zone lymphoma\n 3. No receiving chemotherapy before enrollment\n 4. Indications for treatment: 1) symptoms related to tumor; 2) end-organ function damage;\n 3) large mass; 4) continuous or rapid progress of disease; 5) patient's willingness\n 5. Having at least one measurable lesions\n 6. World health organization-Eastern Cooperative Oncology Group Performance tatus (ECOG)\n 0-1\n 7. Life expectancy no less than 3 months\n 8. enough main organ function\n 9. Pregnancy test within 7 days must be negative for women of childbearing period, and\n appropriate measures should be taken for contraception for women in childbearing\n period during the study and six months after this study\n 10. Agreeing to sign the written informed consents\n Exclusion Criteria:\n 1. Diagnosed as central nervous system lymphoma\n 2. World health organization-Eastern Cooperative Oncology Group Performance tatus (ECOG)\n \u22652\n 3. Other malignant tumor history or active malignant tumor need be treated\n 4. Serious surgery and trauma less than two weeks\n 5. Systemic therapy for serious acute/chronic infection\n 6. Congestive heart failure, uncontrolled coronary heart disease, arrhythmia and heart\n infarction less than 6 months\n 7. Active tuberculosis. Patients suspected of active TB need to be examined for chest\n X-ray, sputum and clinical symptoms and signs\n 8. HIV-positive, AIDS patients and untreated active hepatitis\uff08HBV/HBV and HCV\uff09\n 9. Patients with a history of deep vein thrombosis or pulmonary embolism less than 12\n months\n 10. Patients with a history of mental illness\n 11. Researchers determine unsuited to participate in this trial", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
-{"input": "The study comprises two phases: Phase 1a and Phase 1b. The purpose of the study is to observe\n the safety\uff0c tolerability and efficacy of FS-1502.\n ;\n ;\n Inclusion Criteria:\n 1. Age \u226518 years at the time of study registration (men and women eligible);\n 2. Phase Ia dose-escalation study:\n Patients with HER2-expressing advanced malignant solid tumors who had failed to\n standard therapy(including surgery, chemotherapy, radiation therapy or biotherapy) ,\n or can not receive standard therapy, or no standard therapy is available.\n 1. HER2 expression: IHC3+, IHC2+/FISH+\n 2. HER2 expression: IHC1+, IHC2+/FISH-\n Phase Ib dose-expanded study:\n Histologically or cytologically confirmed HER2-positive patients with advanced breast\n cancer who had previously received at least 2 line therapy and had failed anti-HER2\n therapy. Details as follows:\n 1. HER2 positive (defined as IHC3+ or IHC2+/FISH+);\n 2. For patients with advanced breast cancer who had previously failed anti-HER2\n therapy and had received at least 2-line therapy, postoperative adjuvant therapy\n which could be considered as a treatment line number if disease progression\n during treatment and within 12 months after completion of treatment.\n 3. Provide evidence of disease progression or intolerable toxicity as confirmed by\n the investigator or medical history recorded prior to enrollment.\n 4. The enrollment can be based on written HER2 test report from certified local lab,\n and if patients had no HER2 test report, they should provide sufficient paraffin\n sections or fresh tumor tissue specimens which should be sent to the local lab or\n the central laboratory for testing and confirmation.\n Pivotal clinical study:\n Patients with locally advanced or relapsed metastatic breast cancer who have been\n histologically or cytologically confirmed to be HER2-positive and who have received\n two or more lines of anti-HER2 therapy in the past. Details as follows:\n 1. Her2-positive patients: Patients with IHC3+ or IHC2+ and FISH positive patients\n should provide enough tumor tissue samples within 5 years for the central\n laboratory to confirm HER2 status. Patients with HER2-positive patients are\n considered to be eligible for inclusion in this study; If the specimens provided\n are undetectable or are not available, a positive HER2 test from a local\n laboratory approved by the NMPA may be reported for entrainment.\n 2. Previous treatment with two or more lines of anti-HER2 therapy, neoadjuvant\n therapy or adjuvant therapy can be used as a treatment line number if the disease\n progresses during or within 12 months after treatment.\n 3. Evidence of investigator-confirmed or documented disease progression or\n intolerance of toxicity prior to enrollment.\n 3. The ECOG performance status must be 0 or 1.\n 4. Expected survival for at least 12 weeks.\n 5. Has adequate organ and bone marrow function: absolute neutrophil count (ANC) \u2265\n 1.0x1E9/L(without colony stimulating factor within 7 days); hemoglobin \u2265 90g/L\n (without red blood cell infusion within 14 days); platelet count \u2265 100x1E9/L(without\n thrombopoietin or thrombopoietin receptor agonists within 7 days nor platelet infusion\n within 14 days); Total bilirubin \u2264 1.5x upper limit normal (ULN), or \u2264 3x ULN if with\n Gilbert syndrome; aspartate aminotransferase (AST) and alanine aminotransferase (ALT)\n \u2264 2.5x ULN; AST and ALT \u2264 5x ULN if liver metastasis; Serum creatinine < 1.5x ULN and\n creatinine clearance \u2265 50mL/min (Cockroft-Gault formula calculation); Serum potassium\n \u22653.5 mmol/L\uff1balbumin \u2265 3g/dL; left ventricular ejection fraction (LVEF) >50%\uff1burinary\n protein \u22641+ or 24-hour urinary protein dose < 1.0g.\n 6. Has at least one non-intracranial measurable lesion by RECIST version 1.1.\n 7. Male or female patients with fertility must agree to use effective contraceptive\n methods during the study period and within 3 months of the last dose of study therapy,\n such as dual barrier contraceptive methods, condoms, oral or injectable\n contraceptives, and intrauterine devices.\n 8. Ability to understand and voluntarily sign written informed consent.\n Exclusion Criteria:\n 1. Patients who received chemotherapy, targeted therapy, radiotherapy, etc., 14 days or\n within 5 half-lives periods, whichever is shorter, prior to the start of dosing.\n Patients who received major surgery, tumor immunotherapy, or monoclonal antitumor\n therapy within 4 weeks prior to the start of dosing.\n 2. Patients who have participated in other clinical trials 4 weeks before the start of\n study drug administration or within 5 half-lives periods, whichever is shorter.\n 3. Patients previously treated with anti-HER2 ADC drugs.\n 4. Patients with central nervous system metastasis.\n 5. Clinically uncontrolled mass pleural effusion, pericardial effusion, or abdominal\n effusion (2 weeks before first administration).\n 6. Non-recovery of toxic effects from previous antitumor therapy (> NCI-CTCAE 5.0 grade\n 1) alopecia, neurotoxicity, or other toxicity that had become chronic as assessed by\n the investigator and did not affect the safety of the investigational medication was\n admitted to NCI-CTCAE 5.0 grade 2 or below.\n 7. Patients with corneal epitheliopathy (other than mild punctiform keratopathy or\n existing eye diseases affecting the evaluation of ocular toxicity after trial\n administration) or who were unwilling to stop wearing contact lenses during the study.\n 8. Patients take medications that prolong the QTc interval (mainly Ia, Ic, Class III\n antiarrhythmic drugs) or have risk factors that prolong the QTc interval, such as\n uncorrectable hypokalemia, hereditary long QT syndrome;\n 9. Cardiac function and disease conform to one of the following conditions:\n 1. Three 12-lead electrocardiogram (ECG) measurements were performed at the research\n center during the screening period, and three mean values were calculated\n according to the QTc formula adopted by the instrument, QTc > 470 ms;\n 2. New York Heart Association (NYHA)Grade \u2265 2 for congestive heart failure;\n 3. arrhythmia of clinical significance grade \u2265 2.\n 4. History of myocardial infarction or severe arteriovenous thrombosis within 6\n months.\n 10. Pregnant or lactating women;\n 11. Known allergy to any excipients of FS-1502;\n 12. Active infections requiring systemic treatment;\n 13. Persons with active hepatitis B (HBV surface antigen positive with HBV DNA exceeding\n 1000 IU/ml or meeting the research Center criteria for diagnosis of active hepatitis B\n infection) or hepatitis C (HCV RNA positive), human immunodeficiency virus infection\n (HIV positive);\n 14. Had been diagnosed with any other malignancies within the 5 years prior to study\n participation, other than early malignancies that have undergone radical treatment\n (carcinoma in situ), such as adequately treated basal or squamous cell skin cancers or\n carcinoma in situ of the cervix;\n 15. Any other clinically significant disease or condition that the investigator believes\n may affect protocol compliance or affect the patient's signing of the ICF.", "output": {"inclusion_biomarker": [["HER2-expression"], ["HER2 positive"]], "exclusion_biomarker": []}}
-{"input": "Diffuse intrinsic pontine gliomas (DIPGs), which diffusely occupy the pons of brainstem, are\n the deadliest primary brain cancer in children. Biopsy for pathology plus radiotherapy\n remains the current standard-of-care treatment that is minimal effective. Thus, the median\n overall survival after diagnosis is just 10 months. Recent studies have identified a lysine\n 27-to-methionine (K27M) somatic mutation at histone H3 variant (H3.3), as a feature mutation\n in DIPGs. Several preclinical studies have already demonstrated H3.3-K27M as a promising\n target for immunotherapy. The researched vaccine is a cancer-treatment vaccine containing an\n H3.3-K27M targeted neoantigen peptide, that can be taken up by antigen-presenting cells\n (APCs). APCs can present the peptide with the major histocompatibility complex (MHC)\n molecules on cell surface, thereby activating neoantigen-specific T cells and triggering\n corresponding cytotoxic T cell immune responses to eliminate H3.3-K27M-expressing DIPG cells.\n The main goal of this study is investigating the safety and preliminary efficacy of the\n vaccine in treating newly-diagnosed DIPGs when the vaccine is administered in combination\n with the standard-of-care treatment.\n ;NA;\n Inclusion Criteria:\n A. First entry criteria\n 1. Age \u2265 5 years old;\n 2. Newly-diagnosed patients with DIPG appearance on MRI image;\n 3. HLA-A2 subtype;\n 4. The expected survival time exceeds 24 weeks;\n 5. The KPS score is greater than 50; B. Second entry criteria\n 1. The KPS score is greater than 50; 2. DIPG is diagnosed histologically on tumor tissue\n obtained by biopsy or surgical resection; 3. H3.3K27M mutation is detected on tumor tissue\n obtained by biopsy or surgical resection ; 4. Adequate organ functions that meet the\n following criteria: The absolute number of neutrophils: \u22651500/mm3 Platelet count: \u226575000/uL\n Hemoglobin: \u226580 g/L Creatinine\u22641.5\u00d7ULN Bilirubin\u22641.5\u00d7ULN ALT\u22643\u00d7ULN AST\u22643\u00d7ULN 5. Ability to\n comprehend and sign an informed consent form.\n Exclusion Criteria:\n 1. With past medical history of malignant tumors (except being asymptomatic for more than\n 3 years);\n 2. History of allergy to chemotherapeutics or radiosensitizers for the treatment of\n cancer in central nervous system and head/neck;\n 3. History of allergy to the vaccine and its ingredients;\n 4. Comorbidity with HIV infection and/or acute phase of hepatitis B/C;\n 5. Any progressive diseases that hinder participation in the trial;\n 6. With unstable cardiovascular diseases such as coronary heart disease, angina pectoris,\n myocardial infarction, arrhythmia et.al.;\n 7. History of uncontrolled mental illnesses;\n 8. Inability to comprehend or sign informed consent form or abide by the research\n procedures;\n 9. Other conditions believed to hinder participation in this trial at investigator'\n discretion.", "output": {"inclusion_biomarker": [["H3.3 K27M"], ["H3.3 K27M"]], "exclusion_biomarker": []}}
+{"input": "The study comprises two phases: Phase 1a and Phase 1b. The purpose of the study is to observe\n the safety\uff0c tolerability and efficacy of FS-1502.\n ;\n ;\n Inclusion Criteria:\n 1. Age \u226518 years at the time of study registration (men and women eligible);\n 2. Phase Ia dose-escalation study:\n Patients with HER2-expressing advanced malignant solid tumors who had failed to\n standard therapy(including surgery, chemotherapy, radiation therapy or biotherapy) ,\n or can not receive standard therapy, or no standard therapy is available.\n 1. HER2 expression: IHC3+, IHC2+/FISH+\n 2. HER2 expression: IHC1+, IHC2+/FISH-\n Phase Ib dose-expanded study:\n Histologically or cytologically confirmed HER2-positive patients with advanced breast\n cancer who had previously received at least 2 line therapy and had failed anti-HER2\n therapy. Details as follows:\n 1. HER2 positive (defined as IHC3+ or IHC2+/FISH+);\n 2. For patients with advanced breast cancer who had previously failed anti-HER2\n therapy and had received at least 2-line therapy, postoperative adjuvant therapy\n which could be considered as a treatment line number if disease progression\n during treatment and within 12 months after completion of treatment.\n 3. Provide evidence of disease progression or intolerable toxicity as confirmed by\n the investigator or medical history recorded prior to enrollment.\n 4. The enrollment can be based on written HER2 test report from certified local lab,\n and if patients had no HER2 test report, they should provide sufficient paraffin\n sections or fresh tumor tissue specimens which should be sent to the local lab or\n the central laboratory for testing and confirmation.\n Pivotal clinical study:\n Patients with locally advanced or relapsed metastatic breast cancer who have been\n histologically or cytologically confirmed to be HER2-positive and who have received\n two or more lines of anti-HER2 therapy in the past. Details as follows:\n 1. Her2-positive patients: Patients with IHC3+ or IHC2+ and FISH positive patients\n should provide enough tumor tissue samples within 5 years for the central\n laboratory to confirm HER2 status. Patients with HER2-positive patients are\n considered to be eligible for inclusion in this study; If the specimens provided\n are undetectable or are not available, a positive HER2 test from a local\n laboratory approved by the NMPA may be reported for entrainment.\n 2. Previous treatment with two or more lines of anti-HER2 therapy, neoadjuvant\n therapy or adjuvant therapy can be used as a treatment line number if the disease\n progresses during or within 12 months after treatment.\n 3. Evidence of investigator-confirmed or documented disease progression or\n intolerance of toxicity prior to enrollment.\n 3. The ECOG performance status must be 0 or 1.\n 4. Expected survival for at least 12 weeks.\n 5. Has adequate organ and bone marrow function: absolute neutrophil count (ANC) \u2265\n 1.0x1E9/L(without colony stimulating factor within 7 days); hemoglobin \u2265 90g/L\n (without red blood cell infusion within 14 days); platelet count \u2265 100x1E9/L(without\n thrombopoietin or thrombopoietin receptor agonists within 7 days nor platelet infusion\n within 14 days); Total bilirubin \u2264 1.5x upper limit normal (ULN), or \u2264 3x ULN if with\n Gilbert syndrome; aspartate aminotransferase (AST) and alanine aminotransferase (ALT)\n \u2264 2.5x ULN; AST and ALT \u2264 5x ULN if liver metastasis; Serum creatinine < 1.5x ULN and\n creatinine clearance \u2265 50mL/min (Cockroft-Gault formula calculation); Serum potassium\n \u22653.5 mmol/L\uff1balbumin \u2265 3g/dL; left ventricular ejection fraction (LVEF) >50%\uff1burinary\n protein \u22641+ or 24-hour urinary protein dose < 1.0g.\n 6. Has at least one non-intracranial measurable lesion by RECIST version 1.1.\n 7. Male or female patients with fertility must agree to use effective contraceptive\n methods during the study period and within 3 months of the last dose of study therapy,\n such as dual barrier contraceptive methods, condoms, oral or injectable\n contraceptives, and intrauterine devices.\n 8. Ability to understand and voluntarily sign written informed consent.\n Exclusion Criteria:\n 1. Patients who received chemotherapy, targeted therapy, radiotherapy, etc., 14 days or\n within 5 half-lives periods, whichever is shorter, prior to the start of dosing.\n Patients who received major surgery, tumor immunotherapy, or monoclonal antitumor\n therapy within 4 weeks prior to the start of dosing.\n 2. Patients who have participated in other clinical trials 4 weeks before the start of\n study drug administration or within 5 half-lives periods, whichever is shorter.\n 3. Patients previously treated with anti-HER2 ADC drugs.\n 4. Patients with central nervous system metastasis.\n 5. Clinically uncontrolled mass pleural effusion, pericardial effusion, or abdominal\n effusion (2 weeks before first administration).\n 6. Non-recovery of toxic effects from previous antitumor therapy (> NCI-CTCAE 5.0 grade\n 1) alopecia, neurotoxicity, or other toxicity that had become chronic as assessed by\n the investigator and did not affect the safety of the investigational medication was\n admitted to NCI-CTCAE 5.0 grade 2 or below.\n 7. Patients with corneal epitheliopathy (other than mild punctiform keratopathy or\n existing eye diseases affecting the evaluation of ocular toxicity after trial\n administration) or who were unwilling to stop wearing contact lenses during the study.\n 8. Patients take medications that prolong the QTc interval (mainly Ia, Ic, Class III\n antiarrhythmic drugs) or have risk factors that prolong the QTc interval, such as\n uncorrectable hypokalemia, hereditary long QT syndrome;\n 9. Cardiac function and disease conform to one of the following conditions:\n 1. Three 12-lead electrocardiogram (ECG) measurements were performed at the research\n center during the screening period, and three mean values were calculated\n according to the QTc formula adopted by the instrument, QTc > 470 ms;\n 2. New York Heart Association (NYHA)Grade \u2265 2 for congestive heart failure;\n 3. arrhythmia of clinical significance grade \u2265 2.\n 4. History of myocardial infarction or severe arteriovenous thrombosis within 6\n months.\n 10. Pregnant or lactating women;\n 11. Known allergy to any excipients of FS-1502;\n 12. Active infections requiring systemic treatment;\n 13. Persons with active hepatitis B (HBV surface antigen positive with HBV DNA exceeding\n 1000 IU/ml or meeting the research Center criteria for diagnosis of active hepatitis B\n infection) or hepatitis C (HCV RNA positive), human immunodeficiency virus infection\n (HIV positive);\n 14. Had been diagnosed with any other malignancies within the 5 years prior to study\n participation, other than early malignancies that have undergone radical treatment\n (carcinoma in situ), such as adequately treated basal or squamous cell skin cancers or\n carcinoma in situ of the cervix;\n 15. Any other clinically significant disease or condition that the investigator believes\n may affect protocol compliance or affect the patient's signing of the ICF.", "output": {"inclusion_biomarker": [["HER2 expression"], ["HER2 positive"]], "exclusion_biomarker": []}}
+{"input": "Diffuse intrinsic pontine gliomas (DIPGs), which diffusely occupy the pons of brainstem, are\n the deadliest primary brain cancer in children. Biopsy for pathology plus radiotherapy\n remains the current standard-of-care treatment that is minimal effective. Thus, the median\n overall survival after diagnosis is just 10 months. Recent studies have identified a lysine\n 27-to-methionine (K27M) somatic mutation at histone H3 variant (H3.3), as a feature mutation\n in DIPGs. Several preclinical studies have already demonstrated H3.3-K27M as a promising\n target for immunotherapy. The researched vaccine is a cancer-treatment vaccine containing an\n H3.3-K27M targeted neoantigen peptide, that can be taken up by antigen-presenting cells\n (APCs). APCs can present the peptide with the major histocompatibility complex (MHC)\n molecules on cell surface, thereby activating neoantigen-specific T cells and triggering\n corresponding cytotoxic T cell immune responses to eliminate H3.3-K27M-expressing DIPG cells.\n The main goal of this study is investigating the safety and preliminary efficacy of the\n vaccine in treating newly-diagnosed DIPGs when the vaccine is administered in combination\n with the standard-of-care treatment.\n ;NA;\n Inclusion Criteria:\n A. First entry criteria\n 1. Age \u2265 5 years old;\n 2. Newly-diagnosed patients with DIPG appearance on MRI image;\n 3. HLA-A2 subtype;\n 4. The expected survival time exceeds 24 weeks;\n 5. The KPS score is greater than 50; B. Second entry criteria\n 1. The KPS score is greater than 50; 2. DIPG is diagnosed histologically on tumor tissue\n obtained by biopsy or surgical resection; 3. H3.3K27M mutation is detected on tumor tissue\n obtained by biopsy or surgical resection ; 4. Adequate organ functions that meet the\n following criteria: The absolute number of neutrophils: \u22651500/mm3 Platelet count: \u226575000/uL\n Hemoglobin: \u226580 g/L Creatinine\u22641.5\u00d7ULN Bilirubin\u22641.5\u00d7ULN ALT\u22643\u00d7ULN AST\u22643\u00d7ULN 5. Ability to\n comprehend and sign an informed consent form.\n Exclusion Criteria:\n 1. With past medical history of malignant tumors (except being asymptomatic for more than\n 3 years);\n 2. History of allergy to chemotherapeutics or radiosensitizers for the treatment of\n cancer in central nervous system and head/neck;\n 3. History of allergy to the vaccine and its ingredients;\n 4. Comorbidity with HIV infection and/or acute phase of hepatitis B/C;\n 5. Any progressive diseases that hinder participation in the trial;\n 6. With unstable cardiovascular diseases such as coronary heart disease, angina pectoris,\n myocardial infarction, arrhythmia et.al.;\n 7. History of uncontrolled mental illnesses;\n 8. Inability to comprehend or sign informed consent form or abide by the research\n procedures;\n 9. Other conditions believed to hinder participation in this trial at investigator'\n discretion.", "output": {"inclusion_biomarker": [["HLA-A2 subtype"], ["H3.3 K27M"]], "exclusion_biomarker": []}}
 {"input": "The purpose of this study is to determine the Predictive value of a SNP signature and liquid\n biopsy in patients with natural killer T-cell lymphoma.\n ;NA;\n Inclusion Criteria:\n - biopsy proved Natural Killer T-cell Lymphoma\n - newly diagnosed patients\n Exclusion Criteria:\n - patients with biopsy samples unavailable", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
 {"input": "Talazoparib has shown clinical efficacy in breast cancer patients with germline BRCA1 or\n BRCA2 mutations. Beyond BRCA1 and BRCA2 mutations, it is plausible that talazoparib may have\n activity in patients with homologous recombination defects (HRD).\n ;\n ;\n Inclusion Criteria:\n 1. Adults \u226519 years old.\n 2. Pathologically documented breast cancer that is unresectable or metastatic\n 3. Tumor with homologous recombination deficiency (HRD) defined by\n - Germline or Somatic BRCA1/2 mutation\n - Homologous recombination repair (HRR) genes mutation\n - HRD detected through RAD51 foci formation functional assay\n - HRR genes: ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B,\n RAD51C, RAD51D, and RAD54L\n 4. Previously treated with a taxane, unless this treatment was contraindicated (whether\n in recurrent/metastatic setting or in neoadjuvant/adjuvant setting).\n 5. Previous treatment with platinum therapy in the advanced or metastatic setting is\n permitted, provided the patient did not have a progression during the platinum\n treatment. If the patient was treated with neoadjuvant or adjuvant platinum therapy,\n at least 6 months of disease-free interval is required after the last dose.\n 6. Documented radiologic progression (during or after most recent treatment or within 6\n months after completing adjuvant therapy).\n - If the patients had relapsed within 6 months after adjuvant therapy, this will be\n counted as a systemic chemotherapy for advanced or metastatic disease.\n 7. At least 3 weeks has passed since last chemotherapy treatment\n 8. At least 2 weeks has passed since last hormone therapy or radiation therapy (including\n palliative radiation).\n 9. Eastern Cooperative Oncology Group (ECOG) performance status of 0, or 1\n 10. At least one measurable lesion that can be accurately assessed at baseline by computed\n tomography (CT) (magnetic resonance imaging [MRI] where CT is not feasible) and is\n suitable for repeated assessment as per RECIST v.1.1.\n 11. Male and female subjects of reproductive/childbearing potential must agree to use a\n highly effective form of contraception or avoid intercourse during and upon completion\n of the study and for at least 7.0 months after the last dose of study treatment.\n - This study recommend \"Copper T intrauterine device\" as a highly effective methods of\n contraception (<1% failure rate)\n 12. Adequate normal organ and marrow function measured within 28 days prior to\n administration of study treatment\n - Hemoglobin \u22659.0 g/dL\n - Absolute neutrophil count (ANC) \u2265 1.5 x 109/L\n - Platelet count \u2265 75 x 109/L\n - Serum bilirubin \u2264 2.0mg/dL [This will not apply to patients with confirmed\n Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is\n predominantly unconjugated in the absence of hemolysis or hepatic pathology), who\n will be allowed only in consultation with their physician.]\n - AST (SGOT)/ALT (SGPT) \u22642.5 x institutional upper limit of normal unless liver\n metastases are present, in which case it must be \u22645x ULN\n - Adequate renal function: Serum creatinine \u22641.5mg/dL or estimated creatinine\n clearance >60 mL/min\n 13. Negative urine pregnancy test within 7 days prior to registration in premenopausal\n patients.\n 14. Ability to understand and comply with protocol during study period\n 15. Patients should sign a written informed consent before study entry\n Exclusion Criteria:\n 1. Prior treatment PARP inhibitor\n 2. However, if the patient participated in a clinical trial evaluating adjuvant PARP\n inhibitor, patient is allowed to be included in the present study if the patient\n recurred 6 months after completing PARP inhibitor. No more than three line of previous\n systemic chemotherapy, excluding neo-adjuvant and adjuvant chemotherapy. (No\n limitation on hormone therapy. Hormone therapy is not counted as previous line)\n 3. If there is a standard treatment available for metastatic breast cancer.\n 4. History of another primary malignancy except for\n - Malignancy treated with curative intent and with no known active disease \u22653 years\n - contralateral breast cancer\n - Adequately treated non-melanoma skin cancer or lentigo malignancy without\n evidence of disease\n - Adequately treated carcinoma in situ without evidence of disease\n 5. Patients with GI tract disease resulting in an inability to take oral medication,\n malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures\n affecting absorption, uncontrolled GI disease (e.g., Crohn's disease, ulcerative\n colitis)\n 6. History of leptomeningeal carcinomatosis\n 7. Brain metastases or spinal cord compression.\n - Patients with symptomatic uncontrolled brain metastases. A scan to confirm the\n absence of brain metastases is not required. The patient can receive a stable dose of\n corticosteroids before and during the study as long as these were started at least 4\n weeks prior to treatment. Patients with spinal cord compression unless considered to\n have received definitive treatment for this and evidence of clinically stable disease\n for 28 days\n 8. active infection or immunocompromised patients including tuberculosis (clinical\n evaluation that includes clinical history, physical examination and radiographic\n findings, and TB testing in line with local practice), hepatitis B , hepatitis C, or\n human immunodeficiency virus (positive HIV 1/2 antibodies).\n - Subjects with simple HBV carrier, a past or resolved HBV infection (defined as the\n presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible.\n Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain\n reaction is negative for HCV RNA.\n 9. Patients who have a known immediate or delayed hypersensitivity reaction or\n idiosyncrasy to drugs chemically related to any of the study agents or their\n excipients.\n 10. Female patients who are pregnant or breastfeeding.\n 11. Judgment by the investigator that the patient is unsuitable to participate in the\n study and the patient is unlikely to comply with study procedures, restrictions and\n requirements.", "output": {"inclusion_biomarker": [["BRCA1 mutation (germline)"], ["BRCA2 mutation (germline)"], ["BRCA1 mutation (somatic)"], ["BRCA2 mutation (somatic)"], ["ATM mutation"], ["BARD1 mutation"], ["BRIP1 mutation"], ["CDK12 mutation"], ["CHEK1 mutation"], ["CHEK2 mutation"], ["FANCL mutation"], ["PALB2 mutation"], ["PPP2R2A mutation"], ["RAD51B mutation"], ["RAD51C mutation"], ["RAD51D mutation"], ["RAD54L mutation"]], "exclusion_biomarker": []}}
-{"input": "This clinical trial is a Phase 1-2, open-label, sequential-group, dose-escalation and\n cohort-expansion study evaluating the safety, pharmacokinetics (PK), pharmacodynamics, and\n antitumor activity of Zotatifin (eFT226) in subjects with selected advanced solid tumor\n malignancies.\n ;\n ;\n Key Criteria:\n Parts 1a and 1b (Dose Escalation + Fulvestrant):\n - Patient has histological or cytological confirmation of breast cancer.\n - Patient has metastatic disease or locoregionally recurrent disease which is refractory\n or intolerant to existing therapy(ies) known to provide clinical benefit.\n - Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows:\n - Minimum of one prior line of therapy for advanced/metastatic disease.\n - Maximum of five prior lines of therapy for advanced/metastatic disease.\n - Recurrence or progression on at least one line of endocrine therapy in the\n advanced/metastatic disease setting.\n - Prior treatment has included a CDK4/6 inhibitor.\n - Tumor is ER+ (defined as ER IHC staining > 0%).\n Cohort EMNK:\n - Patient has undergone treatment with platinum-based chemotherapy and an anti-PD-1/L1\n agent, if appropriate.\n - Tumor has a known KRAS-activating mutation; Patients with KRAS G12C mutations are\n excluded.\n Cohort EMBF:\n - Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows:\n - Minimum of one prior line of therapy for advanced/metastatic disease.\n - Maximum of five prior lines of therapy for advanced/metastatic disease.\n - Recurrence or progression on at least one line of endocrine therapy in the\n advanced/metastatic disease setting, which may include combination therapy (eg,\n with a CDK4/6 inhibitor).\n - Tumor is ER+ (defined as ER IHC staining > 0%) and has FGFR amplification.\n Cohort EMBH:\n - Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows:\n - Minimum of one prior line of therapy for advanced/metastatic disease.\n - Minimum of one line of HER2-directed therapy Note: Prior treatment with CDK4/6\n inhibitors is permitted.\n - Tumor is ER+ (defined as ER IHC staining > 0%) and HER2+ (defined as HER2 3+ IHC\n staining or HER2 2+ and FISH+).\n Cohort ECNS:\n - Patient has histologically or cytologically confirmed stage IIIB (pleural or\n pericardial effusion) or stage IV NSCLC.\n - Patient has undergone treatment with platinum-based chemotherapy and an anti-PD-1/L1\n agent, if appropriate. Note: Patients who have declined approved therapy(ies) or who\n per treating physician are not eligible for approved therapy(ies) (eg, due to\n intolerance) may be eligible following discussion with the Medical Monitor.\n - Tumor has a known G12C KRAS-activating mutation. Note: Patients who have been\n previously treated with KRAS-specific therapy are excluded.\n Cohort ECBF:\n - Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows:\n - Minimum of one prior line of therapy for advanced/metastatic disease.\n - Maximum of five prior lines of therapy for advanced/metastatic disease.\n - Recurrence or progression on at least one line of endocrine therapy in the\n advanced/metastatic disease setting.\n - Prior treatment has included a CDK4/6 inhibitor.\n - Tumor is ER+ (defined as ER IHC staining > 0%).\n Cohort ECBF+A:\n - Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows:\n - Minimum of one prior line of therapy for advanced/metastatic disease.\n - Maximum of five prior lines of therapy for advanced/metastatic disease.\n - Recurrence or progression on at least one line of endocrine therapy in the\n advanced/metastatic disease setting.\n - Tumor is ER+ (defined as ER IHC staining > 0%) and HER2- (defined as absence of HER2\n 3+ IHC staining and/or absence of FISH+).\n Cohort ECBT:\n - Patient has progressed after treatment with at least one approved anti-HER2 agent and\n has been administered at least one line of chemotherapy.\n - Tumor is HER2+ (defined as HER2 3+ IHC staining or HER2 2+ and FISH+). Cohorts EMBF,\n EMBH, ECBF, ECBF+A: There is no limit on the number of lines of prior endocrine\n therapies.\n Cohort ECBF-D1:\n - Patient has metastatic disease or locoregionally recurrent disease which is refractory\n or intolerant to existing therapy(ies) known to provide clinical benefit.\n - Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows:\n - Minimum of one prior line of therapy for advanced/metastatic disease.\n - Maximum of five prior lines of therapy for advanced/metastatic disease.\n - Recurrence or progression on at least one line of endocrine therapy in the\n advanced/metastatic disease setting.\n - Prior treatment has included a CDK4/6 inhibitor.\n - Tumor is ER+ (defined as ER IHC staining > 0%).\n - Tumor has amplification of Cyclin D1 as determined by next generation sequencing or in\n situ hybridization.", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
+{"input": "This clinical trial is a Phase 1-2, open-label, sequential-group, dose-escalation and\n cohort-expansion study evaluating the safety, pharmacokinetics (PK), pharmacodynamics, and\n antitumor activity of Zotatifin (eFT226) in subjects with selected advanced solid tumor\n malignancies.\n ;\n ;\n Key Criteria:\n Parts 1a and 1b (Dose Escalation + Fulvestrant):\n - Patient has histological or cytological confirmation of breast cancer.\n - Patient has metastatic disease or locoregionally recurrent disease which is refractory\n or intolerant to existing therapy(ies) known to provide clinical benefit.\n - Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows:\n - Minimum of one prior line of therapy for advanced/metastatic disease.\n - Maximum of five prior lines of therapy for advanced/metastatic disease.\n - Recurrence or progression on at least one line of endocrine therapy in the\n advanced/metastatic disease setting.\n - Prior treatment has included a CDK4/6 inhibitor.\n - Tumor is ER+ (defined as ER IHC staining > 0%).\n Cohort EMNK:\n - Patient has undergone treatment with platinum-based chemotherapy and an anti-PD-1/L1\n agent, if appropriate.\n - Tumor has a known KRAS-activating mutation; Patients with KRAS G12C mutations are\n excluded.\n Cohort EMBF:\n - Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows:\n - Minimum of one prior line of therapy for advanced/metastatic disease.\n - Maximum of five prior lines of therapy for advanced/metastatic disease.\n - Recurrence or progression on at least one line of endocrine therapy in the\n advanced/metastatic disease setting, which may include combination therapy (eg,\n with a CDK4/6 inhibitor).\n - Tumor is ER+ (defined as ER IHC staining > 0%) and has FGFR amplification.\n Cohort EMBH:\n - Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows:\n - Minimum of one prior line of therapy for advanced/metastatic disease.\n - Minimum of one line of HER2-directed therapy Note: Prior treatment with CDK4/6\n inhibitors is permitted.\n - Tumor is ER+ (defined as ER IHC staining > 0%) and HER2+ (defined as HER2 3+ IHC\n staining or HER2 2+ and FISH+).\n Cohort ECNS:\n - Patient has histologically or cytologically confirmed stage IIIB (pleural or\n pericardial effusion) or stage IV NSCLC.\n - Patient has undergone treatment with platinum-based chemotherapy and an anti-PD-1/L1\n agent, if appropriate. Note: Patients who have declined approved therapy(ies) or who\n per treating physician are not eligible for approved therapy(ies) (eg, due to\n intolerance) may be eligible following discussion with the Medical Monitor.\n - Tumor has a known G12C KRAS-activating mutation. Note: Patients who have been\n previously treated with KRAS-specific therapy are excluded.\n Cohort ECBF:\n - Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows:\n - Minimum of one prior line of therapy for advanced/metastatic disease.\n - Maximum of five prior lines of therapy for advanced/metastatic disease.\n - Recurrence or progression on at least one line of endocrine therapy in the\n advanced/metastatic disease setting.\n - Prior treatment has included a CDK4/6 inhibitor.\n - Tumor is ER+ (defined as ER IHC staining > 0%).\n Cohort ECBF+A:\n - Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows:\n - Minimum of one prior line of therapy for advanced/metastatic disease.\n - Maximum of five prior lines of therapy for advanced/metastatic disease.\n - Recurrence or progression on at least one line of endocrine therapy in the\n advanced/metastatic disease setting.\n - Tumor is ER+ (defined as ER IHC staining > 0%) and HER2- (defined as absence of HER2\n 3+ IHC staining and/or absence of FISH+).\n Cohort ECBT:\n - Patient has progressed after treatment with at least one approved anti-HER2 agent and\n has been administered at least one line of chemotherapy.\n - Tumor is HER2+ (defined as HER2 3+ IHC staining or HER2 2+ and FISH+). Cohorts EMBF,\n EMBH, ECBF, ECBF+A: There is no limit on the number of lines of prior endocrine\n therapies.\n Cohort ECBF-D1:\n - Patient has metastatic disease or locoregionally recurrent disease which is refractory\n or intolerant to existing therapy(ies) known to provide clinical benefit.\n - Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows:\n - Minimum of one prior line of therapy for advanced/metastatic disease.\n - Maximum of five prior lines of therapy for advanced/metastatic disease.\n - Recurrence or progression on at least one line of endocrine therapy in the\n advanced/metastatic disease setting.\n - Prior treatment has included a CDK4/6 inhibitor.\n - Tumor is ER+ (defined as ER IHC staining > 0%).\n - Tumor has amplification of Cyclin D1 as determined by next generation sequencing or in\n situ hybridization.", "output": {"inclusion_biomarker": [["ER positive"], ["KRAS activating mutation"], ["ER positive", "FGFR amplification"], ["ER positive", "HER2 positive"], ["KRAS G12C"], ["ER positive", "HER2 negative"], ["HER2 positive"]], "exclusion_biomarker": [["KRAS G12C"]]}}
 {"input": "This first-time-in-human (FTIH) study will evaluate the safety, tolerability,\n pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of escalating\n doses of GSK6097608 given as monotherapy and in combination with dostarlimab in participants\n with advanced solid tumors. In addition, dostarlimab will be given as monotherapy and in\n combination with GSK6097608 and with GSK4428859A (EOS884448) in Japanese and Chinese\n participants. Drug name mentioned as GSK4428859A and EOS884448 are interchangeable for the\n same compound. In the rest of the document, the drug will be referred to as GSK4428859A\n (EOS884448).\n ;NA;\n Inclusion Criteria:\n - Adults 18 years of age or older (or >=20 years of age in Arm-A Japan, Arm-D Japan, Arm\n E-Japan, and Arm F-Japan);\n - Female participants of childbearing potential must agree to use a highly effective\n form of contraception;\n - Histological or cytological documentation of locally advanced, recurrent, or\n metastatic solid malignancy;\n - Disease that has progressed after standard therapy for the specific tumor type, or for\n which standard therapy has proven to be ineffective, intolerable, or is considered\n inappropriate, or if no further standard therapy exists;\n - Participants in a PK/PD cohort must provide fresh tumor biopsies.\n - Eastern cooperative oncology group (ECOG) performance status (PS) 0 to 1\n - Life expectancy of at least 12 weeks.\n - Adequate organ function as determined by laboratory assessments.\n - Adequate cardiac ejection fraction as measured by echocardiogram.\n - Arm A-Japan, Arm D-Japan, Arm E-Japan, and Arm F-Japan only: lives in Japan and is\n racially Japanese, defined as all biological grandparents being Japanese.\n - Arm A-China, Arm B-China, Arm D-China, Arm E-China and Arm F-China only: is of Chinese\n descent and lives in China.\n - Arm D, Arm E, and Arm F only: has been deemed suitable for assigned treatment based on\n assessment by the investigator.\n Exclusion Criteria:\n - Prior anti-cancer treatment including investigational agents, immune checkpoint\n inhibitors, chemotherapy, targeted therapy, and biological therapy: within 4 weeks or\n 5 half-lives of the drug, whichever is shorter.\n - Prior allogenic or autologous bone marrow transplantation or other solid organ\n transplantation.\n - Toxicity from previous anticancer treatment, including; greater than or equal to Grade\n 3 immune-mediated toxicity considered related to prior immunotherapy and that led to\n treatment discontinuation; or toxicity related to prior treatment that has not\n resolved; or myocarditis of any grade considered related to prior immuno-oncology\n therapy that led to treatment discontinuation.\n - Known additional malignancy that progressed or required active treatment within the\n last 2 years.\n - Uncontrolled or symptomatic central nervous system (CNS) metastases and/or\n carcinomatous meningitis.\n - Active autoimmune disease that has required systemic disease-modifying or\n immunosuppressive treatment within the last 2 years.\n - Concurrent medical condition requiring the use of systemic immunosuppressive\n treatment.\n - Cirrhosis or current unstable liver or biliary disease per investigator assessment.\n - Active infection requiring systemic treatment, known human immunodeficiency virus\n infection, or positive test for hepatitis B surface antigen (HBsAg) or hepatitis C\n virus (HCV)\n - Prolonged QT as measured by electrocardiogram.\n - Allergen desensitization therapy within 4 weeks of starting study intervention.\n - History of hypersensitivity to any of the study interventions or their excipients.\n - History or evidence of significant cardiovascular (CV) risk.\n - Recent history (within 6 months) of uncontrolled symptomatic ascites or pleural\n effusions.\n - History of idiopathic pulmonary fibrosis; interstitial lung disease; organizing\n pneumonia; noninfectious pneumonitis that required steroids, or evidence of active,\n noninfectious pneumonitis.\n - Pregnant or lactating woman.\n - Receipt of live vaccine within 30 days of the start of study intervention.\n - Receipt of transfusion of blood products or administration of colony-stimulating\n factors within 14 days before the first dose of study intervention.\n - Major surgery less than 4 weeks before the first dose of study intervention.\n - Known drug or alcohol abuse.", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
-{"input": "The main objective of this trial is to explore the activity of chlorambucil, an alkylating\n agent commonly used in chronic lymphocytic leukemia treatment, in metastatic patients, gBRCA,\n including VUS, or DDR mutated, previously treated with a platinum-containing chemotherapy.\n ;\n ;\n Inclusion Criteria:\n 1. Pathologically confirmed pancreatic adenocarcinoma\n 2. Age \u2265 18 years\n 3. ECOG PS 0-2\n 4. Stage IV disease\n 5. Identified genetic aberrations that are associated with homologous recombination\n deficiency (HRD)\n 1. Cohort A: Documented mutation in gBRCA1 or gBRCA2 that is predicted to be\n deleterious or suspected deleterious\n 2. Cohort B: BRCA1 or BRCA2 mutations that are considered to be of uncertain/unknown\n significance (VUS)\n 3. Cohort C: Patients with other identified genetic aberrations that are associated\n with HRD\n 6. Adequate PFS during previous platinum-based chemotherapy for at least 4 months before\n progression\n 7. Screening laboratory values:\n Leukocytes > 3000/mmc Thrombocytes > 150000/mmc Hemoglobin > 10 g/dl Creatinine <2.0\n times upper normal limit (unless normal creatinine clearance). Total bilirubin < 2.0\n times upper normal limit (unless due to Gilbert's syndrome).\n Alanine aminotransferase (ALT) < 3.0 times upper normal limit.\n 8. Able to take oral medication\n 9. Progression during or after platinum-based chemotherapy\n 10. Other prior chemotherapy apart from first-line treatment for pancreatic cancer, are\n allowed, including maintenance treatment with PARP inhibitors\n 11. More than 2 weeks since prior chemotherapy end\n 12. Signed written informed consent\n 13. QTc <450 msec or QTc <480 msec for patients with bundle branch block\n Exclusion Criteria:\n 1. Clinically significant cardiac disease including unstable angina, acute myocardial\n infarction within 6 months prior to screening, congestive heart failure, and\n arrhythmia requiring therapy, with the exception of extra systoles or minor conduction\n abnormalities\n 2. Active and uncontrolled bacterial, viral, or fungal infection(s) requiring systemic\n therapy\n 3. Vaccination with vaccines called \"live\", since this treatment causes a drop of\n immunity defenses and a serious infection could result fatal.\n 4. History of seizure, head trauma and treatment with anti-epileptogenic drugs\n 5. Hypersensitivity to chlorambucil or to any excipients, in particular lactose\n 6. Recent radiotherapy (at least 4 weeks) or previous treatment with other cytotoxic\n agents\n 7. BRCA-mutated advanced pancreatic cancer who did not undergo maintenance with olaparib\n after platinum-based chemotherapy\n 8. Mismatch repair (MMR)/high levels of microsatellite instability (MSI-H), or high\n levels of tumor mutational burden (TMB) pancreatic cancer who did not undergo\n immunotherapy with pembrolizumab monotherapy or any other anti-PD1 agent\n 9. Concomitant PARP inhibitors therapy\n 10. Life expectancy less than 3 months, in the opinion of the investigator\n 11. Other past or current malignancy. Subjects who have been free of malignancy for at\n least 5 years, or have a history of completely resected non-melanoma skin cancer, or\n successfully treated in situ carcinoma are eligible\n 12. Symptomatic duodenal stenosis\n 13. CT contrast medium allergy and claustrophobia to RM investigation\n 14. Any significant medical condition laboratory abnormality, or psychiatric illness that\n would prevent the subject from participating in the study\n 15. Any condition including the presence of laboratory abnormalities, which places the\n subject at unacceptable risk if he/she were to participate in the study\n 16. Any condition that confounds the ability to interpret data from the study\n 17. Any familiar, sociologic or geographic conditions that can potentially interfere with\n the adhesion to the protocol or to the follow-up\n 18. Pregnant or nursing. Adequate contraception is defined as oral hormonal birth control,\n intrauterine device, and male partner sterilization (if male partner is sole partner\n for that subject) and the double barrier method (condom or occlusive cap plus\n spermicidal agent).\n 19. Concurrent treatment with other experimental drugs", "output": {"inclusion_biomarker": [["gBRCA1 mutation"], ["gBRCA2 mutation"], ["BRCA1 VUS"], ["BRCA2 VUS"], ["Genetic aberrations associated with HRD"]], "exclusion_biomarker": [["BRCA mutation"], ["MSI-H"], ["TMB-H"]]}}
+{"input": "The main objective of this trial is to explore the activity of chlorambucil, an alkylating\n agent commonly used in chronic lymphocytic leukemia treatment, in metastatic patients, gBRCA,\n including VUS, or DDR mutated, previously treated with a platinum-containing chemotherapy.\n ;\n ;\n Inclusion Criteria:\n 1. Pathologically confirmed pancreatic adenocarcinoma\n 2. Age \u2265 18 years\n 3. ECOG PS 0-2\n 4. Stage IV disease\n 5. Identified genetic aberrations that are associated with homologous recombination\n deficiency (HRD)\n 1. Cohort A: Documented mutation in gBRCA1 or gBRCA2 that is predicted to be\n deleterious or suspected deleterious\n 2. Cohort B: BRCA1 or BRCA2 mutations that are considered to be of uncertain/unknown\n significance (VUS)\n 3. Cohort C: Patients with other identified genetic aberrations that are associated\n with HRD\n 6. Adequate PFS during previous platinum-based chemotherapy for at least 4 months before\n progression\n 7. Screening laboratory values:\n Leukocytes > 3000/mmc Thrombocytes > 150000/mmc Hemoglobin > 10 g/dl Creatinine <2.0\n times upper normal limit (unless normal creatinine clearance). Total bilirubin < 2.0\n times upper normal limit (unless due to Gilbert's syndrome).\n Alanine aminotransferase (ALT) < 3.0 times upper normal limit.\n 8. Able to take oral medication\n 9. Progression during or after platinum-based chemotherapy\n 10. Other prior chemotherapy apart from first-line treatment for pancreatic cancer, are\n allowed, including maintenance treatment with PARP inhibitors\n 11. More than 2 weeks since prior chemotherapy end\n 12. Signed written informed consent\n 13. QTc <450 msec or QTc <480 msec for patients with bundle branch block\n Exclusion Criteria:\n 1. Clinically significant cardiac disease including unstable angina, acute myocardial\n infarction within 6 months prior to screening, congestive heart failure, and\n arrhythmia requiring therapy, with the exception of extra systoles or minor conduction\n abnormalities\n 2. Active and uncontrolled bacterial, viral, or fungal infection(s) requiring systemic\n therapy\n 3. Vaccination with vaccines called \"live\", since this treatment causes a drop of\n immunity defenses and a serious infection could result fatal.\n 4. History of seizure, head trauma and treatment with anti-epileptogenic drugs\n 5. Hypersensitivity to chlorambucil or to any excipients, in particular lactose\n 6. Recent radiotherapy (at least 4 weeks) or previous treatment with other cytotoxic\n agents\n 7. BRCA-mutated advanced pancreatic cancer who did not undergo maintenance with olaparib\n after platinum-based chemotherapy\n 8. Mismatch repair (MMR)/high levels of microsatellite instability (MSI-H), or high\n levels of tumor mutational burden (TMB) pancreatic cancer who did not undergo\n immunotherapy with pembrolizumab monotherapy or any other anti-PD1 agent\n 9. Concomitant PARP inhibitors therapy\n 10. Life expectancy less than 3 months, in the opinion of the investigator\n 11. Other past or current malignancy. Subjects who have been free of malignancy for at\n least 5 years, or have a history of completely resected non-melanoma skin cancer, or\n successfully treated in situ carcinoma are eligible\n 12. Symptomatic duodenal stenosis\n 13. CT contrast medium allergy and claustrophobia to RM investigation\n 14. Any significant medical condition laboratory abnormality, or psychiatric illness that\n would prevent the subject from participating in the study\n 15. Any condition including the presence of laboratory abnormalities, which places the\n subject at unacceptable risk if he/she were to participate in the study\n 16. Any condition that confounds the ability to interpret data from the study\n 17. Any familiar, sociologic or geographic conditions that can potentially interfere with\n the adhesion to the protocol or to the follow-up\n 18. Pregnant or nursing. Adequate contraception is defined as oral hormonal birth control,\n intrauterine device, and male partner sterilization (if male partner is sole partner\n for that subject) and the double barrier method (condom or occlusive cap plus\n spermicidal agent).\n 19. Concurrent treatment with other experimental drugs", "output": {"inclusion_biomarker": [["gBRCA1 deleterious mutation"], ["gBRCA2 deleterious mutation"], ["BRCA1 uncertain significance"], ["BRCA2 uncertain significance"], ["Genetic aberrations associated with HRD"]], "exclusion_biomarker": [["BRCA mutation"], ["Mismatch repair"], ["microsatellite instability-high"], ["tumor mutational burden-high"]]}}
 {"input": "The purpose of this clinical trial is to assess the feasibility, safety and efficacy of\n 4SCAR-CD44v6 T-cell therapy targeting multiple cancers. The study also aims to learn more\n about the function of the CD44v6 CAR-T cells and their persistency in the patients.\n ;\n ;\n Inclusion Criteria:\n 1. Age older than 6 months.\n 2. Confirmed expression of CD44v6 in tumor specimens by immuno-histochemical staining or\n flow cytometry.\n 3. Karnofsky performance status (KPS) score is higher than 70 and life expectancy > 3\n months.\n 4. Adequate bone marrow, liver and renal function as assessed by the following laboratory\n requirements: cardiac ejection fraction \u2265 50%, oxygen saturation \u2265 90%, creatinine \u2264\n 2.5 \u00d7 upper limit of normal, aspartate aminotransferase (AST) and alanine\n aminotransferase (ALT) \u2264 3 \u00d7 upper limit of normal, total bilirubin \u2264 2.0mg/dL.\n 5. Hgb\u226580g/L.\n 6. No cell separation contraindications.\n 7. Abilities to understand and the willingness to provide written informed consent.\n Exclusion Criteria:\n 1. Sever illness or medical condition, which would not permit the patient to be managed\n according to the protocol, including active uncontrolled infection.\n 2. Active bacterial, fungal or viral infection not controlled by adequate treatment.\n 3. Known HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.\n 4. Pregnant or nursing women may not participate.\n 5. Use of glucocorticoid for systemic therapy within one week prior to entering the\n trial.\n 6. Receive treatment related to CD44v6 targeted therapy.\n 7. Patients, in the opinion of investigators, may not be able to comply with the study.", "output": {"inclusion_biomarker": [["CD44v6 expression"]], "exclusion_biomarker": []}}
 {"input": "BioEXALK is a prospective study evaluating the biological characteristics of advanced\n ALK-rearranged NSCLC treated with next generation TKIs in first line, included in the\n national EXPLORE ALK cohort (GFPC 03-2019), a non-interventional, national, multi-center\n cohort of ALK-rearranged NSCLC patients.\n BioExALK study will be proposed to every patient included in the Explore ALK GFPC 03-2019\n study.\n Biological analysis will be performed on tumor tissue at diagnosis and at the time of disease\n progression when available and on circulating tumor DNA (ctDNA).\n For plasma testing, after obtained patient consent, blood samples will be taken and analyzed\n at the L\u00e9on B\u00e9rard Center (Lyon).\n Biological analysis on tissue obtained at diagnosis and at disease progression will be\n collected and be sent for centralized analysis to the Rouen University Hospital.\n ;\n ;\n Inclusion Criteria:\n - Stage IIIB/IV NSCLC non eligible to locoregional treatment with curative intent\n - ALK rearrangement confirmed by IHC and/or FISH or NGS according to local methods\n - Patient included in the EXPLORE ALK study\n - Age > or = 18 years\n - Patient treated with first-line new generation ALKi\n - Patient agrees to sign an informed consent form and to collect blood samples at\n inclusion, first tumor evaluation and progression and for whom tumor biopsy at\n diagnosis is available\n - Patient enrolled in the french National Health Insurance program or with a third-\n party payer\n Exclusion Criteria:\n - Patients who do not wish to participate in Bioexalk\n - Patients under guardianship", "output": {"inclusion_biomarker": [["ALK rearrangement"]], "exclusion_biomarker": []}}
 {"input": "This phase I trial studies the biological effects of DS-8201a on patients with HER2 positive\n cancer that has spread to other places in the body (advanced). DS-8201a works by binding to a\n protein called HER2 that is present on the surface of tumor cells. This allows DS-8201a to\n kill the tumor cells by damaging their deoxyribonucleic acid (DNA), resulting in tumor cell\n death. This study looks at how DS-8201a may affect the levels of certain proteins and immune\n cells in tumors and how well the drug works against tumor cells by examining cells from a\n small piece tumor taken before and after DS-8201a is given.\n ;\n ;\n Inclusion Criteria:\n - Patients must have histologically confirmed malignancy that is metastatic or\n unresectable and for which standard curative or palliative measures do not exist or\n are no longer effective\n - Patients must have measurable or evaluable disease\n - Age >= 18 years of age\n - Patients must have HER2-positive or HER2-expressing tumors as defined by Clinical\n Laboratory Improvement Act (CLIA)-certified labs. Patients must have either:\n - A tumor HER2 immunohistochemistry (IHC) score of 1+ or greater (as determined by\n a CLIA-certified IHC test, per criteria specified) or\n - A tumor with HER2 amplification (as determined by CLIA-certified in situ\n hybridization (ISH) or a CLIA-certified next-generation sequencing assay)\n - Patients with HER2 mutations are eligible, as are patients with HER2-positive breast\n cancer\n - Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =< 1\n (Karnofsky >= 70%)\n - Absolute neutrophil count >= 1,500/mcL (within 8 days of enrollment)\n - Platelets >= 100,000/mcL (within 8 days of enrollment)\n - Leukocytes >= 3,000/mcL (within 8 days of enrollment)\n - Hemoglobin >= 9 g/dL (>= 8.0 g/dL for gastric cancer [GC] only) (within 8 days of\n enrollment)\n - Serum albumin >= 2.5 g/dL (GC only) (within 8 days of enrollment)\n - Total bilirubin =< 1.5 x institutional upper limit of normal (=< 3 x upper limit of\n normal in the presence of documented Gilbert's syndrome or liver metastases at\n baseline) (within 8 days of enrollment)\n - Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase\n [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])\n =< 3 x institutional upper limit of normal OR =< 5 x institutional upper limit of\n normal for patients with liver metastases at baseline (within 8 days of enrollment)\n - Creatinine =< 1.5 x institutional upper limit of normal OR creatinine clearance >= 60\n mL/min/1.73 m^2 for patients with creatinine levels above 1.5 x institutional normal\n (within 8 days of enrollment)\n - No transfusions with red blood cells or platelets are allowed within 1 week prior to\n screening assessment\n - No administration of granulocyte colony-stimulating factor (G-CSF) is allowed within 1\n week prior to screening assessment\n - International normalized ratio (INR)/prothrombin time (PT) and either partial\n thromboplastin or activated partial thromboplastin time (aPTT) =< 1.5 x upper limit of\n normal (ULN)\n - Ability to understand and the willingness to sign a written informed consent document\n - Willingness to provide blood samples for research purposes\n - Patients must have a lesion or lesions amenable to biopsy and must be willing to\n undergo 3 core needle biopsy procedures for research purposes\n - Patients must have left ventricular ejection fraction (LVEF) >= 50% by either an\n echocardiogram (ECHO), multigated acquisition (MUGA), or cardiac MRI scan within 28\n days prior to enrollment\n - Patients who are human immunodeficiency virus (HIV) positive may participate IF they\n meet the following eligibility requirements:\n - They must be stable on their anti-retroviral regimen, and they must be healthy\n from an HIV perspective\n - They must have a CD4 count of greater than 250 cells/mcL over the past 6 months\n on this same anti-retroviral regimen and must not have had a CD4 count < 200\n cells/uL over the past 2 years, unless it was deemed related to the cancer and/or\n immunotherapy-induced bone marrow suppression\n - For patients who have received chemotherapy in the past 6 months, a CD4\n count < 250 cells/ul during chemotherapy is permitted as long as viral loads\n were undetectable during this same chemotherapy\n - They must have an undetectable viral load and a CD4 count >= 250 cells/uL within\n 8 days of enrollment\n - They must not be currently receiving prophylactic therapy for an opportunistic\n infection and must not have had an opportunistic infection within the past 6\n months HIV-infected patients should be monitored every 12 weeks for viral load\n and CD4 counts\n - For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral\n load must be undetectable on suppressive therapy, if indicated\n - Patients with a history of hepatitis C virus (HCV) infection must have been treated\n and cured. For patients with HCV infection who are currently on treatment, they are\n eligible if they have an undetectable HCV viral load\n - Patients with treated brain metastases are eligible if follow-up brain imaging after\n central nervous system (CNS)-directed therapy shows no evidence of progression for >=\n 1 month after treatment of the brain metastases\n - Patients with a prior or concurrent malignancy whose natural history or treatment does\n not have the potential to interfere with the safety or efficacy assessment of the\n investigational regimen are eligible for this trial\n - The effects of DS-8201a on the developing human fetus are unknown. For this reason and\n because HER2 antibodies conjugated to topoisomerase 1 inhibitor agents are known to be\n teratogenic, women of child-bearing potential and men must agree to use adequate\n contraception (hormonal or barrier method of birth control or abstinence) prior to\n study entry and for the duration of study participation and for at least 7 months\n after the last dose of study drug. Should a woman become pregnant or suspect she is\n pregnant while she or her partner is participating in this study, she should inform\n her treating physician immediately. Men treated or enrolled on this protocol must also\n agree to use adequate contraception prior to the study, for the duration of study\n participation, and 4 months after completion of DS-8201a administration\n - Women of non-child-bearing potential defined as pre-menopausal females with a\n documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of\n spontaneous amenorrhea (in questionable cases, a blood sample with simultaneous\n follicle-stimulating hormone [FSH] > 40 mIU/mL and estradiol < 40 pg/mL [< 147 pmol/L]\n is confirmatory) are eligible. Females on hormone replacement therapy (HRT) and whose\n menopausal status is in doubt will be required to use one of the contraception methods\n outlined for women of child-bearing potential if they wish to continue their HRT\n during the study. Otherwise, they must discontinue HRT to allow confirmation of\n post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4\n weeks will elapse between the cessation of therapy and the blood draw; this interval\n depends on the type and dosage of HRT. Following confirmation of their post-menopausal\n status, they can resume use of HRT during the study without use of a contraceptive\n method\n - Subjects must not freeze, donate, or retrieve for their own use ova or sperm starting\n at screening, throughout the study period, and for at least 4.5 months after the final\n study drug administration. Preservation of sperm or ova should be considered prior to\n enrollment in this study\n - Because there is an unknown but potential risk for adverse events in nursing infants\n secondary to treatment of the mother with DS-8201a, breastfeeding should be\n discontinued if the mother is treated with DS-8201a\n Exclusion Criteria:\n - Patients who have had:\n - Chemotherapy (including antibody drug therapy, retinoid therapy, hormonal therapy\n for cancer) within:\n - 4 weeks or five half-lives, whichever is shorter, for small-molecule\n targeted agents such as 5-fluorouracil-based agents, folinate agents, weekly\n paclitaxel or\n - 6 weeks for nitrosoureas or mitomycin C or\n - Immunotherapy, including monoclonal antibody therapy, within 4 weeks\n - Patients with any of the following pulmonary-related illnesses:\n - A history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that\n required steroids, current ILD/pneumonitis, or for whom suspected ILD/pneumonitis\n cannot be ruled out by imaging at screening\n - Clinically severe pulmonary compromise resulting from intercurrent pulmonary\n illnesses including, but not limited to, any underlying pulmonary disorder (i.e.,\n pulmonary emboli within three months of the study enrollment, severe asthma,\n severe chronic obstructive pulmonary disease [COPD] grade 3-4 per Global\n Initiative for Obstructive Lung Disease [GOLD] criteria, restrictive lung\n disease, pleural effusion, etc.), and any autoimmune, connective tissue, or\n inflammatory disorders with potential pulmonary involvement (i.e., Rheumatoid\n arthritis, Sjogren's, sarcoidosis, etc.), or prior pneumonectomy.\n - Patients who have had radiation therapy within 4 weeks (or palliative stereotactic\n radiation therapy within 2 weeks)\n - Patients who have had a major surgery within 4 weeks\n - Patients who are receiving any other investigational agents\n - Patients with a medical history of myocardial infarction within 6 months before\n enrollment, symptomatic congestive heart failure (CHF) (New York Heart Association\n class II to IV), or with troponin levels consistent with myocardial infarction (as\n defined according to the assay manufacturer) 28 days prior to enrollment\n - History of allergic reactions attributed to compounds of similar chemical or biologic\n composition to DS-8201a (e.g., other topoisomerase I inhibitors) or the inactive\n ingredients in the drug product\n - Patients who have a history of severe hypersensitivity reactions to other monoclonal\n antibodies\n - Patients with a Fridericia's formula-corrected QT interval (QTcF) prolongation to >\n 470 ms (females) or > 450 ms (males) based on average of the screening triplicate\n 12-lead electrocardiogram (ECG)\n - Patients with spinal cord compression or clinically active central nervous system\n metastases, defined as untreated and symptomatic, or requiring therapy with\n corticosteroids or anticonvulsants to control associated symptoms\n - Patients with an uncontrolled infection requiring IV antibiotics, antivirals, or\n antifungals\n - Patients with unresolved toxicities from previous anticancer therapy, defined as\n toxicities (other than alopecia) not yet resolved to grade =< 1 or baseline. Subjects\n with chronic grade 2 toxicities (e.g., grade 2 chemotherapy-induced neuropathy) may be\n eligible per the discretion of the investigator after consultation with the sponsor\n medical monitor or designee. Subjects should no longer be symptomatic nor require\n treatment with corticosteroids or anticonvulsants and must have recovered from the\n acute toxic effect of radiotherapy\n - Patients with substance abuse or any other medical conditions that would increase the\n safety risk to the subject or interfere with participation of the subject or\n evaluation of the clinical study in the opinion of the investigator\n - Patients with uncontrolled intercurrent illness\n - Patients with psychiatric illness/social situations that would limit compliance with\n study requirements\n - Pregnant women are excluded from this study because DS-8201a is a HER2 antibody\n conjugated to a topoisomerase 1 inhibitor agent with the potential for teratogenic or\n abortifacient effects. Because there is an unknown but potential risk for adverse\n events in nursing infants secondary to treatment of the mother with DS-8201a,\n breastfeeding should be discontinued if the mother is treated with DS-8201a\n - Patients are not allowed to receive chloroquine/hydroxychloroquine. Patients receiving\n chloroquine/hydroxychloroquine require a washout of > 14 days", "output": {"inclusion_biomarker": [["HER2 positive"], ["HER2 expression"], ["HER2 amplification"], ["HER2 mutation"]], "exclusion_biomarker": []}}
 {"input": "Open-label, multi-center, non-randomized, multiple dose, safety, tolerability,\n pharmacokinetic, and pharmacodynamics and clinical activity study of PF-06940434 (Integrin\n alpha-V/beta-8 Antagonist) in patients with SCCHN (Squamous Cell Carcinoma of the Head and\n Neck), renal cell carcinoma (RCC - clear cell and papillary), ovarian, gastric, esophageal,\n esophageal (adeno and squamous), lung squamous cell, pancreatic and biliary duct,\n endometrial, melanoma and urothelial tumors. This study contains two parts, single agent dose\n escalation (Part 1A), dose finding of PF 06940434 in combination with anti-PD-1 (Part 1B) and\n dose expansion (Part 2). Part 2 Dose Combination Expansion will enroll participants into 2\n cohorts at doses determined from Part 1B in order to further evaluate the safety of\n PF-06940434 in combination with anti-PD-1.\n ;NA;\n Inclusion Criteria:\n - Histological or cytological diagnosis of SCCHN, RCC (clear cell and papillary cell),\n ovarian, gastric, esophageal (adeno and squamous), lung squamous cell, pancreatic and\n biliary duct, endometrial, melanoma, or urothelial cancer.\n Part 2:\n - Arm A SCCHN:\n - Primary tumor location of the oral cavity, oropharynx, hypopharynx or larynx.\n - PDL-1 expression positive and CPS \u22651. No prior systemic therapy administered in\n the recurrent or metastatic setting (except for systemic therapy given as part of\n a multimodal treatment for locally advanced disease).\n - Arm B RCC (clear cell):\n - 1 or 2 prior lines of therapy including PD-L1/PD-1 immunotherapy in combination\n or sequentially with antiangiogenic directed treatment\n - Adequate bone marrow, kidney and liver function.\n - Performance status of 0 or 1.\n Exclusion Criteria:\n - Participant disease status is suitable for local therapy administered with curative\n intent.\n - Hypertension that cannot be controlled by medications.\n - Active or prior autoimmune disease\n - Active, uncontrolled bacterial, fungal, or viral infection, including (but not limited\n to) Hepatitis B, Hepatitis C, and known Human Immunodeficiency Virus infection or\n Acquired Immunodeficiency Syndrome-related illness", "output": {"inclusion_biomarker": [["PDL-1 expression"]], "exclusion_biomarker": []}}
-{"input": "Researchers are looking for a better way to treat people who have advanced non-small cell\n lung cancer (NSCLC), a group of lung cancers that have spread to nearby tissues or to other\n parts of the body.\n Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2)\n are proteins that help cells to grow and divide. A damage (also called mutation) to the\n building plans (genes) for these proteins in cancer cells leads to a production of abnormal\n EGFR and/or HER2. These abnormal proteins drive the growth and the spread of the cancer.\n Several EGFR and/or HER2 mutations exist in the cancer cells. Two mutations observed in NSCLC\n are called EGFR- or HER2exon20ins and EGFR C797X. The study treatment, BAY2927088, works by\n blocking the mutated EGFR protein and also its ex20ins version which are present in NSCLC. It\n is also believed to work against HER2 and HER2ex20ins mutations. Researchers think this may\n help stop the further spread of NSCLC cancer.\n This is the first time that researchers will study BAY2927088 in humans. In this study, the\n researchers want to learn more about using BAY2927088 in participants who have NSCLC with\n EGFR and/or HER2 mutations including EGFRex20ins and/or HER2ex20ins mutations.\n The main aims of this study are to find for BAY2927088\n - how safe BAY2927088 is\n - how it affects the body (also referred to as tolerability)\n - how BAY2927088 moves into, through and out of the body\n - the maximum amount of BAY2927088 that the participants can take without too many side\n effects.\n The researchers will also study the action of BAY2927088 against the cancer. The study will\n have three parts: Dose Escalation, Backfill, and Dose Expansion. Each participant of the\n first, so called dose escalation part, will be assigned to one of specific sequential dose\n groups for BAY2927088. The amount of BAY2927088 that is given increases stepwise from one\n group to the next.\n The second may be initiated at any dose that has already been tested during the first part\n and found to be safe and to have either reached a predicted efficacious exposure range or to\n have induced an objective response. The first part and second part will run concurrently.\n The participants of the third, so called dose expansion part, will receive the most\n appropriate dose of BAY2927088 found in the first and second parts. The third part may be\n initiated in parallel with the first and second part based on emerging data.\n During the study, the participants will take the study treatment in 3 week periods called\n \"cycles\". They will in general take BAY2927088 once daily until their cancer gets worse,\n until they have medical problems, until they leave the study or until the study is\n terminated. Participants will have around 5 visits in each cycle.\n During the study, the study team will:\n - take blood and urine samples\n - take regular CT or MRI scans to check if the participants' cancer has gotten better or\n worse\n - check the participants' overall health and heart health\n - ask the participants questions about how they are feeling and what adverse events they\n are having.\n An adverse event is any medical problem that a participant has during a study. Doctors keep\n track of all adverse events that happen in studies, even if they do not think the adverse\n events might be related to the study treatments.\n ;NA;\n Inclusion Criteria:\n - Documented histologically or cytologically confirmed locally advanced NSCLC, not\n suitable for definitive therapy or recurrent or metastatic NSCLC at screening (small\n cell or mixed histologies are excluded).\n - Documented disease progression after treatment with at least one prior systemic\n therapy for advanced disease. Participants who do not have standard of care access due\n to any reason, are intolerant to, or are not eligible for standard treatments, may\n also be eligible.\n - Adequate archival tumor tissue (ideally taken after last targeted treatment and not\n older than 6 months) has to be available, either from primary or metastatic sites. If\n archival material is not available, a fresh tumor biopsy should be performed if\n feasible and if the procedure poses no significant risk for the participant.\n - Measurable disease by RECIST v1.1 with at least one lesion not chosen for biopsy\n during the screening period (if a biopsy is taken during screening) that can be\n accurately measured at baseline with computed tomography (CT) or magnetic resonance\n imaging (MRI) and that is suitable for accurate repeated measurements. A biopsied\n lesion should not be used as a target lesion for RECIST 1.1 tumor assessments.\n Previously irradiated lesions must have shown progression to be considered measurable.\n - Documented activating EGFR and/or HER2 mutation assessed by a Clinical Laboratory\n Improvement Amendments (CLIA)-certified (United States [US] sites) or an equally\n accredited (outside of the US) local laboratory\n - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.\n - Minimum life expectancy of 12 weeks.\n - Adequate bone marrow function as assessed by the following laboratory tests to be\n conducted within 7 days before the first dose of study treatment:\n 1. Hemoglobin \u2265 9.0 g/dL. Criteria must be met without erythropoietin dependency and\n without packed red blood cell (pRBC) transfusion within 2 weeks prior to testing.\n 2. Platelets \u2265 100 \u00d7 10^9 cells/L.\n 3. Absolute neutrophil count \u2265 1.5 \u00d710^9 cells/L. Criteria must be met without the\n use of hematopoietic growth factors (e.g., G-CSF) within 2 weeks prior to\n testing.\n - Adequate kidney function as assessed by following laboratory test to be conducted\n within 7 days before the first dose of study treatment:\n a. Estimated glomerular filtration rate (eGFR) > 60 mL/min per 1.73 m^2 according to\n the Modification of Diet in renal Disease Study Group (MDRD) formula.\n - Adequate liver function as assessed by following laboratory tests to be conducted\n within 7 days before the first dose of study treatment:\n 1. Total bilirubin \u2264 1.5 \u00d7 ULN (or \u2264 3 X ULN for participants with documented\n Gilbert-Meulengracht Syndrome, or for participants with hyperbilirubinemia\n considered due to liver metastasis).\n 2. Aspartate transaminase and alanine transaminase \u2264 2.5 \u00d7 ULN (or \u2264 5 \u00d7 ULN if due\n to liver involvement by tumor).\n Exclusion Criteria:\n - Treatment with an EGFR tyrosine kinase inhibitor (TKI) \u2264 8 days or 5x the terminal\n phase, elimination half-lives, whichever is shorter, prior to the first dose of study\n drug.\n - Treatment with a systemic anti-cancer treatment (excluding EGFR TKIs as described\n above) \u2264 14 days prior to the first dose of study drug.\n - Radiation therapy, stereotactic radiosurgery (SRS) and palliative radiation \u2264 14 days\n prior to the first dose of study drug.\n - Treatment with immunotherapy \u2264 28 days prior to the first dose of study drug.\n - Have any unresolved toxicity of Grade \u2265 2 from previous anti-cancer treatment, except\n for alopecia and skin pigmentation. Participants with chronic, but stable Grade 2\n toxicities may be allowed to enroll after agreement between the Investigator and\n Sponsor.\n - Any history of primary brain or leptomeningeal disease (symptomatic or asymptomatic),\n presence of symptomatic central nervous system (CNS) metastases, or CNS metastases\n that require local treatment (such as radiotherapy or surgery).\n - History of spinal cord compression or brain metastases with the following exceptions:\n 1. Participants with treated brain metastases that are asymptomatic at screening and\n who are off or receiving low-dose of corticosteroids (\u226410 mg prednisone or\n equivalent) for at least 7 days prior to first dose of BAY 2927088 are eligible\n to enroll in Dose Escalation and Backfill.\n 2. Participants with treated brain metastases that are asymptomatic at screening are\n eligible in Dose Expansion if all of the following criteria are met:\n - there is no evidence of progression (new or enlarging brain metastases) for\n at least 4 weeks after CNS-directed treatment, as ascertained by clinical\n examination and brain imaging (MRI or CT) during the screening period.\n - Participants must be off or receiving low-dose of corticosteroids (\u226410 mg\n prednisone or equivalent) for 7 days prior to first dose of BAY2927088.\n 3. Participants with history of spinal cord compression >3 months from definitive\n therapy and stable by imaging (MRI or CT) during the screening period and\n clinically asymptomatic.\n - History of congestive heart failure (CHF) Class >II according to the New York Heart\n Association (NYHA) Functional Classification or serious cardiac arrhythmias requiring\n treatment (e.g. ventricular arrhythmias, atrial fibrillation) or any clinically\n important abnormalities in rhythm, conduction or morphology or resting ECG (e.g.,\n complete left bundle branch block, third degree heart block, second degree heart\n block, PR interval >250 msec)\n - Participants with:\n 1. Known human immunodeficiency virus (HIV), except as noted below: Participants\n with history of HIV infection are eligible at the Investigator's discretion\n provided that: \u2022 CD4+ T-cell (CD4+) counts are \u2265 350 cells/uL \u2022 The participant\n has been on established antiretroviral therapy (ART) for at least 4 weeks prior\n to the start of study drug and has an HIV viral load less than 400 copies/mL\n prior to start of the study treatment \u2022 The ART being used does not contain\n strong inducers or inhibitors of CYP3A4, and is not anticipated to cause\n overlapping toxicities with study drug \u2022 The participant has not had an\n opportunistic infection within the past 12 months\n 2. Active Hepatitis B infection (positive for Hepatitis B surface antigen [HbsAg])\n and Hepatitis B virus [HBV] DNA).\n 3. Active Hepatitis C infection (positive anti-HCV Antibody and quantitative HCV RNA\n results greater than the lower limits of detection of the assay).\n NOTE: Participants with history of chronic HBV or HCV infection are eligible at\n the Investigator's discretion provided that the disease is stable and\n sufficiently controlled under treatment.\n - Use of strong CYP3A4 inhibitors and inducers from 14 days prior to first\n administration of study drug. Strong CYP3A4 inhibitors and inducers are prohibited\n during the study and until Safety FU (follow up) visit.", "output": {"inclusion_biomarker": [["EGFR mutation"], ["HER2 mutation"], ["EGFR ex20ins"], ["HER2 ex20ins"]], "exclusion_biomarker": []}}
+{"input": "Researchers are looking for a better way to treat people who have advanced non-small cell\n lung cancer (NSCLC), a group of lung cancers that have spread to nearby tissues or to other\n parts of the body.\n Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2)\n are proteins that help cells to grow and divide. A damage (also called mutation) to the\n building plans (genes) for these proteins in cancer cells leads to a production of abnormal\n EGFR and/or HER2. These abnormal proteins drive the growth and the spread of the cancer.\n Several EGFR and/or HER2 mutations exist in the cancer cells. Two mutations observed in NSCLC\n are called EGFR- or HER2exon20ins and EGFR C797X. The study treatment, BAY2927088, works by\n blocking the mutated EGFR protein and also its ex20ins version which are present in NSCLC. It\n is also believed to work against HER2 and HER2ex20ins mutations. Researchers think this may\n help stop the further spread of NSCLC cancer.\n This is the first time that researchers will study BAY2927088 in humans. In this study, the\n researchers want to learn more about using BAY2927088 in participants who have NSCLC with\n EGFR and/or HER2 mutations including EGFRex20ins and/or HER2ex20ins mutations.\n The main aims of this study are to find for BAY2927088\n - how safe BAY2927088 is\n - how it affects the body (also referred to as tolerability)\n - how BAY2927088 moves into, through and out of the body\n - the maximum amount of BAY2927088 that the participants can take without too many side\n effects.\n The researchers will also study the action of BAY2927088 against the cancer. The study will\n have three parts: Dose Escalation, Backfill, and Dose Expansion. Each participant of the\n first, so called dose escalation part, will be assigned to one of specific sequential dose\n groups for BAY2927088. The amount of BAY2927088 that is given increases stepwise from one\n group to the next.\n The second may be initiated at any dose that has already been tested during the first part\n and found to be safe and to have either reached a predicted efficacious exposure range or to\n have induced an objective response. The first part and second part will run concurrently.\n The participants of the third, so called dose expansion part, will receive the most\n appropriate dose of BAY2927088 found in the first and second parts. The third part may be\n initiated in parallel with the first and second part based on emerging data.\n During the study, the participants will take the study treatment in 3 week periods called\n \"cycles\". They will in general take BAY2927088 once daily until their cancer gets worse,\n until they have medical problems, until they leave the study or until the study is\n terminated. Participants will have around 5 visits in each cycle.\n During the study, the study team will:\n - take blood and urine samples\n - take regular CT or MRI scans to check if the participants' cancer has gotten better or\n worse\n - check the participants' overall health and heart health\n - ask the participants questions about how they are feeling and what adverse events they\n are having.\n An adverse event is any medical problem that a participant has during a study. Doctors keep\n track of all adverse events that happen in studies, even if they do not think the adverse\n events might be related to the study treatments.\n ;NA;\n Inclusion Criteria:\n - Documented histologically or cytologically confirmed locally advanced NSCLC, not\n suitable for definitive therapy or recurrent or metastatic NSCLC at screening (small\n cell or mixed histologies are excluded).\n - Documented disease progression after treatment with at least one prior systemic\n therapy for advanced disease. Participants who do not have standard of care access due\n to any reason, are intolerant to, or are not eligible for standard treatments, may\n also be eligible.\n - Adequate archival tumor tissue (ideally taken after last targeted treatment and not\n older than 6 months) has to be available, either from primary or metastatic sites. If\n archival material is not available, a fresh tumor biopsy should be performed if\n feasible and if the procedure poses no significant risk for the participant.\n - Measurable disease by RECIST v1.1 with at least one lesion not chosen for biopsy\n during the screening period (if a biopsy is taken during screening) that can be\n accurately measured at baseline with computed tomography (CT) or magnetic resonance\n imaging (MRI) and that is suitable for accurate repeated measurements. A biopsied\n lesion should not be used as a target lesion for RECIST 1.1 tumor assessments.\n Previously irradiated lesions must have shown progression to be considered measurable.\n - Documented activating EGFR and/or HER2 mutation assessed by a Clinical Laboratory\n Improvement Amendments (CLIA)-certified (United States [US] sites) or an equally\n accredited (outside of the US) local laboratory\n - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.\n - Minimum life expectancy of 12 weeks.\n - Adequate bone marrow function as assessed by the following laboratory tests to be\n conducted within 7 days before the first dose of study treatment:\n 1. Hemoglobin \u2265 9.0 g/dL. Criteria must be met without erythropoietin dependency and\n without packed red blood cell (pRBC) transfusion within 2 weeks prior to testing.\n 2. Platelets \u2265 100 \u00d7 10^9 cells/L.\n 3. Absolute neutrophil count \u2265 1.5 \u00d710^9 cells/L. Criteria must be met without the\n use of hematopoietic growth factors (e.g., G-CSF) within 2 weeks prior to\n testing.\n - Adequate kidney function as assessed by following laboratory test to be conducted\n within 7 days before the first dose of study treatment:\n a. Estimated glomerular filtration rate (eGFR) > 60 mL/min per 1.73 m^2 according to\n the Modification of Diet in renal Disease Study Group (MDRD) formula.\n - Adequate liver function as assessed by following laboratory tests to be conducted\n within 7 days before the first dose of study treatment:\n 1. Total bilirubin \u2264 1.5 \u00d7 ULN (or \u2264 3 X ULN for participants with documented\n Gilbert-Meulengracht Syndrome, or for participants with hyperbilirubinemia\n considered due to liver metastasis).\n 2. Aspartate transaminase and alanine transaminase \u2264 2.5 \u00d7 ULN (or \u2264 5 \u00d7 ULN if due\n to liver involvement by tumor).\n Exclusion Criteria:\n - Treatment with an EGFR tyrosine kinase inhibitor (TKI) \u2264 8 days or 5x the terminal\n phase, elimination half-lives, whichever is shorter, prior to the first dose of study\n drug.\n - Treatment with a systemic anti-cancer treatment (excluding EGFR TKIs as described\n above) \u2264 14 days prior to the first dose of study drug.\n - Radiation therapy, stereotactic radiosurgery (SRS) and palliative radiation \u2264 14 days\n prior to the first dose of study drug.\n - Treatment with immunotherapy \u2264 28 days prior to the first dose of study drug.\n - Have any unresolved toxicity of Grade \u2265 2 from previous anti-cancer treatment, except\n for alopecia and skin pigmentation. Participants with chronic, but stable Grade 2\n toxicities may be allowed to enroll after agreement between the Investigator and\n Sponsor.\n - Any history of primary brain or leptomeningeal disease (symptomatic or asymptomatic),\n presence of symptomatic central nervous system (CNS) metastases, or CNS metastases\n that require local treatment (such as radiotherapy or surgery).\n - History of spinal cord compression or brain metastases with the following exceptions:\n 1. Participants with treated brain metastases that are asymptomatic at screening and\n who are off or receiving low-dose of corticosteroids (\u226410 mg prednisone or\n equivalent) for at least 7 days prior to first dose of BAY 2927088 are eligible\n to enroll in Dose Escalation and Backfill.\n 2. Participants with treated brain metastases that are asymptomatic at screening are\n eligible in Dose Expansion if all of the following criteria are met:\n - there is no evidence of progression (new or enlarging brain metastases) for\n at least 4 weeks after CNS-directed treatment, as ascertained by clinical\n examination and brain imaging (MRI or CT) during the screening period.\n - Participants must be off or receiving low-dose of corticosteroids (\u226410 mg\n prednisone or equivalent) for 7 days prior to first dose of BAY2927088.\n 3. Participants with history of spinal cord compression >3 months from definitive\n therapy and stable by imaging (MRI or CT) during the screening period and\n clinically asymptomatic.\n - History of congestive heart failure (CHF) Class >II according to the New York Heart\n Association (NYHA) Functional Classification or serious cardiac arrhythmias requiring\n treatment (e.g. ventricular arrhythmias, atrial fibrillation) or any clinically\n important abnormalities in rhythm, conduction or morphology or resting ECG (e.g.,\n complete left bundle branch block, third degree heart block, second degree heart\n block, PR interval >250 msec)\n - Participants with:\n 1. Known human immunodeficiency virus (HIV), except as noted below: Participants\n with history of HIV infection are eligible at the Investigator's discretion\n provided that: \u2022 CD4+ T-cell (CD4+) counts are \u2265 350 cells/uL \u2022 The participant\n has been on established antiretroviral therapy (ART) for at least 4 weeks prior\n to the start of study drug and has an HIV viral load less than 400 copies/mL\n prior to start of the study treatment \u2022 The ART being used does not contain\n strong inducers or inhibitors of CYP3A4, and is not anticipated to cause\n overlapping toxicities with study drug \u2022 The participant has not had an\n opportunistic infection within the past 12 months\n 2. Active Hepatitis B infection (positive for Hepatitis B surface antigen [HbsAg])\n and Hepatitis B virus [HBV] DNA).\n 3. Active Hepatitis C infection (positive anti-HCV Antibody and quantitative HCV RNA\n results greater than the lower limits of detection of the assay).\n NOTE: Participants with history of chronic HBV or HCV infection are eligible at\n the Investigator's discretion provided that the disease is stable and\n sufficiently controlled under treatment.\n - Use of strong CYP3A4 inhibitors and inducers from 14 days prior to first\n administration of study drug. Strong CYP3A4 inhibitors and inducers are prohibited\n during the study and until Safety FU (follow up) visit.", "output": {"inclusion_biomarker": [["EGFR activating mutation"], ["HER2 activating mutation"]], "exclusion_biomarker": []}}
 {"input": "It is an exploratory clinical study aimed to evaluate the efficacy and safety of TACE\n combined with Camrelizumab in the treatment of patients with BCLC stage B and C HCC.Treatment\n will continue until disease progression or intolerable toxicity or patients withdrawal of\n consent,and the target sample size is 60 individuals.\n ;\n ;\n Inclusion Criteria:\n - 1.Patients voluntarily entered the study and signed informed consent form (ICF) 2.\n Age: 18 - 80 years old and life expectancy of at least 12 weeks.; 3. Clinically or\n histologically diagnosed as HCC; 4. There are measurable lesions that meet the\n RECIST1.1 standard on the baseline imaging examination; 5. Child-pugh classification A\n or B (score < 7); 6. The BCLC stage is stage B or C, and it is unable or unwilling to\n undergo surgical treatment; 7. ECOG : 0 ~ 1 ; 8. No previous immune checkpoint\n inhibitor treatment (including PD-1 / PD-L1 antibody and CTLA-4 inhibitor); 9.\n HBV-deoxyribonucleic acid (DNA) must be <500IU / mL, and receive at least 14 days of\n anti-HBV treatment before the start of study treatment Treatment;\n Exclusion Criteria:\n - 1. History of treatment with any local treatment (exception of liver transplantation),\n systemic .anti-cancer therapy, or immunotherapy; 2. Those whose tumor thrombus reaches\n or exceeds the main portal vein; 3. Existing or concurrently suffering from other\n malignant tumors, except for fully treated non-melanoma skin cancer, cervical\n carcinoma in situ, and papillary thyroid carcinoma; 4. There is any active autoimmune\n disease or has a history of autoimmune disease and may relapse; 5. Use strong CYP3A4 /\n CYP2C19 inducers including rifampicin and Hypericum perforatum or strong CYP3A4 /\n CYP2C19 inhibitors within 14 days before starting the study treatment; 6. Known\n history of severe allergy to any monoclonal antibody; 7. Patients who are going to\n undergo or have undergone organ or allogeneic bone marrow transplantation; 8.\n Non-compliance with TACE or Camrelizumab; 9. Moderate and severe ascites with clinical\n symptoms require therapeutic puncture, drainage, or Childa-Pugh score> 2 (except\n imaging only shows a small amount of ascites but not accompanied by clinical\n symptoms); uncontrolled or moderate and Above pleural effusion and pericardial\n effusion; 10. Abdominal fistula, gastrointestinal perforation or abdominal abscess\n occurred within 6 months before the start of the study treatment; 11. Thrombosis or\n embolism occurred within 6 months before the start of study treatment, such as\n cerebrovascular accident (including temporary ischemic attack, cerebral hemorrhage,\n cerebral infarction, pulmonary embolism, etc.) 12. Known inherited or acquired\n bleeding or thrombophilia ; currently or recently (10 days prior to the start of study\n treatment) have used full dose oral or Injection of anticoagulant drugs or\n thrombolytic drugs (prophylactic use of low-dose aspirin and low molecular weight\n heparin); 13. Major vascular disease within 6 months before the study treatment; 22.\n Past or present central nervous system metastasis; 14. Metastatic diseases involving\n major airways or blood vessels or a large mediastinal tumor mass in the center (<30 mm\n from the crest) 15. Those with a history of hepatic encephalopathy; 16. Palliative\n radiotherapy for non-target lesions allowed for symptom control must be completed at\n least 2 weeks before the start of study treatment. Adverse events caused by\n radiotherapy have not recovered to \u2264CTCAE level 1; 17. There were severe infections\n within 4 weeks before starting the study treatment; 18. Patients with congenital or\n acquired immune deficiency (such as those infected with HIV); 19. Co-infection with\n hepatitis B and C; 20. For patients with bone metastases, the palliative radiotherapy\n area> 5% bone marrow area received within 4 weeks before participating in the study;", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
-{"input": "This phase II trial studies how well pembrolizumab works before surgery in treating patients\n with mismatch repair deficient solid cancers that have spread to nearby tissue or lymph nodes\n (locally advanced). Cancer is caused by changes (mutations) to genes (DNA) that control the\n way cells function, and some of these mutations can cause tumor cells to grow quickly and out\n of control. Microsatellite instability-high (MSI-H) tumors are made up of cancer cells that\n have a greater than normal number of genetic markers called microsatellites. These cancers\n may have defects in the ability to correct mutations that occur when DNA is copied in the\n cell. Similarly, mismatch repair deficient tumors (dMMR) may have difficulty repairing some\n type of genetic mutation during cellular replication that may affect tumor's response to\n cancer therapy. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the\n body's immune system attack the cancer, and may interfere with the ability of tumor cells to\n grow and spread.\n ;\n ;\n Inclusion Criteria:\n - Male/female participants who are at least 18 years of age on the day of signing\n informed consent with histologically confirmed diagnosis of solid cancer\n - Solid cancer that is deficient in mismatch repair (dMMR) or microsatellite instability\n high (MSI-H) as determined by one of three methods:\n - Immunohistochemistry determined dMMR by complete loss of MLH1, PMS2, MSH2 or MSH6\n - Polymerase chain reaction (PCR) determined microsatellite instability at > 30% of\n tested microsatellites\n - Next-generation sequencing determined MSI-H based upon instability at multiple\n microsatellites as determined by the specific next generation sequencing panel\n - Locally advanced cancer defined as either an unresectable primary cancer or a\n resectable primary cancer with a high chance of recurrence (defined as an estimated\n greater or equal to 20% chance of recurrence by the treating physician). A resectable\n primary may include locoregional disease, as long as all disease is felt by the\n treating physician to be in a resectable distribution\n - The participant (or legally acceptable representative if applicable) provides written\n informed consent for the trial\n - Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST)\n version (v)1.1 (unless discussed and approved by study principal investigator [PI])\n - Have available archival tumor tissue. Availability will be met as long as a request to\n obtain formalin-fixed, paraffin embedded (FFPE) tissue blocks (preferred) or slides\n has been made (unless discussed and approved by study PI)\n - Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.\n Evaluation of ECOG is to be performed within 7 days prior to the date of signing study\n consent\n - A female participant is eligible to participate if she is not pregnant, not\n breastfeeding, and at least one of the following conditions applies:\n - Not a woman of childbearing potential (WOCBP) OR\n - A WOCBP who agrees to follow the contraceptive guidance during the treatment\n period and for at least (120 days [corresponding to time needed to eliminate any\n study treatment(s) plus 30 days (a menstruation cycle) for risk of genotoxicity])\n after the last dose of study treatment\n - Absolute neutrophil count (ANC) >= 1500/uL (within 14 days prior to the start of study\n treatment)\n - Platelets >= 100 000/uL (within 14 days prior to the start of study treatment)\n - Hemoglobin >= 8.0 g/dL or >= 5.6 mmol/L (within 14 days prior to the start of study\n treatment)\n - Criteria must be met without erythropoietin dependency and without packed red\n blood cell (pRBC) transfusion within last 2 weeks\n - Creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine\n clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or\n creatinine clearance [CrCl]) >= 30 mL/min for participant with creatinine levels > 1.5\n x institutional ULN (within 14 days prior to the start of study treatment)\n - Creatinine clearance (CrCl) should be calculated per institutional standard\n - Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for participants with total\n bilirubin levels > 1.5 x ULN (within 14 days prior to the start of study treatment)\n - Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and\n alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x\n ULN (=< 5 x ULN for participants with liver metastases) (within 14 days prior to the\n start of study treatment)\n - International normalized ratio (INR) OR prothrombin time (PT) activated partial\n thromboplastin time (aPTT) =< 1.5 x ULN unless participant is receiving anticoagulant\n therapy as long as PT or aPTT is within therapeutic range of intended use of\n anticoagulants (within 14 days prior to the start of study treatment)\n Exclusion Criteria:\n - A woman of childbearing potential (WOCBP) who has a positive urine pregnancy test\n within 72 hours prior to enrollment. If the urine test is positive or cannot be\n confirmed as negative, a serum pregnancy test will be required. Note: in the event\n that 72 hours have elapsed between the screening pregnancy test and the first dose of\n study treatment, another pregnancy test (urine or serum) must be performed and must be\n negative in order for subject to start receiving study medication\n - Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with\n an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g.,\n CTLA-4, OX 40, CD137)\n - Has received prior systemic anti-cancer therapy including investigational agents\n within 2 weeks of study treatment. Note: Participants must have recovered from all\n adverse events (AEs) due to previous therapies to =< grade 1 or baseline. Participants\n with =< grade 2 neuropathy may be eligible\n - If participant received major surgery, they must have recovered adequately from the\n toxicity and/or complications from the intervention prior to starting study treatment\n - Has received prior radiotherapy within 2 weeks of start of study treatment.\n Participants must have recovered from all radiation-related toxicities, not require\n corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted\n for palliative radiation (=< 2 weeks of radiotherapy) to non-central nervous system\n (CNS) disease\n - Has received a live vaccine within 30 days prior to the first dose of study drug.\n Examples of live vaccines include, but are not limited to, the following: measles,\n mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus\n Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection\n are generally killed virus vaccines and are allowed; however, intranasal influenza\n vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed\n - Is currently participating in or has participated in a study of an investigational\n agent or has used an investigational device within 4 weeks prior to the first dose of\n study treatment. Note: Participants who have entered the follow-up phase of an\n investigational study may participate as long as it has been 4 weeks after the last\n dose of the previous investigational agent\n - Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy\n (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of\n immunosuppressive therapy within 7 days prior to the first dose of study drug\n - Has a known additional malignancy that is progressing or has required active treatment\n within the past 1 year. Note: Participants with basal cell carcinoma of the skin,\n squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma,\n cervical cancer in situ) or other similar good prognosis cancer with recurrence rates\n expected to be < 10% that have undergone potentially curative therapy are not excluded\n - Known metastatic sites of disease. Note: locoregional lymph nodes or tumor deposits\n are not considered metastatic disease\n - Has severe hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients\n - Has active autoimmune disease that has required systemic treatment in the past 2 years\n (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive\n drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid\n replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a\n form of systemic treatment\n - Has a history of (non-infectious) pneumonitis that required steroids or has current\n pneumonitis\n - Has an active infection requiring systemic therapy\n - Has a known history of human immunodeficiency virus (HIV)\n - Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg]\n reactive) or known active hepatitis C virus (defined as HCV ribonucleic acid [RNA]\n [qualitative] is detected) infection. Note: no testing for hepatitis B and hepatitis C\n is required unless mandated by local health authority\n - Has a history or current evidence of any condition, therapy, or laboratory abnormality\n that might confound the results of the study, interfere with the subject's\n participation for the full duration of the study, or is not in the best interest of\n the subject to participate, in the opinion of the treating investigator\n - Has known psychiatric or substance abuse disorders that would interfere with\n cooperation with the requirements of the trial\n - Is pregnant or breastfeeding, or expecting to conceive or father children within the\n projected duration of the study, starting with the screening visit through 120 days\n after the last dose of trial treatment", "output": {"inclusion_biomarker": [["dMMR"], ["MSI-H"], ["MLH1 loss"], ["PMS2 loss"], ["MSH2 loss"], ["MSH6 loss"]], "exclusion_biomarker": []}}
+{"input": "This phase II trial studies how well pembrolizumab works before surgery in treating patients\n with mismatch repair deficient solid cancers that have spread to nearby tissue or lymph nodes\n (locally advanced). Cancer is caused by changes (mutations) to genes (DNA) that control the\n way cells function, and some of these mutations can cause tumor cells to grow quickly and out\n of control. Microsatellite instability-high (MSI-H) tumors are made up of cancer cells that\n have a greater than normal number of genetic markers called microsatellites. These cancers\n may have defects in the ability to correct mutations that occur when DNA is copied in the\n cell. Similarly, mismatch repair deficient tumors (dMMR) may have difficulty repairing some\n type of genetic mutation during cellular replication that may affect tumor's response to\n cancer therapy. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the\n body's immune system attack the cancer, and may interfere with the ability of tumor cells to\n grow and spread.\n ;\n ;\n Inclusion Criteria:\n - Male/female participants who are at least 18 years of age on the day of signing\n informed consent with histologically confirmed diagnosis of solid cancer\n - Solid cancer that is deficient in mismatch repair (dMMR) or microsatellite instability\n high (MSI-H) as determined by one of three methods:\n - Immunohistochemistry determined dMMR by complete loss of MLH1, PMS2, MSH2 or MSH6\n - Polymerase chain reaction (PCR) determined microsatellite instability at > 30% of\n tested microsatellites\n - Next-generation sequencing determined MSI-H based upon instability at multiple\n microsatellites as determined by the specific next generation sequencing panel\n - Locally advanced cancer defined as either an unresectable primary cancer or a\n resectable primary cancer with a high chance of recurrence (defined as an estimated\n greater or equal to 20% chance of recurrence by the treating physician). A resectable\n primary may include locoregional disease, as long as all disease is felt by the\n treating physician to be in a resectable distribution\n - The participant (or legally acceptable representative if applicable) provides written\n informed consent for the trial\n - Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST)\n version (v)1.1 (unless discussed and approved by study principal investigator [PI])\n - Have available archival tumor tissue. Availability will be met as long as a request to\n obtain formalin-fixed, paraffin embedded (FFPE) tissue blocks (preferred) or slides\n has been made (unless discussed and approved by study PI)\n - Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.\n Evaluation of ECOG is to be performed within 7 days prior to the date of signing study\n consent\n - A female participant is eligible to participate if she is not pregnant, not\n breastfeeding, and at least one of the following conditions applies:\n - Not a woman of childbearing potential (WOCBP) OR\n - A WOCBP who agrees to follow the contraceptive guidance during the treatment\n period and for at least (120 days [corresponding to time needed to eliminate any\n study treatment(s) plus 30 days (a menstruation cycle) for risk of genotoxicity])\n after the last dose of study treatment\n - Absolute neutrophil count (ANC) >= 1500/uL (within 14 days prior to the start of study\n treatment)\n - Platelets >= 100 000/uL (within 14 days prior to the start of study treatment)\n - Hemoglobin >= 8.0 g/dL or >= 5.6 mmol/L (within 14 days prior to the start of study\n treatment)\n - Criteria must be met without erythropoietin dependency and without packed red\n blood cell (pRBC) transfusion within last 2 weeks\n - Creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine\n clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or\n creatinine clearance [CrCl]) >= 30 mL/min for participant with creatinine levels > 1.5\n x institutional ULN (within 14 days prior to the start of study treatment)\n - Creatinine clearance (CrCl) should be calculated per institutional standard\n - Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for participants with total\n bilirubin levels > 1.5 x ULN (within 14 days prior to the start of study treatment)\n - Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and\n alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x\n ULN (=< 5 x ULN for participants with liver metastases) (within 14 days prior to the\n start of study treatment)\n - International normalized ratio (INR) OR prothrombin time (PT) activated partial\n thromboplastin time (aPTT) =< 1.5 x ULN unless participant is receiving anticoagulant\n therapy as long as PT or aPTT is within therapeutic range of intended use of\n anticoagulants (within 14 days prior to the start of study treatment)\n Exclusion Criteria:\n - A woman of childbearing potential (WOCBP) who has a positive urine pregnancy test\n within 72 hours prior to enrollment. If the urine test is positive or cannot be\n confirmed as negative, a serum pregnancy test will be required. Note: in the event\n that 72 hours have elapsed between the screening pregnancy test and the first dose of\n study treatment, another pregnancy test (urine or serum) must be performed and must be\n negative in order for subject to start receiving study medication\n - Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with\n an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g.,\n CTLA-4, OX 40, CD137)\n - Has received prior systemic anti-cancer therapy including investigational agents\n within 2 weeks of study treatment. Note: Participants must have recovered from all\n adverse events (AEs) due to previous therapies to =< grade 1 or baseline. Participants\n with =< grade 2 neuropathy may be eligible\n - If participant received major surgery, they must have recovered adequately from the\n toxicity and/or complications from the intervention prior to starting study treatment\n - Has received prior radiotherapy within 2 weeks of start of study treatment.\n Participants must have recovered from all radiation-related toxicities, not require\n corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted\n for palliative radiation (=< 2 weeks of radiotherapy) to non-central nervous system\n (CNS) disease\n - Has received a live vaccine within 30 days prior to the first dose of study drug.\n Examples of live vaccines include, but are not limited to, the following: measles,\n mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus\n Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection\n are generally killed virus vaccines and are allowed; however, intranasal influenza\n vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed\n - Is currently participating in or has participated in a study of an investigational\n agent or has used an investigational device within 4 weeks prior to the first dose of\n study treatment. Note: Participants who have entered the follow-up phase of an\n investigational study may participate as long as it has been 4 weeks after the last\n dose of the previous investigational agent\n - Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy\n (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of\n immunosuppressive therapy within 7 days prior to the first dose of study drug\n - Has a known additional malignancy that is progressing or has required active treatment\n within the past 1 year. Note: Participants with basal cell carcinoma of the skin,\n squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma,\n cervical cancer in situ) or other similar good prognosis cancer with recurrence rates\n expected to be < 10% that have undergone potentially curative therapy are not excluded\n - Known metastatic sites of disease. Note: locoregional lymph nodes or tumor deposits\n are not considered metastatic disease\n - Has severe hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients\n - Has active autoimmune disease that has required systemic treatment in the past 2 years\n (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive\n drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid\n replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a\n form of systemic treatment\n - Has a history of (non-infectious) pneumonitis that required steroids or has current\n pneumonitis\n - Has an active infection requiring systemic therapy\n - Has a known history of human immunodeficiency virus (HIV)\n - Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg]\n reactive) or known active hepatitis C virus (defined as HCV ribonucleic acid [RNA]\n [qualitative] is detected) infection. Note: no testing for hepatitis B and hepatitis C\n is required unless mandated by local health authority\n - Has a history or current evidence of any condition, therapy, or laboratory abnormality\n that might confound the results of the study, interfere with the subject's\n participation for the full duration of the study, or is not in the best interest of\n the subject to participate, in the opinion of the treating investigator\n - Has known psychiatric or substance abuse disorders that would interfere with\n cooperation with the requirements of the trial\n - Is pregnant or breastfeeding, or expecting to conceive or father children within the\n projected duration of the study, starting with the screening visit through 120 days\n after the last dose of trial treatment", "output": {"inclusion_biomarker": [["mismatch repair deficient"], ["Microsatellite instability-high"], ["MLH1 loss"], ["PMS2 loss"], ["MSH2 loss"], ["MSH6 loss"]], "exclusion_biomarker": []}}
 {"input": "The purpose of this study is to evaluate the safety, tolerability, and preliminary clinical\n activity of CC-95251 as a single agent and in combination with cetuximab and rituximab in\n participants with advanced solid and hematologic cancers.\n ;NA;\n Inclusion Criteria:\n - Progressed on standard anticancer therapy or for whom no other approved conventional\n therapy exists and have histological or cytological confirmation of advanced\n unresectable solid tumors, advanced unresectable colorectal cancer, or squamous cell\n carcinoma of the head and neck, or CD20-positive non-Hodgkin's lymphoma, or diffuse\n large B cell lymphoma, or follicular lymphoma\n - Solid tumors must have at least one site of measurable disease as determined by RECIST\n v1.1\n - Eastern cooperative oncology group performance status of 0 or 1\n Exclusion Criteria:\n - High-grade lymphomas (Burkitt's or lymphoblastic)\n - Has cancer with symptomatic central nervous system (CNS) involvement\n - History of class III or IV congestive heart failure (CHF) or severe non-ischemic\n cardiomyopathy, unstable angina, myocardial infarction, or ventricular arrhythmia\n within the previous 6 months\n Other protocol-defined inclusion/exclusion criteria apply", "output": {"inclusion_biomarker": [["CD20 positive"]], "exclusion_biomarker": []}}
 {"input": "This phase II clinical trial tests a chemotherapy regimen (dose-adjusted etoposide,\n prednisone, vincristine, cyclophosphamide and doxorubicin with or without rituximab\n [DA-EPOCH+/-R]) with the addition of targeted therapy (tafasitamab) for the treatment of\n patients with newly diagnosed Philadelphia chromosome negative (Ph-) B acute lymphoblastic\n leukemia (B-ALL). Chemotherapy drugs, such as those in EPOCH+/-R, work in different ways to\n stop the growth of cancer cells, either by killing the cells, by stopping them from dividing,\n or by stopping them from spreading. Tafasitamab is in a class of medications called\n monoclonal antibodies. It works by helping the body to slow or stop the growth of cancer\n cells. Adding tafasitamab to the DA-EPOCH+/-R regimen may work better than DA-EPOCH+/-R alone\n in treating newly diagnosed Ph- B-ALL.\n ;\n ;\n Inclusion Criteria:\n - Adults (age 18 years and older) with newly-diagnosed CD19+ Ph- B-ALL\n - In the opinion of the treating investigator, patients must be an unsuitable candidate\n for a pediatric-inspired regimen, reasons for which may include (but not be limited\n to) older age (e.g., >= 40 years), practical/logistical barriers to or toxicity\n concerns from administration of a pediatric-inspired regimen\n - Marrow or blood involvement detectable by MFC\n - Total bilirubin =< 2.0 x upper limit of normal (ULN) (unless attributed to Gilbert's\n disease or other causes of inherited indirect hyperbilirubinemia, at which point total\n bilirubin must be =< 4.0 x ULN)\n - Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase\n [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])\n =< 5.0 x institutional ULN. (Note: Patients with liver test abnormalities attributable\n to hepatic involvement by ALL will be permitted if the total bilirubin is =< 5.0 x ULN\n and ALT/AST are =< 8.0 x ULN)\n - Calculated creatinine clearance of > 30 ml/min, as measured by the Modification of\n Diet in Renal Disease (MDRD) equation, will be eligible\n - As patients with ALL frequently have cytopenias, no hematologic parameters will be\n required for enrollment or to receive the first cycle of treatment. However, adequate\n recovery of blood counts will be required to receive subsequent cycles\n - Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2. (Performance\n status of 3 will be allowed if poor performance status is thought to be directly\n secondary to ALL)\n - Ability to give informed consent and comply with the protocol\n - Anticipated survival of at least 3 months, independent of ALL\n Exclusion Criteria:\n - Burkitt lymphoma/leukemia\n - No prior systemic therapy for ALL except to control acute symptoms and/or\n hyperleukocytosis (e.g., corticosteroids, cytarabine, etc.)\n - No isolated extramedullary or known parenchymal central nervous system (CNS) disease\n - Known hypersensitivity or intolerance to any of the agents under investigation\n - Other medical or psychiatric conditions that in the opinion of the investigator would\n preclude safe participation in the protocol\n - May not be pregnant or nursing\n - Pregnancy test is only required in women, unless they are highly unlikely to\n conceive (defined as [1] surgically sterilized, or [2] postmenopausal [i.e., a\n woman who is > 50 years old or who has not had menses for >=1 year], or [3] not\n heterosexually active)", "output": {"inclusion_biomarker": [["CD19 positive", "Philadelphia chromosome negative"]], "exclusion_biomarker": []}}
-{"input": "The application of ALK inhibitors in the first-line cancer treatment can significantly\n increase the PFS and ORR of patients those with EML4-ALK fusion. The contemporary clinical\n ALK fusion detection are mainly via FISH and ICH while biopsies are needed. For locations\n where are difficult to take biopsies, these routine examinations can hardly been adopted.\n Apart from these, part of ALK fusion patients are resistant to ALK inhibitors, also making an\n accurate and efficient prognostic indicator for efficacy evaluation and identifying high-risk\n recurrent population an urgent priority.\n The bilayer membrane structure of exosome helps maintain its internal genetic stability,\n making detection of EML4-ALK fusion via plasma exosomes in advanced NSCLC patients a feasible\n way, which might provide a non-invasive and more convenient approach for NSCLC diagnosis and\n efficacy monitoring. Firstly, this study will evaluate the performance of exosome EML4-ALK\n fusion detection in NSCLC diagnosis, which sensitivity and specificity would be compared with\n the FDA approved IHC (ALK [D5F3] CDx Assay) test. Subsequently, this study would monitor the\n dynamic changes of EML4-ALK fusion in exosome examination diagnosed ALK fusion positive NSCLC\n patients both before and after treatment. It aims to prospectively evaluate the potential\n value of this approach on efficacy and prognosis prediction in NSCLC therapy and determining\n whether exosome ALK fusion could assess the curative effect more accurately than imaging\n examination and tumor markers. Thirdly, FISH diagnosed EML4-ALK positive NSCLC patients will\n be divided into the positive or negative subgroup according to their post-treatment exosome\n ALK fusion expression which were determined at 2-3 months after ALK inhibitor were adopted.\n The prognostic value of monitoring exosome EML4-ALK fusion expression is assessed through the\n comparison of patients PFS and OS.\n ;NA;\n Inclusion Criteria:\n - All eligible patients must have histologically or cytologically confirmed stage\n IIIB-IV unresectable NSCLC positive or negative for EML4-ALK4 fusion as defined by\n FISH. Patients must have an ECOG PS of 0- 1 and have at least 1 measurable lesions\n (RECIST 1.1 standard). For eligible patients, prior ALK inhibitor therapy or previous\n systemic anticancer therapy is not allowed or has been completed over 12 months.\n Patients with brain metastasis are eligible only in a stable central nervous system\n condition and treatment outcome, cannot receive glucocorticoids and drugs prohibited\n in the exclusion criteria \u226414 days before the first dose of study drug.\n Exclusion Criteria:\n - Eligible patients must not have received any major surgery \u226428 days before the first\n dose of study drug and must not have received any minor surgery or radiotherapy \u226414\n days before the first dose of study drug. Any acute toxic reaction must have recovered\n to \u2264 Grade 1 (except for hair loss). Patients with carcinomatous meningitis,\n leptomeningeal disease or spinal cord compression must be excluded.", "output": {"inclusion_biomarker": [["EML4-ALK4 fusion positive"], ["EML4-ALK4 fusion negative"]], "exclusion_biomarker": []}}
+{"input": "The application of ALK inhibitors in the first-line cancer treatment can significantly\n increase the PFS and ORR of patients those with EML4-ALK fusion. The contemporary clinical\n ALK fusion detection are mainly via FISH and ICH while biopsies are needed. For locations\n where are difficult to take biopsies, these routine examinations can hardly been adopted.\n Apart from these, part of ALK fusion patients are resistant to ALK inhibitors, also making an\n accurate and efficient prognostic indicator for efficacy evaluation and identifying high-risk\n recurrent population an urgent priority.\n The bilayer membrane structure of exosome helps maintain its internal genetic stability,\n making detection of EML4-ALK fusion via plasma exosomes in advanced NSCLC patients a feasible\n way, which might provide a non-invasive and more convenient approach for NSCLC diagnosis and\n efficacy monitoring. Firstly, this study will evaluate the performance of exosome EML4-ALK\n fusion detection in NSCLC diagnosis, which sensitivity and specificity would be compared with\n the FDA approved IHC (ALK [D5F3] CDx Assay) test. Subsequently, this study would monitor the\n dynamic changes of EML4-ALK fusion in exosome examination diagnosed ALK fusion positive NSCLC\n patients both before and after treatment. It aims to prospectively evaluate the potential\n value of this approach on efficacy and prognosis prediction in NSCLC therapy and determining\n whether exosome ALK fusion could assess the curative effect more accurately than imaging\n examination and tumor markers. Thirdly, FISH diagnosed EML4-ALK positive NSCLC patients will\n be divided into the positive or negative subgroup according to their post-treatment exosome\n ALK fusion expression which were determined at 2-3 months after ALK inhibitor were adopted.\n The prognostic value of monitoring exosome EML4-ALK fusion expression is assessed through the\n comparison of patients PFS and OS.\n ;NA;\n Inclusion Criteria:\n - All eligible patients must have histologically or cytologically confirmed stage\n IIIB-IV unresectable NSCLC positive or negative for EML4-ALK4 fusion as defined by\n FISH. Patients must have an ECOG PS of 0- 1 and have at least 1 measurable lesions\n (RECIST 1.1 standard). For eligible patients, prior ALK inhibitor therapy or previous\n systemic anticancer therapy is not allowed or has been completed over 12 months.\n Patients with brain metastasis are eligible only in a stable central nervous system\n condition and treatment outcome, cannot receive glucocorticoids and drugs prohibited\n in the exclusion criteria \u226414 days before the first dose of study drug.\n Exclusion Criteria:\n - Eligible patients must not have received any major surgery \u226428 days before the first\n dose of study drug and must not have received any minor surgery or radiotherapy \u226414\n days before the first dose of study drug. Any acute toxic reaction must have recovered\n to \u2264 Grade 1 (except for hair loss). Patients with carcinomatous meningitis,\n leptomeningeal disease or spinal cord compression must be excluded.", "output": {"inclusion_biomarker": [["ALK EML4-ALK"]], "exclusion_biomarker": []}}
 {"input": "This is a single-arm, multicenter, exploratory clinical study to evaluate the safety and\n efficacy of the combination of etoposide, cytarabine and PEG-rhG-CSF (EAP regimen) on\n hematopoietic stem cell mobilization in poor mobilization patients with hematological\n malignancies. All eligible patients will receive EAP regimen treatment, then the number of\n CD34+ cells and white blood cells will be monitoring. When the collection standard is met,\n hematopoietic stem cell collection will be started.\n ;NA;\n Inclusion Criteria:\n 1. According to the diagnostic criteria of the Italian transplantation working group,\n patients with hematological malignancies diagnosed as \"confirmed poor mobilization\" or\n \"predicted poor mobilization\".\n 2. Patients with auto-HSCT indication.\n 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0~2.\n 4. Patients should be within age range of \u226518 and \u226475 years old.\n 5. Life expectancy \u2265 3 months.\n 6. Patients must be able to sign informed consent.\n Exclusion Criteria:\n 1. Patients with severe cardiac, hepatic or renal insufficiency, such as:\n - Cardiac function class II or higher or severe arrhythmia;\n - Serum direct bilirubin (DBIL)>2\u00d7 upper limit of normal (ULN);\n - Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2\u00d7 ULN;\n - Serum creatinine clearance rate\u226450%.\n 2. Patients with active infection.\n 3. History of allergy to Etoposide (VP-16), Cytarabine (Ara-C), or PEG-rhG-CSF.\n 4. Women who are pregnant or breastfeeding.\n 5. Have received live vaccine and attenuated live vaccine within 4 weeks before\n enrollment.\n 6. For any other reasons, the patients are believed not suitable for participation in\n this study by investigators", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
 {"input": "This research study is done to test the safety, effectiveness and pharmacokinetic\n characteristics of SIM1803-1A in patients with locally advanced/metastatic solid tumors with\n NTRK, ROS1 or ALK gene fusion mutations. The cancer must have a change in a particular gene\n (NTRK1, NTRK2, NTRK3, ROS1 or ALK). SIM1803-1A is a drug that blocks the actions of these\n NTRK/ ROS1 /ALK genes in cancer cells and can therefore be used to treat cancer.\n ;NA;\n Inclusion Criteria:\n - Adult patients with a locally advanced or metastatic solid tumor that has progressed\n or was nonresponsive to available therapies, are unfit for standard chemotherapy or\n for which no standard or available curative therapy exists\uff1bProof of a malignancy\n harboring a NTRK\u3001ROS1 or ALK fusion\uff1bEastern Cooperative Oncology Group (ECOG) score of\n 0 or 1 and a life expectancy of at least 3 month\uff1bAdequate hematologic, hepatic, and\n renal function\uff1bSigned informed consent form\uff1b\n Exclusion Criteria:\n - Any contraindications as listed in the local approved product information\uff1bPatients\n with unstable primary central-nervous-system tumors or metastasis, exceptions\n possible\uff1bPregnancy or lactation\uff1bClinically significant active cardiovascular disease\n or history of myocardial infarction\uff1bParticipation in an investigational program with\n interventions outside of routine clinical practice\uff1bPrior treatment with other kinase\n inhibitor with tropomyosin receptor kinase inhibition\uff1bActive uncontrolled systemic\n bacterial, viral, or fungal infection\uff1bCurrent treatment with a strong CYP3A4 inhibitor\n or inducer\uff1b", "output": {"inclusion_biomarker": [["NTRK1 fusion"], ["NTRK2 fusion"], ["NTRK3 fusion"], ["ROS1 fusion"], ["ALK fusion"]], "exclusion_biomarker": []}}
 {"input": "transoral Robotic surgery for rECurrent tumours of the Upper aerodigestive Tract\n ;\n ;\n Inclusion Criteria:\n - Aged over 18\n - Previous HNC treated with radiotherapy\n - Undergoing TORS as part of their management for recurrent disease\n - Surgery performed on or before July 31st 2018.\n Exclusion Criteria:\n - TORS used in a diagnostic setting only\n - Nasopharyngeal and thyroid cancers", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
@@ -67,14 +67,14 @@
 {"input": "This is a Phase I/Ib study in which the safety of the combination therapy of RMC-4630 and\n LY3214996 in the treatment of KRAS mutant cancers will be studied.\n ;\n ;\n Inclusion Criteria:\n 1. Part A: Histological or cytological proof of advanced KRASm NSCLC, CRC or PDAC; PART\n B: Histological or cytological proof of advanced KRASm PDAC.\n 2. Age => 18 years;\n 3. Able and willing to give written informed consent;\n 4. WHO performance status of 0 or 1\n 5. Able and willing to undergo blood sampling for PK and PD analysis;\n 6. Able and willing to undergo tumor biopsies prior to start (or have undergone a biopsy\n within 2 months of inclusion), while on study treatment and upon progression of\n disease;\n 7. Life expectancy => 3 months and no deterioration or hospitalizations within 2 weeks\n leading to C1D1, allowing adequate follow up of toxicity evaluation and antitumor\n activity;\n 8. Evaluable disease according to RECIST 1.1 criteria; (PART A and PART B);\n 9. Women of childbearing potential must have a negative serum pregnancy test within 14\n days prior to registration and agree to use effective contraceptive methods, as\n defined in section 5.9.3, through-out the treatment period, and for 4 months after the\n study treatment\n 10. Adequate organ system function.\n Exclusion Criteria:\n 1. Part A: No excluded genotypes\n Part B: Excluded genotypes (including co occurring mutations):\n - NRAS (except G12A/C)\n - RASQ61\n - KRASG13\n - BRAF Class 1, 2, or unclassified\n - PIK3CA\n - STK11\n - KEAP1\n 2. Any treatment with investigational drugs within 30 days prior to receiving the first\n dose of investigational treatment;\n 3. Patients currently using concomitant medication that are strong inhibitors or inducers\n of CYP3A4;\n 4. History of another malignancy Exception PART A: Patients who have been disease-free\n for at least 3 years, or patients with a history of completely resected non-melanoma\n skin cancer and/or patients with indolent completely resected second malignancies are\n eligible. Exception PART B: Adequately treated carcinoma in situ of the cervix and\n adequately treated basal cell carcinoma of the skin.\n 5. Symptomatic or untreated leptomeningeal disease\n 6. Symptomatic brain metastasis. Patients previously treated or untreated for these\n conditions that are asymptomatic in the absence of corticosteroid and anticonvulsant\n therapy (for at least 4 weeks) are allowed to enroll. Radiotherapy for brain\n metastasis must have been completed at least 6 weeks prior to start of study\n treatment. Brain metastasis must be stable with verification by imaging (e.g.\n brain MRI or CT completed at screening demonstrating no current evidence of\n progressive brain metastases). Patients are not permitted to receive antiepileptic\n drugs or corticosteroids.\n 7. Patients who have had previous treatment with any targeted drug combination known to\n interfere RAS/MEK/MAPK pathway components.\n 8. Toxicities related to prior treatments > grade 1 (excluding alopecia)\n 9. History of interstitial lung disease or pneumonitis\n 10. Woman who are breast feeding;\n 11. Patients who have undergone any major surgery within the last 4 weeks prior to\n starting study drug or who would not have fully recovered from previous surgery.\n 12. Radio- or chemotherapy within the last 4 weeks prior to receiving the first dose of\n investigational treatment; except a palliative dose of radiation of 8 Gy, which is\n allowed up to one week before study start and should not be applied to the target\n lesion.\n 13. Uncontrolled infectious disease or known Human Immunodeficiency Virus HIV-1 or HIV-2\n type patients;\n 14. Patients with a known history of or uncontrolled hepatitis B (HBV) or C (HCV);\n 15. Patients with known alcoholism, drug addiction and/or psychiatric of physiological\n condition which in the opinion of the investigator would impair study compliance;\n 16. Patients with cardiac comorbidities (myocardial infarct within 6 months of study\n start, NYHA class \u2265 III, congestive heart failure or instable angina pectoris),\n uncontrolled hypertension (systolic blood pressure > 160 mm Hg and/or diastolic\n pressure > 90 mm Hg), prolonged QT interval(> 440 ms for men, > 460 ms for women) or\n patients who have had a stroke within 6 months prior to start study.\n 17. Other severe, acute, or chronic medical or psychiatric condition, laboratory\n abnormality active infections that may increase the risk associated with study\n participation or study drug administration or that may interfere with the\n interpretation of study results and, in the judgment of the investigator, would make\n the patient inappropriate for the study.\n 18. Patients with pulmonary embolisms or deep venous thrombosis (DVT) within 3 months\n prior to start\n 19. Known hypersensitivity to one of the study drugs or excipients.\n 20. Baseline diarrhea and/or any condition that would impair absorption of oral agents\n 21. Patient with a history or findings of central or branch retinal artery or venous\n occlusion with significant vision loss or other retinal diseases that cause current\n visual impairment or would likely cause visual impairment over the time period of the\n study, as assessed by an ophthalmologist.", "output": {"inclusion_biomarker": [["KRAS mutation"]], "exclusion_biomarker": [["NRAS mutation"], ["RAS Q61"], ["KRAS G13"], ["BRAF class 1 mutation"], ["BRAF class 2 mutation"], ["BRAF unclassified mutation"], ["PIK3CA mutation"], ["STK11 mutation"], ["KEAP1 mutation"]]}}
 {"input": "Tumours require a blood supply to provide them with oxygen and nutrients and to enable spread\n of cancer through blood vessels to other organs (metastasis). The formation of new blood\n vessels is known as angiogenesis, which is controlled by a growth factor (like a hormone)\n called Vascular Endothelial Growth Factor (VEGF). Many drugs have been developed that block\n VEGF and, in most tumour types, including ovarian cancer, the addition of VEGF inhibitors\n (VEGFi) to conventional anti-cancer therapy postpones recurrence of the disease. In ovarian\n cancer, VEGFi improve the overall outcome from the cancer in patients who have advanced stage\n and high-risk disease. VEGFi are now widely used in cancer medicine, yet until now there have\n not been any biomarkers (tests) that could be used to tell patients and their doctors whether\n the drugs were working or not. This is important, as VEGFi have side effects that are\n unpleasant for the patient. Additionally, VEGFi treatments are expensive.\n The VALTIVE team has discovered the first biomarker that informs doctors whether a VEGFi is\n blocking a tumour's blood supply. The test involves measuring a protein in the blood called\n Tie2, which can be measured from routine blood tests that patients have when going to the\n hospital. If the test shows that the amount of Tie2 decreases in the blood, it means that\n tumour blood vessels are blocked by VEGFi; if, on the contrary, the level increases, the\n blood vessels have escaped the control of VEGFi.\n The investigators have shown that the Tie2 test works in their initial studies in ovarian and\n bowel cancer. In these studies, the Tie2 blood test was based in the research laboratories.\n The investigators now wish to establish the test in the Christie Hospital NHS Biochemistry\n laboratory in Manchester so that it can be used in clinical practice rather than just as a\n research tool. The investigators wish to measure the relationship between loss of control of\n VEGF inhibitors as measured by TIE 2 and other standard ways of measuring loss of control of\n the tumour like increases on CT scans. There are several reasons why this test is needed for\n patients with ovarian cancer:\n - VEGFi are effective during a patient's first or subsequent treatments for advanced\n ovarian cancer, but it is not clear which individuals are benefitting from treatment\n whilst they are on treatment.\n - Patients who have already had one course of VEGFi can be re-treated successfully.\n - Patients can avoid needless side effects, if there is a way of demonstrating that the\n treatment is of no benefit to them.\n - This test will help doctors choose the best drug to control ovarian cancer and how long\n to continue treatment. This is very important, since other maintenance therapies are now\n available and the optimal duration of VEGFi therapy is well known.\n - Around the world many teams are developing new combination treatments including VEGFi.\n If these new combinations prove effective, it would be possible to use them as\n efficiently as possible, as they will be very expensive and may therefore be less\n accessible to patients.\n These issues highlight the critical need to establish a test in the NHS that tells patients\n and their doctors when VEGFi are working and when they stop working.\n In VALTIVE1 study, blood samples will be taken from patients who are receiving a VEGFi called\n bevacizumab for ovarian cancer. Patients' management will not change during their\n participation to the trial. The analysis of the blood sample will support the hypothesis that\n patients whose Tie2 level decreases in response to bevacizumab will have ovarian cancer that\n is controlled for much longer than those where the Tie2 level does not decrease. These\n results will be used to design a second trial where the investigators will prove conclusively\n the value of the Tie2 test.\n The purpose of VALTIVE1 is to optimise sample acquisition time points and analytical\n algorithms to support the design of VALTIVE2, a randomised discontinuation trial. In\n VALTIVE2, Tie2-defined, vascular non-responding patients will be randomly allocated to stop\n bevacizumab after 9 weeks, by when a response can be detected, or to continue bevacizumab for\n the conventional year of treatment.\n Both VALTIVE 1 and VALTIVE2 will test the theory that there is no advantage in continuing\n bevacizumab in a patient whose Tie2 level does not reduce in response to VEGFi.\n ;\n ;\n Inclusion Criteria:\n In order to be eligible for participation in this trial, the patient must:\n 1. Be willing and able to provide written informed consent for the trial\n 2. Age 16 years or over on day of signing informed consent\n 3. 3. Histologically proven ovarian, primary peritoneal or fallopian tube cancer\n (henceforth referred to collectively as Ovarian Cancer - OC) FIGO stage III with\n residual disease of more than 1cm; or stage IV; or stage III at presentation treated\n with neoadjuvant chemotherapy; or stage III with contraindication to debulking surgery\n chemotherapy\n 4. Planned to receive treatment with bevacizumab or biosimilar bevacizumab\n 5. Be scheduled to receive at least 2 successive doses of bevacizumab with 6 or more\n weeks of follow up blood samples after the first dose of bevacizumab if given\n pre-operatively; or to start bevacizumab post-operatively\n 6. Be eligible for receiving treatment with first line, 3-weekly carboplatin and\n paclitaxel chemotherapy\n 7. Be willing to provide blood samples and comply with trial-specific procedures\n Exclusion Criteria:\n The patient must be excluded from participating in the trial if the patient:\n 1. Is unsuitable for treatment with VEGF inhibitors\n 2. Is unable or unwilling to comply with study procedures\n 3. Is participating in a clinical study with an investigational product other than\n carboplatin, paclitaxel and bevacizumab\n 4. Is judged by the investigator to be unlikely to comply with study procedures\n 5. Is pregnant or could become pregnant and is not using adequate contraception\n 6. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)\n 7. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g. HCV RNA is\n detected). Testing only required if patient has a history of either of these", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
 {"input": "Multicenter, retrospective and prospective, cohort, observational study evaluating the\n clinical efficacy and tolerability of Eribulin as second-line treatment in accordance with\n the indications authorized by AIFA in patients with triple negative advanced breast cancer in\n a real world setting.\n ;\n ;\n Inclusion Criteria:\n - Performance status according to ECOG equal to 0-2\n - Locally advanced or triple negative metastatic breast cancer (HR- and HER2-) confirmed\n histologically\n - Progressing after first-line chemotherapy for advanced disease\n - Previous anthracyclines and taxanes therapy (in an adjuvant, neoadjuvant or\n metastatic), unless the patient is ineligible to receive such treatments\n - Treatment with Eribulin mesylate since 2017, in accordance with AIFA indications\n - Adequate haematological, renal and hepatic function, as per clinical practice\n - Written informed consent\n Exclusion Criteria:\n - Breast cancer HER2 + or HR +\n - Treatment with Eribulin in the context of clinical studies\n - Patients unsuitable for treatment with Eribulin\n - Diagnosis of other malignancies in the two years prior to enrollment, with one\n exception of adequately treated localized basal cell or squamous cell carcinomas of\n the skin o cervical carcinomas undergoing curative treatment", "output": {"inclusion_biomarker": [["HR negative", "HER2 negative"]], "exclusion_biomarker": [["HER2 positive"], ["HR positive"]]}}
-{"input": "Over-expression of Epidermal Growth Factor Receptor (EGFR) on cells occurs in all aggressive\n cancers of epithelial origin. Existing tests for monitoring EGFR expression are invasive and\n not reliable. There needs to be a better way to measure EGFR expression in cancerous tumors\n to better tailor cancer treatments.\n This clinical trial aims to demonstrate the feasibility of imaging cancers that express EGFR\n using 89Zr-DFO-nimotuzumab and Positron Emission Tomography (PET)/Computerized Tomography\n (CT). By non-invasively imaging the status of EGFR, 89Zr-DFO-nimotuzumab could be used to\n assist in the identification of patients who are likely to respond to anti-EGFR treatments,\n including nimotuzumab. The hypothesis is that 89Zr-DFO-nimotuzumab will accumulate to tumors\n over-expressing EGFR making them visible when imaged with PET/CT. This hypothesis will be\n tested in this study, along with the optimal imaging time and diagnostic ability.\n ;NA;\n Inclusion Criteria:\n - Male or female between 18 and 80 years old.\n - EGFR-positive cancer defined by a board certified pathologist\n - Primary or metastatic lesion size >= 1.5 cm as determined by imaging studies\n (ultrasonography, mammography, CT or MRI) or physical examination.\n - Able to give informed consent.\n - Not currently pregnant or nursing: If female subject must be surgically sterile (has\n had a documented bilateral oophorectomy and/or documented hysterectomy),\n post-menopausal (cessation of menses for > 1 year), non-lactating, or of childbearing\n potential for whom a urine pregnancy test is negative when taken within the 24 h\n before administration of 89Zr-DFO-nimotuzumab.\n - WHO performance status of 0 - 2\n - Patients na\u00efve to anti-EGFR antibodies treatment.\n Exclusion Criteria:\n - Unable to tolerate 60 min of PET imaging per session.", "output": {"inclusion_biomarker": [["EGFR positive"]], "exclusion_biomarker": []}}
-{"input": "The purpose of this first in human (FIH) trial is to characterize the safety and tolerability\n of the SHP2 inhibitor TNO155 alone and in combination with EGF816 (nazartinib) and identify a\n recommended dose for future studies in adult patients with advanced solid tumors in selected\n indications.\n ;\n ;\n Inclusion Criteria:\n 1. Able to understand and voluntarily sign the ICF and able to comply with the study\n visit schedule and the other protocol requirements.\n 2. Patient (male or female) \u226518 years of age willing to agree to not father a\n child/become pregnant and comply with effective contraception criteria.\n 3. Must have progressed following standard therapy, or for whom, in the opinion of the\n Investigator, no effective standard therapy exists, is tolerated or is appropriate.\n 4. ECOG (Eastern cooperative oncology group) performance status \u22642\n Additional criteria only appying to TNO155 in combination with EGF816 (nazartinib):\n 5. Patients must be screened for Hepatitis B virus and Hepatitis C virus\n Exclusion Criteria:\n 1. Tumors harboring known activating KRAS, NRAS, HRAS, BRAF or PTPN11 (SHP2) mutations.\n (Exceptions are KRAS G12-mutant NSCLC's)\n 2. History or current evidence of retinal vein occlusion (RVO) or current risk factors\n for RVO.\n 3. Any medical condition that would, in the investigator's judgment, prevent the\n patient's participation in the clinical study due to safety concerns or compliance\n with clinical study procedures.\n 4. Clinically significant cardiac disease.\n 5. Active diarrhea or inflammatory bowel disease\n 6. Insufficient bone marrow function\n 7. Insufficient hepatic and renal function.\n Additional criteria only appying to TNO155 in combination with EGF816 (nazartinib):\n 8. Patients with a known history of human immunodeficiency virus (HIV) seropositivity.\n 9. Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use\n at the time of study entry.\n 10. Patients who have undergone a bone marrow or solid organ transplant\n 11. Patients with a history or presence of interstitial lung disease or interstitial\n pneumonitis\n 12. Bullous and exfoliative skin disorders at screening of any grade\n 13. Presence of clinically significant ophthalmological abnormalities that might increase\n the risk of corneal epithelial injury", "output": {"inclusion_biomarker": [], "exclusion_biomarker": [["KRAS mutation"], ["NRAS mutation"], ["HRAS mutation"], ["BRAF mutation"], ["PTPN11 mutation"]]}}
-{"input": "This phase II trial studies the side effects and how well azacitidine and enasidenib work in\n treating patients with IDH2-mutant myelodysplastic syndrome. Azacitidine and enasidenib may\n stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.\n ;\n ;\n Inclusion Criteria:\n - Signed, informed consent must be obtained prior to any study specific procedures\n - Subjects with a histologically confirmed diagnosis of MDS, including both MDS and\n refractory anemia with excess blasts in transformation (RAEB-T) (acute myeloid\n leukemia [AML] with 20-30% blasts and multilineage dysplasia by\n French-American-British [FAB] criteria) by World Health Organization (WHO), and\n chronic myelomonocytic leukemia (CMML) are eligible\n - Subjects must have an IDH2 gene mutation (IDH2-R140 or R172) as determined by local\n laboratory result\n - (Arm A only): Subject must be hypomethylating agent naive (i.e. prior azacitidine,\n decitabine, SGI-110 is exclusionary). Receipt of other MDS-directed therapy such as\n lenalidomide is allowed\n - (Arm A only): Subjects with high-risk MDS (i.e. International Prostate Symptom Score\n [IPSS] intermediate-2 or high-risk; or revised [R]-IPSS high or very-high risk).\n Patients with intermediate-1 risk by IPSS or intermediate risk by R-IPSS with\n high-risk molecular features including TP53, ASXL1, EZH2, and/or RUNX1 mutations are\n also eligible\n - (Arm B only): Subject must be relapsed or refractory to prior hypomethylating agent\n therapy, defined as prior receipt of 6 cycles of HMA therapy with failure to attain a\n response, or relapse after prior response to HMA therapy\n - Eastern Cooperative Oncology Group (ECOG) performance status of 0-2\n - Serum bilirubin =< 2 x the upper limit of normal (ULN) (except for patients with\n Gilbert's disease)\n - Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) =< 3 x the\n laboratory ULN\n - Serum creatinine =< 2 x the ULN\n - Able to understand and voluntarily sign a written informed consent, and willing and\n able to comply with protocol requirements\n - Resolution of all clinically significant treatment-related, non-hematological\n toxicities, except alopecia, from any previous cancer therapy to =< grade 1 prior to\n the first dose of study treatment\n - Female patients of childbearing potential must have a negative serum or urine\n pregnancy test within 7 days of the first dose of study drug and agree to use dual\n methods of contraception during the study and for a minimum of 3 months following the\n last dose of study drug. Post-menopausal females (> 45 years old and without menses\n for > 1 year) and surgically sterilized females are exempt from these requirements.\n Male patients must use an effective barrier method of contraception during the study\n and for a minimum of 3 months following the last dose of study drug if sexually active\n with a female of childbearing potential\n Exclusion Criteria:\n - Any prior or coexisting medical condition that in the investigator's judgment will\n substantially increase the risk associated with the subject's participation in the\n study\n - Subject has received a prior targeted IDH2 inhibitor\n - Psychiatric disorders or altered mental status precluding understanding of the\n informed consent process and/or completion of the necessary study procedures\n - Active uncontrolled infection at study enrollment including known diagnosis of human\n immunodeficiency virus or chronic active hepatitis B or C infection\n - Clinically significant gastrointestinal conditions or disorders that may interfere\n with study drug absorption, including prior gastrectomy\n - Patients with known active central nervous system (CNS) disease, including\n leptomeningeal involvement\n - Impaired cardiac function, uncontrolled cardiac arrhythmia, or clinically significant\n cardiac disease including the following: a) New York Heart Association grade III or IV\n congestive heart failure, b) myocardial infarction within the last 6 months\n - Subjects with a corrected QT (QTc) > 480 ms (QTc > 510 msec for subjects with a bundle\n branch block at baseline\n - Nursing or pregnant women\n - Subjects with known hypersensitivity to study drugs or their excipients", "output": {"inclusion_biomarker": [["IDH2 R140"], ["IDH2 R172"]], "exclusion_biomarker": []}}
+{"input": "Over-expression of Epidermal Growth Factor Receptor (EGFR) on cells occurs in all aggressive\n cancers of epithelial origin. Existing tests for monitoring EGFR expression are invasive and\n not reliable. There needs to be a better way to measure EGFR expression in cancerous tumors\n to better tailor cancer treatments.\n This clinical trial aims to demonstrate the feasibility of imaging cancers that express EGFR\n using 89Zr-DFO-nimotuzumab and Positron Emission Tomography (PET)/Computerized Tomography\n (CT). By non-invasively imaging the status of EGFR, 89Zr-DFO-nimotuzumab could be used to\n assist in the identification of patients who are likely to respond to anti-EGFR treatments,\n including nimotuzumab. The hypothesis is that 89Zr-DFO-nimotuzumab will accumulate to tumors\n over-expressing EGFR making them visible when imaged with PET/CT. This hypothesis will be\n tested in this study, along with the optimal imaging time and diagnostic ability.\n ;NA;\n Inclusion Criteria:\n - Male or female between 18 and 80 years old.\n - EGFR-positive cancer defined by a board certified pathologist\n - Primary or metastatic lesion size >= 1.5 cm as determined by imaging studies\n (ultrasonography, mammography, CT or MRI) or physical examination.\n - Able to give informed consent.\n - Not currently pregnant or nursing: If female subject must be surgically sterile (has\n had a documented bilateral oophorectomy and/or documented hysterectomy),\n post-menopausal (cessation of menses for > 1 year), non-lactating, or of childbearing\n potential for whom a urine pregnancy test is negative when taken within the 24 h\n before administration of 89Zr-DFO-nimotuzumab.\n - WHO performance status of 0 - 2\n - Patients na\u00efve to anti-EGFR antibodies treatment.\n Exclusion Criteria:\n - Unable to tolerate 60 min of PET imaging per session.", "output": {"inclusion_biomarker": [["EGFR expression"]], "exclusion_biomarker": []}}
+{"input": "The purpose of this first in human (FIH) trial is to characterize the safety and tolerability\n of the SHP2 inhibitor TNO155 alone and in combination with EGF816 (nazartinib) and identify a\n recommended dose for future studies in adult patients with advanced solid tumors in selected\n indications.\n ;\n ;\n Inclusion Criteria:\n 1. Able to understand and voluntarily sign the ICF and able to comply with the study\n visit schedule and the other protocol requirements.\n 2. Patient (male or female) \u226518 years of age willing to agree to not father a\n child/become pregnant and comply with effective contraception criteria.\n 3. Must have progressed following standard therapy, or for whom, in the opinion of the\n Investigator, no effective standard therapy exists, is tolerated or is appropriate.\n 4. ECOG (Eastern cooperative oncology group) performance status \u22642\n Additional criteria only appying to TNO155 in combination with EGF816 (nazartinib):\n 5. Patients must be screened for Hepatitis B virus and Hepatitis C virus\n Exclusion Criteria:\n 1. Tumors harboring known activating KRAS, NRAS, HRAS, BRAF or PTPN11 (SHP2) mutations.\n (Exceptions are KRAS G12-mutant NSCLC's)\n 2. History or current evidence of retinal vein occlusion (RVO) or current risk factors\n for RVO.\n 3. Any medical condition that would, in the investigator's judgment, prevent the\n patient's participation in the clinical study due to safety concerns or compliance\n with clinical study procedures.\n 4. Clinically significant cardiac disease.\n 5. Active diarrhea or inflammatory bowel disease\n 6. Insufficient bone marrow function\n 7. Insufficient hepatic and renal function.\n Additional criteria only appying to TNO155 in combination with EGF816 (nazartinib):\n 8. Patients with a known history of human immunodeficiency virus (HIV) seropositivity.\n 9. Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use\n at the time of study entry.\n 10. Patients who have undergone a bone marrow or solid organ transplant\n 11. Patients with a history or presence of interstitial lung disease or interstitial\n pneumonitis\n 12. Bullous and exfoliative skin disorders at screening of any grade\n 13. Presence of clinically significant ophthalmological abnormalities that might increase\n the risk of corneal epithelial injury", "output": {"inclusion_biomarker": [], "exclusion_biomarker": [["KRAS activating mutation"], ["NRAS activating mutation"], ["HRAS activating mutation"], ["BRAF activating mutation"], ["PTPN11 activating mutation"]]}}
+{"input": "This phase II trial studies the side effects and how well azacitidine and enasidenib work in\n treating patients with IDH2-mutant myelodysplastic syndrome. Azacitidine and enasidenib may\n stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.\n ;\n ;\n Inclusion Criteria:\n - Signed, informed consent must be obtained prior to any study specific procedures\n - Subjects with a histologically confirmed diagnosis of MDS, including both MDS and\n refractory anemia with excess blasts in transformation (RAEB-T) (acute myeloid\n leukemia [AML] with 20-30% blasts and multilineage dysplasia by\n French-American-British [FAB] criteria) by World Health Organization (WHO), and\n chronic myelomonocytic leukemia (CMML) are eligible\n - Subjects must have an IDH2 gene mutation (IDH2-R140 or R172) as determined by local\n laboratory result\n - (Arm A only): Subject must be hypomethylating agent naive (i.e. prior azacitidine,\n decitabine, SGI-110 is exclusionary). Receipt of other MDS-directed therapy such as\n lenalidomide is allowed\n - (Arm A only): Subjects with high-risk MDS (i.e. International Prostate Symptom Score\n [IPSS] intermediate-2 or high-risk; or revised [R]-IPSS high or very-high risk).\n Patients with intermediate-1 risk by IPSS or intermediate risk by R-IPSS with\n high-risk molecular features including TP53, ASXL1, EZH2, and/or RUNX1 mutations are\n also eligible\n - (Arm B only): Subject must be relapsed or refractory to prior hypomethylating agent\n therapy, defined as prior receipt of 6 cycles of HMA therapy with failure to attain a\n response, or relapse after prior response to HMA therapy\n - Eastern Cooperative Oncology Group (ECOG) performance status of 0-2\n - Serum bilirubin =< 2 x the upper limit of normal (ULN) (except for patients with\n Gilbert's disease)\n - Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) =< 3 x the\n laboratory ULN\n - Serum creatinine =< 2 x the ULN\n - Able to understand and voluntarily sign a written informed consent, and willing and\n able to comply with protocol requirements\n - Resolution of all clinically significant treatment-related, non-hematological\n toxicities, except alopecia, from any previous cancer therapy to =< grade 1 prior to\n the first dose of study treatment\n - Female patients of childbearing potential must have a negative serum or urine\n pregnancy test within 7 days of the first dose of study drug and agree to use dual\n methods of contraception during the study and for a minimum of 3 months following the\n last dose of study drug. Post-menopausal females (> 45 years old and without menses\n for > 1 year) and surgically sterilized females are exempt from these requirements.\n Male patients must use an effective barrier method of contraception during the study\n and for a minimum of 3 months following the last dose of study drug if sexually active\n with a female of childbearing potential\n Exclusion Criteria:\n - Any prior or coexisting medical condition that in the investigator's judgment will\n substantially increase the risk associated with the subject's participation in the\n study\n - Subject has received a prior targeted IDH2 inhibitor\n - Psychiatric disorders or altered mental status precluding understanding of the\n informed consent process and/or completion of the necessary study procedures\n - Active uncontrolled infection at study enrollment including known diagnosis of human\n immunodeficiency virus or chronic active hepatitis B or C infection\n - Clinically significant gastrointestinal conditions or disorders that may interfere\n with study drug absorption, including prior gastrectomy\n - Patients with known active central nervous system (CNS) disease, including\n leptomeningeal involvement\n - Impaired cardiac function, uncontrolled cardiac arrhythmia, or clinically significant\n cardiac disease including the following: a) New York Heart Association grade III or IV\n congestive heart failure, b) myocardial infarction within the last 6 months\n - Subjects with a corrected QT (QTc) > 480 ms (QTc > 510 msec for subjects with a bundle\n branch block at baseline\n - Nursing or pregnant women\n - Subjects with known hypersensitivity to study drugs or their excipients", "output": {"inclusion_biomarker": [["IDH2 R140"], ["IDH2 R172"], ["IDH2 R140", "TP53 mutation"], ["IDH2 R172", "TP53 mutation"], ["IDH2 R140", "ASXL1 mutation"], ["IDH2 R172", "ASXL1 mutation"], ["IDH2 R140", "EZH2 mutation"], ["IDH2 R172", "EZH2 mutation"], ["IDH2 R140", "RUNX1 mutation"], ["IDH2 R172", "RUNX1 mutation"]], "exclusion_biomarker": []}}
 {"input": "This will be a Phase 1 Open-label, dose escalation and expansion study of MT-6402 (an\n Engineered Toxin Body (ETB)) in subjects with advanced solid cancer that expresses PD-L1\n ;\n ;\n Inclusion Criteria:\n Part A\n 1. Subject must be at least 18 years old and must have histologically confirmed,\n unresectable, locally advanced, or metastatic PD-L1-expressing solid cancer not\n amenable to standard treatment, or standard treatment is not available, or in the\n Investigator's opinion the standard treatment would not be in the subject's best\n interest. Any level of PD-L1 expression assessed by using any Food and Drug\n Administration (FDA) approved PD-L1 immunohistochemistry (IHC) assay is accepted. The\n assessment should have been performed on the most recent available tissue from a site\n of metastatic disease (if possible).\n 2. Subject must have evaluable or measurable disease.\n Part B\n 1. Subject must be at least 18 years old and must have histologically confirmed,\n unresectable, locally advanced or metastatic PD-L1-expressing solid cancer (defined\n below) not amenable to standard treatment, or standard treatment is not available, or\n in the Investigator's opinion the standard treatment would not be in the subject's\n best interest. PD-L1 expression must be assessed at screening by the study's central\n laboratory, using VENTANA SP263 PD-L1 assay on a tissue from a site of metastatic\n disease (if possible). For this purpose, recent archived tissue suitable for PD-L1\n expression assessment by IHC (obtained after the last treatment and within 6 months)\n or fresh biopsy material can be used. The PD-L1 assessment must show at least 5% vCPS\n (visually estimated Combined Positive Score) for eligibility.\n - Arm 1: Histologically confirmed recurrent or metastatic NSCLC not amenable to\n standard treatment, or standard treatment is not available, or in the\n Investigator's opinion the standard treatment would not be in the subject's best\n interest. NOTE: subjects with driver mutations are only eligible if they have\n received all appropriate targeted therapies.\n - Arm 2: Histologically confirmed recurrent or metastatic SCCHN (oral cavity,\n oropharynx, hypopharynx, or larynx) not amenable to standard treatment, or\n standard treatment is not available, or in the Investigator's opinion the\n standard treatment would not be in the subject's best interest. Subjects who\n refuse radical resection are eligible. NOTE: squamous cell carcinoma of any other\n primary anatomic location in the head and neck, subjects with SCCHN of unknown\n primary, and subjects with skin squamous cell carcinoma (SCC) of the head and\n neck are not eligible for this arm. The tumor must be platinum resistant or the\n subject ineligible for platinum therapy due to hypersensitivity or concerns with\n ototoxicity.\n - Arm 3: Subjects with any other relapsed or refractory PD-L1 positive solid tumor\n not amenable to standard treatment, or standard treatment is not available, or in\n the Investigator's opinion the standard treatment would not be in the subject's\n best interest, who received PD-1/PD-L1 treatment. Subjects with PD-L1 positive\n solid tumor types, for which PD-1/PD-L1 treatment is not approved, could be\n enrolled at the Investigator's discretion and after discussion with the Medical\n Monitor.\n 2. Subject must have at least 1 measurable tumor lesion according to RECIST 1.1.\n Parts A and B\n 3. Subject must have Eastern Cooperative Oncology Group (ECOG) performance score of 0 or\n 1.\n 4. Prior treatment must include a CPI (i.e., PD-1 inhibitors, PD-L1 inhibitors with or\n without CTLA-4 inhibitors) if there is an approved CPI for the specific cancer type.\n Subjects may also have received CPIs in an investigational setting. Subjects who have\n not received a CPI and where there is no approved CPI for the specific cancer type\n could be enrolled at the Investigator's discretion and after discussion with the\n Medical Monitor.\n 5. Subject must have adequate bone marrow function (NOTE: administration of blood\n products and growth factors is not allowed within 2 weeks prior to screening\n laboratory tests):\n - absolute neutrophil count (ANC) \u2265 1,500/\u03bcL\n - platelet count \u2265 100,000/\u03bcL\n - hemoglobin \u2265 8.0 g/dL\n 6. Subject must have adequate renal function, based on estimated creatinine clearance\n (eCrCl) \u2265 50 mL/min, calculated by the Cockcroft-Gault equation.\n NOTE: At the Investigator's discretion, the eCrCl result < 50 mL/min may be verified\n by measured creatinine clearance (mCrCl) based on the 24-hour urine collection.\n Subjects with mCrCl \u2265 50 mL/min will be eligible irrespective of the eCrCl result\n calculated by the Cockcroft-Gault equation.\n 7. Subject must have adequate hepatic function, as determined by:\n - total bilirubin (or direct bilirubin for subjects with Gilbert's disease) < 1.5 \u00d7\n upper limit of normal (ULN)\n - aspartate aminotransferase (AST) \u2264 3 \u00d7 ULN (or \u2264 5 \u00d7 ULN if liver metastasis)\n - alanine aminotransferase (ALT) \u2264 3 \u00d7 ULN (or \u2264 5 \u00d7 ULN if liver metastasis)\n 8. Subject must have adequate serum albumin (albumin \u2265 2.5 g/dL)\n 9. Women of reproductive potential must have a negative highly sensitive pregnancy test\n within 72 hours before the start of treatment. Women who are postmenopausal (> 1 year\n since last menstrual cycle) or permanently sterilized (e.g., bilateral tubal\n occlusion, hysterectomy, bilateral salpingectomy) may be considered as not of\n reproductive potential.\n 10. Subjects of reproductive potential must agree either to abstain continuously from\n heterosexual intercourse or to use a highly effective birth control method from\n signing the informed consent until 30 days after the last dose of MT-6402 for females\n and until 90 days after the last dose of MT-6402 for males.\n Exclusion Criteria:\n Part A\n 1. Subjects without available tissue from a site of metastatic disease or easily biopsiable\n lesion (biopsy sites of non significant risk, in the opinion of the Investigator) or\n unwilling to consent to biopsy.\n Part B\n 1. Subjects without easily biopsiable lesions (biopsy sites of non significant risk, in\n the opinion of the Investigator) or unwilling to consent to biopsy.\n Parts A and B\n 2. History or current evidence of another neoplastic disease, except cervical carcinoma\n in situ, superficial noninvasive bladder tumors, curatively treated Stage I to II non\n melanoma skin cancer or any previous cancer curatively treated > 2 years before the\n start of treatment.\n 3. Active autoimmune disease currently under treatment or required systemic treatment\n within 2 years (replacement therapy, e.g., thyroxine, insulin, or physiologic\n corticosteroid replacement therapy for adrenal or pituitary insufficiency is allowed).\n Subjects who have not required systemic treatment of an auto-immune disease for at\n least 2 years may be enrolled if permission is provided after discussion with the\n Medical Monitor.\n 4. Ongoing > Grade 1 immune related toxicity caused by prior CPI therapy (i.e., PD-1\n inhibitors, PD-L1 inhibitors, or CTLA-4 inhibitors). Subjects with stable\n endocrinological AEs, e.g., hypothyroidism, adrenal insufficiency, hypopituitarism, or\n diabetes mellitus, must have been on a stable dose of supplemental therapy for at\n least 2 weeks before screening to be eligible for this study.\n 5. Evidence of active noninfectious \u2265 Grade 2 pneumonitis or current evidence of \u2265 Grade\n 3 other underlying pulmonary disease.\n 6. Received any of the following PD-L1 inhibitors within the following time periods prior\n to the first dose of MT-6402: atezolizumab - 12 months; durvalumab - 7 months;\n avelumab - 2 months.\n 7. Any concurrent cancer treatment, apart from local treatment of non-target lesions for\n palliative intent (e.g., local surgery or radiotherapy).\n 8. Prior radiation therapy within 4 weeks before the start of study treatment. NOTE: A\n lesion in a previously irradiated area can only be considered target lesion if there\n has been radiographical disease progression since the end of radiation therapy.\n 9. Received approved or investigational treatment for the disease under study (except PD\n L1 inhibitors where exclusion criterion 6 applies) within 4 weeks before the start of\n treatment. For small molecules (MW < 0.9 kDa), the washout is 5 half-lives, but at\n least 2 weeks.\n 10. Subjects who have had allogeneic tissue or solid organ transplantation.\n 11. Current evidence of new or growing central nervous system (CNS) metastases during\n screening. Subjects with known asymptomatic CNS metastases will be eligible if they\n meet all the following criteria:\n 1. Had radiotherapy or another appropriate therapy for the CNS metastases.\n 2. Have stable CNS disease on the computed tomography (CT) or magnetic resonance\n imaging (MRI) scan within 4 weeks before screening compared with prior neuro\n imaging.\n 12. Major surgical procedure (as defined by the Investigator) within 28 days prior to the\n start of study treatment.\n 13. History or current evidence of significant cardiovascular disease before the start of\n treatment, including but not limited to the following conditions:\n 1. Angina pectoris requiring anti-anginal medication, (chest pain: Common\n Terminology Criteria for Adverse Events [CTCAE] Grade \u2265 2)\n 2. Clinically significant valvular disease.\n 3. Myocardial infarction within 12 months prior to the start of treatment.\n 4. Arterial thrombosis or pulmonary embolism within 3 months before the start of\n treatment.\n 5. History of Grade \u2265 2 symptomatic congestive heart failure (CHF) or New York Heart\n Association (NYHA) criteria Class \u2265 II.\n 6. Left ventricular ejection fraction (LVEF) < 55%, assessed preferably by\n echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan if ECHO is not\n available, within 28 days before starting study treatment.\n 7. High-risk uncontrolled arrhythmias (i.e., atrial tachycardia with a heart rate >\n 100/min at rest and upon repeated testing, significant ventricular arrhythmia\n (CTCAE Grade \u2265 2 [ventricular tachycardia], or higher-grade atrioventricular\n [AV]-block [second degree AV-block Type 2 [Mobitz 2] or third-degree AV-block])\n or left ventricular bundle branch block. Subjects receiving digoxin, calcium\n channel blockers, or beta adrenergic blockers are eligible at the Investigator's\n discretion after consultation with the Medical Monitor if the dose has been\n stable for \u2265 2 weeks before the start of treatment with MT-6402.\n 8. Any of the following within 3 months before the start of treatment: pericarditis\n (any CTCAE Grade), pericardial effusion (CTCAE Grade \u2265 2), non-malignant pleural\n effusion (CTCAE Grade \u2265 2) or malignant pleural effusion (CTCAE Grade \u2265 3)\n (subjects with pleural effusion that is manageable and stable > 3 months prior to\n study are eligible).\n 9. QT interval correction for heart rate using Fridericia's formula (QTcF) \u2265 470 ms\n (average from 3 QTcF values on the triplicate 12-lead electrocardiogram [ECG]) at\n screening. In subjects with right bundle branch blocks, additional corrections\n will be performed to calculate the QT equivalent JT, and depending on the result\n the subject may be eligible with the agreement of the Medical Monitor.\n 14. Current evidence of uncontrolled human immunodeficiency virus (HIV), hepatitis B virus\n (HBV), or hepatitis C virus (HCV) at screening. Serology testing is not required if\n seronegativity is documented in the medical history, and if there are no clinical\n signs suggestive of HIV or hepatitis infections, or suspected exposure. The following\n exceptions apply for subjects with positive viral serology:\n 1. Subjects with HIV and an undetectable viral load and CD4 + T-cell (CD4+) counts \u2265\n 350 cells/mL may be enrolled, but must be taking appropriate opportunistic\n infection prophylaxis, if clinically relevant.\n 2. Subjects with positive HBV serology are eligible if they have an undetectable\n viral load and the subject will receive antiviral prophylaxis for potential HBV\n reactivation per institutional guidelines.\n 3. Subjects with positive HCV serology are eligible if quantitative polymerase chain\n reaction (PCR) for plasma HCV RNA is below the lower limit of detection.\n Concurrent antiviral HCV treatment per institutional guidelines is allowed.\n 15. Current treatment requiring systemic steroids at doses > 10 mg/day prednisone\n equivalent.\n 16. Subjects with a history of hypersensitivity or serious toxic reactions to kanamycin or\n other aminoglycosides.\n 17. Subjects with unintentional weight loss > 10% of their body weight over the preceding\n 2 months or less before screening.\n 18. Female subjects who are pregnant or breastfeeding.\n 19. History or evidence of any other clinically significant disorder, condition or disease\n (with the exception of those outlined above) that, in the opinion of the Investigator\n or Medical Monitor, if consulted, would pose a risk to subject safety or interfere\n with the study evaluation, procedures or completion.", "output": {"inclusion_biomarker": [["PD-L1 expression"]], "exclusion_biomarker": []}}
 {"input": "This is a global, multicenter, open-label pre-approval access program to provide access to\n pralsetinib (BLU-667) until such time that pralsetinib becomes available through other\n mechanisms or the Sponsor chooses to discontinue the program.\n ;NA;\n Inclusion Criteria:\n 1a. Pathologically documented and definitively diagnosed non-resectable or metastatic NSCLC\n with a RET fusion for patients who are either treatment na\u00efve, or who have been previously\n treated with systemic therapy. In the presence of a primary driver mutation, such as EGFR,\n ALK, ROS1, NTRK, or BRAF, the patient must be treated with the appropriate targeted therapy\n first. Patient is eligible if RET fusion is confirmed AND patient has undergone initial\n therapy for his/her driver mutation, or\n 1b. Pathologically documented and definitively diagnosed RET mutation in advanced MTC\n patients who are treatment na\u00efve or who have been previously treated with MKI therapy, or\n 1c. Pathologically documented and definitively diagnosed advanced solid tumor with an\n oncogenic RET fusion previously treated with standard of care appropriate for the tumor\n type.\n 2. If previously treated with a selective RET inhibitor (e.g., RETEVMO), confirm patient\n has not progressed but has discontinued due to adverse event(s).\n 3. Patient is not eligible for an ongoing study of pralsetinib or cannot access an ongoing\n study of pralsetinib.\n 4. Patient is \u2265 12 years of age. 5. Patient has adequate vital organ function, including\n heart, lungs, liver, kidneys, bone marrow and endocrine, and is expected to tolerate\n therapy with a tyrosine kinase inhibitor.\n 6. No presence of clinically symptomatic interstitial lung disease or interstitial\n pneumonitis, including radiation pneumonitis (i.e., affecting activities of daily living or\n requiring therapeutic intervention).\n 7. Patient or patient's legal guardian, if permitted by local regulatory authorities,\n intends to provide informed consent prior to the start of treatment with pralsetinib.\n 8. Patient does not require therapy with a concomitant medication that is a strong\n inhibitor or strong inducer of cytochrome P450 (CYP) 3A4.\n 9. Patient has not received treatment with any systemic anticancer therapy (except for\n immunotherapy or other antibody therapies) and all forms of radiotherapy within 14 days or\n 5 half-lives prior to the first dose of pralsetinib. Pralsetinib may be started within\n these washout periods if considered by the healthcare provider to be safe and within the\n best interest of the patient, with prior Sponsor approval.\n 10. Patient has not received treatment with any immunotherapy or other antibody therapy\n within 28 days prior to the first dose of pralsetinib (immune related toxicities must have\n resolved to < Grade 2 prior to starting pralsetinib).\n 11. Patient has not had a major surgical procedure (minor surgical procedures such as\n central venous catheter placement, tumor needle biopsy, and feeding tube placement are not\n considered major surgical procedures) within 14 days prior to the first dose of\n pralsetinib.\n 12. Women must be willing, if not postmenopausal or surgically sterile, to abstain from\n sexual intercourse or employ highly effective contraception during pralsetinib\n administration period and for at least 30 days after the last dose of pralsetinib. Men, if\n not surgically sterile, must be willing to abstain from sexual intercourse or employ highly\n effective contraception during pralsetinib administration period and for at least 90 days\n after the last dose of pralsetinib.\n 13. Women must not be pregnant or breastfeeding.", "output": {"inclusion_biomarker": [["RET fusion"], ["RET fusion", "EGFR mutation"], ["RET fusion", "ALK mutation"], ["RET fusion", "ROS1 mutation"], ["RET fusion", "NTRK mutation"], ["RET fusion", "BRAF mutation"], ["RET mutation"]], "exclusion_biomarker": []}}
 {"input": "The purpose of this study is to evaluate the efficacy and safety of selinexor as a\n maintenance treatment in patients with p53 wt endometrial carcinoma (EC), who have achieved a\n partial response (PR) or complete response (CR) (per Response Evaluation Criteria in Solid\n Tumors version 1.1 [RECIST v 1.1]) after completing at least 12 weeks of platinum-based\n therapy. A total of 220 participants will be enrolled in the study and randomized in a 1:1\n ratio to maintenance therapy with either selinexor or placebo.\n ;NA;\n Inclusion Criteria:\n - At least 18 years of age at the time of signing informed consent.\n - Histologically confirmed EC including: endometrioid, serous, undifferentiated, and\n carcinosarcoma.\n - TP53 wt assessed by next generation sequencing (NGS), evaluated by a central vendor.\n - Completed a single line, at least 12 weeks of platinum-based therapy (not including\n adjuvant or neoadjuvant therapy for Stage I-III disease) and achieved confirmed\n partial or complete response (PR or CR) by imaging, according to RECIST version 1.1.\n The participants should have received treatment for:\n Primary Stage IV disease, defined as:\n - had a primary or later debulking surgery during first-line platinum-based therapy with\n R0 resection (R0 resection indicates a macroscopic complete resection of all visible\n tumor) and achieved CR after at least 12 weeks platinum-based therapy, OR\n - had a primary or later debulking surgery during first-line platinum-based therapy with\n R1 resection (R1 resection indicates incomplete removal of all macroscopic disease)\n and achieved PR or CR after at least 12 weeks platinum-based chemotherapy, OR\n - had no surgery and achieved PR or CR after at least 12 weeks platinum-based\n chemotherapy\n OR\n At first relapse (i.e., relapse after primary therapy including surgery and/or chemotherapy\n and/or immunotherapy for Stage I-IV disease), defined as:\n - had Stage I - III disease at diagnosis and received, at initial diagnosis, adjuvant\n chemotherapy and relapsed later. Participants should have PR or CR after at least 12\n weeks of platinum-based chemotherapy compared with the start of this chemotherapy at\n the time of relapse,\n - had Stage I-III disease at diagnosis and did not receive adjuvant chemotherapy at\n initial diagnosis and relapsed later. Participants should have PR or CR after at least\n 12 weeks of platinum-based chemotherapy compared with the start of this chemotherapy\n at the time of relapse, OR\n - had Stage IV disease at diagnosis and received initially chemotherapy with or without\n surgery and relapsed later. At the time of relapse, participants should have PR or CR\n after at least 12 weeks of platinum-based chemotherapy compared with the start of this\n chemotherapy at the time of relapse.\n - Previous treatment with anti-programmed cell death protein 1(PD-1) or\n anti-programmed death-ligand 1(PD-L1) monoclonal antibody and concomitant\n biologic agents (e.g., bevacizumab, trastuzumab) is allowed.\n - Must be able to initiate study drug 3 to 8 weeks after completion of their final\n dose of chemotherapy.\n - Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.\n - Participants must have adequate bone marrow function and organ function within 2\n weeks before starting study drug as defined by the following laboratory criteria:\n - Hepatic function: total bilirubin up to less than (<) 3*upper limit of normal (ULN);\n alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal\n to (<=) 2.5*ULN in participants without liver metastasis. For participants with known\n liver involvement of their tumor: AST and ALT (<=) 5*ULN\n - Hematopoietic function within 1 week: Absolute neutrophil count (ANC) greater than or\n equal to (>=) 1.5*10^9/liter (L); platelet count >= 100*10^9/L; hemoglobin >= 9.0 gram\n per deciliter (g/dL) per local laboratory results\n - Renal function: estimated creatinine clearance (CrCl) of >= 20 milliliter per minute\n (mL/min), calculated using the standard local formula, as applicable\n - In the opinion of the Investigator, the participant must:\n - Have a life expectancy of at least 12 weeks, and\n - Be fit to receive investigational therapy\n - Premenopausal females of childbearing potential must have a negative pregnancy\n test (serum \u03b2-human chorionic gonadotropin test) prior to the first dose of study\n drug. Female participants of childbearing potential must agree to use highly\n effective methods of contraception throughout the study and for 90 days following\n the last dose of study drug.\n - Written informed consent signed in accordance with federal, local, and\n institutional guidelines prior to the first screening procedure.\n Exclusion Criteria:\n - Participants meeting any of the following exclusion criteria are not eligible to\n enroll in this study:\n - Has any uterine sarcomas (carcinosarcomas - not excluded), clear cell or small cell\n carcinoma with neuroendocrine differentiation\n - Received a blood or platelet transfusion during the 2 weeks prior to Cycle 1 Day 1\n (C1D1). Participants' hemoglobin must be assessed within 2 weeks of screening and at\n least 1 week post transfusion\n - Concurrent systemic steroid therapy higher than physiologic dose (> 10 milligram per\n day [mg/day] of prednisone or equivalent). Systemic steroid therapy as pre-medication\n for taxane is allowed\n - Insufficient time since or not recovered from procedures or anti-cancer therapy,\n defined as:\n - Not recovered from major surgery <= 28 days prior to Day 1 dosing. Minor\n procedures, such as biopsies, dental work, or placement of a port or intravenous\n (IV) line for infusion are permitted\n - Having ongoing clinically significant anti-cancer therapy-related toxicities CTCAE\n Grade > 1, with the exception of alopecia. In specific cases, participants whose\n toxicity has stabilized or with Grade 2 non-hematologic toxicities can be allowed\n following documented approval by the Sponsor's Medical Monitor\n - Palliative radiotherapy within 14 days of the intended C1D1. Palliative radiotherapy\n may be permitted for symptomatic control of pain from bone metastases, provided that\n the radiotherapy does not involve target lesions, and the reason for the radiotherapy\n does not reflect evidence of disease progression.\n - Any gastrointestinal dysfunctions that could interfere with the absorption of\n selinexor (e.g., bowel obstruction, inability to swallow tablets, malabsorption\n syndrome, unresolved nausea, vomiting, diarrhea CTCAE v 5.0 > grade 1).\n - Participants unable to tolerate two forms of antiemetics for at least 2 cycles will\n not be eligible for the trial.\n - Active, ongoing or uncontrolled active infection requiring parenteral antibiotics,\n antivirals, or antifungals within 1 week of screening.\n - Serious psychiatric or medical condition that could interfere with participation in\n the study or in the opinion of the Investigator would make study involvement\n unreasonably hazardous.\n - Previous treatment with an XPO1 inhibitor.\n - Stable disease or PD on the post-chemotherapy scan or clinical evidence of progression\n prior to randomization.\n - Participants who received any systemic anticancer therapy including investigational\n agents <= 3 weeks (or <= 5 half-lives of the drug [whichever is shorter]) prior to\n C1D1.\n - Major injuries or surgery within 14 days prior to C1D1 and/or planned major surgery\n during the on-treatment study period.\n - Other malignant disease with disease-free <= 3 years except: curatively treated\n carcinoma in situ of the cervix, basal cell carcinoma of the skin, or ductal carcinoma\n in situ (DCIS) of the breast.\n - History of allergic reactions attributed to compounds of similar chemical or biologic\n composition to selinexor, or other agents used in the study.\n - Active brain metastases (e.g., stable for < 8 weeks, no adequate previous treatment\n with radiotherapy and/or surgery, symptomatic, requiring treatment with\n anti-convulsant therapy. Corticoid therapy is allowed if administered as stable dose\n for at least 1 month before randomization).\n - Females who are pregnant or lactating.\n - Any other life-threatening illness, active medical condition, organ system\n dysfunction, or serious active psychiatric issue which, in the Investigator's opinion,\n could compromise the participant's safety or the participant's ability to remain\n compliant with study procedures.", "output": {"inclusion_biomarker": [["TP53 wt"]], "exclusion_biomarker": []}}
-{"input": "This study will be a single arm multicenter Phase II open-label, dose escalation study of\n asciminib in patients with CML-CP without T315I mutation who have had 1 prior TKIs for which\n they did not respond to treatment or were intolerant to treatment.\n ;\n ;\n Inclusion Criteria:\n Signed informed consent must be obtained prior to participation in the study 2. Chronic\n Myelogenous Leukemia (CML-CP,) no previous Accelerated Phase (AP) or Blast Crisis (BC) 3. \u2265\n 18 years of age 4. For CML-CP patients with treatment failure/resistance to first line (1L)\n Tyrosine Kinase Inhibitor (TKI,) BCR-ABL1IS at screening:\n 1. >10% if 1L treatment duration between 6 and 12 months\n 2. >1% if 1L treatment longer than 12 months 5. For CML-CP patients with treatment\n intolerance to 1L TKI, BCR-ABL1IS > 0.1% at screening 6. Previously treated with 1\n Adenosine triphosphate- (ATP)-binding site TKI for at least 6 months of therapy 7.\n Intolerance of TKI therapy and/or resistance to TKI therapy (European Leukemia Network\n (ELN) 2020)\n Intolerance is defined as:\n - Non-hematologic intolerance: Patients with grade 3 or 4 toxicity while on therapy, or\n with persistent grade 2 toxicity, unresponsive to optimal management, including dose\n adjustments (unless dose reduction is not considered in the best interest of the\n patient if response is already suboptimal)\n - Hematologic intolerance: Patients with grade 3 or 4 toxicity (absolute neutrophil\n count [ANC] or platelets) while on therapy that is recurrent after dose reduction to\n the lowest doses recommended by manufacturer\n Resistance/Failure is defined for CML-CP patients (CP at the time of initiation of last\n therapy) as follows . Patients must meet at least 1 of the following criteria:\n - Three months after the initiation of therapy: No Complete Hematological Response (CHR)\n or > 95% Philadelphia Chromosome Positive (Ph+) metaphases\n - Six months after the initiation of therapy: BCR-ABL1 ratio > 10% IS and/or >65% Ph+\n metaphases\n - Twelve months after initiation of therapy: BCR-ABL1 ratio > 1% IS and/or >35% Ph+\n metaphases\n - At any time after the initiation of therapy, loss of CHR, Complete Cytogenetic\n Response (CCyR) or Partial Cytogenetic Response (PCyR)\n - At any time after the initiation of therapy, the development of new BCR-ABL1 mutations\n which potentially cause resistance to study treatment\n - At any time after the initiation of therapy, confirmed loss of Major Molecular\n Response (MMR) in 2 consecutive tests, of which one must have a BCR-ABL1 ratio \u2265 1% IS\n - At any time after the initiation of therapy, new clonal chromosome abnormalities in\n Ph+ cells: CCA/Ph+ 8. Adequate end organ function within 12 days before the first dose\n of asciminib treatment. Patients with mild to moderate renal and hepatic impairment\n are eligible if:\n - Total bilirubin \u2264 3.0 x ULN without AST/ALT increase\n - Aspartate transaminase (AST) \u2264 5.0 x ULN\n - Alanine transaminase (ALT) \u2264 5.0 x ULN\n - Serum lipase \u2264 1.5 x ULN. For serum lipase > ULN and \u2264 1.5 x ULN, value should be\n considered not clinically significant and not associated with risk factors for acute\n pancreatitis\n - Alkaline phosphatase \u2264 2.5 x ULN\n - Creatinine clearance \u2265 30 mL/min as calculated using Cockcroft-Gault formula\n Exclusion Criteria:\n - 1. Previous treatment with 2 or more ATP-binding site TKIs 2. Previous treatment with\n asciminib 3. Known presence of the T315I mutation at any time prior to study entry 4.\n Known second chronic phase of CML after previous progression to AP/BC 5. Previous\n treatment with a hematopoietic stem-cell transplantation 6. Patient planning to\n undergo allogeneic hematopoietic stem cell transplantation 7. Cardiac or cardiac\n repolarization abnormality, including any of the following:\n - History within 6 months prior to starting study treatment of myocardial\n infarction (MI), angina pectoris, coronary artery bypass graft (CABG)\n - Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia),\n complete left bundle branch block, high-grade AV block (e.g., bifascicular block,\n Mobitz type II and third-degree AV block)\n - QTcF at screening \u2265450 msec (male patients), \u2265460 msec (female patients)\n - Long QT syndrome, family history of idiopathic sudden death or congenital long QT\n syndrome, or any of the following:\n - Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or\n hypomagnesemia, history of cardiac failure, or history of clinically\n significant/symptomatic bradycardia\n - Concomitant medication(s) with a \"Known risk of Torsades de Pointes\" per\n www.crediblemeds.org that cannot be discontinued or replaced 7 days prior to\n starting study drug by safe alternative medication.\n - Inability to determine the QTcF interval 8. History of acute pancreatitis within\n 1 year of study entry or past medical history of chronic pancreatitis 9.\n Participation in a prior investigational study within 30 days prior to\n randomization or within 5 half-lives of the investigational product, whichever is\n longer 10. Treatment with medications that meet one of the following criteria is\n not allowed and should be switched to an alternative at least one week prior to\n the start of treatment with study treatment:\n - Strong inducers of CYP3A for patients on the dose of 80 mg QD and 200mg QD\n - Strong inducers and inhibitors of CYP3A for patients on the dose of 200 mg BID\n 11. Pregnant or nursing (lactating) women 12. Women of child-bearing potential,\n defined as all women physiologically capable of becoming pregnant, unless they\n are using highly effective methods of contraception.\n - Highly effective contraception methods include:\n - Total abstinence (when this is in line with the preferred and usual lifestyle of\n the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal,\n post-ovulation methods) and withdrawal are not acceptable methods of\n contraception\n - Female sterilization (have had surgical bilateral oophorectomy (with or without\n hysterectomy) total hysterectomy or bilateral tubal ligation at least six weeks\n before taking study treatment). In case of oophorectomy alone, only when the\n reproductive status of the woman has been confirmed by follow up hormone level\n assessment\n - Male sterilization (at least 6 months prior to screening). The vasectomized male\n partner should be the sole partner for that subject\n - Use of oral, injected or implanted hormonal methods of contraception or placement\n of an intrauterine device (IUD) or intrauterine system (IUS) or other forms of\n hormonal contraception that have comparable efficacy (failure rate <1%), for\n example hormone vaginal ring or transdermal hormone contraception\n - In case of use of oral contraception women should have been stable on the same\n pill for a minimum of 3 months before taking study treatment\n - Women are considered post-menopausal and not of child bearing potential if they\n have had 12 months of natural (spontaneous) amenorrhea with an appropriate\n clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have\n had surgical bilateral oophorectomy (with or without hysterectomy), total\n hysterectomy or bilateral tubal ligation at least six weeks before taking study\n medication. In the case of oophorectomy alone, women are considered\n post-menopausal and not of child-bearing potential only when the reproductive\n status of the woman has been confirmed by follow up hormone level assessment.\n - Highly effective contraception for women should be maintained throughout the\n study and for at least 7 days after the last dose.\n 13. Sexually active males unwilling to use a condom during intercourse while\n taking study treatment and for 7 days after stopping study (only for patients\n treated with asciminib). A condom is required for all sexually active male\n participants on asciminib treatment to prevent them from fathering a child AND to\n prevent delivery of study treatment via seminal fluid to their partner. In\n addition, these male participants must not donate sperm for the time period\n specified above.", "output": {"inclusion_biomarker": [["loss of MMR"]], "exclusion_biomarker": []}}
-{"input": "This phase I trial studies the side effects of CD19/CD22 chimeric antigen receptor (CAR) T\n cells when given together with chemotherapy and NKTR-255, and to see how well they work in\n treating patients with CD19 positive B acute lymphoblastic leukemia that has come back or\n does not respond to treatment. A CAR is a genetically-engineered receptor made so that immune\n cells (T cells) can attack cancer cells by recognizing and responding to the CD19/CD22\n proteins. These proteins are commonly found on diffuse large B-cell lymphoma and B acute\n lymphoblastic leukemia. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine\n phosphate, work in different ways to stop the growth of cancer cells, either by killing the\n cells, by stopping them from dividing, or by stopping them from spreading. NKTR-255 is an\n investigational IL-15 receptor agonist designed to boost the immune system's natural ability\n to fight cancer. Giving CD19/CD22-CAR T cells and chemotherapy in combination with NKTR-255\n may work better in treating patients with diffuse large B-cell lymphoma or B acute\n lymphoblastic leukemia.\n ;\n ;\n For B acute lymphoblastic leukemia (ALL)\n 1. Confirmed diagnosis of relapsed or refractory B-cell ALL of one of the following\n types:\n - Chemotherapy refractory disease in subjects with B-ALL, defined as progression or\n stable disease after one line of therapy.\n - Recurrence of disease after achieving CR.\n 2. Subjects with persistent or relapsed minimal residual disease (MRD) (by flow\n cytometry, PCR, FISH, or next generation sequencing) require verification of MRD\n positivity on two occasions at least 4 weeks apart.\n 3. Subjects with Philadelphia Chromosome positive acute lymphoblastic leukemia (Ph+ALL)\n subjects are eligible if they progressed after receiving a tyrosine kinase inhibitor\n (TKI).\n 4. Subjects with recurrence of isolated CNS relapse after achieving complete remission\n (CR); if relapsed with MRD, will require verification of MRD positivity on two\n occasions at least 4 weeks apart.\n 5. CD19 positive expression- CD19 expression is required at any time since diagnosis. If\n patient has received anti-CD19 targeted therapy (i.e. Blinatumomab or CD19-CAR T\n cells), then CD19 expression must be subsequently demonstrated. CD19 expression may be\n detected by immunohistochemistry or by flow cytometry. The choice of whether to use\n flow cytometry or immunohistochemistry will be determined by what is the most easily\n available tissue sample in each subject. In general, immunohistochemistry will be used\n for lymph node biopsies, flow cytometry will be used for peripheral blood and bone\n marrow samples.\n 6. Subjects who have undergone autologous SCT with disease progression or relapse\n following SCT are eligible. Subjects who have undergone allogeneic SCT will be\n eligible if, in addition to meeting other eligibility criteria, they have elelino\n evidence of GVHD and have been without immunosuppressive agents for at least 30 days.\n 7. Subjects who have undergone prior anti-CD19 or anti-CD22 CAR therapy must be at least\n 30 days post CAR infusion and may not have eficence of persistnce of CAR T cells in\n blood smples (circulating levels of genetically modified cels of >/= 5% by flow\n cytometry.\n 8. Must have evaluable or measurable disease. Lesions that have been previously\n irradiated will be considered measurable only if progression has been documented\n following completion of radiation therapy.\n 9. At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any\n prior systemic therapy at the time the subject is planned for leukapheresis, except\n for systemic inhibitory/stimulatory immune checkpoint therapy, which requires 5\n half-lives.\n Exceptions:\n 1. There is no time restriction with regard to prior intrathecal chemotherapy (incl.\n steroids) provided there is complete recovery from any acute toxic effects;\n 2. Subjects who are on standard ALL maintenance type chemotherapy (vincristine,\n 6-mercaptopurine or oral methotrexate) may be enrolled provided that chemotherapy\n is discontinued at least 1 week or 5 half-lives (whichever is shorter) prior to\n apheresis.\n 3. Subjects receiving steroid therapy at physiologic replacement doses (\u22645 mg/day of\n prednisone or equivalent doses of other corticosteroids) only are allowed\n provided there has been no increase in dose for at least 2 weeks prior to\n starting apheresis;\n 4. For radiation therapy: Radiation therapy must have been completed at least 3\n weeks prior to apheresis, with the exception that there is no time restriction if\n the volume of bone marrow treated is less than 10% and also the subject has\n measurable/evaluable disease outside the radiation port.\n 10. Toxicities due to prior therapy must be stable and recovered to \u2264 Grade 1 (except for\n clinically non-significant toxicities such as alopecia)\n 11. Age 18 or older\n 12. Eastern cooperative oncology group (ECOG) performance status of 0, 1, or 2; or\n Karnofsky \u2265 60%\n 13. Normal Organ and Marrow Function (supportive care is allowed per institutional\n standards, i.e. filgrastim, transfusion)\n 1. ANC \u2265 1000/uL*\n 2. Platelet count \u2265 50,000/uL*\n 3. Absolute lymphocyte count \u2265 300/uL*\n 4. Adequate renal, hepatic, pulmonary and cardiac function defined as:\n 5. Creatinine \u2264 2 mg/dL or creatinine clearance \u2265 60 mL/min\n 6. Serum ALT or AST \u2264 5x ULN (Elevated ALT/AST associated with leukemia or lymphoma\n involvement of the liver will not disqualify a subject; only one value required\n for eligibility).\n 7. Total bilirubin \u2264 1.5 mg/dl, except in subjects with Gilbert's syndrome.\n 8. Cardiac ejection fraction \u2265 45%, no evidence of physiologically significant\n pericardial effusion as determined by an ECHO, MUGA or Cardiac MRI [performed\n within 180 days or after most recent anthracycline based treatment or mediastinal\n radiation therapy (whichever is most recent)]\n 9. No clinically significant ECG findings\n 10. No clinically significant pleural effusion\n 11. Baseline oxygen saturation > 92% on room air * A subject will not be excluded\n because of cytopenia if it is felt by the investigator to be due to underlying\n leukemia/lymphoma.\n 14. Subjects with CNS involvement are eligible as long as there are no overt signs or\n symptoms that in the evaluation of the investigator would mask or interfere with the\n neurological assessment of toxicity.\n 15. Females of childbearing potential must have a negative serum or urine pregnancy test\n (females who have undergone surgical sterilization or who have been postmenopausal for\n at least 2 years are not considered to be of childbearing potential)\n 16. Subjects of child-bearing or child-fathering potential must be willing to practice\n birth control from the time of enrollment on this study and for four (4) months after\n receiving the preparative lymphodepletion regimen or 1 month after the last dose of\n NKTR_255, whichever is later.\n 17. Ability to give informed consent. Must be able to give informed consent. Subjects\n unable to give informed consent will not be eligible for this study.\n =ELIGIBILITY TO RECEIVE NKTR-255=\n - Received a CD19/CD22 CAR-T infusion\n - No persisting grade \u22651 CRS or greater than grade 1 fever within 12 hours preceding\n NKTR-255 infusion\n - No grade 4 CRS within 96 hours preceding NKTR-255 infusion\n - No persisting grade \u2265 2 neurotoxicity on the day of NKTR-255 infusion\n - No previous grade \u2265 3 neurotoxicity of > 48 hours duration at any time preceding\n NKTR-255 infusion\n - ANC \u2265 1000/\u00b5L\n - No intervention with tocilizumab and/or dexamethasone within 48 hours preceding\n NKTR-255 infusion\n - No active, serious, and uncontrolled infection(s)\n - No contraindications according to the PI's assessment\n - Life expectancy > 30 days\n Exclusion Criteria:\n 1. History of other malignancy, unless disease free for at least 3 years. At the\n discretion of the Principal Investigator, subjects in remission for 1-2 years prior to\n enrollment may be deemed eligible after considering the nature of other malignancy,\n likelihood of recurrence during one year following CAR therapy, and impact of prior\n treatment on risk of CD19/CD22-CAR T cells. Subjects in remission <1 year are not\n eligible.\n - Exception: Nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder,\n breast) is eligible.\n - Hormonal therapy in subjects in remission >1 year will be allowed.\n 2. Presence of fungal, bacterial, viral, or other infection that is uncontrolled. Simple\n UTI and uncomplicated bacterial pharyngitis are permitted if responding to active\n treatment.\n 3. Known history of infection with any of the following:\n - HIV\n - Hepatitis B (HBsAg positive)\n - Hepatitis C virus (anti-HCV positive) A history of hepatitis B or hepatitis C is\n permitted if the viral load is undetectable per quantitative PCR and/or nucleic\n acid testing.\n 4. Presence of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia,\n cerebellar disease, or any autoimmune disease with CNS involvement that in the\n judgment of the investigator may impair the ability to evaluate neurotoxicity.\n 5. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or\n other clinically significant cardiac disease within 12 months of enrollment\n 6. Any medical condition that in the judgement of the investigator is likely to interfere\n with assessment of safety or efficacy of study treatment\n 7. History of severe immediate hypersensitivity reaction to any of the agents used in\n this study\n 8. Women who are pregnant or breastfeeding\n 9. In the investigator's judgment, the subject is unlikely to complete all\n protocol-required study visits or procedures, including follow-up visits, or comply\n with the study requirements for participation.\n 10. Previous treatment with interleukin-2 or interleukin-15.\n 11. Confirmed diagnosis of relapsed/refractory biphenotypic BT cell ALL\n 12. Primary immunodeficiency or history of autoimmune disease (e.g. Crohns, rheumatoid\n arthritis, systemic lupus) requiring systemic immunosuppression/systemic disease\n modifying agents within the last 2 years", "output": {"inclusion_biomarker": [["CD19 expression"]], "exclusion_biomarker": []}}
+{"input": "This study will be a single arm multicenter Phase II open-label, dose escalation study of\n asciminib in patients with CML-CP without T315I mutation who have had 1 prior TKIs for which\n they did not respond to treatment or were intolerant to treatment.\n ;\n ;\n Inclusion Criteria:\n Signed informed consent must be obtained prior to participation in the study 2. Chronic\n Myelogenous Leukemia (CML-CP,) no previous Accelerated Phase (AP) or Blast Crisis (BC) 3. \u2265\n 18 years of age 4. For CML-CP patients with treatment failure/resistance to first line (1L)\n Tyrosine Kinase Inhibitor (TKI,) BCR-ABL1IS at screening:\n 1. >10% if 1L treatment duration between 6 and 12 months\n 2. >1% if 1L treatment longer than 12 months 5. For CML-CP patients with treatment\n intolerance to 1L TKI, BCR-ABL1IS > 0.1% at screening 6. Previously treated with 1\n Adenosine triphosphate- (ATP)-binding site TKI for at least 6 months of therapy 7.\n Intolerance of TKI therapy and/or resistance to TKI therapy (European Leukemia Network\n (ELN) 2020)\n Intolerance is defined as:\n - Non-hematologic intolerance: Patients with grade 3 or 4 toxicity while on therapy, or\n with persistent grade 2 toxicity, unresponsive to optimal management, including dose\n adjustments (unless dose reduction is not considered in the best interest of the\n patient if response is already suboptimal)\n - Hematologic intolerance: Patients with grade 3 or 4 toxicity (absolute neutrophil\n count [ANC] or platelets) while on therapy that is recurrent after dose reduction to\n the lowest doses recommended by manufacturer\n Resistance/Failure is defined for CML-CP patients (CP at the time of initiation of last\n therapy) as follows . Patients must meet at least 1 of the following criteria:\n - Three months after the initiation of therapy: No Complete Hematological Response (CHR)\n or > 95% Philadelphia Chromosome Positive (Ph+) metaphases\n - Six months after the initiation of therapy: BCR-ABL1 ratio > 10% IS and/or >65% Ph+\n metaphases\n - Twelve months after initiation of therapy: BCR-ABL1 ratio > 1% IS and/or >35% Ph+\n metaphases\n - At any time after the initiation of therapy, loss of CHR, Complete Cytogenetic\n Response (CCyR) or Partial Cytogenetic Response (PCyR)\n - At any time after the initiation of therapy, the development of new BCR-ABL1 mutations\n which potentially cause resistance to study treatment\n - At any time after the initiation of therapy, confirmed loss of Major Molecular\n Response (MMR) in 2 consecutive tests, of which one must have a BCR-ABL1 ratio \u2265 1% IS\n - At any time after the initiation of therapy, new clonal chromosome abnormalities in\n Ph+ cells: CCA/Ph+ 8. Adequate end organ function within 12 days before the first dose\n of asciminib treatment. Patients with mild to moderate renal and hepatic impairment\n are eligible if:\n - Total bilirubin \u2264 3.0 x ULN without AST/ALT increase\n - Aspartate transaminase (AST) \u2264 5.0 x ULN\n - Alanine transaminase (ALT) \u2264 5.0 x ULN\n - Serum lipase \u2264 1.5 x ULN. For serum lipase > ULN and \u2264 1.5 x ULN, value should be\n considered not clinically significant and not associated with risk factors for acute\n pancreatitis\n - Alkaline phosphatase \u2264 2.5 x ULN\n - Creatinine clearance \u2265 30 mL/min as calculated using Cockcroft-Gault formula\n Exclusion Criteria:\n - 1. Previous treatment with 2 or more ATP-binding site TKIs 2. Previous treatment with\n asciminib 3. Known presence of the T315I mutation at any time prior to study entry 4.\n Known second chronic phase of CML after previous progression to AP/BC 5. Previous\n treatment with a hematopoietic stem-cell transplantation 6. Patient planning to\n undergo allogeneic hematopoietic stem cell transplantation 7. Cardiac or cardiac\n repolarization abnormality, including any of the following:\n - History within 6 months prior to starting study treatment of myocardial\n infarction (MI), angina pectoris, coronary artery bypass graft (CABG)\n - Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia),\n complete left bundle branch block, high-grade AV block (e.g., bifascicular block,\n Mobitz type II and third-degree AV block)\n - QTcF at screening \u2265450 msec (male patients), \u2265460 msec (female patients)\n - Long QT syndrome, family history of idiopathic sudden death or congenital long QT\n syndrome, or any of the following:\n - Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or\n hypomagnesemia, history of cardiac failure, or history of clinically\n significant/symptomatic bradycardia\n - Concomitant medication(s) with a \"Known risk of Torsades de Pointes\" per\n www.crediblemeds.org that cannot be discontinued or replaced 7 days prior to\n starting study drug by safe alternative medication.\n - Inability to determine the QTcF interval 8. History of acute pancreatitis within\n 1 year of study entry or past medical history of chronic pancreatitis 9.\n Participation in a prior investigational study within 30 days prior to\n randomization or within 5 half-lives of the investigational product, whichever is\n longer 10. Treatment with medications that meet one of the following criteria is\n not allowed and should be switched to an alternative at least one week prior to\n the start of treatment with study treatment:\n - Strong inducers of CYP3A for patients on the dose of 80 mg QD and 200mg QD\n - Strong inducers and inhibitors of CYP3A for patients on the dose of 200 mg BID\n 11. Pregnant or nursing (lactating) women 12. Women of child-bearing potential,\n defined as all women physiologically capable of becoming pregnant, unless they\n are using highly effective methods of contraception.\n - Highly effective contraception methods include:\n - Total abstinence (when this is in line with the preferred and usual lifestyle of\n the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal,\n post-ovulation methods) and withdrawal are not acceptable methods of\n contraception\n - Female sterilization (have had surgical bilateral oophorectomy (with or without\n hysterectomy) total hysterectomy or bilateral tubal ligation at least six weeks\n before taking study treatment). In case of oophorectomy alone, only when the\n reproductive status of the woman has been confirmed by follow up hormone level\n assessment\n - Male sterilization (at least 6 months prior to screening). The vasectomized male\n partner should be the sole partner for that subject\n - Use of oral, injected or implanted hormonal methods of contraception or placement\n of an intrauterine device (IUD) or intrauterine system (IUS) or other forms of\n hormonal contraception that have comparable efficacy (failure rate <1%), for\n example hormone vaginal ring or transdermal hormone contraception\n - In case of use of oral contraception women should have been stable on the same\n pill for a minimum of 3 months before taking study treatment\n - Women are considered post-menopausal and not of child bearing potential if they\n have had 12 months of natural (spontaneous) amenorrhea with an appropriate\n clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have\n had surgical bilateral oophorectomy (with or without hysterectomy), total\n hysterectomy or bilateral tubal ligation at least six weeks before taking study\n medication. In the case of oophorectomy alone, women are considered\n post-menopausal and not of child-bearing potential only when the reproductive\n status of the woman has been confirmed by follow up hormone level assessment.\n - Highly effective contraception for women should be maintained throughout the\n study and for at least 7 days after the last dose.\n 13. Sexually active males unwilling to use a condom during intercourse while\n taking study treatment and for 7 days after stopping study (only for patients\n treated with asciminib). A condom is required for all sexually active male\n participants on asciminib treatment to prevent them from fathering a child AND to\n prevent delivery of study treatment via seminal fluid to their partner. In\n addition, these male participants must not donate sperm for the time period\n specified above.", "output": {"inclusion_biomarker": [["BCR-ABL1 mutation"], ["CCA/Ph positive"]], "exclusion_biomarker": []}}
+{"input": "This phase I trial studies the side effects of CD19/CD22 chimeric antigen receptor (CAR) T\n cells when given together with chemotherapy and NKTR-255, and to see how well they work in\n treating patients with CD19 positive B acute lymphoblastic leukemia that has come back or\n does not respond to treatment. A CAR is a genetically-engineered receptor made so that immune\n cells (T cells) can attack cancer cells by recognizing and responding to the CD19/CD22\n proteins. These proteins are commonly found on diffuse large B-cell lymphoma and B acute\n lymphoblastic leukemia. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine\n phosphate, work in different ways to stop the growth of cancer cells, either by killing the\n cells, by stopping them from dividing, or by stopping them from spreading. NKTR-255 is an\n investigational IL-15 receptor agonist designed to boost the immune system's natural ability\n to fight cancer. Giving CD19/CD22-CAR T cells and chemotherapy in combination with NKTR-255\n may work better in treating patients with diffuse large B-cell lymphoma or B acute\n lymphoblastic leukemia.\n ;\n ;\n For B acute lymphoblastic leukemia (ALL)\n 1. Confirmed diagnosis of relapsed or refractory B-cell ALL of one of the following\n types:\n - Chemotherapy refractory disease in subjects with B-ALL, defined as progression or\n stable disease after one line of therapy.\n - Recurrence of disease after achieving CR.\n 2. Subjects with persistent or relapsed minimal residual disease (MRD) (by flow\n cytometry, PCR, FISH, or next generation sequencing) require verification of MRD\n positivity on two occasions at least 4 weeks apart.\n 3. Subjects with Philadelphia Chromosome positive acute lymphoblastic leukemia (Ph+ALL)\n subjects are eligible if they progressed after receiving a tyrosine kinase inhibitor\n (TKI).\n 4. Subjects with recurrence of isolated CNS relapse after achieving complete remission\n (CR); if relapsed with MRD, will require verification of MRD positivity on two\n occasions at least 4 weeks apart.\n 5. CD19 positive expression- CD19 expression is required at any time since diagnosis. If\n patient has received anti-CD19 targeted therapy (i.e. Blinatumomab or CD19-CAR T\n cells), then CD19 expression must be subsequently demonstrated. CD19 expression may be\n detected by immunohistochemistry or by flow cytometry. The choice of whether to use\n flow cytometry or immunohistochemistry will be determined by what is the most easily\n available tissue sample in each subject. In general, immunohistochemistry will be used\n for lymph node biopsies, flow cytometry will be used for peripheral blood and bone\n marrow samples.\n 6. Subjects who have undergone autologous SCT with disease progression or relapse\n following SCT are eligible. Subjects who have undergone allogeneic SCT will be\n eligible if, in addition to meeting other eligibility criteria, they have elelino\n evidence of GVHD and have been without immunosuppressive agents for at least 30 days.\n 7. Subjects who have undergone prior anti-CD19 or anti-CD22 CAR therapy must be at least\n 30 days post CAR infusion and may not have eficence of persistnce of CAR T cells in\n blood smples (circulating levels of genetically modified cels of >/= 5% by flow\n cytometry.\n 8. Must have evaluable or measurable disease. Lesions that have been previously\n irradiated will be considered measurable only if progression has been documented\n following completion of radiation therapy.\n 9. At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any\n prior systemic therapy at the time the subject is planned for leukapheresis, except\n for systemic inhibitory/stimulatory immune checkpoint therapy, which requires 5\n half-lives.\n Exceptions:\n 1. There is no time restriction with regard to prior intrathecal chemotherapy (incl.\n steroids) provided there is complete recovery from any acute toxic effects;\n 2. Subjects who are on standard ALL maintenance type chemotherapy (vincristine,\n 6-mercaptopurine or oral methotrexate) may be enrolled provided that chemotherapy\n is discontinued at least 1 week or 5 half-lives (whichever is shorter) prior to\n apheresis.\n 3. Subjects receiving steroid therapy at physiologic replacement doses (\u22645 mg/day of\n prednisone or equivalent doses of other corticosteroids) only are allowed\n provided there has been no increase in dose for at least 2 weeks prior to\n starting apheresis;\n 4. For radiation therapy: Radiation therapy must have been completed at least 3\n weeks prior to apheresis, with the exception that there is no time restriction if\n the volume of bone marrow treated is less than 10% and also the subject has\n measurable/evaluable disease outside the radiation port.\n 10. Toxicities due to prior therapy must be stable and recovered to \u2264 Grade 1 (except for\n clinically non-significant toxicities such as alopecia)\n 11. Age 18 or older\n 12. Eastern cooperative oncology group (ECOG) performance status of 0, 1, or 2; or\n Karnofsky \u2265 60%\n 13. Normal Organ and Marrow Function (supportive care is allowed per institutional\n standards, i.e. filgrastim, transfusion)\n 1. ANC \u2265 1000/uL*\n 2. Platelet count \u2265 50,000/uL*\n 3. Absolute lymphocyte count \u2265 300/uL*\n 4. Adequate renal, hepatic, pulmonary and cardiac function defined as:\n 5. Creatinine \u2264 2 mg/dL or creatinine clearance \u2265 60 mL/min\n 6. Serum ALT or AST \u2264 5x ULN (Elevated ALT/AST associated with leukemia or lymphoma\n involvement of the liver will not disqualify a subject; only one value required\n for eligibility).\n 7. Total bilirubin \u2264 1.5 mg/dl, except in subjects with Gilbert's syndrome.\n 8. Cardiac ejection fraction \u2265 45%, no evidence of physiologically significant\n pericardial effusion as determined by an ECHO, MUGA or Cardiac MRI [performed\n within 180 days or after most recent anthracycline based treatment or mediastinal\n radiation therapy (whichever is most recent)]\n 9. No clinically significant ECG findings\n 10. No clinically significant pleural effusion\n 11. Baseline oxygen saturation > 92% on room air * A subject will not be excluded\n because of cytopenia if it is felt by the investigator to be due to underlying\n leukemia/lymphoma.\n 14. Subjects with CNS involvement are eligible as long as there are no overt signs or\n symptoms that in the evaluation of the investigator would mask or interfere with the\n neurological assessment of toxicity.\n 15. Females of childbearing potential must have a negative serum or urine pregnancy test\n (females who have undergone surgical sterilization or who have been postmenopausal for\n at least 2 years are not considered to be of childbearing potential)\n 16. Subjects of child-bearing or child-fathering potential must be willing to practice\n birth control from the time of enrollment on this study and for four (4) months after\n receiving the preparative lymphodepletion regimen or 1 month after the last dose of\n NKTR_255, whichever is later.\n 17. Ability to give informed consent. Must be able to give informed consent. Subjects\n unable to give informed consent will not be eligible for this study.\n =ELIGIBILITY TO RECEIVE NKTR-255=\n - Received a CD19/CD22 CAR-T infusion\n - No persisting grade \u22651 CRS or greater than grade 1 fever within 12 hours preceding\n NKTR-255 infusion\n - No grade 4 CRS within 96 hours preceding NKTR-255 infusion\n - No persisting grade \u2265 2 neurotoxicity on the day of NKTR-255 infusion\n - No previous grade \u2265 3 neurotoxicity of > 48 hours duration at any time preceding\n NKTR-255 infusion\n - ANC \u2265 1000/\u00b5L\n - No intervention with tocilizumab and/or dexamethasone within 48 hours preceding\n NKTR-255 infusion\n - No active, serious, and uncontrolled infection(s)\n - No contraindications according to the PI's assessment\n - Life expectancy > 30 days\n Exclusion Criteria:\n 1. History of other malignancy, unless disease free for at least 3 years. At the\n discretion of the Principal Investigator, subjects in remission for 1-2 years prior to\n enrollment may be deemed eligible after considering the nature of other malignancy,\n likelihood of recurrence during one year following CAR therapy, and impact of prior\n treatment on risk of CD19/CD22-CAR T cells. Subjects in remission <1 year are not\n eligible.\n - Exception: Nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder,\n breast) is eligible.\n - Hormonal therapy in subjects in remission >1 year will be allowed.\n 2. Presence of fungal, bacterial, viral, or other infection that is uncontrolled. Simple\n UTI and uncomplicated bacterial pharyngitis are permitted if responding to active\n treatment.\n 3. Known history of infection with any of the following:\n - HIV\n - Hepatitis B (HBsAg positive)\n - Hepatitis C virus (anti-HCV positive) A history of hepatitis B or hepatitis C is\n permitted if the viral load is undetectable per quantitative PCR and/or nucleic\n acid testing.\n 4. Presence of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia,\n cerebellar disease, or any autoimmune disease with CNS involvement that in the\n judgment of the investigator may impair the ability to evaluate neurotoxicity.\n 5. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or\n other clinically significant cardiac disease within 12 months of enrollment\n 6. Any medical condition that in the judgement of the investigator is likely to interfere\n with assessment of safety or efficacy of study treatment\n 7. History of severe immediate hypersensitivity reaction to any of the agents used in\n this study\n 8. Women who are pregnant or breastfeeding\n 9. In the investigator's judgment, the subject is unlikely to complete all\n protocol-required study visits or procedures, including follow-up visits, or comply\n with the study requirements for participation.\n 10. Previous treatment with interleukin-2 or interleukin-15.\n 11. Confirmed diagnosis of relapsed/refractory biphenotypic BT cell ALL\n 12. Primary immunodeficiency or history of autoimmune disease (e.g. Crohns, rheumatoid\n arthritis, systemic lupus) requiring systemic immunosuppression/systemic disease\n modifying agents within the last 2 years", "output": {"inclusion_biomarker": [["Philadelphia Chromosome positive"], ["CD19 expression"]], "exclusion_biomarker": []}}
 {"input": "This is a multicenter, global, Phase 2, open-label, 2-part, first-line study to investigate\n the safety, tolerability, and anti-tumor activity of ZW25 (zanidatamab) plus standard\n first-line combination chemotherapy regimens for selected gastrointestinal (GI) cancers.\n Eligible patients include those with unresectable, locally advanced, recurrent or metastatic\n HER2-expressing gastroesophageal adenocarcinoma (GEA), biliary tract cancer (BTC), or\n colorectal cancer (CRC).\n ;\n ;\n Inclusion:\n - Disease diagnosis:\n - Part 1:\n - GEA: Unresectable, locally advanced, recurrent or metastatic HER2-expressing GEA\n (IHC 3+ or 2+ with or without gene amplification based upon local assessment or\n central assessment)\n - BTC: Unresectable, locally advanced, recurrent or metastatic HER2-expressing BTC\n (including intrahepatic cholangiocarcinoma [ICC], extrahepatic cholangiocarcinoma\n [ECC], or gallbladder cancer [GBC]) (IHC 3+ with or without gene amplification;\n or IHC 0, 1+ or 2+ with gene amplification, based upon central assessment)\n - CRC: Unresectable, locally advanced, recurrent or metastatic HER2-expressing CRC\n (IHC 3+ with or without gene amplification; or IHC 0, 1+ or 2+ with gene\n amplification, based upon central assessment). Patients will be required to be\n extended RAS (KRAS and NRAS) and BRAF wild-type based upon central assessment.\n - Part 2:\n - GEA: Unresectable, locally advanced, recurrent or metastatic HER2-expressing GEA\n (IHC 3+, or IHC 2+ and FISH+ by central assessment)\n - BTC: Same as Part 1\n - CRC: Same as Part 1\n - Tumor measurements as per Response Evaluation Criteria in Solid Tumors (RECIST)\n version 1.1:\n - Part 1: Measurable or non-measurable disease\n - Part 2: Measurable disease\n - An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1\n - Adequate organ function\n - Adequate cardiac left ventricular function, as defined by a LVEF >/= institutional\n standard of normal\n Exclusion:\n - Prior treatment with a HER2-targeted agent\n - Prior systemic anti-cancer therapy (including investigational products) except prior\n adjuvant/neoadjuvant therapy, which must be completed at least 6 months prior to first\n study treatment dosing. For subjects with BTC and CRC the following additional\n exceptions apply:\n - BTC: patients may have started therapy for advanced disease but may not have\n received more than one cycle of any standard gemcitabine-based chemotherapy\n regimen.\n - CRC: patients may have started therapy for advanced disease but may not have\n received more than one cycle of 5-FU-based chemotherapy (< 1 month of therapy).\n - Patients with certain contraindications to bevacizumab cannot be enrolled on the\n mFOLFOX6-2 with bevacizumab arm.\n - Palliative radiotherapy is allowed if completed at least 2 weeks prior to first study\n treatment dosing\n - Untreated known brain metastases (patients with treated brain metastases who are off\n steroids, off antiseizure medications, and stable for at least 1 month at the time of\n screening are eligible)\n - Clinically significant cardiac disease, such as ventricular arrhythmia requiring\n therapy, uncontrolled hypertension or any history of symptomatic congestive heart\n failure (CHF). Patients with known myocardial infarction or unstable angina within 6\n months prior to randomization are also excluded.\n - QTc Fridericia (QTcF) > 470 ms. For patients with longer QTcF on initial\n electrocardiogram (ECG), follow-up ECG may be performed in triplicate to determine\n eligibility\n - Peripheral neuropathy > Grade 1 per NCI-CTCAE v5.0\n - Clinically significant interstitial lung disease\n - Prior or concurrent malignancy whose natural history or treatment has the potential to\n interfere with the safety or efficacy assessment of the investigational regimen\n - Active hepatitis B or hepatitis C infection or infection with Human Immunodeficiency\n Virus (HIV)-1 or HIV-2 (Exception: patients with well controlled HIV [e.g., CD4 >\n 350/mm3 and undetectable viral load] are eligible)", "output": {"inclusion_biomarker": [["HER2 expression"], ["HER2 expression", "KRAS wildtype", "NRAS wildtype", "BRAF wildtype"]], "exclusion_biomarker": []}}
 {"input": "This is a Phase 1/2a, nonrandomized, open-label, parallel assignment, dose-escalation, and\n dose-optimization study to evaluate the safety and clinical activity of PBCAR0191 in adults\n with r/r B ALL (Cohort A) and in adults with r/r B-cell NHL (Cohort N) and identify a\n treatment regimen most likely to result in clinical efficacy while maintaining a favorable\n safety profile.\n ;\n ;\n Key Inclusion Criteria*\n Criteria for B-ALL:\n - Subject has unequivocal r/r CD19+ B-ALL that has been confirmed by morphology, flow\n cytometry, or a validated minimal residual disease assay.\n - Subjects with Philadelphia chromosome positive disease can be eligible if they are\n intolerant to tyrosine kinase inhibitor therapy or if they have r/r disease.\n Criteria for NHL:\n - Subject has unequivocal aggressive CD19+ r/r B-cell NHL that is confirmed by archived\n tumor biopsy tissue from last relapse after CD19-directed therapy and corresponding\n pathology report. Alternatively, if at least 1 tumor involved site is accessible at\n time of Screening, the subject's diagnosis is confirmed by pretreatment biopsy\n (excisional when possible) or by flow cytometry of fine needle aspirate. If a subject\n never had a CR, a sample from the most recent biopsy is acceptable. NHL subtypes\n included but are not limited to:\n - Diffuse large B-cell lymphoma (DLBCL) including Richter's transformation\n - FL including Grade 3 or transformed FL\n - High-grade B-cell lymphoma\n - Primary mediastinal lymphoma\n - Subject has measurable or detectable (for example positron emission\n tomography-positive) disease according to the Lugano Classification.\n - Subject must have received at least 2 prior chemotherapy-containing regimens,\n consistent with standard of care treatment guidance (e.g., NCCN), unless no second\n line therapy of known benefit exists for a given subject. Other than those\n specifically prohibited, other therapies are allowed until 7 days prior to initiation\n of LD. In that case, all Screening safety laboratories and disease assessments must be\n performed after the last dose of prior therapy. For Richter's transformation, only 1\n prior line of therapy is required for the DLBCL component.\n - Subject has received no more than 7 systemic lines of anti-cancer therapy for the\n disease under study.\n - Subjects previously treated with CD19-directed autologous CAR T therapies have\n received no more than 2 lines of therapy after administration of their previous CAR T\n product.\n - Expansion cohort only: Subjects must have received autologous CD19-directed CAR T\n therapy and demonstrated clinical response to the treatment at Day 28 or later,\n followed by relapse.\n Criteria for both B-ALL and NHL:\n - Eastern Cooperative Oncology Group performance status score of 0 or 1.\n - An estimated life expectancy of at least 12 weeks according to the investigator's\n judgment.\n - Seronegative for human immunodeficiency virus antibody (i.e., intact immune function).\n - Subject has adequate bone marrow, renal, hepatic, pulmonary, and cardiac function\n defined as:\n 1. Estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2 (calculated using\n the CKD-EPI equation [Levey et al, 2009]). If there is a concern that eGFR\n calculation is not an accurate reflection of renal function, a 24-hour urine\n collection for creatinine clearance may be used at the investigator's discretion.\n 2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels both\n \u22643 times of upper limit of normal (ULN), unless there is suspected disease in the\n liver.\n 3. Total bilirubin <2.0 mg/dL, except in subjects with Gilbert's syndrome.\n 4. Platelet count \u226550,000/\u03bcL and absolute neutrophil count of \u22651000/ \u03bcL. Platelet\n transfusions within 14 days of screening are not allowed except for subjects in\n B-ALL disease cohort with extensive bone marrow disease burden, in which case\n adequate bone marrow recovery after prior treatment is required to be documented.\n 5. C-reactive protein (CRP) <2x ULN; subjects with CRP elevation within 2x ULN,\n ruling out infectious cause will be required.\n 6. Left ventricular ejection fraction >45% as assessed by echocardiogram (ECHO) or\n multiple gated acquisition scan performed within 1 month before starting\n lymphodepleting chemotherapy. ECHO results performed within 6 months before\n Screening and at least 28 days after the last cancer treatment may be acceptable\n if the subject has not received any treatment with cardiotoxicity risks.\n 7. No clinically significant evidence of pericardial effusion or pleural effusion\n causing clinical symptoms and needing immediate intervention, based on the\n investigator's opinion. Any known effusion must be stable without need for\n drainage within 2 weeks of enrollment.\n 8. No clinically significant renal/pulmonary comorbidities.\n 9. Baseline oxygen saturation >92% on room air.\n Key Exclusion Criteria*\n Criteria for B-ALL:\n - Burkitt cell (L3 ALL) or mixed-lineage acute leukemia.\n - No active central nervous system (CNS) disease. Subjects with a history of CNS\n involvement must have a documented CR on at least 2 imaging studies at least 3 months\n apart (with no masses in parenchyma and no ocular involvement) and a negative\n cerebrospinal fluid cytology on at least 2 evaluations (one evaluation may be during\n the Screening Period and the other must be at least 3 months prior).\n Criteria for NHL:\n - No prior or active CNS disease.\n - Requirement for urgent therapy due to tumor mass effects such as bowel obstruction or\n blood vessel compression.\n - Active hemolytic anemia.\n Criteria for B-ALL and NHL:\n - Subject has had a malignancy, besides the malignancies of inclusion (B-ALL or NHL),\n that in the investigator's opinion, has a high risk of relapse in the next 2 years. In\n the case of Richter's transformation, subjects may be enrolled with ongoing chronic\n lymphocytic leukemia/small lymphocytic lymphoma.\n - Uncontrolled and serious fungal, bacterial, viral, protozoal, or other infection that\n has not resolved and does require therapeutic anti-microbial medications at least 7\n days prior to LD. Subjects with elevated CRP must undergo infectious disease workup\n and the recommendations discussed with medical monitor to be considered on an\n individual basis. The CRP must be trending toward the normal range for the laboratory\n with the exception when it's deemed related to the underlying malignancy.\n - Any form of primary immunodeficiency (e.g., severe combined immunodeficiency disease).\n - Active hepatitis B or hepatitis C confirmed by PCR. Subject positive for inactive\n hepatitis B is allowed to enroll if on prophylactic treatment.\n 1. Subject is seropositive for hepatitis B antigen with confirmation. If\n confirmatory tests are negative, the subject can be enrolled.\n 2. Subject is seropositive for hepatitis C antibody unless antigen negative. If\n hepatitis C antibody test is positive, the subject must be tested for the\n presence of RNA by reverse transcription PCR and be hepatitis C virus-RNA\n negative.\n - Any known uncontrolled cardiovascular disease at the time of Screening that, in the\n investigator's opinion, renders the subject ineligible, including but not limited to:\n 1. Active ventricular or atrial dysrhythmia \u2265 Grade 2, bradycardia \u2265 Grade 2.\n 2. Myocardial infarction within 6 months before Screening.\n 3. Pulmonary embolism, deep vein thrombosis, or any other significant coagulopathy\n including disseminated intravascular coagulation.\n - History of hypertension crisis or hypertensive encephalopathy within 3 months prior to\n Screening. In case of hypertensive crisis caused by omission of well-established\n treatment regimen, transient and promptly stabilized, enrollment must be discussed and\n agreed upon with sponsor and medical monitor.\n - History of severe immediate hypersensitivity reaction to any of the agents used in\n this study.\n - Presence of a CNS disorder that, in the opinion of the investigator, renders the\n subject ineligible for treatment.\n - Abnormal findings during the Screening Period or any other medical condition(s) or\n laboratory findings that, in the opinion of the investigator, might jeopardize the\n subject's safety.\n - History of concomitant genetic syndrome such as Fanconi anemia, Kostmann syndrome,\n Shwachman-Diamond syndrome, or any other known bone marrow failure syndrome.\n - Active uncontrolled autoimmune disease requiring active immunosuppression at the time\n of Screening (excluding subjects needing steroids for physiologic replacement).\n - Subject has received stem cell transplant within 90 days before Screening.\n - Subject has active GvHD symptoms.\n - Subject has received systemic biologic agent for treatment of disease under study\n within 28 days of LD or other systemic anti-cancer therapy within 10 days of LD Note:\n this criterion does not apply if the subject has clear evidence of disease progression\n after such an agent has been administered and all AEs have resolved to a Grade 2 or\n less in severity. This should be discussed with the medical monitor for confirmation.\n - Participation in noninterventional registries or epidemiological studies is not\n excluded.\n - Radiotherapy within 4 weeks before Screening should be discussed with monitor and\n determined on a case-by-case basis.\n - Presence of pleural/peritoneal/pericardial catheter, as well as biliary and ureteral\n stents (does not apply to intravenous lines).\n - Subject has received live vaccine within 4 weeks before Screening. Non-live virus\n vaccines are not excluded.\n - Subject has received CD19-directed therapy other than autologous CD19-directed CAR T\n therapy within 90 days of the anticipated start date of LD.\n - Additional criteria apply", "output": {"inclusion_biomarker": [["CD19 positive"]], "exclusion_biomarker": []}}
 {"input": "This phase Ib trial is to find out the best dose, possible benefits and/or side effects of\n talazoparib when given in combination with palbociclib, axitinib, or crizotinib in treating\n patients with solid tumors that has spread to nearby tissue or lymph nodes (locally advanced)\n or other places in the body (metastatic). PARPs are proteins that help repair damaged DNA,\n the genetic material that serves as the body's instruction book. PARP inhibitors, such as\n talazoparib, can keep PARP from working, so tumor cells can't repair themselves, and they may\n stop growing. Palbociclib, axitinib, and crizotinib may stop the growth of tumor cells by\n blocking some of the enzymes needed for cell growth. Giving talazoparib in combination with\n palbociclib, axitinib, or crizotinib may help control locally advanced or metastatic solid\n tumors.\n ;\n ;\n Inclusion Criteria:\n - Pathogenic or likely pathogenic germline or somatic gene defect as determined by local\n assessment and classification in at least one of the following:\n - Defect in DNA damage response (DDR) genes such as: BRCA1/2, PALB2, RAD51C/D, or\n other related genes at the discretion of the principal investigator in\n consultation with the MD Anderson Cancer Center Institute for Personalized Cancer\n Therapy Precision Oncology Decision Support (PODS) group (Arms A-C)\n - Defect in MET, ALK or ROS1, e.g. MET mutations or amplifications, high MET\n expression, ALK translocations, ROS1 translocations (eligible for Arm C:\n talazoparib + crizotinib)\n - NOTE: Patients with metastatic castration-resistant prostate cancer can enroll in\n Arm B with talazoparib + axitinib without a specific and/or selected mutation\n - Patients who are eligible for more than one Arm will be assigned according to\n physician preference\n - Histological or cytological diagnosis of a solid tumor that is advanced/metastatic,\n intolerable to standard therapy, resistant to effective standard therapy, or for which\n no standard therapy is available\n - Availability of a fresh or recent tumor tissue sample from a diagnostic biopsy/surgery\n or a metastatic tumor biopsy; the sample must have been obtained within 12 months\n prior to study enrollment. When only bone disease is present, an archival tumor tissue\n sample obtained within 5 years prior to study enrollment may be accepted for\n non-prostate cancer patients and a fresh bone biopsy may be accepted for prostate\n cancer patients only NOTE: A fresh biopsy should be encouraged for all patients at\n time of enrollment even if a previous biopsy is available. Optional on-treatment and\n at-progression biopsies will be encouraged for all patients\n - Have measurable disease at study enrollment as defined by RECIST v1.1 with at least 1\n measurable lesion that has not previously been irradiated; or patients may have bone\n metastatic disease evaluable by Prostate Cancer Working Group 2 (PCWG2) for subjects\n with metastatic castration-resistant prostate cancer (mCRPC), or according to the\n tumor evaluation criteria best suited and accepted for the tumor type being evaluated)\n - Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 1\n - Absolute Neutrophil Count (ANC) >= 1,500/mm^3 or >= 1.5 x 10^9/L (without\n hematopoietic growth factor or transfusion support within 14 days prior to study\n enrollment)\n - Platelets >= 100,000/mm^3 or >= 100 x 10^9/L (without hematopoietic growth factor or\n transfusion support within 14 days prior to study enrollment)\n - Hemoglobin >= 9 g/dL (>= 5.6 mmol/L) (without hematopoietic growth factor or\n transfusion support within 14 days prior to study enrollment)\n - estimated creatinine clearance >= 60 mL/min will be required during dose-escalation\n phase, according to the Cockcroft-Gault formula\n - Where creatinine clearance (CLCR) (creatinine clearance) is measured in mL/min,\n age is expressed in years, weight in kilograms (kg), and SCR (serum creatinine)\n in mg/dL\n - Or as measured by 24h urine assessment NOTE: Patients with moderate renal\n impairment (30-59 mL/min) will be considered during the dose expansion phase. A\n reduced starting dose for talazoparib will be considered in these patients\n - Total serum bilirubin =< 1.5 x the upper limit of normal range (ULN)\n - Aspartate and Alanine aminotransferase (aspartate aminotransferase [AST] and alanine\n aminotransferase [ALT]) =< 5 x ULN\n - Female Patients of childbearing potential must have negative serum pregnancy or urine\n pregnancy test at screening. Female patients of non-childbearing potential must meet\n at least one of the following criteria:\n - Achieved postmenopausal status, defined as follows: cessation of regular menses\n for at least 12 consecutive months with no alternative pathological or\n physiological cause and have a serum follicle-stimulating hormone (FSH) level\n confirming the postmenopausal state\n - Have undergone a documented hysterectomy and/or bilateral oophorectomy\n - Have medically confirmed ovarian failure All other female patients are considered\n to be of childbearing potential\n - Evidence of a personally signed and dated informed consent document, within > 28 days\n prior to enrollment, indicating that the patient has been informed of all pertinent\n aspects of the study\n - Willing and able to comply with scheduled visits, treatment plan, laboratory tests,\n and other study procedures\n - Able to swallow the study drug, have no known intolerance to study drugs or\n excipients, and comply with study requirements\n Exclusion Criteria:\n - Prior anti-cancer therapy within 2 weeks prior to study enrollment or prior radiation\n therapy within 2 weeks prior to study enrollment. Prior palliative radiotherapy to\n metastatic lesion(s) is permitted, provided it has been completed at least 2 days\n prior to study enrollment and no clinically significant toxicities are expected (e.g.\n mucositis, esophagitis)\n - Major surgery within 4 weeks prior to study enrollment\n - Patients with known hypersensitivity to either talazoparib or the additional study\n drug to be received per treatment arm: palbociclib (Arm A), axitinib (Arm B),\n crizotinib (Arm C)\n - Diagnosis of myelodysplastic syndrome (MDS)\n - Known symptomatic brain metastases requiring steroids. Patients with previously\n diagnosed brain metastases are eligible if they have completed their treatment and\n have recovered from the acute effects of radiation therapy or surgery prior to study\n enrollment, have discontinued corticosteroid treatment for these metastases for at\n least 2 weeks, and are neurologically stable. Of note, patients who required a single\n dose of corticosteroids on days receiving radiation treatment do not require a 2-week\n washout\n - Participation in other studies involving investigational drug(s) within 4 weeks prior\n to study entry and/or during study participation\n - Persisting toxicity related to prior therapy (National Cancer Institute [NCI] Common\n Terminology Criteria for Adverse Events [CTCAE] version [v]5.0 Grade > 1). However,\n alopecia and sensory neuropathy Grade =< 2, or other Grade =< 2 adverse events not\n constituting a safety risk, based on the investigator's judgement, are acceptable\n - Active infection requiring systemic therapy. Minor infections, e.g. periodontal\n infection or urinary tract infection (UTI), which may be treated with short term oral\n antibiotics are allowed\n - Patients with known uncontrolled human immunodeficiency virus (HIV) virus or acquired\n immunodeficiency syndrome. Note: Patients with history of controlled HIV virus will be\n considered eligible for this trial\n - Patients with uncontrolled hepatitis B virus (HBV) or hepatitis C virus (HCV)\n infection at screening. Note: Patients with controlled hepatitis B or hepatitis C will\n be considered eligible for this trial\n - Clinically significant cardiovascular disease, including any of the following:\n - Myocardial infarction or symptomatic cardiac ischemia within 6 months before\n screening\n - Congestive heart failure New York Heart Association class III or IV\n - History of clinically significant ventricular arrhythmias (eg, sustained\n ventricular tachycardia, ventricular fibrillation, torsade de pointes) within 1\n year before screening\n - History of Mobitz II second degree or third degree heart block unless a permanent\n pacemaker is in place\n - Hypotension as indicated by systolic blood pressure < 86 mm Hg at screening\n - Bradycardia as indicated by a heart rate of <45 beats per minute on the screening\n electrocardiogram\n - Uncontrolled hypertension as indicated by systolic blood pressure > 170 mm Hg or\n diastolic blood pressure > 105 mm Hg at screening\n - Current use of potent P-gp inhibitors within 7 days prior to enrollment: amiodarone,\n carvedilol, clarithromycin, cobicistat, dronedarone, erythromycin,\n glecaprevir/pibrentasvir, indinavir, itraconazole, ketoconazole, lapatinib, lopinavir,\n propafenone, quinidine, ranolazine, ritonavir, saquinavir,\n sofosbuvir/velpatasvir/voxilaprevir, telaprevir, tipranavir, valspodar, and verapamil.\n - NOTE: Patients who have recently been on enzalutamide require a 28 day washout\n period due to longer elimination half-life of this therapy\n - Patients treated within the last 7 days prior to enrollment with:\n - Food or drugs that are known to be strong CYP (cytochrome P-450) 3A4 inhibitors\n (ie, amprenavir, atazanavir, boceprevir, clarithromycin, conivaptan, delavirdine,\n diltiazem, erythromycin, fosamprenavir, indinavir, itraconazole, ketoconazole,\n lopinavir, mibefradil, miconazole, nefazodone, nelfinavir, posaconazole,\n ritonavir, saquinavir, telaprevir, telithromycin, verapamil, voriconazole, and\n grapefruit or grapefruit juice). Drugs that are known to be strong CYP3A4\n inducers (ie, carbamazepine, felbamate, nevirapine, phenobarbital, phenytoin,\n primidone, rifabutin, rifampin, rifapentin, and St. John's wort\n - Inability to swallow capsules, known malabsorption syndrome, or other conditions that\n may impair absorption of study drugs\n - Bisphosphonate or denosumab dosage that was not stable (i.e. not the same) for at\n least 2 weeks before study enrollment for patients receiving these therapies\n - Other acute or chronic medical or psychiatric condition including recent (within the\n past year) or active suicidal ideation or behavior or laboratory abnormality that may\n increase the risk associated with study participation or investigational product\n administration or may interfere with the interpretation of study results and, in the\n judgement of the investigator, would make the patient inappropriate for entry into\n this study\n - Medical, psychological, or social conditions that may interfere with the patient's\n participation in the study, or with the evaluation of the study results\n - Diagnosis of any other malignancy within 2 years prior to study enrollment, except for\n adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of\n the breast, bladder, or cervix, or low grade (Gleason =< 6) prostate cancer on\n surveillance without any plans for treatment intervention (e.g. surgery, radiation, or\n castration), or other early-stage low risk cancers\n - Pregnant female patients; breastfeeding female patients; fertile male patients; and\n female patients of childbearing potential who are unwilling or unable to use 2 methods\n of contraception for the duration of the study and for at least 7 months after the\n last dose of study drugs for female patients or 4 months after the last dose of study\n drugs for male patients, whichever is later for the individual patient. Male patients\n are prohibited from sperm donation while enrolled in this study and for 4 months after\n the last dose of the study drugs. Highly effective methods of contraception are those\n that alone or in combination, result in a failure rate of less than 1% per year when\n used consistently and correctly. These methods include:\n - Established use of oral, inserted, or injected or implanted hormonal methods of\n contraception are allowed provided the patient remains on the same treatment\n throughout the entire study and has been using that hormonal contraceptive for an\n adequate period of time to ensure effectiveness\n - Correctly placed copper containing intrauterine device (IUD)\n - Male condom or female condom used with spermicide (i.e. foam, gel, film, cream or\n suppository)\n - Male sterilization with appropriately confirmed absence of sperm in the\n postvasectomy ejaculate\n - Bilateral tubal ligation or bilateral oophorectomy", "output": {"inclusion_biomarker": [["BRCA1 defect"], ["BRCA2 defect"], ["PALB2 defect"], ["RAD51C defect"], ["RAD51D defect"], ["MET mutation"], ["MET amplification"], ["MET overexpression"], ["ALK translocation"], ["ROS1 translocation"]], "exclusion_biomarker": []}}
@@ -83,7 +83,7 @@
 {"input": "This phase Ib trial studies the side effects and possible benefits of AL101 before surgery in\n treating patients with notch activated adenoid cystic cancer. AL101 may stop the growth of\n tumor cells by blocking some of the enzymes needed for cell growth. Giving AL101 before\n surgery may help to control adenoid cystic cancer that has a NOTCH pathway activation.\n ;\n ;\n Inclusion Criteria:\n - Capable of giving signed informed consent which includes compliance with the\n requirements and restrictions listed in the informed consent and in this protocol\n - Age >= 18 years old\n - Histologically/cytological confirmed adenoid cystic carcinoma (ACC) of any primary\n site\n - Evidence of NOTCH1 pathway activation as determined by NICD1 IHC nuclear staining in\n >= 70% of tumor cells\n - Patients must have surgically resectable disease, either with a curative intent or for\n local control in the setting of metastatic disease, in the opinion of the treating\n physician\n - Patients must be willing to undergo baseline biopsy to obtain tumor material\n - Disease must be measurable by RECIST 1.1\n - Performance status Eastern Cooperative Oncology Group (ECOG) 0 or 1\n - Neutrophils < 1500/mm^3\n - Platelet count < 100,000/mm^3\n - Hemoglobin < 9 g/dL\n - Total bilirubin > 1.5 upper limit of normal (ULN) (except known Gilbert's syndrome)\n - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 2.5 of upper\n limit of normality (ULN) OR > 5 ULN for patients with liver metastases\n - Creatinine clearance < 40 mL/min (Calculation of creatinine clearance [CrCl] will be\n based on acceptable institution standard)\n - Female patients with reproductive potential must practice two effective contraceptive\n measures for the duration of study drug therapy and for at least 90 days after\n completion of AL101 therapy. The two birth control methods can be either two barrier\n methods or a barrier method plus a hormonal method to prevent pregnancy. The following\n are considered adequate barrier methods of contraception: diaphragm, condom, copper\n intrauterine device, sponge, or spermicide. Appropriate hormonal contraceptives will\n include any registered and marketed contraceptive agent that contains an estrogen\n and/or a progestational agent (including oral, subcutaneous, intrauterine, or\n intramuscular agents)\n - Male patients who are sexually active with women with reproductive potential must\n agree to use contraception for the duration of treatment and for at least 90 days\n after completion of AL101 therapy\n Exclusion Criteria:\n - Prior radiotherapy, chemotherapy, or biologic therapy is allowed in patients with\n loco-regional recurrent disease, if administered at least 4 weeks prior to study\n enrollment\n - Prior treatment with gamma-secretase inhibitor\n - History of previous malignancy other than malignancy treated with curative intent and\n with no evidence of active disease >= 2 years before the first dose of study drug and\n of low potential risk for recurrence. Patients with the following diagnoses represents\n an exception and may enroll:\n - Non-melanoma skin cancers with no current evidence of disease\n - Melanoma in situ with no current evidence of disease\n - Localized cancer of the prostate with prostate-specific antigen of < 0.1 ng/mL\n - Treated or localized well-differentiated thyroid cancer\n - Treated cervical carcinoma in situ\n - Treated ductal/lobular carcinoma in situ of the breast\n - Current or recent (within 2 months of investigational product administration)\n gastrointestinal disease such as disorders that increase the risk of diarrhea (e.g.:\n inflammatory bowel disease). Non-chronic conditions (e.g., infectious diarrhea) that\n are completely resolved for at least 2 weeks prior to starting investigational product\n are not exclusionary\n - Evidence of clinically significant bleeding diathesis or coagulopathy (in the absence\n of therapeutic anticoagulation)\n - Evidence of uncontrolled, active infection, requiring systemic anti-bacterial,\n anti-viral or anti-fungal therapy =< 7 days prior to administration of investigational\n product such as known active infection with hepatitis B and hepatitis C (HCV) at\n Screening\n - Symptomatic central nervous system (CNS) metastases. Patients with asymptomatic CNS\n metastases as well as those with previously treated CNS metastases are eligible for\n enrollment in the study if at least four weeks has elapsed since last whole brain\n radiation treatment or at least two weeks has elapsed since last focal radiation\n treatment and the patient is deemed clinically stable by the investigator\n - Unstable or severe uncontrolled medical condition (e.g., unstable cardiac or pulmonary\n function or uncontrolled diabetes) or any important medical illness or abnormal\n laboratory finding that would, in the investigator's judgment, increase the risk to\n the patient associated with his or her participation in the study\n - Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) >= 480\n msec\n - Female subjects who are pregnant or breast-feeding\n - Hypersensitivity and/or history of allergy to the investigational product excipients", "output": {"inclusion_biomarker": [["NOTCH1 pathway activation"]], "exclusion_biomarker": []}}
 {"input": "An open-label, multicenter phase II clinical study to evaluate safety, efficacy and PK of\n HLX208 for advanced melanoma with BRAF V600 mutation\n ;NA;\n Inclusion Criteria:\n - Age>=18Y\n - Good Organ Function\n - Expected survival time \u2265 3 months\n - advanced melanoma with BRAF V600 mutation that have been diagnosed\n - ECOG score 0-1;\n Exclusion Criteria:\n - Previous treatment with BRAF inhibitors or MEK inhibitors\n - Symptomatic brain or meningeal metastases (unless the patient has beenon > treatment\n for 3 months, has no evidence of progress on imagingwithin 4 weeks prior to initial\n administration, and tumor-related clinicalsymptoms are stable).\n - Severe active infections requiring systemic anti-infective therapy\n - A history of other malignancies within two years, except for cured carcinoma in situ\n of the cervix or basal cell carcinoma of the skin.", "output": {"inclusion_biomarker": [["BRAF V600"]], "exclusion_biomarker": []}}
 {"input": "This is a Phase II study for patients with MIBG avid tumors. The study is to determine the\n response rate to <131>I-MIBG in patients with de novo, relapsed or refractory neuroblastoma\n or other MIBG avid malignant tumors 42 days post MIBG therapy. It will also be evaluating the\n tolerability and safety of the study agent by evaluating the hematopoietic and\n non-hematopoietic toxicity of <131>I-MIBG therapy. Tumor response will be evaluated by\n comparing the patient's disease pre-treatment against the patient's day +42 post <131>I-MIBG\n treatment. The evaluations may include the following: <131>I-MIBG scan, CT or MRI, urine\n catecholamine, bone marrow analyses and any other tests considered standard of care for\n cancer evaluation. To be eligible for participation, patients must have tumors that are MIBG\n avid. Patients must also have a stem cell source for autologous rescue in the event of\n protracted therapy associated cytopenias. Peripheral stem cell collections are preferred as\n the hematopoietic cell source. Bone marrow harvests for a hematopoietic cell source is an\n alternative. This study will provide data for future clinical trials utilizing <131>I-MIBG\n therapies. A room on H12 has been prepared with lead lined walls, and many radiation safety\n components to accomodate this treatment. <131>I metaiodobenzlguanidine (<131>I-MIBG) is a\n radiopharmaceutical that concentrates within adrenomedullary tissue. The agent was initially\n used for tumor imaging due to its capability to locate pheochromocytomas, neuroblastomas and\n other neuroendocrine tumors. <131>I-MIBG was subsequently used as an therapeutic agent for\n these tumor types. Phase I and II therapeutic trials targeting neuroblastoma have reported\n response rates of 10-50%. Toxicities observed have been mainly hematopoietic, with ~50% of\n patients receiving 15mCi/kg requiring stem cell reinfusion. Observed non-hematopoietic\n toxicities have been mild. Most recently, trials have been conducted combining the study\n agent with myeloablative chemotherapy and stem cell reinfusion have been performed with\n initial response rates of ~50%.\n ;NA;\n Inclusion Criteria:\n - Patients must be between 12 months and 65 years at the time of enrollment\n - Diagnosis: diagnosis of neuroblastoma or at the time of relapse by histology and/or\n demonstration of clumps of tumor cells in bone marrow with elevated urinary\n catecholamine metabolites\n - Disease Status:\n 1. The presence of refractory or progressive disease (PD)\n 2. For patients with neuroblastoma, the presence of mixed response (MR), or no\n response (NR) following the completion of A3973 or equivalent induction therapy,\n or the presence of a partial response (PR) with high Curie score (>2) following\n induction therapy.\n 3. Patients with de novo high risk neuroblastoma who have completed standard\n induction therapy and do not achieve a CR, VGPR, or PR with low Curie score post\n induction.\n - Patients must have evidence of MIBG avid disease as determined by diagnostic\n MIBG scan obtained within 4 weeks of study entry.\n - Patients who receive greater than 12 mCi/kg are required to have stem cell rescue\n products harvested prior to study treatment.\n - Performance Level and Life Expectancy: Patients must have a Lansky Play Scale17 of 60%\n (<16 yrs old), Karnofsky score 60% (>16 yrs old), or ECOG score of < or equal to 2 and\n a life expectancy of 2 months.\n - Patients may enter this study with or without salvage therapy for recurrent tumor.\n Patients must have fully recovered from the toxic effects of any prior therapy.\n - Organ Function requirements:\n Hematopoietic Criteria:\n 1. Hemoglobin- 10 gl/dl (transfusion allowed)\n 2. ANC- 550 / cu mm (off myeloid growth factors)\n 3. Platelets- > 50,000/cu mm. (transfusion allowed - however patients must not require\n more than two platelet transfusions per week).\n Renal Function:\n a. Serum Creatinine- < 2 x ULN for age.\n Hepatic Function:\n Total bilirubin <1.5 x ULN for age SGPT (ALT) and SGOT (AST) < 10 x ULN for age\n Cardiac Function:\n For children with NBL: Normal ejection fraction (>55%) documented by echocardiogram or\n radionuclide MUGA evaluation OR normal fractional shortening (>27%) documented by\n echocardiogram.\n For subjects with paraganglioma/ pheochromocytoma: No clinically significant cardiac\n dysfunction.\n Pulmonary Function:\n Patients must have clinically normal lung function as manifested by no dyspnea at rest and\n no oxygen requirement\n Reproductive Function:\n 1. Females of childbearing potential must have a negative pregnancy test within 1 week\n prior to treatment with 131I-MIBG.\n 2. Patients of childbearing potential must agree to use an effective birth control\n method.\n 3. Female patients who are lactating must agree to stop breast feeding\n Exclusion Criteria:\n - Pregnancy or breast feeding\n - Have undergone a prior allogeneic BMT.\n - Patients with disease of any major organ system that would compromise their ability to\n withstand therapy. Any significant organ impairment should be discussed with the Study\n Chair prior to patient entry.\n - Patients who are on hemodialysis.\n - Hepatitis B surface antigen (+) or Hepatitis C positive in preceding six months.\n - Patients with an active infection requiring intravenous antivirals, antibiotics or\n antifungals. Patients on prolonged antifungal therapy are still eligible if they are\n culture negative and biopsy negative in suspected residual radiographic lesions have\n stabilized or regressed and they meet other organ function criteria.\n - Prior total body irradiation, prior total abdominal or whole liver radiation\n - Any medical or psychological condition or situation deemed by the PI to put the\n patient at increased risk of complications or noncompliance.\n - Patients with curative treatment options.\n - Patients for whom busulfan/ melphalan consolidation therapy following treatment with\n 131I-MIBG is planned.\n - Patients for who CEM (carboplatin, etoposide, melphalan) therapy is administered\n within 30 days prior to 131I-MIBG therapy or for whom this therapy is planned within\n 30 days following administration of 131I-MIBG.", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
-{"input": "This open-label phase II trial studies how well niraparib works in treating patients with\n advanced, metastatic melanoma with the homologous recombination (HR) pathway gene mutation /\n alteration. Niraparib may stop the growth of tumor cells by blocking some of the enzymes\n needed for cell growth. The trial is designed to assess the efficacy and safety of niraparib\n in patients with HR mutation/ alteration whose disease progressed on prior immunotherapy\n and/or BRAF-targeting therapy.\n ;\n ;\n Inclusion Criteria:\n - Have genetic homologous recombination (HR) mutation/ alteration including ARID1A/B,\n ARID2, ATM, ATR, ATRX, BARD1, BRCA1/2, BAP1, BRIP1, CHEK2, FANCD2, MRN11A, PALB2,\n RAD50, RAD51, RAD54B\n - Disease must have progressed on the standard systemic therapies or they could not have\n tolerated the standard therapies.\n - ECOG PS >/=1\n - Have measurable metastatic disease according to RECIST 1.1\n - Prior systemic cytotoxic therapy up to 1 regimens is allowed; There is no limit on the\n number of prior immunotherapy or targeted therapy regimens.\n - All adverse events associated with prior treatment must have resolved to \u2264 Grade 1\n prior to day 1 of the study drug administration.\n Exclusion Criteria:\n - Previously treated with a PARP inhibitor\n - Symptomatic brain metastasis or active brain lesions \u22656 mm size or those\n - Require steroid treatment for brain lesions or leptomeningeal disease\n - Systemic cancer therapy within 14 days prior to day 1 of the study drug administration\n - Any major surgery \u2264 3 weeks of starting the study and patient must have recovered from\n any effects of any major surgery\n - Investigational therapy administered \u2264 4 weeks, or within a time interval less than at\n least 5 half-lives of the investigational\n - Prior radiotherapy encompassing > 20% of the bone marrow within 2 weeks; or any\n radiation therapy within 1 week prior to Day 1 of protocol therapy\n - Medical history of immunocompromised condition\n - Systemic treatment of another type of cancer \u2264 2 years prior to registration\n - Known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)", "output": {"inclusion_biomarker": [["ARID1A mutation"], ["ARID1B mutation"], ["ARID2 mutation"], ["ATM mutation"], ["ATR mutation"], ["ATRX mutation"], ["BARD1 mutation"], ["BRCA1 mutation"], ["BRCA2 mutation"], ["BAP1 mutation"], ["BRIP1 mutation"], ["CHEK2 mutation"], ["FANCD2 mutation"], ["MRN11A mutation"], ["PALB2 mutation"], ["RAD50 mutation"], ["RAD51 mutation"], ["RAD54B mutation"]], "exclusion_biomarker": []}}
+{"input": "This open-label phase II trial studies how well niraparib works in treating patients with\n advanced, metastatic melanoma with the homologous recombination (HR) pathway gene mutation /\n alteration. Niraparib may stop the growth of tumor cells by blocking some of the enzymes\n needed for cell growth. The trial is designed to assess the efficacy and safety of niraparib\n in patients with HR mutation/ alteration whose disease progressed on prior immunotherapy\n and/or BRAF-targeting therapy.\n ;\n ;\n Inclusion Criteria:\n - Have genetic homologous recombination (HR) mutation/ alteration including ARID1A/B,\n ARID2, ATM, ATR, ATRX, BARD1, BRCA1/2, BAP1, BRIP1, CHEK2, FANCD2, MRN11A, PALB2,\n RAD50, RAD51, RAD54B\n - Disease must have progressed on the standard systemic therapies or they could not have\n tolerated the standard therapies.\n - ECOG PS >/=1\n - Have measurable metastatic disease according to RECIST 1.1\n - Prior systemic cytotoxic therapy up to 1 regimens is allowed; There is no limit on the\n number of prior immunotherapy or targeted therapy regimens.\n - All adverse events associated with prior treatment must have resolved to \u2264 Grade 1\n prior to day 1 of the study drug administration.\n Exclusion Criteria:\n - Previously treated with a PARP inhibitor\n - Symptomatic brain metastasis or active brain lesions \u22656 mm size or those\n - Require steroid treatment for brain lesions or leptomeningeal disease\n - Systemic cancer therapy within 14 days prior to day 1 of the study drug administration\n - Any major surgery \u2264 3 weeks of starting the study and patient must have recovered from\n any effects of any major surgery\n - Investigational therapy administered \u2264 4 weeks, or within a time interval less than at\n least 5 half-lives of the investigational\n - Prior radiotherapy encompassing > 20% of the bone marrow within 2 weeks; or any\n radiation therapy within 1 week prior to Day 1 of protocol therapy\n - Medical history of immunocompromised condition\n - Systemic treatment of another type of cancer \u2264 2 years prior to registration\n - Known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)", "output": {"inclusion_biomarker": [["ARID1A mutation"], ["ARID1B mutation"], ["ARID2 mutation"], ["ATM mutation"], ["ATR mutation"], ["ATRX mutation"], ["BARD1 mutation"], ["BRCA1 mutation"], ["BRCA2 mutation"], ["BAP1 mutation"], ["BRIP1 mutation"], ["CHEK2 mutation"], ["FANCD2 mutation"], ["MRN11A mutation"], ["PALB2 mutation"], ["RAD50 mutation"], ["RAD51 mutation"], ["RAD54B mutation"], ["ARID1A mutation"], ["ARID1B mutation"], ["ARID2 mutation"], ["ATM mutation"], ["ATR mutation"], ["ATRX mutation"], ["BARD1 mutation"], ["BRCA1 alteration"], ["BRCA2 alteration"], ["BAP1 alteration"], ["BRIP1 alteration"], ["CHEK2 alteration"], ["FANCD2 alteration"], ["MRN11A alteration"], ["PALB2 alteration"], ["RAD50 alteration"], ["RAD51 alteration"], ["RAD54B alteration"]], "exclusion_biomarker": []}}
 {"input": "UP-NEXT is a double-blind, randomized, placebo-controlled study of the antibody-drug\n conjugate (ADC) XMT-1536 (upifitamab rilsodotin) administered as an intravenous infusion once\n every four weeks in patients with recurrent, platinum-sensitive high-grade serous ovarian\n cancer (HGSOC), including fallopian tube and primary peritoneal cancer, expressing high\n levels of NaPi2b.\n ;\n ;\n Inclusion Criteria:\n 1. Participant must have a histological diagnosis of high grade serous ovarian cancer,\n which includes fallopian tube and primary peritoneal cancer, that is metastatic or\n recurrent.\n 2. Participant must have platinum-sensitive recurrent disease, defined as having achieved\n either a partial or complete response to 4 or more cycles in their penultimate\n platinum- containing regimen and their disease progressing more than 6 months after\n completion of the last dose of platinum containing therapy in the penultimate regimen.\n 3. Participant must have had 4 to 8 cycles of platinum-based chemotherapy in 2nd to 4th\n line setting in their most recent treatment regimen as defined below:\n 1. Platinum-based chemotherapy regimens allowed immediately preceding enrollment to\n the study: carboplatin or cisplatin \u00b1: paclitaxel, docetaxel, pegylated liposomal\n doxorubicin or gemcitabine.\n 2. Participant must receive first study treatment infusion between 4 and 12 weeks\n after completing final dose of platinum in the most recent platinum-based\n regimen.\n 4. Participant must have had as their best response to last line of treatment one of the\n following: No Evidence of Disease (NED); Complete Response (CR); Partial Response\n (PR); OR Stable Disease (SD)\n 5. Participants with NED, CR, or PR as their best response to most recent line of\n treatment and who have not received treatment with a prior PARP inhibitor must have\n definitive BRCA1 and BRCA2 testing results that demonstrate no evidence of a\n deleterious BRCA1 or BRCA2 mutation. Somatic BRCA mutation testing is required for\n participants who are classified as not having a deleterious mutation by germline\n testing alone.\n 6. Participant must provide either a tumor tissue block or fresh cut slides for\n measurement of NaPi2b expression by a central laboratory. If sufficient archival tumor\n tissue is not available, then a tumor tissue block or slides must be obtained from a\n fresh biopsy and provided to the central laboratory. Confirmation of a\n NaPi2b-H/positive tumor by the central laboratory is required prior to randomization.\n Exclusion Criteria:\n 1. Participant has received prior treatment with mirvetuximab soravtansine or another ADC\n containing an auristatin or maytansinoid payload.\n 2. Participant has received bevacizumab in combination with last platinum-based regiment\n or plans to receive maintenance therapy outside the study intervention.\n 3. Participant has clinical signs or symptoms of gastrointestinal obstruction and/or\n requirement for parenteral hydration or nutrition.\n 4. Participant has ascites or pleural effusion managed with therapeutic paracentesis or\n thoracentesis within 28 days prior to signing the principal study consent form.\n 5. Participant has history of cirrhosis, hepatic fibrosis, esophageal or gastric varices,\n or other clinically significant liver disease. Testing beyond laboratory studies\n otherwise defined in the eligibility criteria, to diagnose potentially clinically\n significant liver disease based on risk factors such as hepatic steatosis or history\n of excessive alcohol intake, will be based on clinical judgement of the investigator.\n 6. Participant has history of or suspected pneumonitis or interstitial lung disease.\n 7. Participant has untreated CNS metastases (including new and progressive brain\n metastases), history of leptomeningeal metastasis, or carcinomatous meningitis.", "output": {"inclusion_biomarker": [["NaPi2b-H"], ["NaPi2b positive"]], "exclusion_biomarker": [["BRCA1 mutation"], ["BRCA2 mutation"]]}}
 {"input": "The primary objectives of the study are:\n In the Dose Escalation Phase:\n - To assess the safety, tolerability, and pharmacokinetics (PK) of REGN5668 alone and in\n separate combinations with cemiplimab or REGN4018, in order to determine a maximally\n tolerated dose(s) (MTD) or recommended phase 2 dose(s) (RP2D) of these combinations\n In the Dose Expansion Phase:\n - To assess the preliminary efficacy of REGN5668 in combination with cemiplimab or\n REGN4018, (separately by cohort and combination) as determined by the objective response\n rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1\n The secondary objectives of the study are:\n In the Dose Escalation Phase:\n - To assess the preliminary efficacy of REGN5668 in combination with cemiplimab or\n REGN4018 (separately by cohort and combination) as determined by ORR by RECIST 1.1\n In the Dose Expansion Phase:\n - To characterize the safety profile in each expansion cohort\n - To characterize the PK of REGN5668 in combination with cemiplimab or REGN4018\n (separately by cohort and combination)\n In both the Dose Escalation and Dose Expansion Phases:\n - To assess preliminary efficacy of REGN5668 in combination with cemiplimab or REGN4018\n (separately by cohort and combination) as measured by ORR based on immune based therapy\n RECIST (iRECIST), best overall response (BOR), duration of response (DOR), disease\n control rate (DCR), and progression-free survival (PFS) based on RECIST 1.1 and iRECIST\n - To assess changes in CA-125 levels from baseline after treatment with REGN5668 in\n combinations with cemiplimab or REGN4018 (separately by cohort and combination)\n - Immunogenicity of REGN5668, alone and in combinations with cemiplimab or REGN4018\n ;NA;\n Key Inclusion Criteria:\n 1. Has histologically or cytologically confirmed diagnosis of advanced epithelial ovarian\n cancer (except carcinosarcoma), primary peritoneal, or fallopian tube cancer that has\n received at least 1 line of platinum-based systemic therapy as defined in the protocol\n 2. Has a serum CA-125 level \u22652x ULN (in screening)\n 3. Has adequate organ and bone marrow function as defined in the protocol\n 4. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n 5. Has a life expectancy of at least 3 months\n Key Exclusion Criteria:\n 1. Prior anti-cancer immunotherapy as defined in the protocol\n 2. Recent treatment with anti-Programmed Cell Death (PD-1)/PDL-1 therapy\n 3. Has had another malignancy within the last 5 years that is progressing, requires\n active treatment, or has a high likelihood of recurrence as defined in the protocol\n 4. Prior treatment with a MUC16-targeted therapy\n 5. Expansion cohorts only: More than 3 prior lines of cytotoxic chemotherapy for\n platinum-experienced and/or intolerant disease\n 6. Has any condition that requires ongoing/continuous corticosteroid therapy as defined\n in the protocol within 1 week prior to the first dose of study drug\n 7. Has ongoing or recent (within 5 years) evidence of significant autoimmune disease that\n required treatment with systemic immunosuppressive treatments as defined in the\n protocol\n 8. Has untreated or active primary brain tumor, CNS metastases, leptomeningeal disease,\n or spinal cord compression as defined in the protocol\n 9. Has history of clinically significant cardiovascular disease as defined in the\n protocol\n Note: Other protocol-defined Inclusion/Exclusion criteria apply", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
 {"input": "VG161 is a recombinant human-IL12/15/PDL1B oncolytic HSV-1 Injectable. This Phase I study\n will be conducted in HSV-seropositive subjects with advanced malignant solid tumors that are\n refractory to conventional therapies. This is an open label study to determine the safety and\n tolerability of VG161, and recommended dose of VG161 for Phase II trials.\n ;\n ;\n Inclusion Criteria:\n 1. Males or females aged within 18 to 80 years.\n 2. Subject with late stage carcinoma which is refractory/relapsed after and/or intolerant\n of standard therapies or for which no standard therapy exists.\n 3. There is at lease one injectable tumor lesion that meet the requirements of the\n assigned dose level. The superficial lesions are preferred, and the deep lesions that\n can be injected under the guidance of B ultrasound or computed tomography (CT) scan\n can also be selected.\n 4. Eastern Cooperative Oncology Group (ECOG) scores 0 or 1.\n 5. Life expectancy is at least 3 months.\n 6. Required organ function:\n 1) Hematology blood (no blood transfusion or colony stimulating factor treatment within 14\n days): Absolute neutrophil count (ANC)\u22651.5\u00d710^9L, Platelets ( PLT)\u226575\u00d710^9L, hemoglobin\n (Hb)\u226585g/L; 2) Liver function: Total Serum bilirubin (TBIL)\u22641.5\u00d7ULN (the upper limit of the\n reference range), Alanine aminotransferase (ALT)\u22643\u00d7ULN, aspartate aminotransferase\n (AST)\u22643\u00d7ULN (acceptable for patients with liver metastasis or liver cancer: TBIL\u22645\u00d7ULN,\n AST\u22645\u00d7ULN, ALT\u22645\u00d7ULN); 3) Renal function: Serum creatinine\u22641.5\u00d7ULN, and creatinine\n clearance\u226550 ml/min (calculated per Cockcroft-Gault formula); 4) Coagulation function:\n activated partial thromboplastin time (APTT)\u22641.5\u00d7ULN, international standardized ratio\n (INR)\u22641.5\u00d7ULN.\n 7. Subjects of childbearing potential (male and female) must agree to use a reliable\n contraceptive method (hormone or barrier method or abstinence) during the study and for at\n least 90 days following the last dose; females of childbearing potential must have a\n negative blood or urine pregnancy test within 7 days of study enrollment.\n 8. Signed written informed consent.\n Exclusion Criteria:\n 1. Subject in prior anti-tumor therapies such as chemotherapy, radiotherapy, biotherapy,\n endocrinotherapy, targeted therapy, immunotherapy within 4 weeks of study treatment\n initiation.\n 2. Participation in clinical trials of any other investigational agents within 4 weeks of\n study treatment initiation.\n 3. Major organ surgery (excluding puncture biopsy) or significant trauma within 4 weeks\n of study treatment initiation.\n 4. Patients who received systemic treatment with either corticosteroids ( >10 mg/ daily\n prednisone or equivalent) or other immunosuppressive medications within 14 days of\n study treatment initiation.\n 5. Subjects with any \u2265Grade 1 toxicity (as per NCI CTC AE Version 5.0) related to prior\n anti-cancer therapy (except for toxicity that the investigator assessed to be no\n safety risk, such as alopecia.).\n 6. Subjects with any uncontrolled active Central Nervous System (CNS) metastasis or\n meningeal metastasis with clinical symptoms.\n 7. Seronegative for Herpes Simplex Virus (HSV) (HSV-1IgG and HSV-1IgM).\n 8. Subjects with the relapse of HSV infection and relevant clinical manifestations, such\n as lip herpes, herpes keratitis, herpes dermatitis, and genital herpes.\n 9. Subjects with other uncontrolled active infections.\n 10. Known history of immunodeficiency and test positive of human immunodeficiency virus\n (HIV).\n 11. Active infection of hepatitis B (HBV) (hepatitis b virus titer higher than the\n detection limit or those requiring antiviral therapy), or hepatitis C virus (HCV).\n 12. History of severe cardiovascular disease:\n 1)Ventricular arrhythmias requiring clinical intervention; 2)QTc interval >480 ms; 3)Acute\n coronary syndrome, congestive heart failure, stroke or other cardiovascular events of III\n grade or above within 6 months; 4)The cardiac function grade\u2265II or left ventricular\n ejection fraction (LVEF) <50% per the New York Heart Association (NYA); 5)Uncontrolled\n hypertension. 13. Subjects with active or past autoimmune diseases that are likely to recur\n (e.g. systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.); acceptable for\n patients with clinically stable autoimmune thyroiditis.\n 14. Subjects with any prior \u2265Grade 3 immune-related adverse event (irAE) while receiving\n any previous immunotherapy agent.\n 15. known to have alcohol or drug dependence. 16. Persons with mental disorders or poor\n compliance. 17. Pregnant or lactating women. 18. Subjects with any significant unrelated\n systemic illness that to the investigator's opinion would compromise the subject's\n eligibility to participate the study.", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}