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+++ "b/ft_validation.jsonl"
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-{"input": "TAK-981 is being tested in combination with anti-CD38 monoclonal antibodies (mAbs) to treat\n participants who have relapsed or refractory multiple myeloma (RRMM).\n The main aims of the study are to evaluate the safety and efficacy of TAK-981 in combination\n with anti-CD38 (mAbs) and to determine the recommended Phase 2 dose (RP2D).\n Participants will be on this combination treatment for 28-day cycles. They will continue with\n this treatment until disease progression or unacceptable toxicity.\n ;\n ;\n Inclusion Criteria:\n 1. Participants must have RRMM with measurable disease:\n a) Has measurable disease defined as one of the following:\n - Serum M-protein \u22650.5 g/dL (\u22655 g/L).\n - Urine M-protein \u2265200 mg/24 hours.\n - In participants without measurable M-protein in serum protein electrophoresis\n (SPEP) or urine protein electrophoresis (UPEP), a serum free light chain (FLC)\n assay result with involved FLC level \u226510 mg/dL (\u2265100 mg/L), provided serum FLC\n ratio is abnormal.\n 2. Has undergone stem cell transplant or is considered transplant ineligible.\n 3. Has failed at least 3 prior lines of anti-myeloma treatments and is either refractory,\n or intolerant to at least 1 immunomodulatory drug ( IMiD); (ie, lenalidomide or\n pomalidomide [thalidomide excluded]), at least 1 proteasome inhibitor (ie, bortezomib,\n ixazomib or carfilzomib), and refractory to at least 1 anti-CD38 antibody and who have\n demonstrated disease progression with the last therapy.\n 5.Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG)\n Performance Scale.\n 6.Have recovered to Grade 1 or baseline from all toxicity associated with previous therapy\n or have the toxicity established as sequela.\n Exclusion Criteria:\n 1. Received treatment with systemic anticancer treatments within 14 days before the first\n dose of study drug.\n 2. Current participation in another interventional study, including other clinical trials\n with investigational agents (including investigational vaccines or investigational\n medical device for disease under study) within 4 weeks of the first dose of TAK-981\n and throughout the duration of this trial.\n 3. Prior radiation therapy within 14 days of the first dose of TAK-981.\n 4. Major surgery within 4 weeks before C1D1. participants should be fully recovered from\n any surgically related complications.\n 5. Plasmapheresis within 28 days of randomization.\n 6. Diagnosis of primary amyloidosis, Waldenstr\u00f6m's disease, monoclonal gammopathy of\n undetermined significance or smoldering multiple myeloma (SMM), plasma cell leukemia\n POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and\n skin changes), myelodysplastic syndrome, or myeloproliferative syndrome.\n 7. With disease where the only measurable parameter is plasmacytoma.\n 8. Second malignancy within the previous 3 years, except treated basal cell or localized\n squamous skin carcinomas, localized prostate cancer, cervical carcinoma in situ,\n resected colorectal adenomatous polyps, breast cancer in situ, or other malignancy for\n which the participant is not on active anticancer therapy.\n 9. Prior treatment with more than 1 anti-CD38 antibody.\n 10. Requires the use of drugs known to prolong the corrected QT interval (QTc) (during\n Phase 1b only).\n 11. History of QT interval with Fridericia's correction (QTcF) >480 ms.\n 12. History of human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C\n infection.\n 13. Systemic infection requiring systemic antibiotic therapy.\n 14. Active or history pneumonitis.\n 15. Receipt of any live vaccine (eg, varicella, pneumococcus) within 4 weeks of initiation\n of study drug.\n 16. Receiving strong or moderate Cytochrome P450 (CYP) 3A4/5 inhibitors or inducers.\n 17. History of unstable cardiac comorbidities in the following 6 months.", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
+{"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": "The purpose of the study is to learn from the real world practice of prescribing targeted\n therapies to patients with advanced cancer whose tumor harbors a genomic variant known to be\n a drug target or to predict sensitivity to a drug.\n NOTE: Due to character limits, the arms section does NOT include all TAPUR Study relevant\n biomarkers. For additional information, contact TAPUR@asco.org, or if a patient, your nearest\n participating TAPUR site (see participating centers).\n *********************************************************************************************\n *********************************************************************************\n Results in publication or poster presentation format are posted as they become available for\n individual cohorts at www.tapur.org/news. The results may be accessed at any time. All\n results will be made available on clinicaltrials.gov at the end of the study. Indexing of\n available results on PubMed is in progress.\n *********************************************************************************************\n *********************************************************************************\n ;\n ;\n Inclusion Criteria:\n - 12 years of age or older (*Restrictions apply. Not all therapies are available for\n patients <18)\n - Histologically-proven locally advanced or metastatic solid tumor, multiple myeloma or\n B cell non-Hodgkin lymphoma who is no longer benefiting from standard anti-cancer\n treatment or for whom, in the opinion of the treating physician, no such treatment is\n available or indicated\n - Performance status 0-2 (Per Eastern Cooperative Oncology Group (ECOG) criteria)\n - Patients must have acceptable organ function as defined below. However, as noted\n above, drug-specific inclusion/exclusion criteria specified in the protocol appendix\n for each agent will take precedence for this and all inclusion criteria:\n 1. Absolute neutrophil count \u2265 1.5 x 106/\u00b5l\n 2. Hemoglobin > 9.0 g/dl\n 3. Platelets > 75,000/\u00b5l\n 4. Total bilirubin < 2.0 mg/ dl, except in patients with Gilbert's Syndrome\n 5. Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)\n and alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT) <\n 2.5 x institutional upper limit of normal (ULN) (or < 5 x ULN in patients with\n known hepatic metastases)\n 6. Serum creatinine \u2264 1.5 \u00d7 ULN or calculated or measured creatinine clearance \u2265 50\n mL/min/1.73 m2\n - Patients must have disease that can be objectively measured by physicial or\n radiographic exam or evaluable disease (per RECIST v1.1 for solid tumor, Lugano\n criteria for non Hodgkin lymphoma or International Myeloma Working Group criteria for\n multiple myeloma), defined as at least one lesion that can be accurately measured in\n at least one dimension (longest diameter to be recorded for non-nodal lesions and\n short axis for nodal lesions) as \u226520 mm with conventional techniques or as \u226510 mm with\n spiral computed tomography (CT) scan, Magnetic Resonance Imaging (MRI), or a\n subcutaneous or superficial lesion that can be measured with calipers by clinical\n exam. For lymph nodes, the short axis must be \u226515 mm. Patients who have assessable\n disease by physical or radiographic examination but do not meet these definitions of\n measurable disease are eligible and will be considered to have evaluable disease.\n Patient's whose disease cannot be objectively measured by physical or radiographic\n examination (e.g., elevated serum tumor marker only, bone-only disease without an\n identifiable soft tissue component, or patients with only assessable non-measurable\n disease) are NOT eligible.\n - Results must be available from a genomic test or immunohistochemistry (IHC) test for\n protein expression performed in a Clinical Laboratory Improvement Amendments\n (CLIA)-certified and College of American Pathologists (CAP)-accredited or New York\n State accredited (for labs offering services to residents of NY) laboratory. Labs that\n have registered the test with the NIH Genetic Testing Registry or that provide a\n report that has been designated as optimized for TAPUR participation are preferred,\n but not required. The genomic or IHC test used to qualify a patient for participation\n in TAPUR may have been performed on any specimen of the patient's tumor obtained at\n any point during the patient's care at the discretion of the patient's treating\n physician. Genomic assays performed on cell-free DNA in plasma (\"liquid biopsies\")\n will also be acceptable if the genomic analysis is performed in a laboratory that\n meets the criteria described above.\n - Ability to understand and the willingness to sign a written informed consent/assent\n document.\n - Have a tumor genomic profile for which single agent treatment with one of the FDA\n approved targeted anti-cancer drugs included in this study has potential clinical\n benefit based on the criteria described in protocol.\n - For orally administered drugs, the patient must be able to swallow and tolerate oral\n medication and must have no known malabsorption syndrome.\n - Because of the risks of drug treatment to the developing fetus, women of child-bearing\n potential and men must agree to use adequate contraception (hormonal or barrier method\n of birth control; abstinence) for the duration of study participation, and for four\n months following completion of study therapy. Should a woman become pregnant or\n suspect she is pregnant while participating in this study or if she is the partner of\n a male participant in this study and becomes pregnant while he is participating in\n this study, she should inform her or her partner's treating physician immediately as\n well as her obstetrician. Female study patients who become pregnant must immediately\n discontinue treatment with any study therapy. Male patients should avoid impregnating\n a female partner. Male study patients, even if surgically sterilized, (i.e.\n post-vasectomy) must agree to one of the following: practice effective barrier\n contraception during the entire study treatment period and for a specified amount of\n time the last dose of study drug, or completely abstain from sexual intercourse.\n Note: TAPUR does not explicitly exclude any type of solid tumor, but the patient must have\n measurable and evaluable disease per RECIST v1.1.\n Exclusion Criteria:\n - Patients whose disease is not measurable or cannot be assessed by radiographic imaging\n or physical examination (e.g., elevated serum tumor marker only) are not eligible\n - Patients with primary brain tumors or leptomeningeal metastases are excluded.\n - Patients with previously treated brain metastases are eligible, provided that the\n patient has not experienced a seizure or had a clinically significant change in\n neurological status within the 3 months prior to registration. All patients with\n previously treated brain metastases must be clinically stable for at least 1 month\n after completion of treatment and off steroid treatment for one month prior to study\n enrollment.\n - Patients with known progressive brain metastases are eligible but additional\n eligibility criteria apply.\n Note: there are additional exclusion criteria that may apply", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
-{"input": "This study aims to describe the treatment patterns in clinical practice in adult patients\n with mNSCLC with a BRAF V600E mutation. This study will also describe Real-World\n Progression-Free Survival (rwPFS) and Overall Survival (OS) for treatments prescribed in\n routine practice for mNSCLC with BRAF V600E mutation. Adverse events (AEs) related to\n treatment management will also be described.\n ;NA;\n Inclusion Criteria:\n - Age \u2265 18 years at the time of first-line treatment initiation for mNSCLC,\n - Patients who initiated a first systemic treatment for mNSCLC in the metastatic setting\n from 01 December 2017 and before their study entry date (retrospectively enrolled\n patients), or Patients who initiated a first systemic treatment for mNSCLC (metastatic\n setting) at or after their study entry date (prospectively enrolled patients),\n - Confirmed diagnosis of Stage IV mNSCLCat any time before study inclusion Stage IV M1a,\n M1borM1c, as per the American Joint Committee on Cancer (AJCC cancer) staging manual,\n - Confirmed presence of BRAF V600E mutation - via tumor biopsy, metastasectomy, or\n liquid biopsy - at anytime before study inclusion,\n - Signed ICF or non-opposition to study participation,according to local regulations.\n Patients eligible for prospective QoL data collection must, in addition to the above\n mentioned criteria, meet ALL of the following criteria to be eligible for the study:\n - Patients who initiate a first or second systemic treatment line for mNSCLC (metastatic\n setting) with a BRAF V600E mutation at or after their study entry date\n Exclusion Criteria:\n - Concurrent or another previous malignancy within 2 years of study entry, except\n curatively treated basal or squamous cell skin cancer, prostate intraepithelial\n neoplasm, in-situcarcinoma of the cervix, Bowen's disease or Gleason \u2264 6 prostate\n cancer,\n - Previous, ongoing, or planned participation in a clinical trial involving an\n interventional drug as a first-or second-line systemic treatment for mNSCLC.", "output": {"inclusion_biomarker": [["BRAF V600E"]], "exclusion_biomarker": []}}
-{"input": "For metastatic/advanced NSCLC patients who do not have targetable mutations, either\n immunotherapy targeting the programmed death-1 and its ligand (PD-1/L1) pathway alone or in\n combination with platinum doublet chemotherapy is now a standard of care. However, still\n about half of the patients do not benefit due to treatment resistance. It is therefore\n critically important to find novel therapies and combinations to benefit patients who have\n failed or are intolerant to 1st line immunotherapy.\n This study hypothesizes that ipatasertib in combination with taxane (e.g. docetaxel) can be\n an effective strategy. Ipatasertib is a novel adenosine triphosphate (ATP)-competitive\n inhibitor that has demonstrated robust and selective targeting of protein kinase B (PKB, also\n known as AKT) in cancer patients. Importantly, evidence from preclinical studies has\n demonstrated that AKT inhibitors (e.g. ipatasertib) can enhance the therapeutic effect of\n chemotherapy as well as immunotherapy via modulating Phosphatidylinositol 3-kinase\n (PI3'K)-AKT activity.\n ;NA;\n Inclusion Criteria:\n - Ability of participant OR Legally Authorized Representative (LAR) to understand this\n study, and participant or LAR willingness to sign a written informed consent\n - Life expectancy \u226512 weeks\n - Males and females age \u2265 18 years\n - Allowable type and amount of prior therapy:\n First line anti-Programmed death receptor and ligand (PD1/PD-L1), either single agent or in\n combination with chemotherapy\n - Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1\n - Measurable disease per RECIST version 1.1\n - Diagnoses of advanced/metastatic NSCLC and have failed or are intolerant to 1st line\n anti-PD1/PD-L1, either single agent or in combination with chemotherapy, and have\n either exhausted or decline or not be candidates for all available standard of care\n therapies.\n - Adequate organ function\n - Women of child-bearing potential and men with partners of child-bearing potential must\n agree to practice sexual abstinence, or to use an acceptable form of contraception for\n the duration of study participation, and for 90 days following completion of therapy\n - Men of child-bearing potential must agree not to donate sperm while on this study and\n for 90 days after their last study treatment\n Exclusion Criteria:\n - Is not concurrent enrolled in another clinical study, unless it is an observational\n (non-interventional) clinical study or if the participant is in the follow-up period\n of an interventional study\n - Is not currently on or is not anticipated to use other investigational agents within\n 14 days prior to and while participating in this study\n - Does not have mixed small cell and non-small cell lung cancer histology\n - Does not have any unresolved toxicity CTCAE >Grade 2 from the prior 1st immunotherapy.\n Patients with irreversible toxicity that is not reasonably expected to be exacerbated\n by study drug may be included\n - Patients who have targetable mutations that qualify for targeted therapy (e.g.\n mutations of epidermal growth factor receptor (EGFR), serine/ threonine- protein\n kinase (BRAF), anaplastic lymphoma kinase (ALK), tyrosine- protein kinase (ROS1),\n neurotrophic receptor tyrosine kinase (NTRAK)) will be excluded from this study\n - Is not on concomitant therapy intended for the treatment of cancer (including, but not\n limited to, chemotherapy, hormonal therapy, immunotherapy, radiotherapy, and herbal\n therapy) for 14 days prior to starting study treatment, depending on the agent and\n during study treatment, until disease progression is documented and the patient has\n discontinued study treatment, with the exception of palliative radiotherapy and local\n therapy per PI discretion\n - Does not chronically use a strong cytochrome P4503A4 (CYP3A4/5) inhibitor or inducer,\n or sensitive CYP3A substrates with a narrow therapeutic window\n - Has not had recent major surgery within 4 weeks prior to entry into the study\n (excluding the placement of vascular access) that would prevent administration of\n study drug\n - Does not have uncontrolled systemic disease\n - Does not have uncontrolled brain metastasis\n - Does not have history of allergy to taxanes\n - Does not have history of leptomeningeal carcinomatosis\n - Does not have recent history of myocardial infarction (MI) or symptomatic coronary\n artery disease within 6 months of screening\n - Is not receiving active therapy for HIV, hepatitis B or hepatitis C\n - Does not have history of malabsorption syndrome or other condition that would\n interfere with enteral absorption or results in the inability or unwillingness to\n swallow pills\n - Does not have history of Type I or Type II diabetes mellitus requiring insulin\n (Patients who are on a stable dose of oral diabetes medication greater than or equal\n to 2 weeks prior to initiation of study treatment\n - Does not have Grade greater than or equal to 2 uncontrolled or untreated\n hypercholesterolemia or hypertriglyceridemia\n - Does not have history of or active inflammatory bowel disease (e.g., Crohn's disease\n and ulcerative colitis) or active bowel inflammation (e.g., diverticulitis)\n - Does not have active pneumonitis\n - Does not have history of lung disease: interstitial lung disease, idiopathic pulmonary\n fibrosis, cystic fibrosis, Aspergillosis, active tuberculosis, or history of\n opportunistic infections\n - Does not have uncontrolled pleural effusion/pericardial effusion/or ascites as\n determined by the investigator\n - Does not have active ventricular arrhythmia requiring medication\n - Does not have psychiatric illness/social situations that would limit compliance with\n study requirements or compromise the ability of the patient to give written informed\n consent\n - Is not pregnant, breast feeding or planning to become pregnant while receiving study\n treatment or for less than 90 days after the last dose of study treatment\n - For males with partners of childbearing potential, is not planning to father a child\n or donate sperm while receiving study treatment or for less than 90 days after the\n last dose of study treatment\n - Does not have any condition that, in the opinion of the investigator, would interfere\n with evaluation or interpretation of patient safety or study results", "output": {"inclusion_biomarker": [], "exclusion_biomarker": [["EGFR mutation"], ["BRAF mutation"], ["ALK mutation"], ["ROS1 mutation"], ["NTRAK mutation"]]}}
-{"input": "This single-arm, Phase II study was designed to evaluate the safety and efficacy of\n Camrelizumab (anti-programmed death-receptor 1 [PD-1] antibody) combination with Apatinib in\n participants with ES-SCLC who was response or stable disease after firstline standard\n chemotherapy. Participants will be receive camrelizumab +apatinib on 21-day cycles until\n progressive disease (PD) as assessed by the investigator using Response Evaluation Criteria\n in Solid Tumors Version 1.1 (RECIST v1.1). Treatment can be continued until persistent\n radiographic PD or symptomatic deterioration.\n ;NA;\n Inclusion Criteria:\n - Male or female patients aged 18 and 75 years old;\n - Signed the informed consent form prior to patient entry;\n - Eastern Cooperative Oncology Group performance status of 0 or 1;\n - Expected Survival Time: Over 3 months;\n - Pathological or cytologically proven extensive-Stage small cell lung cancer(according\n to Veterans Administration Lung Study Group)and without progression after Cycles 4-6\n 21-day cycles of first-line Standard chemotherapy(Evaluation was CR /PR/SD based on\n RECIST1.1);\n - If prophylactic cranial irradiation (PCI) was not planned,informed consent was\n required to be written between 3 weeks and 5 weeks after day 1 of the last cycle of\n chemotherapy. If PCI was planned or already performe, informed consent was required to\n be written between 3 weeks and 8 weeks after day 1 of the last cycle of chemotherapy.\n Exclusion Criteria:\n - Has prior therapy with anti-programmed cell death (PD)-1, anti-PD-L1,anti Cytotoxic T\n lymphocyte-associated Antigen(CTLA)-4 or other Drugs that target T cells;\n - Has prior therapy with angiogenesis inhibitors,Such as sunitinib, bevacizumab,\n apatinib, anlotinib;\n - Has active or untreated central nervous system (CNS) metastases and/or cancerous\n meningitis;\n - Imaging (CT or MRI) shows that tumor invades large blood vessels or the boundary with\n blood vessels is unclear;\n - Has spinal cord compression which was not cured or relieved through surgery and/or\n radiotherapy, or diagnosed spinal cord compression after treatment showed no clinical\n evidence of disease stabilization prior to allocation \u22651 week;\n - Within the past 2 weeks have used high dose antibiotics;\n - According to the judgement of the researchers, there are other factors that may lead\n to the termination of the study.", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
-{"input": "Nivolumab (BMS-936558) is a fully human, IgG4 (kappa) isotype mAb that binds PD-1 on\n activated immune cells and disrupts engagement of the receptor with its ligands PD-L1 (B7\n H1/CD274) and PD-L2 (B7-DC/CD273), thereby abrogating inhibitory signals and augmenting the\n host antitumor response. In early clinical trials, nivolumab has demonstrated activity in\n several tumor types, including melanoma, renal cell carcinoma (RCC), and non-small cell lung\n cancer (NSCLC).\n Nivolumab is in clinical development for the treatment of patients with NSCLC, RCC, melanoma,\n squamous cell carcinoma of the head and neck (SCCHN) and other tumors (eg, glioblastoma\n multiforme, mesothelioma, small cell lung cancer, gastric).\n Nivolumab is approved in the United States (US), European Union, and other countries for the\n treatment of patients with unresectable or metastatic melanoma, advanced NSCLC with\n progression on or after platinum-based chemotherapy, advanced RCC whose disease progressed on\n an antiangiogenic therapy, classical Hodgkin lymphoma that has relapsed or progressed after\n autologous hematopoietic stem cell transplantation and post-transplantation brentuximab\n vedotin treatment, and recurrent or metastatic squamous cell carcinoma of the head and neck\n with disease progression on or after a platinum-based therapy.\n The proposed study will evaluate the efficacy and safety of preoperative administration of\n Nivolumab or Nivolumab combined with nab-paclitaxel and carboplatin in neoadjuvant setting\n and administration of Nivolumab in adjuvant setting in patients with high-risk resectable\n NSCLC, and will facilitate a comprehensive exploratory characterization of the tumor immune\n microenvironment and circulating immune cells in these patients. Data obtained in this study\n will provide valuable information for planning further prospective clinical trials of\n anti-PD-1 and other immunotherapies in NSCLC, both in the peri-operative and advanced disease\n setting. Ultimately, it is highly desirable to discover prospective biomarkers of response\n and toxicity to allow patients with NSCLC who are most likely to derive benefit to receive\n anti-PD-1 treatment, and conversely to minimize the risk of toxicity and ineffective\n treatment for patients who are unlikely to benefit.\n ;NA;\n Inclusion Criteria:\n - Early stage IB-IIIA, operable non-small cell lung cancer, confirmed in tissue\n - Lung function capacity capable of tolerating the proposed lung surgery\n - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1\n - Available tissue of primary lung tumor\n Exclusion Criteria:\n - Presence of locally advanced, inoperable or metastatic disease\n - Participants with active, known or suspected autoimmune disease\n - Prior treatment with any drug that targets T cell co-stimulations pathways (such as\n checkpoint inhibitors)\n Other protocol defined inclusion/exclusion criteria could apply", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
-{"input": "CC-90009-AML-001 is a phase 1, open-label, dose escalation and expansion, study in subjects\n with relapsed or refractory acute myeloid leukemia and relapsed or refractory higher-risk\n myelodysplastic syndrome.\n ;\n ;\n Inclusion Criteria:\n 1. Men and women \u2265 18 years of age, at the time of signing the ICD (Informed Consent\n Document).\n 2. Subject must understand and voluntarily sign an ICD prior to any study-related\n assessments/procedures being conducted.\n 3. Relapsed or refractory AML (Acute Myeloid Leukemia) (Parts A and B) or relapsed or\n refractory (R/R) higher-risk MDS (Myelodysplastic Syndrome) (HR-MDS) (Part B only) as\n defined by World Health Organization criteria who are not suitable for other\n established therapies.\n 1. In Part A, R/R AML\n 2. In Part B, R/R AML including\n - Relapsed after allogeneic HSCT or\n - In second or later relapse or\n - Refractory to initial induction or re-induction treatment or\n - Refractory or relapse after HMA treatment (HMA failure defined as primary\n progression or lack of clinical benefit after a minimum of 6 cycles or\n unable to tolerate HMA due to toxicity) or\n - Refractory within 1 year of initial treatment (excluding those with\n favorable risk based on cytogenetics)\n 3. In Part B, R/R HR-MDS (Revised International Prognostic Scoring System score\n (IPSS-R) > 3.5 points, IPSS-R calculated during screening period):\n - IPSS-R intermediate risk (in combination with more than 10% bone marrow\n blasts or poor or very poor IPSS-R cytogenetic risk) or\n - IPSS-R high or\n - IPSS-R very high risk\n 4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2.\n 5. At least 4 weeks (from first dose) has elapsed from donor lymphocyte infusion (DLI)\n without conditioning.\n 6. Subjects must have the following screening laboratory values:\n - Corrected serum Ca or free (ionized) serum Ca within normal limits (WNL).\n o Corrected Ca (mg/dL) = Total Ca (mg/dL) - 0.8 (albumin [g/dL] - 4)\n - Total White Blood Cell count (WBC) < 25 x 10^9/L prior to first infusion. Prior\n or concurrent treatment with hydroxyurea to achieve this level is allowed.\n - Potassium and magnesium within normal limits or correctable with supplements.\n - Aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) or\n alanine aminotransferase/serum glutamate pyruvic transaminase (ALT/SGPT) \u2264 2.5 x\n Upper Limit of Normal (ULN).\n - Uric acid \u2264 7.5 mg/dL (446 \u03bcmol/L). Prior and/or concurrent treatment with\n hypouricemic agents (eg, allopurinol, rasburicase) are allowed.\n - Selected electrolytes within normal limits or correctable with supplements.\n - Serum bilirubin \u2264 1.5 x ULN (upper limit of normal).\n - Estimated serum creatinine clearance of \u2265 60 mL/min using the Cockcroft-Gault\n equation. Measured creatinine clearance from a 24-hour urine collection is\n acceptable if clinically indicated.\n - International normalized ratio (INR) < 1.5 x ULN and Partial thromboplastin time\n (PTT) < 1.5 x ULN.\n Exclusion Criteria:\n 1. Subjects with acute promyelocytic leukemia (APL)\n 2. Subjects with clinical symptoms suggesting active central nervous system (CNS)\n leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid is only required if\n there is clinical suspicion of CNS involvement by leukemia during screening.\n 3. Patients with prior autologous hematopoietic stem cell transplant who, in the\n investigator's judgment, have not fully recovered from the effects of the last\n transplant (e.g., transplant related side effects).\n 4. Prior allogeneic hematopoietic stem cell transplant (HSCT) with either standard or\n reduced intensity conditioning \u2264 6 months prior to starting CC-90009.\n 5. Subjects on systemic immunosuppressive therapy post HSCT at the time of screening, or\n with clinically significant graft-versus-host disease (GVHD).\n 6. Prior systemic cancer-directed treatments or investigational modalities \u2264 5 half lives\n or 4 weeks prior to starting CC-90009, whichever is shorter. Hydroxyurea is allowed to\n control peripheral leukemia blasts.\n 7. Leukapheresis \u2264 2 weeks prior to starting CC-90009.", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
-{"input": "The purpose of this study is to determine the efficacy of treating patients with intermediate\n risk smoldering multiple myeloma (SMM) with combinational therapy with dexamethasone and\n lenalidomide (Rd) and patients with high risk SMM with combinational therapy with Rd and\n carfilzomib.\n ;\n ;\n Inclusion Criteria:\n Participants that are diagnosed with MM, high- or intermediate-risk SMM in the iStopMM\n study will be invited to participate in this study. Each patient must meet all the\n following inclusion criteria to be enrolled in the study:\n 1. Age more than 18 years.\n 2. Active MM or\n 3. Smoldering myeloma, which is untreated, as defined by: Measurable M spike OR\n pathological FLC ratio AND bone marrow PC% > 10%\n 4. The following laboratory values obtained \u2264 30 days prior to registration\n - Calculated creatinine clearance \u2265 30mL/min (using CKD-EPI equation)\n - Absolute neutrophil count (ANC) > 1000/mm3\n - Platelet count > 75000/mm3\n - Hemoglobin \u2265 8.0 g/dL\n - Total bilirubin \u2264 1.5 x ULN\n - ALT and AST \u2264 3 x ULN\n 5. Measurable disease as defined by at least one of the following:\n - Serum monoclonal protein > 1.0g/L\n - > 200 mg of monoclonal protein in the urine on 24 hour electrophoresis\n - Serum immunoglobulin free light chain \u2265 10 mg/dL and abnormal serum\n immunoglobulin kappa to lambda free light chain ratio\n 6. Prior therapy for the treatment of solitary plasmacytoma is permitted, but >7 days\n should have elapsed from the last day of radiation. NOTE: Prior therapy with\n clarithromycin, DHEA, anakinra, pamidronate or zoledronic acid is permitted. Any\n additional agents not listed must be approved by the Principal Investigator.\n 7. ECOG performance status 0, 1 or 2\n 8. Negative pregnancy test done \u22647 days prior to C1D1, for women of childbearing\n potential only.\n 9. Willing to follow strict birth control measures as outlined in the protocol.\n 10. Female subjects: If they are of childbearing potential, agree to one of the following:\n Practice 2 effective methods of contraception, at the same time, from the time of\n signing the informed consent form through 90 days after the last dose of trial drug,\n AND must also adhere to the guidelines of any treatment-specific pregnancy prevention\n program (appendix 1), if applicable, OR Agree to practice true abstinence when this is\n in line with the preferred and usual lifestyle of the subject. (Periodic abstinence\n [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are\n not acceptable methods of contraception.)\n 11. Male subjects: even if surgically sterilized (i.e., status post-vasectomy), must agree\n to one of the following: Agree to practice effective barrier contraception during the\n entire trial treatment period and through 90 days after the last dose of trial drug,\n OR Must also adhere to the guidelines of any treatment-specific pregnancy prevention\n program (appendix 1), if applicable, OR Agree to practice true abstinence when this is\n in line with the preferred and usual lifestyle of the subject. (Periodic abstinence\n (e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are\n not acceptable methods of contraception). Willing to return to enrolling institution\n for follow-up during the Active Treatment Phase of the trial. Agree not to donate\n sperm for at least 90 days after the last dose of carfilzomib\n 12. Willing to provide samples for planned research\n 13. Life expectancy > 6 months\n Exclusion Criteria:\n 1. MGUS or low-risk smoldering myeloma.\n 2. Diagnosed or treated for another malignancy \u2264 2 years before trial enrollment or\n previously diagnosed with another malignancy and have any evidence of residual\n disease. NOTE: Subjects with nonmelanoma skin cancer or carcinoma in situ of any type\n are not excluded if they have undergone complete resection.\n 3. If any of the following exist at screening, subject will not be eligible for trial\n because this trial involves an investigational agent whose genotoxic, mutagenic and\n teratogenic effects on the developing fetus and newborn are unknown: Pregnant women\n Nursing women Men or women of childbearing potential who are unwilling to employ\n adequate contraception (per protocol)\n 4. Other co-morbidity which would interfere with subject's ability to participate in\n trial, e.g. uncontrolled infection, uncompensated heart or lung disease\n 5. Other concurrent chemotherapy, or any ancillary therapy considered investigational.\n NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and\n are thus allowed while on protocol treatment.\n 6. Peripheral neuropathy > Grade 3 on clinical examination or grade 2 with pain within 30\n days prior to C1D1.\n 7. Major surgery \u226414 days prior to C1D1.\n 8. Evidence of current uncontrolled cardiovascular conditions, including hypertension,\n cardiac arrhythmias, congestive heart failure, unstable angina, or myocardial\n infarction within the past 6 months. Note: Prior to trial entry, any ECG abnormality\n at screening must be documented by the investigator as not medically relevant.\n 9. Known human immunodeficiency virus (HIV) positive.\n 10. Known hepatitis B surface antigen-positive status, or known or suspected active\n hepatitis C infection.\n 11. Any medical or psychiatric illness that could, in the investigator's opinion,\n potentially interfere with the completion of treatment according to this protocol.\n 12. Known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal\n antibodies or human proteins, or their excipients (refer to respective package inserts\n or Investigator's Brochure), or known sensitivity to mammalian-derived products.\n Known allergies, hypersensitivity, or intolerance to trial drugs.\n 13. Inability to comply with protocol/procedures.\n 14. LVEF < 40% for patients treated with carfilzomib.", "output": {"inclusion_biomarker": [], "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": "The purpose of this study was to assess efficacy, safety and PK in anaplastic thyroid cancer\n (ATC) given HLX208 (BRAF V600E inhibitor).\n ;NA;\n Inclusion Criteria:\n 1. Age>=18Y;\n 2. Good Organ Function;\n 3. Expected survival time \u2265 3 months;\n 4. Advanced BRAF V600 ATC that have been diagnosed histologically;\n 5. At least one measurable lesion as per RECIST v1.1;\n 6. ECOG score 0-1.\n Exclusion Criteria:\n 1. Pregnant or lactating women;\n 2. Previous treatment with BRAF inhibitors or MEK inhibitors;\n 3. A history of other malignancies within two years, except for cured cervical carcinoma\n in situ, basal cell carcinoma of the skin;\n 4. Severe active infections requiring systemic anti-infective therapy.", "output": {"inclusion_biomarker": [["BRAF V600"]], "exclusion_biomarker": []}}
+{"input": "This single-arm, Phase II study was designed to evaluate the safety and efficacy of\n Camrelizumab (anti-programmed death-receptor 1 [PD-1] antibody) combination with Apatinib in\n participants with ES-SCLC who was response or stable disease after firstline standard\n chemotherapy. Participants will be receive camrelizumab +apatinib on 21-day cycles until\n progressive disease (PD) as assessed by the investigator using Response Evaluation Criteria\n in Solid Tumors Version 1.1 (RECIST v1.1). Treatment can be continued until persistent\n radiographic PD or symptomatic deterioration.\n ;NA;\n Inclusion Criteria:\n - Male or female patients aged 18 and 75 years old;\n - Signed the informed consent form prior to patient entry;\n - Eastern Cooperative Oncology Group performance status of 0 or 1;\n - Expected Survival Time: Over 3 months;\n - Pathological or cytologically proven extensive-Stage small cell lung cancer(according\n to Veterans Administration Lung Study Group)and without progression after Cycles 4-6\n 21-day cycles of first-line Standard chemotherapy(Evaluation was CR /PR/SD based on\n RECIST1.1);\n - If prophylactic cranial irradiation (PCI) was not planned,informed consent was\n required to be written between 3 weeks and 5 weeks after day 1 of the last cycle of\n chemotherapy. If PCI was planned or already performe, informed consent was required to\n be written between 3 weeks and 8 weeks after day 1 of the last cycle of chemotherapy.\n Exclusion Criteria:\n - Has prior therapy with anti-programmed cell death (PD)-1, anti-PD-L1,anti Cytotoxic T\n lymphocyte-associated Antigen(CTLA)-4 or other Drugs that target T cells;\n - Has prior therapy with angiogenesis inhibitors,Such as sunitinib, bevacizumab,\n apatinib, anlotinib;\n - Has active or untreated central nervous system (CNS) metastases and/or cancerous\n meningitis;\n - Imaging (CT or MRI) shows that tumor invades large blood vessels or the boundary with\n blood vessels is unclear;\n - Has spinal cord compression which was not cured or relieved through surgery and/or\n radiotherapy, or diagnosed spinal cord compression after treatment showed no clinical\n evidence of disease stabilization prior to allocation \u22651 week;\n - Within the past 2 weeks have used high dose antibiotics;\n - According to the judgement of the researchers, there are other factors that may lead\n to the termination of the study.", "output": {"inclusion_biomarker": [], "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": "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": "An open-label, two-part Phase I/Ib study of RP12146 in adult patients with locally advanced\n or metastatic solid tumors. The first part (Part 1) is a Phase I dose-escalation, 3+3 design,\n open-label, MTD determination study and will enroll patients who have tumors known to harbour\n DNA repair deficiencies. The second part (Part 2) is a Phase Ib, dose-expansion at the MTD\n (or optimal dose) and will enroll patients with a confirmed deleterious HRR mutation in their\n tumor as identified by a central genomics testing laboratory.\n ;NA;\n Inclusion Criteria.\n 1. Provision of full informed consent prior to any study-specific procedures.\n 2. Patients must be \u226518 years of age, at the time of signing informed consent.\n 3. Dose escalation phase, patients with histologically and/or cytologically confirmed\n malignant solid tumor whose disease has progressed following at least one standard\n therapy and who have no other acceptable standard treatment options. Tumor types will\n include breast, ovarian, fallopian tube, or peritoneal cancer, extensive-stage small\n cell lung cancer (ES-SCLC), prostate, pancreatic, colorectal gastric, biliary tract,\n and endometrial cancer.\n 4. Dose-expansion phase patients with histologically and/or cytologically confirmed\n malignant solid tumor (breast, ovarian, fallopian tube, or peritoneal cancer,\n extensive-stage small cell lung cancer (ES-SCLC), with one of the documented\n deleterious mutations of specified HRR genes and whose disease has progressed\n following at least one standard therapy.\n 5. Patients with at least one measurable lesion per RECIST version 1.1 at baseline that\n can be accurately assessed by CT-scan or MRI and is suitable for repeated assessment\n at follow up-visits.\n 6. ECOG performance status 0 to 2.\n 7. Use of contraception measures\n Exclusion Criteria:\n 1. Patients with HER2 positive breast cancer\n 2. Patients receiving anticancer therapy\n 3. Patient who has not recovered from acute toxicities of previous therapy except\n treatment-related alopecia.\n 4. Prior treatment with a PARP inhibitor\n 5. Major surgery within 4 weeks of starting study treatment or any patient who has not\n recovered from the effects of major surgery.\n 6. Patient with symptomatic uncontrolled brain metastasis.\n 7. Pregnancy and lactation\n 8. Patients with uncontrolled disease", "output": {"inclusion_biomarker": [["HRR deleterious mutation"]], "exclusion_biomarker": [["HER2 positive"]]}}
+{"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": "This is Phase Ib/II, multicenter, open-label adaptive platform study of JDQ443 with select\n therapies in patients with advanced solid tumors harboring the KRAS G12C mutation.\n ;\n ;\n Inclusion Criteria:\n Dose Escalation:\n - Patients with advanced (metastatic or unresectable) KRAS G12C mutant solid tumors who\n have received standard of care therapy or are ineligible to receive such therapy.\n Phase II:\n - Patients with advanced (metastatic or unresectable) KRAS G12C mutant non-small cell\n lung cancer who have received platinum-based chemotherapy regimen and immune\n checkpoint inhibitor therapy, unless patient was ineligible to receive such therapy\n - Patients with advanced (metastatic or unresectable) KRAS G12C mutant colorectal cancer\n who have received fluropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy,\n unless patient was ineligible to such therapy.\n All patients:\n - ECOG performance status of 0 or 1.\n - Patients must have a site of disease amenable to biopsy and be a candidate for tumor\n biopsy according to the treating institution's guidelines.\n Exclusion Criteria:\n - Tumors harboring driver mutations that have approved targeted therapies, with the\n exception of KRAS G12C mutations\n - Prior treatment with a KRAS G12C inhibitor is excluded for patients in a subset of\n groups in Phase II.\n - Active brain metastases, including symptomatic brain metastases or known\n leptomeningeal disease\n - Clinically significant cardiac disease or risk factors at screening\n - Insufficient bone marrow, hepatic or renal function at screening Other\n protocol-defined inclusion/exclusion criteria may apply", "output": {"inclusion_biomarker": [["KRAS G12C"]], "exclusion_biomarker": []}}
-{"input": "In recent years, the goal of stopping drug therapy, also known as treatment-free remission\n (TFR), is emerging as one of the management goals of chronic myeloid leukemia (CML) therapy.\n Because there is no available data on Asian patients with CML undergoing tyrosine kinase\n inhibitor discontinuation (TKI), the investigators plan to recruit chronic phase CML patients\n with deep treatment response and good medical compliance in Taiwan to evaluate the\n feasibility, safety and clinical consequences of TKI discontinuation.\n ;\n ;\n Inclusion Criteria:\n 1. The participant should be an adult (age \u2a7e20 years) with CP-CML.\n 2. The BCR-ABL fusion should be in the form of either e13a2 or e14a2 (p210)\n 3. The participant should not have documented resistance to a 2nd-generation TKI\n (Nilotinib or Dasatinib)\n 4. The participant should have received \u2265 5 years of consecutive treatment with imatinib,\n or \u2265 4 years of consecutive treatment with a 2nd-generation TKI (Nilotinib or\n Dasatinib)\n 5. The participant should have achieved MR4.5 (BCR-ABL \u2a7d0.0032% IS) or undetectable\n disease in the peripheral blood or bone marrow, for \u2265 2 years, which is documented on\n \u2265 4 separate tests performed \u2265 3 months apart.\n 6. Access to a reliable qPCR-based BCR-ABL test with a sensitivity of detecting of at\n least MR4.5.\n Exclusion Criteria:\n 1. After evaluation, the participant is deemed to be ineligible by the investigator of\n this study.\n 2. The participant has no intention to be recruited into this study.", "output": {"inclusion_biomarker": [["BCR-ABL e13a2"], ["BCR-ABL e14a2"]], "exclusion_biomarker": []}}
-{"input": "HS-10376 is an oral, highly selective, small molecular inhibitor of EGFR/HER2 Exon 20\n insertion mutation. This study will evaluate the safety, tolerability, pharmacokinetics and\n clinical activity of HS-10376 in Chinese advanced Non-Small Cell Lung Cancer (NSCLC)\n patients.\n ;\n ;\n Inclusion Criteria:\n 1. Men or women greater than or equal to 18 years\n 2. Locally advanced or metastatic NSCLC patients confirmed by histology or cytology, for\n which standard treatment is invalid, unavailable or intolerable\n 3. Pathological, tumor tissue samples can be used to test EGFR/HER2 Exon 20 insertion\n mutation by central laboratory for subjects\n 4. At least one measurable lesion in accordance with RECIST 1.1\n 5. Eastern Cooperative Oncology Group (ECOG) performance status: 0~1\n 6. Estimated life expectancy >12 weeks\n 7. Reproductive-age women agree to use adequate contraception and cannot breastfeed while\n participating in this study and for a period of 6 months after the last dose.\n Likewise, men also consent to use adequate contraceptive method within the same time\n limit.\n 8. Females must have the evidence of non-childbearing potential\n 9. Signed and dated Informed Consent Form\n Exclusion Criteria:\n 1. Treatment with any of the following:\n - Previous or current treatment with EGFR Exon 20 insertion inhibitors, HER2 Exon\n 20 insertion inhibitors or EGFR/HER2 Exon 20 insertion inhibitors\n - Any cytotoxic chemotherapy, anticancer Chinese medicine and targeted small\n molecule inhibitors within 14 days of the first dose of HS-10376\n - Any investigational agents and large molecule antibodies within 28 days of the\n first dose of HS-10376\n - Local radiotherapy for palliation within 2 weeks of the first dose of HS-10376,\n or patients received more than 30% of the bone marrow irradiation, or large-scale\n radiotherapy within 4 weeks of the first dose of HS-10376\n - Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4\n weeks of the first dose of HS-10376\n 2. Inadequate bone marrow reserve or serious organ dysfunction\n 3. Uncontrolled pleural, ascites or pericardial effusion\n 4. Untreated, symptomatic or active central nervous system metastases\n 5. Severe or poorly controlled hypertension\n 6. Immunodeficiency disease and active infectious disease\n 7. Refractory nausea, vomiting, or chronic gastrointestinal diseases, or inability to\n swallow oral medications\n 8. History of hypersensitivity to any active or inactive ingredient of HS-10376 or to\n drugs with a similar chemical structure or drugs belonging to the same category of\n HS-10376\n 9. The subject who is unlikely to comply with study procedures, restrictions, or\n requirements judged by the investigator\n 10. The subject whose safety cannot be ensured or study assessments would be interfered\n judged by the investigator\n 11. Pregnant women, breastfeeding women or woman who has a child-bearing plan during the\n study\n 12. History of neuropathy or mental disorders, including epilepsy and dementia", "output": {"inclusion_biomarker": [["EGFR Exon 20 insertion"], ["HER2 Exon 20 insertion"]], "exclusion_biomarker": []}}
-{"input": "This is a prospective, single arm study to investigate the efficacy and safety furmonertinib\n 80mg/d as adjuvant treatment for 3 years post surgery of stage IA with high-risk factors and\n stage IB non-small cell lung cancer. A total of 114 patients would be enrolled. The primary\n endpoint is the disease-free survival rate at 3 years.\n ;NA;\n Inclusion Criteria:\n - Received radical resection of non-small cell lung cancer without prior anti-tumor\n therapies including radiotherapy, chemotherapy, target therapy and immunotherapy.\n - Histologically diagnosed Non-small cell lung cancer based on the judgement of at least\n 2 pathologists.\n - Stage IA with high risk factors including micropapillae or solid components, vascular\n invasion, spread through air spaces, low differentiation, tumor budding and\n insufficient lymph node dissection; Stage IB with or without high-risk factors. The\n pathological stage is based on the 8th edition of AJCC lung cancer staging.\n - EGFR mutation positive according to NGS testing by tissue, including deletions in exon\n 19, L858R, S768I, G719X, L861Q, T790M mutations et al.\n - ECOG performance status 0-1.\n - Sufficient organ function in liver, renal, kidney and hematology.\n - With written signed informed consent form, ability to report adverse events, and good\n adherence to clinical study.\n Exclusion Criteria:\n - Lung cancer with small cell or neuroendocrine cancer cell.\n - EGFR exon 20 insertion positive.\n - Concurrent with other diver mutations including alterations in ALK, ROS1, MET et al.\n - Women who are pregnant or breastfeeding.\n - Use of CYP3A4 strong depressant within 7 days or CYP3A4 strong inducer within 21 days\n prior to initial administration, use of other anti-tumor treatment including\n traditional Chinese medicine within 14 days before enrollment.\n - Concurrent with other malignancies excluding carcinoma in situ.\n - With uncontrolled systematic diseases such as active bleeding, unstable angina, heart\n infarction within 1 year, chronic heart failure and uncontrolled hypertension and\n diabetes mellitus; with active infection of HBV, HCV or HIV, or other infections\n requiring injection of antibiotics.\n - Gastrointestinal disorders which may affect drug taking or absorption.\n - With history of QT prolongation or relative risk factors including heart failure,\n hypokalemia, congenital long QT syndrome, family history of long QT syndrome et al.\n - With history of interstitial lung disease or relative risk.\n - Allergic to any component of furmonertinib tablet.\n - Mental illness or drug abuse.\n - Live vaccination within 30 days before enrollment.\n - Other situation judged by investigator such as failure to follow the rules of study.\n - Attending another study of investigational drug, or received other study drugs or\n medical devices with 4 weeks before enrollment.", "output": {"inclusion_biomarker": [["EGFR mutation"], ["EGFR exon 19 deletion"], ["EGFR L858R"], ["EGFR S768I"], ["EGFR G719X"], ["EGFR L861Q"], ["EGFR T790M"]], "exclusion_biomarker": [["EGFR exon 20 insertion", "ALK alteration"], ["EGFR exon 20 insertion", "ROS1 alteration"], ["EGFR exon 20 insertion", "MET alteration"]]}}
-{"input": "BRAF mutation exists in about 10-12% of colorectal cancer, among which BRAF V600E mutation is\n the most common type, which is an important biomarker for predicting the prognosis and\n precise treatment efficacy of metastatic colorectal cancer (mCRC). The prognosis of\n metastatic colorectal cancer with BRAF V600E mutation is very poor, with OS of about 6-9\n months. Previous studies have shown that single anti-BRAF inhibitor are ineffective, while\n multi-target inhibitions of Ras-Raf -MEK pathway is a possible effective strategy for BRAF\n V600E-mutant mCRC. Currently, the proven effective regimens include the VIC regimen\n (Vemurafenib + cetuximab + Irinotecan) and BEACON regimen (Encorafenib+ cetuximab +/-\n Binimetinib) from the SWOGS1406 study. Furthermore, BRAF inhibitor +MEK inhibitor combined\n with PD-1 monoclonal antibody has been shown to be an effective strategy in BRAF V600E-mutant\n malignant melanoma, which promote the study of the regimens for the treatment of BRAF\n V600E-mutant mCRC. Increasing basic and clinical studies have shown that cetuximab has ADCC\n effect, induces immunogenic cell death, promotes immune cell infiltration and other\n immunomodulatory effects, and has a synergistic effect with PD-1 monoclonal antibody in\n colorectal cancer. Based on those theories, we conducted the phase I study to explore the\n safety and preliminary efficacy of the regimen of Vemurafenib (BRAFi) plus cetuximab (EGFRi)\n combined with PD-1 monoclonal antibody in BRAF V600E-mutant /MSS type mCRC.\n ;NA;\n Inclusion Criteria:\n 1. Male or female \u2265 18 years of age\n 2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2\n 3. Participants must have histologically or cytologically confirmed diagnosis of\n adenocarcinoma of the colon or rectum, with clinical confirmation of unresectable\n and/or metastatic disease that is measurable according to Response Evaluation Criteria\n in Solid Tumors (RECIST 1.1) criteria\n 4. Presence of BRAF V600E in tumor tissue determined by local assay at any time prior to\n screening and confirmed by central laboratory. And confirmation of MSS or pMMR status\n from immunohistochemistry or PCR or NGS;\n 5. Prior treatment with at least one systemic treatment (chemotherapy or target therapy)\n for mCRC, and prior treatment did not include cetuximab\n 6. Adequate organ and marrow function:\n - \u2460Hemoglobin (Hb) \u2265 90 g/L\uff1bPlatelets (PLT) \u2265 75 x 10^9/L\uff1bNeutrophil \u22651.5 x 10^9/L\n - \u2461Total bilirubin \u2264 1.5 x upper limit of normal (ULN)\uff1bAspartate aminotransferase\n (AST) \u22643 x ULN \uff1bAlanine aminotransferase (ALT) \u22643 x ULN\n - \u2462Serum creatinine \u2264 1.5 x ULN, or calculated creatinine clearance (determined as\n per Cockcroft-Gault) \u2265 50 mL/min at screening\n - \u2463INR, APTT, and PT\u2264 1.5 x ULN\n - \u2464Serum albumin\u2265 28 g/L\n - \u2465ECG showed no evident abnormality\n 7. Written informed consent\n Exclusion Criteria:\n 1. Known hypersensitivity or contraindication to any component of cetuximab or PD-1\n monoclonal antibody or macromolecular protein reagent.\n 2. A history of other malignancies with a disease-free survival of less than 5 years,\n with the following exceptions: adequately treated basal or squamous cell skin cancer,\n carcinoma in-situ of the cervix, and gastrointestinal tumors treated curatively with\n endoscopic mucosectomy;\n 3. Any active autoimmune disease or a history of autoimmune disease\n 4. Use of immunosuppressive medications or glucocorticoid therapy \u22642 weeks prior to entry\n 5. Uncontrolled active infection requiring antibiotics\n 6. Known history of HIV infection or active hepatitis\n 7. Severe complications, including any of the following:\n - \u2460Massive gastrointestinal bleeding, perforation, or gastrointestinal obstruction\n - \u2461Symptomatic heart disease\n - \u2462Uncontrolled diabetes and hypertension\n - \u2463Uncontrolled diarrhea\n 8. Women who are pregnant or lactating and people who do not agree to avoid pregnancy\n 9. Patients with serious psychiatric that may interfere treatment.\n 10. Other conditions which are inappropriate to participate in the study confirmed by\n investigators.", "output": {"inclusion_biomarker": [["BRAF V600E", "MSS"], ["BRAF V600E", "pMMR"]], "exclusion_biomarker": []}}
+{"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": "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": "It is often impossible to find therapeutic target in intermediate-risk AML, so it is very\n important to select appropriate chemotherapy protocol to eliminate minimal residual disease\n (MRD) in these AML patients. Recent studies demonstrated that leukemia microenvironment is\n the shelter nich for leukemia stem cells and the essential reason for impossibly eliminating\n MRD. Demethylation drug not only prove the effect of chemotherapy, but also change leukemia\n microenvironment through epigenetics modification. Both of them will result in eliminating\n MRD in patients with AML. The investigators designed a multicenter randomized control\n clinical trail to evaluate the effect of demethylation drug combined with chemotherapy in AML\n patients with intermediate-risk factors after hematological complete remission. Efficacy will\n be evaluated through MRD detected by flow cytometry every 1 month. Continuous negative MRD\n indicates a good prognosis. The patients with continuous negative MRD can select auto-HSCT or\n consolidation chemotherapy, those with continuous positive MRD should be considered as\n candidates of allo-HSCT. Overall survival and relapse free survival will be recorded after\n follow-up every 3 months. It will provide a basis for precision therapy and a new way for\n designing a novel protocol for intermediate-risk AML. This clinical trail will benefit to the\n AML patients with intermediate-risk factors.\n ;NA;\n Inclusion Criteria:\n - AML patients with normal heart, lung, liver and renal function, or without serious\n infection. ECOG score is below 2\n Exclusion Criteria:\n - AML patients with abnormal heart, lung, liver and renal function, or with serious\n infection. ECOG score is over 2", "output": {"inclusion_biomarker": [], "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"]], "exclusion_biomarker": [["1p19q co-deletion"]]}}
 {"input": "Positron emission tomography (PET) molecular imaging provides a valuable tool for the\n diagnosis and differential diagnosis, staging of various tumors. Malignant tumor is composed\n of tumor cells and tumor stroma, which occupies the vast majority of the tumor.\n Cancer-associated fibroblasts (CAF) are an important part of the tumor stroma. Fibroblast\n activation protein (FAP) is over-expressed in CAF, which is closely related to tumor growth,\n invasion, metastasis, immunosuppression and prognosis; and the expression level of FAP in\n normal tissues and organs is very low. So it becomes an excellent target for cancer diagnosis\n and treatment. Radionuclide-labeled fibroblast activation protein inhibitors (FAPI) that\n specifically target to FAP as a tracer for PET imaging can be applied for targeted diagnosis\n and treatment of cancer. Recently, some studies have found that gallium-68 (68Ga) -FAPI as a\n new novel positron tracer has shown to be with good application potential. In this\n prospective study, the investigators will use integrated PET/MR, and PET/CT with the agent\n 68Ga-FAPI and conventional imaging agent [F-18] fluorodeoxyglucose (18F-FDG) to diagnose and\n stage various cancers, the aim is to make up for the deficiency in FDG PET imaging in the\n diagnosis and staging of some cancers.\n ;\n ;\n Inclusion Criteria:\n - Patients with suspected or diagnosed or treated malignant tumors who have completed\n 18F-FDG PET/CT imaging.\n - Subjects are able to understand and sign the informed consent voluntarily, with good\n compliance.\n Exclusion Criteria:\n - Acute systemic diseases and electrolyte disorders.\n - Pregnant or lactating women.\n - Patients refuse to sign the informed consent.", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
 {"input": "The purpose of this study is to examine the combination of osimertinib and carotuximab to\n assess the safety and find the recommended dose for treatment of advanced EGFR-mutated\n non-small cell lung cancer (NSCLC). Safety and tolerability will be measured by the number of\n dose-limiting toxicities, according to National Cancer Institute Common Toxicity Criteria for\n Adverse Events (NCI CTCAE) Version 5, to find the maximum tolerated dose. The secondary\n objectives include evaluating the rate of objective response rate, duration of response,\n progression-free survival, and disease control rate, along with assessing biomarkers through\n tumor tissue and circulating tumor DNA.\n ;NA;\n Inclusion Criteria:\n - Stage IV or recurrent/metastatic non-squamous NSCLC that harbors an EGFR activating\n mutation (Exon 21 L858R, Exon 19 deletion, Exon 18 G719X, Exon 21 L861Q, etc). Local\n testing for EGFR mutations is acceptable provided it was performed in a CLIA certified\n lab.\n - Part I: Progressive disease on at least one prior EGFR TKI\n - Part II, Cohort 1: Progressive disease on osimertinib or other prior EGFR TKIs\n - Part II, Cohort 2: Receiving osimertinib as front line treatment for less than 12\n weeks. Persistent ctDNA with EGFR mutation between weeks 6-12 from the start of\n osimertinib treatment.\n - Age at least 18\n - Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2\n - Archival tissue from a biopsy performed after progression of disease on previous EGFR\n TKI or willing to consent for a fresh tumor biopsy.\n - Measurable disease by RECIST 1.1.\n - Patients with untreated brain metastases are allowed provided that the patient is\n clinically asymptomatic and stable.\n - Patients must have completed prior chemotherapy \u2265 3 weeks or radiotherapy \u2265 2 weeks\n prior to receiving study drugs.\n - If the subject's most recent line of therapy is treatment with osimertinib, then all\n adverse events must be resolved to Grade 2 or better\n - If the subject's most recent line of therapy is any other treatment than osimertinib,\n then all Adverse Events must be resolved to grade 1 or better, with the exception of\n fatigue, alopecia and neuropathy (which must resolve to CTCAE grade 2).\n - Adequate organ function\n - Women of childbearing potential and men must agree to use adequate contraception while\n on study.\n - Written informed consent obtained from subject and ability for subject to comply with\n the requirements of the study.\n Exclusion Criteria:\n - Past medical history of interstitial lung disease, drug-induced interstitial lung\n disease, radiation pneumonitis requiring steroid treatment, or any evidence of\n clinically active interstitial lung disease.\n - Small cell lung cancer histology.\n - Other prior malignancy that might interfere with study endpoints per opinion of the\n investigator.\n - Prior exposure to carotuximab or any CD105 targeted antibody.\n - Any major surgical procedure within 2 weeks of starting therapy.\n - Patients must not have a history of uncontrolled or poorly-controlled hypertension\n defined as SBP > 150 mmHg or DBP > 90 mmHg within 28 days prior to enrollment.\n - Active bleeding or pathologic conditions that carries a high bleeding risk (e.g.\n gastric ulcers).\n - Use of thrombolytics within 10 days prior to the first day of carotuximab.\n - Known hypersensitivity to Chinese hamster ovary products or other recombinant human,\n chimeric, or humanized antibodies.\n - A known diagnosis of Osler-Weber-Rendu syndrome.\n - Ascites or pericardial or pleural effusion requiring external drainage procedures.\n - New evidence of leptomeningeal disease.\n - Acute cardiovascular event within the past 6 months.\n - Pregnancy or breastfeeding.", "output": {"inclusion_biomarker": [["EGFR activating mutation"], ["EGFR Exon 21 L858R"], ["EGFR Exon 19 deletion"], ["EGFR Exon 18 G719X"], ["EGFR Exon 21 L861Q"], ["EGFR mutation"]], "exclusion_biomarker": []}}
-{"input": "This is a FIH, phase I/II, open label, multi-center study of DYP688 as a single agent. The\n purpose of this study is to characterize the safety, tolerability, and anti-tumor activity of\n DYP688 as a single agent in patients with metastatic uveal melanoma (MUM) and other melanomas\n harboring GNAQ/11 mutations.\n ;\n ;\n Inclusion Criteria:\n - Patients in the dose escalation part must be \u2265 18 years of age at the time of informed\n consent (ICF) signature. In the phase II part, patients \u2265 12 years of age at the time\n of informed consent may be eligible for enrollment (not applicable in countries where\n enrollment is restricted by the local health authority to patients \u2265 18 years of age).\n Patients must have a minimum weight of 40 kg.\n - ECOG performance status \u2264 1 for patients \u2265 18 years of age; Karnofsky performance\n status \u2265 70 for patients \u2265 16 and < 18 years of age; Lansky performance status \u2265 70\n for patients \u2265 12 and < 16 years of age\n - Patients must be suitable and willing to undergo study required biopsies according to\n the treating institution's own guidelines and requirements. If a biopsy is not\n medically feasible, exceptions may be considered after documented discussion with\n Novartis.\n For all patients in Dose Escalation\n - MUM: uveal melanoma with histologically or cytologically confirmed metastatic disease.\n Patient must be either treatment naive or have received any number of prior lines and\n progressed on most recent therapy\n - Non-MUM: advanced cutaneous or mucosal melanoma with histologically or cytologically\n confirmed metastatic disease that has progressed following all standard therapies or\n that has no satisfactory alternative therapies and has evidence of GNAQ/11 mutation\n based on local data\n For patients in Phase II\n - Tebentafusp na\u00efve group: Diagnosis of uveal melanoma with histologically or\n cytologically confirmed metastatic disease that has progressed following standard\n therapies or that has no satisfactory alternative therapies\n - Tebentafusp pre-treated group: Diagnosis of uveal melanoma with histologically or\n cytologically confirmed metastatic disease. Patients must be previously treated with\n tebentafusp and have progressed\n - Non-MUM: patients with diagnosis of cutaneous or mucosal melanomas harboring GNAQ/11\n mutations based on local data, with histologically or cytologically confirmed\n metastatic disease that has progressed following all standard therapies or that has no\n satisfactory alternative therapies\n Exclusion Criteria:\n - Malignant disease, other than that being treated in this study.\n - Active brain metastases, i.e. symptomatic brain metastases or known leptomeningeal\n disease.\n - Evidence of active bleeding or bleeding diathesis or significant coagulopathy\n (including familial) or a medical condition requiring long term systemic\n anticoagulation that would interfere with biopsies.\n - History of anaphylactic or other severe hypersensitivity / infusion reactions to ADCs\n or monoclonal antibodies, which in the opinion of the investigator may pose an\n increased risk of serious infusion reaction.\n - Treatment with any of the following anti-cancer therapies prior to the first dose of\n study treatment within the stated timeframes:\n - 2 weeks for fluoropyrimidine therapy\n - 4 weeks for radiation therapy or limited field radiation for palliation within \u2264\n 2 weeks prior to the first dose of study treatment.\n - 4 weeks or \u2264 5 half-lives (whichever is shorter) for chemotherapy or biological\n therapy (including monoclonal antibodies) or continuous or intermittent small\n molecule therapeutics or any other investigational agent.\n - 6 weeks for cytotoxic agents with major delayed toxicities, such as nitrosoureas\n and mitomycin C.\n - 4 weeks for immuno-oncologic therapy, such as CTLA-4, PD-1, or PD-L1 antagonists.\n - Clinically significant and / or uncontrolled heart disease such as congestive heart\n failure requiring treatment (NYHA grade \u2265 2) or clinically significant arrhythmia\n despite medical treatment.\n Other protocol-defined inclusion/exclusion criteria may apply.", "output": {"inclusion_biomarker": [["GNAQ mutation"], ["GNA11 mutation"]], "exclusion_biomarker": []}}
-{"input": "It is often impossible to find therapeutic target in intermediate-risk AML, so it is very\n important to select appropriate chemotherapy protocol to eliminate minimal residual disease\n (MRD) in these AML patients. Recent studies demonstrated that leukemia microenvironment is\n the shelter nich for leukemia stem cells and the essential reason for impossibly eliminating\n MRD. Demethylation drug not only prove the effect of chemotherapy, but also change leukemia\n microenvironment through epigenetics modification. Both of them will result in eliminating\n MRD in patients with AML. The investigators designed a multicenter randomized control\n clinical trail to evaluate the effect of demethylation drug combined with chemotherapy in AML\n patients with intermediate-risk factors after hematological complete remission. Efficacy will\n be evaluated through MRD detected by flow cytometry every 1 month. Continuous negative MRD\n indicates a good prognosis. The patients with continuous negative MRD can select auto-HSCT or\n consolidation chemotherapy, those with continuous positive MRD should be considered as\n candidates of allo-HSCT. Overall survival and relapse free survival will be recorded after\n follow-up every 3 months. It will provide a basis for precision therapy and a new way for\n designing a novel protocol for intermediate-risk AML. This clinical trail will benefit to the\n AML patients with intermediate-risk factors.\n ;NA;\n Inclusion Criteria:\n - AML patients with normal heart, lung, liver and renal function, or without serious\n infection. ECOG score is below 2\n Exclusion Criteria:\n - AML patients with abnormal heart, lung, liver and renal function, or with serious\n infection. ECOG score is over 2", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
-{"input": "This is a first-in-human phase 1 study of SYNCAR-001 + STK-009 in patients with CD19+\n hematologic malignancies.\n ;\n ;\n Selected Inclusion Criteria:\n 1. Histologically confirmed relapsed/refractory hematologic malignancies, including\n Chronic Lymphocytic Lymphoma (CLL/SLL) and selected Non-Hodgkin's Lymphoma (NHL)\n 2. Prior or current documentation of CD19 expression or high likelihood of CD19\n expression based on disease histology\n 3. No signs of symptoms of central nervous system (CNS) disease or detectable evidence of\n CNS or meningeal disease on magnetic resonance imaging (MRI) at the time of screening\n Selected Exclusion Criteria:\n 1. Prior CD19 directed therapy including CD19 CARTs\n 2. Prior allogeneic hematopoietic stem cell transplant within 6 months of enrollment\n 3. Prior autologous hematopoietic stem cell transplant within 6 weeks of enrollment.\n 4. Presence of GVHD", "output": {"inclusion_biomarker": [["CD19 expression"]], "exclusion_biomarker": []}}
-{"input": "Selitrectinib expanded access is for minor and adult patients with cancer having a change in\n a particular gene (NTRK1, NTRK2, or NTRK3 gene fusion). The patients are ineligible for an\n ongoing selitrectinib clinical trial or have other considerations that prevent access to\n selitrectinib through an existing clinical trial. Expanded access is intended to treat\n individual patients with different types of cancers with a NTRK gene fusion, including blood\n cancers, who have previously received tropomyosin receptor kinase (TRK) inhibitor therapy.\n ;NA;\n Inclusion Criteria:\n - Diagnosis of cancer with a NTRK1, NTRK2, and NTRK3 gene fusion\n - Previous treatment with a kinase inhibitor with known activity on TRK inhibition\n - Unable to participate in an ongoing selitrectinib clinical trial\n - Medically suitable for treatment with selitrectinib\n Exclusion Criteria:\n - Currently enrolled in an ongoing clinical study with a TRK inhibitor", "output": {"inclusion_biomarker": [["NTRK1 fusion"], ["NTRK2 fusion"], ["NTRK3 fusion"]], "exclusion_biomarker": []}}
-{"input": "This is a phase 1a/1b, multicentre, open-label, non-randomized study of NG-641 in combination\n with nivolumab in patients with metastatic or advanced epithelial tumours.\n To characterize the safety and tolerability of NG-641 in combination with nivolumab in\n patients with metastatic or advanced epithelial tumours and to determine the recommended dose\n of NG-641 in combination with nivolumab for further development in patients with metastatic\n or advanced epithelial tumours\n ;\n ;\n Inclusion Criteria:\n - Provide written informed consent to participate\n - Patients must have one of eleven histologically or cytologically confirmed\n metastatic/advanced carcinoma or adenocarcinoma that has progressed after at least one\n line of systemic therapy and are incurable by local therapy (contact Sponsor for more\n details regarding the tumour types)\n a. Tumour types included are: urothelial carcinoma, squamous cell carcinoma of the\n head and neck (SCCHN), microsatellite instability (MSI)-high/deficient mismatch repair\n (dMMR) cancer, non-small cell lung cancer (NSCLC), uterine/endometrial cancer,\n cervical cancer, oesophageal cancer, gastric cancer, triple-negative breast cancer\n (TNBC), cutaneous squamous cell carcinoma and hepatocellular carcinoma\n - At least one measurable site of disease according to RECIST Version 1.1 criteria; this\n lesion must be either (i) outside a previously irradiated area or (ii) progressive if\n it is in a previously irradiated area\n - Prior treatment with a PD-1/PD-L1 inhibitor (prior PD-1/PD-L1 may have been given as\n monotherapy or combination therapy)\n - Tumour accessible for biopsy\n - Aged 18 years or over\n - ECOG performance status 0 or 1\n - Predicted life expectancy of \u22656 months\n - Adequate lung reserve (Oxygen saturation on ambient air at sea level \u226595% or the\n equivalent based on altitude (i.e. \u226590% at 5000 feet))\n - Adequate renal function:\n 1. Creatinine \u22641.5 \u00d7 upper limit of normal (ULN) and estimated glomerular filtration\n rate (eGFR) \u226560 mL/minute/1.73m2 (or measured creatinine clearance \u226560 mL/minute)\n 2. Spot albumin-to-creatinine ratio (ACR) for proteinuria at screening and baseline\n \u226430 mg/g. Patients with a spot ACR >30 mg/g who undergo a subsequent 24-hour\n urinary protein test with a result of <1 g/24 h may be included\n - Adequate hepatic function:\n 1. Serum total bilirubin \u22641.5 \u00d7 ULN OR direct bilirubin \u22641 \u00d7 ULN\n 2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \u22643 \u00d7 ULN\n range\n 3. Albumin \u22653 g/dL\n - Adequate bone marrow function:\n 1. Absolute neutrophil count \u22651.5 \u00d7 109/L\n 2. Platelets \u2265100 \u00d7 109/L\n 3. Haemoglobin \u226590 g/L (9 g/dL)\n - Coagulation profile within the normal range\n - Meeting reproductive status requirements:\n 1. Must not be pregnant or breastfeeding\n 2. Female patients of childbearing potential, must have a negative serum or urine\n pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human\n chorionic gonadotrophin) within 24 hours before the first dose of study treatment\n 3. Female patients of childbearing potential who are heterosexually active must\n agree to use a highly effective method of contraception to prevent pregnancy, for\n the duration of study treatment and 6 months following the last dose of study\n treatment. Female patients who are continuously not heterosexually active are\n exempt from contraceptive requirements, but must still undergo pregnancy testing\n 4. Female patients who are heterosexually active, irrespective of childbearing\n status, must ensure their male partner agrees to use a condom with spermicide\n during sexual intercourse for the duration of study treatment and 6 months\n following the last dose of study treatment\n 5. Patients must be willing to refrain from egg donation during treatment and for at\n least 6 months following the last dose of study treatment\n 6. Male patients who are sexually active with men or women must agree to use a\n condom with spermicide during intercourse for the duration of study treatment and\n 6 months following the last dose of study treatment. In addition, patients must\n be willing to refrain from sperm donation during this time.\n - Exclusion Criteria:\n - Prior or planned allogeneic or autologous bone marrow or organ transplantation\n - Splenectomy\n - Active infections requiring antibiotics, physician monitoring or systemic therapy\n within 1 week of the anticipated first dose of study drug, or recurrent fevers\n (>38.0\u02daC) associated with a clinical diagnosis of active infection\n - Treatment with the antiviral agents: ribavirin, adefovir, lamivudine or cidofovir\n within 10 days prior to the first dose of study treatment; or pegylated interferon in\n the 4 weeks before the first dose of study treatment\n - Active viral disease or positive test for hepatitis B virus using hepatitis B surface\n antigen test or positive test for HCV using HCV ribonucleic acid (RNA) or HCV antibody\n test indicating acute or chronic infection. Positive test for HIV or AIDS\n - Patients who have active, known or suspected autoimmune disease that has required\n systemic therapy in the past 2 years, are immunocompromised in the opinion of the\n Investigator, or are receiving systemic immunosuppressive treatment\n a. Patients with vitiligo, type I diabetes mellitus, asthma/atopy, residual\n hypothyroidism due to autoimmune disease (which only requires hormone replacement\n therapy), or conditions not expected to recur in the absence of an external trigger\n are permitted to enrol providing they comply with the other eligibility criteria\n relating to renal function. Use of inhaled corticosteroids, local steroid injection,\n or steroid eye drops is allowed\n - Treatment with any live, live-attenuated or COVID-19 vaccine in the 30 days before the\n first dose of NG-641 or nivolumab (COVID-19 vaccines known not to be\n live/live-attenuated or based on an adenoviral vector (e.g. mRNA vaccines) are not\n subject to the 30-day exclusion)\n - Treatment with any other vaccine (including known non-live/live-attenuated and\n non-adenoviral COVID-19 vaccines) in the 7 days before the first dose of NG-641\n - History of prior Grade 3-4 acute kidney injury or other clinically significant renal\n impairment\n - History of clinically significant interstitial lung disease or non-infectious\n pneumonitis\n - Lymphangitic carcinomatosis (clinically suspected or radiographic evidence)\n - Infectious or inflammatory bowel disease in the 3 months before the first dose of\n study treatment\n - Myocardial infarction, stroke or other significant cardiovascular or cerebrovascular\n event in the 12 months before the first dose of study treatment\n - Pulmonary embolism, deep vein thrombosis, or other uncontrolled thromboembolic event\n in the 12 months before the first dose of study treatment, or current treatment with\n therapeutic or prophylactic anticoagulation therapy\n - Grade 3 or 4 gastrointestinal bleeding (or risk factors for gastrointestinal bleeding)\n or haemoptysis in the 3 months before first dose of study treatment, or any history of\n bleeding requiring an investigative procedure (e.g. endoscopy), transfusion or\n hospitalisation in the 12 months before the first dose of study treatment\n - Tumour location/extent considered by the Investigator to present a significant risk if\n tumour flare or necrosis were to occur (e.g. an initial increase in tumour size that\n may lead to intestinal, airway or ureter obstruction, or penetrating tumour\n infiltration of major blood vessels, or other hollow organs potentially at risk of\n perforation)\n - Use of the following prior therapies/treatments:\n 1. Treatment with any other enadenotucirev-based virus (parent virus or\n transgene-modified variants), or fibroblast activation protein (FAP) targeting\n agent at any time\n 2. Treatment with an investigational or licensed anti-cancer monoclonal antibody\n (mAb), immune checkpoint inhibitor, immune stimulatory treatment or other\n biological therapy in the 28 days prior to the first dose of study treatment.\n - Prior anti-PD-1/PD-L1 therapy is permitted without a 'washout' phase c. Treatment with\n an investigational or licensed chemotherapy, targeted small molecule or other\n investigational drug in the 14 days or five half-lives (whichever is shorter) before\n the first dose of study treatment d. Major surgery in the 28 days before the first\n dose of study treatment e. Radiation therapy in the 14 days before the first dose of\n study treatment f. Treatment with complementary medications (e.g. herbal supplements\n or traditional Chinese medicines) to treat the disease under study within the 14 days\n prior to first study treatment. Such medications are permitted if they are used as\n supportive care g. Bisphosphonate therapy or treatment with Receptor Activator of\n Nuclear factor Kappa-\u0392 (RANK)-ligand inhibitors for metastatic bone disease is\n permitted\n - All toxicities attributed to prior anti-cancer therapy (including radiation therapy)\n other than alopecia must have resolved to Grade 1 or baseline before the first dose of\n study treatment\n - Known allergy or hypersensitivity (Grade \u22653) to NG-641 transgene, immune checkpoint\n inhibitor products or formulation, or other monoclonal antibodies\n - Discontinuation from prior treatment with an immune therapy due to a Grade \u22653\n immune-related AE, or any history of life-threatening toxicity related to prior immune\n therapy\n - Other prior malignancy active within the previous 3 years, except for local or organ\n confined early stage cancer that has been definitively treated with curative intent,\n does not require ongoing treatment, has no evidence of residual disease and has a\n negligible risk of recurrence and is therefore unlikely to interfere with the primary\n and secondary endpoints of the study, including response rate and safety\n - Symptomatic brain metastases or any leptomeningeal metastases that are symptomatic\n and/or requires treatment\n - Any serious or uncontrolled medical disorder that, in the opinion of the Investigator\n or the Medical Monitor, may increase the risk associated with study participation or\n study treatment administration, impair the ability of the patient to receive protocol\n therapy or interfere with the interpretation of study results", "output": {"inclusion_biomarker": [["MSI-high"], ["dMMR"]], "exclusion_biomarker": []}}
-{"input": "This study is an open-label, single arm, dose escalation and dose expansion phase 1 study to\n evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of BPI-21668 in\n solid tumor patients. In dose escalation phase, biomarker status is not required, but in dose\n expansion phase patients are required to harbor PIK3CA mutation.\n ;NA;\n Inclusion Criteria:\n 1. Age \u226518 and \u226470 years, male and female patients;\n 2. Life expectancy \u2265 12 weeks;\n 3. ECOG performance score 0-1;\n 4. Locally advanced or relapsed/metastatic solid tumor patients, who had disease\n progression after standard therapy, intolerable to standard therapy or for whom no\n standard therapy exists, PIK3CA mutation status is required for dose expansion phase;\n 5. Evaluable lesion required for dose escalation phase and measurable lesion as per\n RECIST 1.1 required for dose expansion phase;\n 6. Adequate organ function;\n 7. Signed informed consent.\n Exclusion Criteria:\n 1. Prior use of PI3K\u3001mTOR or AKT inhibitor;\n 2. Prior other malignant tumor;\n 3. Unstable, symptomatic primary CNS tumors/metastasis or leptomeningeal metastases ;\n 4. Type I or type II diabetes;\n 5. Inadequate wash-out of prior anti-cancer therapies;\n 6. Cardiac disorders;\n 7. Instable systemic diseases;\n 8. Acute or chronic pancreatitis;\n 9. Pregnancy or lactation;\n 10. Other protocol specified criteria.", "output": {"inclusion_biomarker": [["PIK3CA mutation"]], "exclusion_biomarker": []}}
-{"input": "An open-label, two-part Phase I/Ib study of RP12146 in adult patients with locally advanced\n or metastatic solid tumors. The first part (Part 1) is a Phase I dose-escalation, 3+3 design,\n open-label, MTD determination study and will enroll patients who have tumors known to harbour\n DNA repair deficiencies. The second part (Part 2) is a Phase Ib, dose-expansion at the MTD\n (or optimal dose) and will enroll patients with a confirmed deleterious HRR mutation in their\n tumor as identified by a central genomics testing laboratory.\n ;NA;\n Inclusion Criteria.\n 1. Provision of full informed consent prior to any study-specific procedures.\n 2. Patients must be \u226518 years of age, at the time of signing informed consent.\n 3. Dose escalation phase, patients with histologically and/or cytologically confirmed\n malignant solid tumor whose disease has progressed following at least one standard\n therapy and who have no other acceptable standard treatment options. Tumor types will\n include breast, ovarian, fallopian tube, or peritoneal cancer, extensive-stage small\n cell lung cancer (ES-SCLC), prostate, pancreatic, colorectal gastric, biliary tract,\n and endometrial cancer.\n 4. Dose-expansion phase patients with histologically and/or cytologically confirmed\n malignant solid tumor (breast, ovarian, fallopian tube, or peritoneal cancer,\n extensive-stage small cell lung cancer (ES-SCLC), with one of the documented\n deleterious mutations of specified HRR genes and whose disease has progressed\n following at least one standard therapy.\n 5. Patients with at least one measurable lesion per RECIST version 1.1 at baseline that\n can be accurately assessed by CT-scan or MRI and is suitable for repeated assessment\n at follow up-visits.\n 6. ECOG performance status 0 to 2.\n 7. Use of contraception measures\n Exclusion Criteria:\n 1. Patients with HER2 positive breast cancer\n 2. Patients receiving anticancer therapy\n 3. Patient who has not recovered from acute toxicities of previous therapy except\n treatment-related alopecia.\n 4. Prior treatment with a PARP inhibitor\n 5. Major surgery within 4 weeks of starting study treatment or any patient who has not\n recovered from the effects of major surgery.\n 6. Patient with symptomatic uncontrolled brain metastasis.\n 7. Pregnancy and lactation\n 8. Patients with uncontrolled disease", "output": {"inclusion_biomarker": [["HRR deleterious mutation"]], "exclusion_biomarker": [["HER2 positive"]]}}
+{"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": "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": "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": "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": "The drug that will be investigated in the study is an antibody, GEN3009. Since this is the\n first study of GEN3009 in humans, the main purpose is to evaluate safety. Besides safety, the\n study will determine the recommended GEN3009 dose to be tested in a larger group of patients\n and assess preliminary clinical activity of GEN3009. GEN3009 will be studied in a broad group\n of cancer patients, having different kinds of lymphomas. All patients will get GEN3009 either\n as a single treatment (monotherapy) or in combination with another antibody-candidate for\n treatment of cancer in the blood. The study consists of two parts: Part 1 tests increasing\n doses of GEN3009 (\"escalation\"), followed by Part 2 which tests the recommended GEN3009 dose\n from Part 1 (\"expansion\").\n ;\n ;\n Key Inclusion Criteria:\n 1. Be at least 18 years of age.\n 2. Must sign an informed consent form prior to any screening procedures.\n 3. Dose Escalation: Has histologically or cytologically confirmed relapsed and/or\n refractory B-cell NHL with no available standard therapy or is not a candidate for\n available standard therapy, and for whom, in the opinion of the investigator, the\n experimental therapy may be beneficial. All subjects must have received at least two\n prior lines of systemic therapy.\n Dose Expansion: Has histologically or cytologically confirmed relapsed or refractory\n B-cell NHL. All subjects must have received at least 2 prior lines of systemic\n therapy, and,\n 1. For FL and DLBCL, at least 1 of the 2 prior lines of treatment must have been a\n CD20 containing systemic regimen;\n 2. For CLL, subjects must have received at least one prior line of BTK inhibitor or\n BCL 2 inhibitor.\n 4. Has one of the eligible subtypes of B-cell NHL :\n Dose Escalation: (DLBCL, HGBCL, PMBCL, FL, MCL, MZL, SLL, or CLL). Dose Expansion:\n (DLBCL, FL, CLL)\n 5. Has measurable disease for B-cell NHL or has active disease for Chronic Lymphocytic\n Leukemia (CLL).\n 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.\n 7. Has adequate hepatic, renal, and bone marrow functions.\n 8. Before the first dose of GEN3009, during the trial, and for 12 months after the last\n dose of GEN3009 and/or the combination, a woman must be either not of childbearing\n potential or of childbearing potential and practicing a highly effective method of\n birth control, and must have a negative serum beta-human chorionic gonadotropin\n (beta-hCG) and urine pregnancy test at screening.\n 9. A man who is sexually active with a woman of childbearing potential and has not had a\n vasectomy must agree to use a barrier method of birth control.\n 10. Subjects must have a life expectancy of at least 3 months.\n Key Exclusion Criteria:\n 1. Prior treatment with a CD37-targeting agent.\n 2. Prior allogeneic Hematopoietic Stem Cell Transplantation (HSCT).\n 3. Prior treatment with a CD3xCD20 bispecific antibody (Combination Expansion cohort\n only).\n 4. Autologous HSCT within 3 months before the first dose of GEN3009.\n 5. Lymphomas leukemic phase: high absolute lymphocyte count or the presence of abnormal\n cells in the peripheral blood indicating circulating lymphoma cells.\n 6. Treatment with an anti-cancer biologic including anti-CD20 therapy, radio-conjugated\n or toxin-conjugated antibody or chimeric antigen receptor (CAR) T-cell therapy within\n 4 weeks or 5 half-lives, whichever is shorter, before the first dose of GEN3009.\n Treatment with small molecules such as BTK inhibitors, BCL2 inhibitors, or PI3K\n inhibitors within 5 half-lives prior to the first dose of GEN3009.\n 7. Chemotherapy or radiation therapy within 2 weeks of the first dose of GEN3009.\n 8. Treatment with an investigational drug or an invasive investigational medical device\n within 4 weeks or 5 half-lives, whichever is shorter, prior to the first dose of\n GEN3009, and at any time during the study treatment period.\n 9. Autoimmune disease or other diseases that require permanent or high-dose\n immunosuppressive therapy.\n 10. Received a cumulative dose of corticosteroids more than the equivalent of 250 mg of\n prednisone within the 2-week period before the first dose of GEN3009.\n 11. Has uncontrolled intercurrent illness.\n 12. Seizure disorder requiring therapy (such as steroids or anti-epileptics) (Combination\n Expansion cohort only).\n 13. Toxicities from previous anti-cancer therapies have not resolved to baseline levels or\n to Grade 1 or less except for alopecia and peripheral neuropathy.\n 14. Primary central nervous system (CNS) lymphoma or known CNS involvement at screening.\n 15. Known past or current malignancy other than inclusion diagnosis.\n 16. Had allergic reactions to anti-CD20 or anti-CD37 monoclonal antibody treatment or\n intolerant to GEN3009 or to the combination therapy excipients.\n 17. Has had major surgery within 4 weeks before screening or will not have fully recovered\n from surgery, or has major surgery planned during the time the subject is expected to\n participate in the trial (or within 4 weeks after the last dose of GEN3009 and/or the\n combination therapy).\n 18. Known history/positive serology for hepatitis B.\n 19. Known medical history or ongoing hepatitis C infection that has not been cured.\n 20. Known history of seropositivity for HIV infection.\n 21. Is a woman who is pregnant or breast-feeding, or who is planning to become pregnant\n while enrolled in this trial or within 12 months after the last dose of GEN3009 and/or\n the combination therapy.\n 22. Is a man who plans to father a child while enrolled in this trial or within 12 months\n after the last dose of GEN3009 and/or the combination therapy.\n 23. Has any condition for which, in the opinion of the investigator, participation would\n not be in the best interest of the subject (eg, compromise the well-being) or that\n could prevent, limit, or confound the protocol-specified assessments. Additionally,\n vulnerable subjects or subjects under guardianship, curatorship, judicial protection\n or deprived of liberty), are excluded from participation in this trial.\n 24. Exposed to live/live attenuated vaccine within 4 weeks prior to initiation of GEN3009\n treatment.\n NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.", "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": [["CD4 positive"]], "exclusion_biomarker": []}}
 {"input": "This is a prospective, open-label, single-center clinical trial. This study will evaluate the\n safety and efficacy of anti-CD7 CAR-T cells in the treatment of relapsed or refractory CD7\n positive T-ALL, T-NHL and AML. The primary endpoints are dose limiting toxicity (DLT) and the\n incidence of treatment emergent adverse event (TEAE).\n ;NA;\n Inclusion Criteria:\n 1. Total bilirubin \u2264 51 \u03bcmol / L, ALT and AST \u2264 3 times of the upper limit of normal\n value, serum creatinine \u2264 176.8 \u03bcmol / L;\n 2. Echocardiography shows left ventricular ejection fraction (LVEF) \u2265 50%;\n 3. There is no active pulmonary infection, and the oxygen saturation during air\n inhalation is more than 92%;\n 4. The estimated survival time is more than 3 months;\n 5. ECOG score was 0-2;\n 6. The patients or their legal guardians voluntarily participated in the trial and signed\n the informed consent.\n For T-ALL:\n 1. Patients is histologically diagnosed with CD7 Positive T-ALL according to the Clinical\n Practice Guidelines for Acute Lymphoblastic Leukemia (ALL) (2020. V1) by National\n Comprehensive Cancer Network (NCCN).\n 2. The diagnosis is consistent with r/r CD7 + T-ALL, and includes any of the following\n conditions:\n 1. No CR was obtained by standard chemotherapy;\n 2. The first induction was CR, but the duration of CR was less than 12 months;\n 3. No CR was obtained after the first or multiple remedial treatment;\n 4. Relapse twice or more;\n 3. The number of blast cells in bone marrow was more than 5% (morphology) and / or > 1%\n (flow cytometry).\n For T-NHL:\n 1. Patients is histologically diagnosed with CD7 Positive T-NHL according to The 2016\n revision of the World Health Organization classification of lymphoid neoplasms.\n 2. r/r T-NHL, and includes any of the following conditions:\n 1. No response or relapse after second or more lines of chemotherapy;\n 2. Primary refractory ot chemotherapy;\n 3. Relapse after autologous stem cell transplantation;\n 3. According to the Lugano 2014 criteria, there is at least one evaluable tumor lesion.\n For AML:\n 1. Patients is histologically diagnosed with CD7 Positive AML according to the Clinical\n Practice Guidelines for Acute Myeloid Leukemia (AML) (2020. V3) by National\n Comprehensive Cancer Network (NCCN).\n 2. The diagnosis is consistent with r/r CD7 + AML, and includes any of the following\n conditions:\n 1. No CR was obtained by standard chemotherapy;\n 2. The first induction was CR, but the duration of CR was less than 12 months;\n 3. No CR was obtained after the first or multiple remedial treatment;\n 4. Relapse twice or more;\n 3. The number of blast cells in bone marrow was more than 5% (morphology) and / or > 1%\n (flow cytometry).\n Exclusion Criteria:\n 1. Patients with history of epilepsy or other central nervous system diseases;\n 2. Patients with prolonged QT or severe heart disease;\n 3. Pregnant or lactating women (the safety of this therapy for unborn children is\n unknown);\n 4. The patients with uncontrolled active infection;\n 5. Active hepatitis B or hepatitis C virus infection;\n 6. Previous application of gene therapy;\n 7. The proiferation rate is less than 5 times response to CD3/CD28 co-stimulation signal;\n 8. Serum creatinine > 2.5mg/dl or ALT / AST > 3 times ULN or bilirubin > 2.0mg/dl;\n 9. Those who suffer from other uncontrolled diseases are not suitable to join the study;\n 10. HIV infection;\n 11. Any situation that the researchers believe may increase the risk of patients or\n interfere with the test results.", "output": {"inclusion_biomarker": [["CD7 positive"]], "exclusion_biomarker": []}}