ft_test.jsonl

{"input": "This is a Phase I/II, multicenter, open-label study to evaluate the safety, efficacy,\n tolerability, and pharmacokinetics of a novel BTK inhibitor, Orelabrutinib (ICP-022) in\n Patients with B-cell malignancies. The study contains two parts, Part 1 (dose escalation) and\n Part 2 (dose expansion).\n ;NA;\n Inclusion Criteria:\n 1. Signed Informed Consent.\n 2. Age \u2265 18 years.\n 3. Part 1: Patients with histologically confirmed relapsed or refractory B-cell\n malignancies, including Grades 1-3a FL, MZL, MCL, and CLL/SLL.\n Part 2: Patients with histologically confirmed B-cell malignancies including r/r FL,\n r/r MZL and CLL/SLL with/without prior treatment.\n 4. Life expectancy (in the opinion of the investigator) of \u2265 4 months.\n 5. ECOG performance status of 0 ~1.\n 6. Must have adequate organ function.\n 7. Negative test results for HBV ([HBsAg (-)] and non-active HBV or HCV infection\n Exclusion Criteria:\n 1. Pregnant or breast-feeding or intending to become pregnant during the study.\n 2. Prior treatment with systemic immunotherapeutic agents.\n 3. Known allergies to Orelabrutinib (ICP-022) or its excipients or infection with HIV.\n 4. Treatment with any chemotherapeutic agent, or any other investigational therapies\n within 4 weeks prior to first dose of the study drug.\n 5. History of allogeneic stem-cell (or other organ) transplantation or confirmed\n progressive PML.\n 6. Any external beam radiation therapy within 6 weeks prior to the first dose of the\n study drug.\n 7. Concurrent use of warfarin or other vitamin K antagonists or anticoagulation therapies\n or strong CYP3A inhibitor.\n 8. Active uncontrolled infections.\n 9. Recent infection requiring IV anti-infective treatment that was completed \u2264 14 days\n before the first dose of study drug.\n 10. Unresolved toxicities from prior anti-cancer therapy.\n 11. Medically apparent CNS lymphoma or leptomeningeal disease.\n 12. Current or previous history of CNS disease.\n 13. Major surgery or significant traumatic injury < 28 days prior to the first dose of the\n study drug.\n 14. Patients with another invasive malignancy in the last 2 years.\n 15. Significant cardiovascular disease or active pulmonary disease.\n 16. Received systemic immunosuppressive medications.", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
{"input": "The purpose of this study is to determine the recommended Phase 2 dose (RP2D) candidate(s) of\n JNJ-75276617 in combination with AML directed therapies (dose selection) and further to\n evaluate safety and tolerability of JNJ-75276617 in combination with AML directed therapies\n at the RP2D(s) (dose expansion).\n ;\n ;\n Inclusion Criteria:\n - Diagnosis of AML according to World Health Organization (WHO) 2016 criteria a) De novo\n or secondary AML; b) relapsed /refractory (Arm A); c) harboring NPM1 / KMT2A\n alterations\n - Pretreatment clinical laboratory values meeting the following criteria -listed below:\n White blood cell (WBC) count: less than or equal to <=25 x 10^9 per liter (/L),\n adequate liver and renal function\n - ECOG performance status grade of 0, 1 or 2\n - A woman of childbearing potential must have a negative highly sensitive serum\n beta-human chorionic gonadotropin at screening and within 48 hours prior to the first\n dose of study treatment\n - Must sign an informed consent form (ICF) indicating participant understands the\n purpose of the study and procedures required for the study and is willing to\n participate in the study.\n - Willing and able to adhere to the prohibitions and restrictions specified in this\n protocol\n Exclusion Criteria:\n - Acute promyelocytic leukemia according to WHO 2016 criteria\n - Leukemic involvement of the central nervous system\n - Recipient of solid organ transplant\n - Cardiovascular disease that is uncontrolled, increases risk for Torsades de Pointes or\n that was diagnosed within 6 months prior to the first dose of study treatment\n including, but not limited to:(a) Myocardial infarction; (b) Severe or unstable\n angina; (c) Clinically significant cardiac arrhythmias, including bradycardia (less\n than [<] 50 beats per minute); (d) Uncontrolled (persistent) hypertension: (example,\n blood pressure greater than [>] 140/90 millimeters of mercury [mm Hg]; (e) Acute\n neurologic events such as stroke or transient ischemic attack, intracranial or\n subarachnoid hemorrhage, intracranial trauma; (f) Venous thromboembolic events\n (example, pulmonary embolism) within 1 month prior to the first dose of study\n treatment (uncomplicated Grade less than or equal to [\u2264]2 deep vein thrombosis is not\n considered exclusionary);(g)Congestive heart failure (NYHA class III to IV); (h)\n Pericarditis or clinically significant pericardial effusion; (i) Myocarditis; (j)\n Endocarditis (k) Clinically significant hypokalemia, hypomagnesemia, hypocalcemia\n (corrected for hypoalbuminemia)\n - Any toxicity (except for alopecia, stable peripheral neuropathy, thrombocytopenia,\n neutropenia, anemia) from previous anticancer therapy that has not resolved to\n baseline or to grade 1 or less\n - Pulmonary compromise that requires the need for supplemental oxygen use to maintain\n adequate oxygenation", "output": {"inclusion_biomarker": [["NPM1 alteration"], ["KMT2A alteration"]], "exclusion_biomarker": []}}
{"input": "Circulating tumor DNA can be used to monitor the treatment effect and identify developing\n resistance mutations during ALK directed TKI treatment.\n ;\n ;\n Inclusion Criteria:\n 1. Patients with ALK translocated metastatic NSCLC, treated with alectinib as 1st line\n therapy in routine clinical practice\n 2. Written (personally dated and signed) informed consent\n Exclusion Criteria:", "output": {"inclusion_biomarker": [["ALK translocation"]], "exclusion_biomarker": []}}
{"input": "Decitabine is a cytosine analogue and is a specific DNA methyltransferase (DNMT) inhibitor.\n It directly inhibits DNMT by phosphorylating DNA and inhibits DNMT, thereby reversing DNA\n methylation and inducing tumor cells to Normal cell differentiation or induction of tumor\n cell apoptosis.Diffuse large B-cell lymphoma (DLBCL) is the most common pathological type in\n non-Hodgkin's lymphoma. The first-line chemotherapy regimen using\n Rituximab+Cyclophosphamide+Doxorubicin +Vincristine+Bonisone\uff08R-CHOP\uff09significantly increases\n the remission rate and disease-free survival of patients with DLBCL, but it is difficult to\n partially relapse. Long-term remission and survival rates in treating patients are not\n satisfactory.Due to the greater cardiac toxicity of adriamycin, more patients can not be\n uncomfortable, so the COP program is also widely used in patients with DLBCL, and achieved a\n good response rate.In 2008, the FDA had approved decitabine for the demethylation treatment\n of Myelodysplastic syndrome\uff08MDS\uff09. Over the years, good initial remission rates and better\n long-term survival rates have been achieved in patients with MDS.There are also a variety of\n clinical trials of decitabine for patients with solid tumors that have achieved significant\n clinical efficacy.Due to the high side effects of high-dose decitabine, patient tolerance is\n poor. Therefore, the purpose of this study was to evaluate the efficacy and safety of\n low-dose decitabine combined with Cyclophosphamide+Vindesine+Bonisone(COP) regimen (D-COP)\n 4-6 course of treatment for relapsed and refractory diffuse large B-cell lymphoma.\n ;\n ;\n Inclusion Criteria:\n 1. Histopathology confirmed as DLBCL.\n 2. Relapsed and refractory patients.\n 3. Age \u2265 18 years old.\n 4. ECOG \u2265 3.\n 5. Women are not lactating, not pregnant, and agree not to become pregnant during the\n study period and within the next 12 months. Male patients agree that their spouse is\n not pregnant during the study period and within the next 12 months\u3002\n 6. There is an assessable lesion (lymph node diameter \u2265 1.0cm; or a dermatologic lesion\n that can be assessed by a physical examination)Signed informed consent\n Exclusion Criteria:\n 1. Bone marrow involvement and lymphoma cells \u2265 25%.\n 2. Severe abnormal liver and kidney function (alanine aminotransferase, bilirubin,\n creatinine> 3 times the upper limit of normal).\n 3. Uncontrolled active infections.\n 4. Organic heart disease and clinical symptoms or abnormal heart function (NYHA \u2265 2).\n 5. Simultaneous presence of other tumors.\n 6. Other psychological conditions that prevent patients from participating in the study\n or signing informed consent", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
{"input": "The primary objective of this study is to assess the safety and tolerability, feasibility of\n the NeoPep Vaccine in newly diagnosed glioblastoma (GB) patients.\n ;\n ;\n Inclusion Criteria:\n 1. Ability of subject to understand and the willingness to sign written informed consent\n for study participation;\n 2. Patients with newly diagnosed high-grade glioma confirmed by histopathological and\n imaging evaluation;\n 3. Gross total resection (as defined by less than 1 cm2 residual tumor mass on the\n largest perpendicular axes in post-operative scan taken within 48 h post-surgery;\n standard MRI conformable to the present national and international guidelines is\n sufficient)\uff1b\n 4. At least 0.5 g tumor tissue freshly cryopreserved during surgery\uff0cand could provide\n adequate amounts of PBMC\uff1b\n 5. Patient is a candidate for and willing to receive standard CRT with TMZ followed by\n maintenance TMZ cycles;\n 6. Age 18-70;\n 7. Life expectancy > 9 months;\n 8. KPS\u226570;\n 9. Sufficient tumor tissue samples and peripheral blood samples can be obtained for\n sequencing analysis, or whole exome sequencing and RNA sequencing of tumor tissue\n samples and peripheral blood samples have been obtained, and the sequencing data meet\n the prediction requirements;\n 10. Consent of women and men of reproductive age to use adequate and effective\n contraception during clinical trials;\n 11. Normal laboratory values for hematology, liver and renal function (serum\n creatinine).In detail the following values apply as inclusion criteria:\n 1. White blood cell count (WBC) \u22653.0\u00d7109/L\uff1b\n 2. Absolutely neutrophil count\u22651.0\u00d7109/L\uff1b\n 3. Platelet count\u226580\u00d7109/L\uff1b\n 4. Hemoglobin content\u226590g/L\uff1b\n 5. Serum creatinine\u22641.5 ULN or Creatinine clearance rate\u226540 mL/min;\n 6. TBil(total bilirubin)\u22641.5 x ULN;\n 7. Aspartic transaminase(AST)\u22642.5x ULN or Alanine aminotransferase\uff08ALT\uff09\u22642.5x\n ULN\uff1bPatients with liver metastases must have \u22645x ULN;\n 8. Blood coagulation function :INR\u22641.5x ULN\uff1bpT and APTT\u22641.5x ULN;\n 9. Urine protein< 2 +;if Urine protein\u22652+,24-hour urinary protein must be less than\n 1g.\n Exclusion Criteria:\n 1. Patients treated with immunosuppressive agents (e.g., cyclosporin CsA, tacrolimus,\n rapamycin, azathioprine, etc.) within the previous month; Other immunotherapy within 3\n months;\n 2. History of other malignancies (except for adequately treated basal or squamous cell\n carcinoma or carcinoma in situ) within the last 5 years unless the patient has been\n disease-free for 5 years;\n 3. Participated in other clinical trials within 30 days prior to screening;\n 4. Have a history of severe allergy or allergic constitution;\n 5. Patients who have undergone splenectomy;\n 6. Persons with primary or secondary immunodeficiency diseases (e.g. AIDS);Patients with\n autoimmune diseases;\n 7. Patients who received multiple oral, intramuscular, or intravenous corticosteroids\n within 30 days before the first dose; However, patients who received a single oral,\n intramuscular, or intravenous dose of dexamethasone of 5mg or less (or another hormone\n of equivalent potency) 14 days before the first dose were allowed; Allow inhaled\n corticosteroids to treat respiratory insufficiency (e.g., chronic obstructive\n pulmonary disease), or topical steroids;\n 8. Patients with uncontrollable seizures, central nervous system disorders, or psychotic\n loss of cognition;\n 9. Uncontrolled central nervous system metastases;\n 10. Patients had a history of chronic alcohol or drug abuse in the 6 months before\n screening;\n 11. With unstable systemic disease, such as active infection, liver cirrhosis, chronic\n renal failure, severe chronic pulmonary disease, unstable hypertension, unstable\n angina pectoris, congestive heart failure, myocardial infarction within one year, etc.\n ;\n 12. According to this procedure, the number of candidate neoantigens that can be used to\n make personalized vaccines is less than 20;\n 13. The investigator did not consider it appropriate to participate in this study.", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
{"input": "Study to investigate the safety and activity of NEO-PTC-01 in patients with unresectable or\n metastatic melanoma. NEO-PTC-01 is an autologous personalized T cell (PTC) product for\n adoptive cell therapy that is manufactured ex vivo and targets neoantigens displayed on the\n patient's tumor and the tumor microenvironment.\n The study will be conducted in two parts, Part 1 (Dose Finding) and Part 2 (Dose Expansion).\n The dose-finding part of the study will test two doses of NEO-PTC-01 and will be structured\n according to a 3+3 dose escalation design. After the highest tolerated NEO-PTC-01 dose is\n identified, 2 additional evaluations in Part 1 are planned, a cohort to investigate\n NEO-PTC-01 in combination with interleukin (IL)-2 and another cohort introducing \u03b1 programmed\n cell death protein 1 (\u03b1PD-1) therapy. The dose expansion part of the study will test the dose\n deemed to be safe in the dose-finding part of the study in an expanded cohort of patients to\n further define the safety of NEO-PTC-01.\n ;NA;\n Inclusion Criteria:\n - Adult (age 18 to 75) men and women willing and able to give written informed consent.\n - Histologically confirmed unresectable or metastatic melanoma.\n - Part 1:\n - Have previously received a PD-1/PD-L1 inhibitor (either as single agent or in\n combination) and a CTLA-4 inhibitor-containing regimen (single agent or\n combination) prior to NEO-PTC-01, with disease progression following these\n therapies or otherwise lack of clinical benefit as determined by the study\n investigator.\n - Part 2:\n - Have received/are currently receiving a PD-1/PD-L1 inhibitor (as a single agent\n or in combination with CTLA-4) for at least 3 months.\n - Have documented SD by RECIST v1.1 or clinically asymptomatic progressive disease\n on the most recent imaging assessment, which must have occurred within 3 months\n of enrollment.\n - In the opinion of the investigator, are medically eligible and able to continue\n with PD-1/PD-L1 inhibitor therapy.\n - In the opinion of the investigator, would benefit from the addition of a T-cell\n based therapy.\n - For known BRAF mutant patients: patients must have also received targeted therapy\n (B-raf inhibitor or B-raf/MEK combination therapy) prior to NEO-PTC-01, unless deemed\n not appropriate to receive these treatments by the investigator.\n - Have at least one site of measurable disease by RECIST v1.1.\n - At least one site of disease must be accessible to biopsy for tumor tissue for\n sequence and immunological analysis. The biopsy site may be the same as the measurable\n site so long as it remains measurable. Surgical resection of the measurable site may\n not be performed if that site is the only measurable lesion. An archival biopsy may be\n used in place if the biopsy was taken within 6 months of informed consent.\n - Have Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.\n - Recovered from all toxicities associated with prior treatment to acceptable baseline\n status (for laboratory toxicities see below limits for inclusion) or an National\n Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version\n 5.0, Grade of 0 or 1, except for toxicities not considered by the treating physician\n to be a safety risk (e.g., alopecia).\n - Screening laboratory values must meet the following criteria and should be obtained\n prior to any production phase assessments:\n 1. White blood cell (WBC) count \u2265 3 \u00d7 10^3/\u03bcL.\n 2. Absolute neutrophil count (ANC) \u2265 1.5 \u00d7 10^3/\u03bcL.\n 3. Platelet count \u2265 100 \u00d7 10^3/\u03bcL.\n 4. Hemoglobin > 9 g/dL or 6 mmol/L.\n 5. Serum creatinine \u2264 1.5 \u00d7 upper limit of normal (ULN) or creatinine clearance\n (CrCl) \u2265 50 mL/min by Cockcroft-Gault.\n 6. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \u2264 3 \u00d7 ULN.\n 7. Total bilirubin \u2264 1.5 \u00d7 ULN (except in patients with Gilbert Syndrome, who can\n have total bilirubin < 3.0 mg/dL).\n 8. International Normalized Ratio (INR), Prothrombin Time (PT), or Activated Partial\n Thromboplastin Time (aPTT) \u2264 1.5 \u00d7 ULN unless the patient is receiving\n anticoagulant therapy, as long as PT or aPTT is within therapeutic range of\n intended use of anticoagulants.\n Exclusion Criteria:\n - Age greater than 75 years or less than 18 years.\n - Received more than three prior lines of therapy for metastatic disease.\n - Have an active or history of autoimmune disease (known or suspected). Exceptions are\n permitted for vitiligo, type I diabetes mellitus, residual hypothyroidism due to\n autoimmune condition requiring only hormone replacement, psoriasis not requiring\n systemic treatment, or conditions not expected to recur in the absence of an external\n trigger.\n - Have known active central nervous system (CNS) metastases and/or carcinomatous\n meningitis. Patients with previously treated brain metastases may participate provided\n they are stable (without evidence of progression by imaging [using the identical\n imaging modality for each assessment, either MRI or CT scan] for at least 4 weeks\n prior to enrollment and any neurologic symptoms have returned to baseline), have no\n evidence of new or enlarging brain metastases, and are not using steroids for at least\n 7 days prior to enrollment. This exception does not include carcinomatous meningitis,\n which is excluded regardless of clinical and/or radiographic stability.\n - Active systemic infections requiring intravenous antimicrobial therapy, coagulation\n disorders or other active major medical illnesses of the cardiovascular, respiratory\n or immune system, as evidenced by a positive stress thallium or comparable test,\n myocardial infarction, clinically significant cardiac arrhythmias such as uncontrolled\n atrial fibrillation, ventricular tachycardia, or second- or third-degree heart block,\n and obstructive or restrictive pulmonary disease.\n - Active major medical illnesses of the immune system including conditions requiring\n systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents)\n or other immunosuppressive medications within 14 days prior to NEO-PTC-01 infusion.\n Inhaled or topical steroids and adrenal replacement doses (\u2264 10 mg daily prednisone\n equivalents) are permitted in the absence of active autoimmune disease.\n - Known human immunodeficiency virus (HIV) infection, active chronic hepatitis B or C,\n and/or life-threatening illnesses unrelated to cancer that could, in the\n investigator's opinion, interfere with participation in this study.\n - Have any underlying medical condition, psychiatric condition, or social situation\n that, in the investigator's opinion, would interfere with participation in the study.\n - Have a planned major surgery that is expected to interfere with study participation or\n confound the ability to analyze study data.\n - Are pregnant or breastfeeding, or expecting to conceive or father children within the\n projected duration of the study, starting with the screening visit through 120 days\n after the end of the trial (EOT) visit. Nursing women are excluded from this study\n because there is an unknown but potential risk of AEs in nursing infants secondary to\n treatment of the mother with treatments to be administered in this study.\n - Have a history of another invasive malignancy aside from melanoma, except for the\n following circumstances:\n 1. Patient has been disease-free for at least 2 years and is deemed by the\n investigator to be at low risk for recurrence of that malignancy.\n 2. Patient was not treated with systemic chemotherapy for carcinoma in situ of the\n breast, oral cavity, or cervix, basal cell, or squamous cell carcinoma of the\n skin.", "output": {"inclusion_biomarker": [["BRAF mutation"]], "exclusion_biomarker": []}}
{"input": "Participants with CD30-positive lympoma will be treated with brentuximab vedotin according to\n their clinic's standard practice.\n The main aim of this study is to collect information on any side effects from treatment with\n brentuximab vedotin. Other aims are to collect information on how brentuximab vedotin is used\n to treat these participants and the outcomes of these participants.\n ;\n ;\n Inclusion Criteria:\n 1. Undergoing treatment with brentuximab vedotin (of less than 3 months from initial\n treatment with brentuximab vedotin) or to be received with brentuximab vedotin.\n 2. CD30-positive lymphoma by INV (any CD30 expression)\n Exclusion Criteria:\n 1. Who currently participates in or with plan to participate in any interventional clinical\n trial.", "output": {"inclusion_biomarker": [["CD30 positive"], ["CD30 expression"]], "exclusion_biomarker": []}}
{"input": "The purpose of the study is to evaluate whether receiving the pneumococcal 13-valent\n conjugate vaccine (PCV13) before and after CD19-targeted CAR T cell therapy will optimize\n cellular and humoral immunity to pneumococcus.\n ;\n ;\n Inclusion Criteria:\n - In good health as evidenced by medical history or diagnosed with relapsed or\n chemotherapy-refractory diffuse large B cell lymphoma (DLBCL), primary mediastinal B\n cell lymphoma (PMLBCL), transformed follicular lymphoma (TFL) high-grade B cell\n lymphoma (HGBCL) or Follicular Lymphoma. Patients must be under consideration for\n treatment with any CD19-targeted CAR T cell therapy, per institutional standards.\n Patients undergoing active vital organ testing with a planned apheresis date for CAR T\n cell therapy may be considered eligible.\n - Signed informed consent form in accordance with institutional and federal law policies\n - Stated willingness to comply with all study procedures and availability for the\n duration of the study\n - Male or female, age over 18\n - For females of reproductive potential: use of highly effective contraception for at\n least 1 month prior to screening and agreement to use such a method during study\n participation\n Exclusion Criteria:\n - Pregnant or lactating woman, as evaluated by serum testing within 2 weeks of\n administration of the first vaccine. Only women of childbearing potential will undergo\n serum/urine pregnancy testing. A woman will be considered of childbearing potential\n unless she is status-post hysterectomy or tubal ligation or without menstrual periods\n in the preceding 12 months.\n - Common variable immunodeficiency or other inherited systemic immunodeficiency syndrome\n - History of severe allergy (e.g., anaphylaxis) to any component of pneumococcal\n conjugate vaccine 7 valent (PCV7), PCV13, or any diphtheria-toxoid containing vaccine.\n - Inclusion on a separate trial in which patients may be randomized or otherwise started\n on maintenance chemotherapies within the first 3 months of CD19-targeted CAR T cell\n therapy\n - Patients with significant psychiatric illness likely to affect compliance, as\n determined by the treating physician\n - Active or uncontrolled infections\n - Platelet count <10,000 cells/microliter\n - Lymphocyte count <200 cells/microliter\n - Intervenous immunoglobulin (IVIG) administration within one month of planned apheresis\n for collection for CD19-targeted CAR T cell manufacture\n - History of PCV13 administration within one month of planned apheresis for collection\n for CD19-targeted CAR T cell manufacture", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
{"input": "The overall objective of this research study is to evaluate outcomes associated with\n flex-dosing in Y90 SIR-Sphere administration in a prospective cohort of unresectable HCC\n patients eligible for segmental/super selective treatment at Methodist Dallas Medical Center\n (MDMC).\n ;\n ;\n Inclusion Criteria:\n - Age 18 years or older\n - All patients diagnosed with unresectable HCC in two of fewer hepatic segments at MDMC\n who undergo at least one SIRT procedure with Y-90 resin microspheres (SIR-Spheres\u00ae,\n Sirtex Medical Limited, Sydney, Australia) will be included in data capture. HCC is\n considered unresectable if it is multifocal or bilobar, or if the patient has\n malignant portal vein thrombosis, portal hypertension, or decompensated liver disease\n (Child-Pugh B or C).\n - Eligible cases for inclusion are those that would have undergone Y-90 resin SIRT and\n had an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2;\n platelets >60,000; creatinine <2 mg/dL; bilirubin <2 mg/dL; and international\n normalized ratio (INR) <1.2.\n Exclusion Criteria:\n - Subjects that do not meet the inclusion criteria\n - Patients are not eligible for SIRT if they had any extrahepatic disease;\n contraindication to hepatic artery catheterization such as vascular abnormalities,\n bleeding diathesis, allergy to contrast dye, concurrent malignancy, refractory\n ascites, previous external beam radiation, or evidence of any uncorrectable flow to\n the gastrointestinal tract; or greater than 30 Gy of radiation estimated to be\n delivered to the lung based on angiography or Tc-99 microaggregated albumin scan\n (shunt fraction of 20% or greater).", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
{"input": "HS-10352 is a highly potent and selective small molecule inhibitor of phosphoinositide\n 3-kinase (p110\u03b1). The purpose of this study is to assess the safety, tolerability,\n pharmacokinetics (PK), and efficacy of HS-10352 plus fulvestrant in patients with hormone\n receptor (HR) positive, human epidermal growth factor 2 (HER2)-negative, advanced breast\n cancer (ABC) harboring PIK3CA mutations.\n ;\n ;\n Inclusion Criteria:\n 1. Men or women aged more than or equal to (\u2265) 18 years\n 2. HR+ HER2- breast cancer confirmed by histology or cytology.\n 3. Locally advanced disease not amenable to curative treatment by surgery or metastatic\n disease.\n 4. Have adequate tumor tissue for the analysis of PIK3CA mutational status. At dose\n expansion stage, participants should be identified as PIK3CA-mutation positive before\n enrollment.\n 5. Females should have postmenopausal status due to either surgical/natural menopause or\n ovarian suppression with a luteinizing hormone releasing hormone (LHRH) agonist before\n enrollment. Males should be pre-treated with a LHRH agonist.\n 6. Have either measurable disease per RECIST v1.1 criteria or at least one predominantly\n lytic bone lesion must be present.\n 7. ECOG performance status was 0-1 and did not deteriorate in the previous 2 weeks.\n 8. Estimated life expectancy for at least three months\n 9. Females should be using adequate contraceptive measures and should not be\n breastfeeding at the time of screening, during the study and until 6 months after\n completion of the study; and have negative results of blood pregnancy test prior to\n C1D1.\n Males should be using adequate contraceptive measures at the time of screening, during\n the study and until 6 months after completion of the study.\n 10. Have signed Informed Consent Form\n 11. Dose escalation stage-Cohort 1: subjects resistant to endocrine therapy Dose expansion\n stage-Cohort 2: subjects resistant to endocrine therapy Dose expansion stage-Cohort 3:\n endocrine therapy-sensitive or endocrine-naive subjects\n Exclusion Criteria:\n 1. Participant with symptomatic visceral disease or any disease burden that makes the\n participant ineligible for endocrine therapy per the investigator's best judgment\n 2. Treatment with any of the following:\n 1. Previous or current treatment with PI3K, AKT or mTOR inhibitors\n 2. For expansion stage, prior treatment with fulvestrant\n 3. Any cytotoxic chemotherapy, investigational agents within 21 days of the first\n dose of study drug; anticancer drugs which have been received within 14 days\n before the first administration.\n 4. Radiotherapy with a limited field of radiation for palliation within 2 weeks of\n the first dose of study drug, or patients received more than 30% of the bone\n marrow irradiation, or large-scale radiotherapy within 4 weeks of the first dose.\n 5. Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4\n weeks of the first dose of study drug.\n 3. With inflammatory breast cancer at screening.\n 4. Inadequate bone marrow reserve or organ function.\n 5. Uncontrolled pleural effusion or ascites or pericardial effusion.\n 6. Known and untreated, or active central nervous system metastases.\n 7. History of primary or secondary diabetes.\n 8. History of acute or chronic pancreatitis\n 9. Refractory nausea, vomiting, or chronic gastrointestinal diseases, or inability to\n swallow the study drug that would preclude adequate absorption of HS-10352 or\n fulvestrant.\n 10. History of hypersensitivity to any active or inactive ingredient of HS-10352/\n fulvestrant or to drugs with a similar chemical structure or class to HS-10352.\n 11. Judgment by the investigator that the patient should not participate in the study if\n the patient is unlikely to comply with study procedures, restrictions, and\n requirements.\n 12. Any disease or condition that, in the opinion of the investigator, would compromise\n the safety of the patient or interfere with study assessments.", "output": {"inclusion_biomarker": [["HR positive", "HER2 negative", "PIK3CA mutation"]], "exclusion_biomarker": []}}
{"input": "This is a first-in-human, open-label, multicenter, Phase I multiple-ascending dose (MAD)\n study of RO7247669, an anti PD-1 (programmed death-1) and LAG-3 (Lymphocyte-activation gene\n 3) bispecific antibody, for participants with advanced and/or metastatic solid tumors. This\n study aims to establish the maximum tolerated dose (MTD) and/or define the recommended phase\n 2 dose (RP2D) based on the safety, tolerability, pharmacokinetic (PK) and/or pharmacodynamic\n (PD) profile of RO7247669, and to evaluate preliminary anti-tumor activity in participants\n with solid tumors. An expansion part of the study is planned to enroll tumor-specific cohorts\n to evaluate anti-tumor activity of the MTD and/or RP2D of RO7247669 and to confirm safety and\n tolerability in participants with selected tumor types.\n ;NA;\n Inclusion criteria\n - Patient must have histologically or cytologically confirmed advanced and/or metastatic\n solid tumor malignancies for which standard curative or palliative measures do not\n exist, are no longer effective, or are not acceptable to the patient\n - Eastern Cooperative Oncology Group Performance Status 0-1\n - Fresh biopsies may be required\n - Women of childbearing potential and male participants must agree to remain abstinent\n or use contraceptive methods as defined by the protocol\n Additional Specific Inclusion Criteria for Participants with Melanoma\n - Histologically confirmed, unresectable stage III or stage IV melanoma\n - Not more than 2 prior lines of treatment for metastatic disease are allowed prior to\n enrolling in the study\n - Prior treatment with an approved anti-PD-1 or anti-PD-L1 agent\n Additional Specific Inclusion Criteria for Participants with Non-Small Cell Lung Cancer who\n Previously Received Treatment for Metastatic Disease\n - Participants with histologically confirmed advanced non-small cell lung cancer\n - Not more than 2 prior lines of treatment for metastatic disease are allowed prior to\n enrolling in the study\n - Previously treated with approved PD-L1/PD-1 inhibitors\n - Tumor PD-L1 expression as determined by immunohistochemistry assay of archival tumor\n tissue or tissue obtained at screening\n Additional Specific Inclusion Criteria for Participants with Esophageal Squamous Cell\n Carcinoma\n - Participants whose major lesion was histologically confirmed as squamous cell\n carcinoma or adenosquamous cell carcinoma of the esophagus\n - Participants who have previously received not more than 1 prior line of treatment for\n metastatic disease prior to enrolling in the study\n Additional Specific Inclusion Criteria for Participants with Non-Small Cell Lung Cancer who\n Previously did not Receive Treatment for Metastatic Disease\n - Participants with histologically confirmed advanced non-small cell lung cancer\n - Tumor PD-L1 expression as determined by immunohistochemistry assay of archival tumor\n tissue or tissue obtained at screening\n Exclusion criteria\n - Pregnancy, lactation, or breastfeeding\n - Known hypersensitivity to any of the components of RO7247669\n - Active or untreated central nervous system (CNS) metastases\n - An active second malignancy\n - Evidence of concomitant diseases, metabolic dysfunction, physical examination finding,\n or clinical laboratory finding giving reasonable suspicion of a disease or condition\n that contraindicates the use of an investigational drug or that may affect the\n interpretation of the results or render the participant at high risk from treatment\n complications\n - Positive HIV, hepatitis B, or hepatitis C test result\n - Known active or uncontrolled bacterial, viral, fungal, mycobacterial, parasitic, or\n other infection\n - Vaccination with live vaccines within 28 days prior to Cycle 1 Day 1\n - Treatment with oral or IV antibiotics within 2 weeks prior to Cycle 1 Day 1\n - Active or history of autoimmune disease or immune deficiency\n - Prior treatment with adoptive cell therapies, such as CAR-T therapies\n - Concurrent therapy with any other investigational drug < 28 days or 5 half-lives of\n the drug, whichever is shorter, prior to the first RO7247669 administration\n - Regular immunosuppressive therapy\n - Radiotherapy within the last 4 weeks before start of study drug treatment, with the\n exception of limited palliative radiotherapy\n - Prior treatment with a lymphocyte activation gene-3 (LAG-3) inhibitor\n Additional Specific Exclusion Criteria for Participants with Non-Small Cell Lung Cancer who\n Previously Received Treatment for Metastatic Disease\n - Participants with the following muations, rearrangements, translocations are not\n eligible: EGFR, ALK, ROS1, BRAFV600E, and NTRK\n Additional Specific Exclusion Criteria for Participants with Esophageal Squamous Cell\n Carcinoma\n - Prior therapy with any immunomodulatory agents\n Additional Specific Exclusion Criteria for Participants with Non-Small Cell Lung Cancer who\n Previously did not Receive Treatment for Metastatic Disease\n - Prior therapy for metastatic disease is not permitted\n - Neo-adjuvant anti-PD-1 or anti-PD-L1 therapy is not allowed", "output": {"inclusion_biomarker": [["PD-L1 expression"]], "exclusion_biomarker": [["EGFR mutation"], ["EGFR rearrangement"], ["EGFR translocation"], ["ALK mutation"], ["ALK rearrangement"], ["ALK translocation"], ["ROS1 mutation"], ["ROS1 rearrangement"], ["ROS1 translocation"], ["BRAF V600E"], ["NTRK mutation"], ["NTRK rearrangement"], ["NTRK translocation"]]}}
{"input": "A transcriptomic analysis of bone marrow from B-ALL patients was performed by our research\n group for identifying novel protein/factor with a putative role of disease biomarker. Along\n with some already known B-ALL biomarkers, our analysis highlighted deregulation of some\n members of an emerging protein class denoted as KCTD (Potassium ChannelTetramerization\n Domain-containing proteins). Starting from our preliminary observations, and considering that\n KCTDs havenever been studied in ALL, we decided to study these proteins in B- and T-ALL\n affected pediatric patients, enrolled by our research group in collaboration with AORN\n Santobono-Pausilipon pediatric oncological hospital.Indeed, the present research program aims\n at opening a new scenario for the study of KCTD proteins in childhood leukemias. The final\n goal of the project will be to evaluate the translational relevance of selected deregulated\n KCTDs as novel biomarkers useful for B-ALL and T-ALL diagnostics, and patient management.\n ;NA;\n Inclusion Criteria:\n - Patients aged 1-18 years of both sexes diagnosed with B- ALL and T-ALL;\n - Patients who will have signed the informed consent\n Exclusion Criteria:\n - Patients who refuse to participate in the study;\n - Patients who do not fall within the age range mentioned above", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
{"input": "This is a Phase 1, nonrandomized, open-label, single-dose, dose-escalation, and\n dose-expansion study to evaluate the safety and clinical activity of PBCAR19B in adult study\n participants with CD-19 expressing malignancies.\n ;NA;\n Inclusion Criteria:\n - Relapsed or refractory CD19+ expressing malignancies\n - At least 2 prior regimens per Standard of Care\n Exclusion Criteria:\n - No history of active CNS involvement", "output": {"inclusion_biomarker": [["CD19 expression"]], "exclusion_biomarker": []}}
{"input": "This study will test the safety of the study drug, GDC-0084, in combination with radiation\n therapy in people who have solid tumor brain metastases or leptomeningeal metastases. All\n participants will have cancer with a PIK3CA mutation. The researchers will test increasing\n doses of GDC-0084 to find the highest dose that causes few or mild side effects in\n participants. The study will also try to find out if the combination of the study drug with\n radiation is effective against participants' cancer.\n ;NA;\n Inclusion Criteria:\n - Histologically confirmed solid tumor malignancies harboring PIK3CA mutations which\n include mutations in any of the following genes: PIK3CA, PIK3CB, PIK3CD, PIK3CG,\n PIK3R1, PIK3R2, PIK3R3, PIK3C2G, PIK3C3, INPP4A, INPP4B, INPPL1, INPP5D, PTEN, AKT1,\n AKT2, AKT3, and MTOR.\n - Brain metastases and/or leptomeningeal metastases involving the brain demonstrated by\n MR imaging of the brain. For patients with brain metastases, measurable lesion by\n RANO-BM is required28. Patients with spine leptomeningeal metastases are eligible for\n the study if they have leptomeningeal metastases of the brain demonstrated by MRI\n imaging of the brain.\n - KPS \u2265 70\n - Age \u2265 18 years\n - Able to provide informed consent.\n - If a patient is on corticosteroid, he/she must be on a stable daily dose of < 4mg\n dexamethasone or equivalent. Patient does not need to be given corticosteroid as\n prophylaxis if not clinically indicated.\n - No limit to prior therapies with the last systemic therapy \u2265 1 week from initiation of\n protocol therapy. Systemic therapy can resume after completion of protocol DLT\n assessment period.\n - Patients with prior SRS are eligible, provided that there are new, non-irradiated\n brain lesions or leptomeningeal metastases. Patients must be \u2265 3 months post prior\n cranial radiation therapy.\n - Patients with seizure history related to brain metastases or leptomeningeal metastases\n controlled on antiepileptic medications are eligible.\n - Patient at reproductive potential must agree to practice an effective contraceptive\n method\n - Patient must be able to swallow and retain oral medication\n - Adequate organ function as assessed by laboratory tests.\n - Adequate bone marrow function\n - Hemoglobin \u2265 8g/dL\n - Absolute neutrophil count \u22651,000/mm^3\n - Platelet count \u2265 100,000/mm^3\n - Adequate liver function\n - Bilirubin \u22641.5 times upper limit normal (ULN)\n - AST and ALT \u2264 2.5 times ULN\n - Alkaline phosphatase \u2264 2 times ULN\n - Adequate renal function \u00b0 BUN and Creatinine \u2264 1.5 times ULN\n Exclusion Criteria:\n - Previous radiotherapy to the intended treatment site that precludes developing a\n treatment plan that respects tissue tolerances\n - Patients with brain metastases eligible for single fraction stereotactic radiation\n therapy\n - Serious medical co-morbidities precluding radiotherapy\n - Insulin-treated diabetes; subjects with diabetes or impaired glucose tolerance that is\n not treated with insulin may be enrolled\n - QT interval \u2265 450 msec on EKG\n - Cardiac dysfunction defined as: myocardial infarction within 6 months of study entry,\n NYHA Class II/III/IV heart failure, unstable angina or unstable cardiac arrhythmias\n - Known hypersensitivity or intolerance to GDC-0084 or to any other inhibitor of the\n PI3K/ Akt/ mTOR pathway\n - Past medical history of interstitial lung disease, drug-induced ILD, radiation\n pneumonitis that required steroid treatment, or any evidence of clinically active\n interstitial lung disease\n - Subject receiving any medications or substances that are moderate and/or potent enzyme\n inducers or inhibitors which may have an effect on the metabolism of GDC-0084.\n - Pregnant or lactating women.", "output": {"inclusion_biomarker": [["PIK3CA mutation"], ["PIK3CB mutation"], ["PIK3CD mutation"], ["PIK3CG mutation"], ["PIK3R1 mutation"], ["PIK3R2 mutation"], ["PIK3R3 mutation"], ["PIK3C2G mutation"], ["PIK3C3 mutation"], ["INPP4A mutation"], ["INPP4B mutation"], ["INPPL1 mutation"], ["INPP5D mutation"], ["PTEN mutation"], ["AKT1 mutation"], ["AKT2 mutation"], ["AKT3 mutation"], ["MTOR mutation"]], "exclusion_biomarker": []}}
{"input": "HS-10365 is a small molecular, oral potent, selective RET inhibitor. The purpose of this\n study is to investigate the safety/tolerability and the pharmacokinetic profile of HS-10365\n in Chinese advanced solid tumor patients. Anti-tumor activity will be also investigated in\n this study.\n ;\n ;\n Inclusion Criteria:\n Subjects must meet all of the following inclusion criteria to be eligible for participation\n in this study:\n 1. Men or women aged more than or equal to (\u2265) 18 years.\n 2. Locally advanced or metastatic cancer patients confirmed by histology or cytology for\n who that standard treatment is invalid, unavailable or intolerable\n 3. Enrollment will be restricted to participants with evidence of a RET gene alteration\n in tumor as determined by local or central testing. And tumor tissue samples should be\n provided before the first administration for retrospective detection of RET gene\n status; blood samples are also allowed.\n 4. At least one extra-cranial measurable lesion according to Response Evaluation Criteria\n in Solid Tumors (RECIST) criteria version 1.1.\n 5. Eastern Cooperative Oncology Group (ECOG) performance status: 0~1.\n 6. Estimated life expectancy greater than (>) 12 weeks.\n 7. Men or women should be using adequate contraceptive measures throughout the study;\n Females should not be breastfeeding at the time of screening, during the study and\n until 6 months after completion of the study\\\n 8. Females must have 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 selective RET inhibitors. Any cytotoxic\n chemotherapy, investigational agents and anticancer drugs within 14 days of the first\n dose of study drug.\n Radiotherapy with a limited field of radiation for palliation within 2 weeks of the\n first dose of study drug, or patients received more than 30% of the bone marrow\n irradiation, or large-scale radiotherapy within 4 weeks of the first dose.\n Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks\n of the first dose of study drug.\n 2. Inadequate bone marrow reserve or organ function.\n 3. Uncontrolled pleural effusion or ascites or pericardial effusion.\n 4. Known and untreated, or active central nervous system metastases.\n 5. Refractory nausea, vomiting, or chronic gastrointestinal diseases, or inability to\n swallow the study drug that would preclude adequate absorption of HS-10365.\n 6. History of hypersensitivity to any active or inactive ingredient of HS-10365 or to\n drugs with a similar chemical structure or class to HS-10365.\n 7. Judgment by the investigator that the patient should not participate in the study if\n the patient is unlikely to comply with study procedures, restrictions, and\n requirements.\n 8. Any disease or condition that, in the opinion of the investigator, would compromise\n the safety of the patient or interfere with study assessments. Pregnant women, women\n who are breastfeeding or who believe they may wish to become pregnant during the\n course of the study.\n 9. History of neuropathy or mental disorders, including epilepsy and dementia\n 10. Determined by the physician, any coexisting disease might lead to life threatening\n complications or avoid the patients from accomplishing the treatment.", "output": {"inclusion_biomarker": [["RET alteration"]], "exclusion_biomarker": [["Primary driver alteration"]]}}
{"input": "This is a Phase 1/2, open-label, multicenter, study of the safety, tolerability, PK, PD, and\n anti-tumor activity of MRTX1719 patients with advanced, unresectable or metastatic solid\n tumor malignancy with homozygous deletion of the MTAP gene.\n ;\n ;\n Inclusion Criteria:\n - Histologically confirmed diagnosis of a solid tumor malignancy with homozygous\n deletion of the MTAP gene detected in tumor tissue or ctDNA\n - Unresectable or metastatic disease.\n - Patients must have received standard therapies appropriate for their tumor type and\n stage with disease progression on or after the most recent treatment.\n 1. Phase 1 dose escalation, RECIST 1.1 measurable or evaluable disease\n 2. Phase 1b and Phase 2 cohorts, RECIST 1.1 measurable disease.\n - Presence of a tumor lesion amenable to mandatory biopsy for pharmacodynamic evaluation\n at baseline and on-study unless Sponsor-confirmed as medically unsafe or infeasible.\n - Age \u2265 18 years.\n - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n - Adequate organ function\n Exclusion Criteria:\n - Prior treatment with a PRMT5 or MAT2A inhibitor therapy (Phase 2 only).\n - Active brain metastases or carcinomatous meningitis.\n - History of significant hemoptysis or hemorrhage within 4 weeks of the first dose of\n study treatment.\n - Major surgery within 4 weeks of first dose of study treatment.\n - History of intestinal disease, inflammatory bowel disease, major gastric surgery, or\n other gastrointestinal conditions (eg, uncontrolled nausea, vomiting, malabsorption\n syndrome) likely to alter absorption of study treatment or result in inability to\n swallow oral medications\n - Cardiac abnormalities", "output": {"inclusion_biomarker": [["MTAP homozygous deletion"]], "exclusion_biomarker": []}}
{"input": "This is a single-arm, open-label, multicenter, investigator-initiated Phase 2 trial to\n evaluate the efficacy and safety of E7090 in patients with advanced or recurrent solid tumors\n harboring FGFR genetic alterations (including fusion, mutation, amplification).\n ;NA;\n Inclusion Criteria:\n 1. Participants with histologically or cytologically confirmed metastatic, unresectable,\n or recurrent solid tumor who agree to provide an archival tumor sample, a residual\n biopsy sample, or a fresh tumor biopsy sample\n 2. Ineffective to or intolerant to initial treatment, or for which standard treatment is\n no longer available\n 3. Participants with an FGFR gene alteration detected by NGS panel, who fall under one of\n the categories of groups A to C defined as below\n Group A: FGFR1-3 fusion\n Group B: FGFR1-3 specific activating mutations as below;\n FGFR1: P150S, T340M, R445W, N546K, K656E\n FGFR2: C62Y, A67V, N82K, D101Y, E160K, E163K, M186T, R203H, R210Q, Q212K, R251Q,\n S252W, P253R, P253L, A264T, W290C, K310R, Y328N, G364E, Y375C, C382R, A389T, V392A,\n R399Q, H416R, I422V, H544Q, N549H, N549K, N549D, N549S, L560F, K659E, K659N, R664W,\n E718K, S791T\n FGFR3: G380E, G380R, A391E, K650T, K650E, K650Q, K650N\n Group C: FGFR1-3 activating mutation not applicable to group B, or FGFR1, 2 gene\n amplification\n 4. For Group D, participants with cholangiocarcinoma who have previously received a\n selective FGFR inhibitor other than E7090 and have demonstrated progressive disease or\n resistance\n 5. Karnofsky Performance Status (KPS) >= 70 for patients with primary CNS tumors.\n Performance Status (ECOG) 0-1 for patients with non-primary CNS tumors\n 6. For patients with non-primary CNS tumors, they have at least 1 lesion of >= 10\n millimeter (mm) in the longest diameter for a non-lymph node or >= 15 mm in the\n short-axis diameter for a lymph node that is considered as serially measurable\n according to RECIST v1.1 using computerized tomography or magnetic resonance imaging\n (CT or MRI) within 28 days of enrollment. However, lesions that have received local\n treatment such as external-beam radiation therapy (EBRT) or radiofrequency ablation\n (RFA) must have progressed after these local treatment to count as measurable lesion\n 7. Participants with primary CNS tumors must meet all of the following criteria:\n 1. Have received prior treatment including radiation and/or chemotherapy, as\n recommended or appropriate for the CNS tumor type\n 2. Have >= 1 site of bi-dimensionally measurable disease (confirmed by magnetic\n resonance imaging (MRI) and evaluable by RANO criteria), with the size of at\n least one of the measurable lesions >= 1 cm in each dimension and noted on more\n than one imaging slice. Imaging study performed within 28 days before enrollment\n 3. Must be neurologically stable based on neurologic exam at least for the last 7\n days prior to enrollment. (based on medical examination/interview)\n 8. Corrected calcium <= 10.1 mg/dL\n 9. Phosphate <= 4.6 mg/dL\n 10. Required treatment washout period, from the last day of prior treatment until\n enrollment of this trial, is as follows:\n 1. Antibody and other investigational drugs: >= 28 days\n 2. Prior chemotherapy (excluding small-molecule targeted therapy), surgical therapy,\n radiation therapy: >= 21 days (>= 90 days from the date of the last radiation\n therapy for primary CNS tumors)\n 3. Endocrine therapy, immunotherapy, small-molecule targeted therapy: >=14 days\n Exclusion Criteria:\n 1. Participants with brain, subdural or leptomeningeal metastases\n 2. Participants with primary CNS tumor located in either cerebellum, brainstem, spinal\n cord, pituitary gland, optic nerve or olfactory nerve\n 3. Positive for either human immunodeficiency virus (HIV) antibody, HBs antigen, or HCV\n antibody (patients with positive HCV antibody but no detectable HCV-RNA are not\n excluded)\n 4. Negative for HBs antigen, but positive for HBs antibody or HBc antibody, and also\n positive for HBV-DNA quantification (not excluded if HBV-DNA is below detection\n sensitivity)\n 5. Child-Pugh score B or C\n 6. Participants with pericardial effusion, pleural effusion, or ascites requiring\n treatment\n 7. Have any of the following ocular diseases\n 1. Grade 2 or higher corneal disorders\n 2. Active retinopathy (e.g., age-related macular degeneration, central serous\n chorioretinal disease, retinal tear)\n 8. Participants whose toxicity of previous treatment has not recovered to Grade 1 or\n lower per Common Terminology Criteria for Adverse Events (CTCAE v5.0), except for\n alopecia, infertility, and the laboratory test results listed in the inclusion\n criteria\n 9. Participants who received a prior selective FGFR inhibitor in the recurrent/metastatic\n disease setting; except for patients with cholangiocarcinoma harboring FGFR2 fusion\n (Group D). Note that prior use of a multi-kinase inhibitor which includes anti-FGFR\n activity is acceptable after review by the lead investigator\n 10. Participants who need the use of drugs that strongly inhibits or induces the\n metabolizing enzyme cytochrome P450 (CYP) 3A\n 11. The presence of FGFR gatekeeper mutations as follows: FGFR1 V561, FGFR2 V564/565,\n FGFR3 V555/557, FGFR4 V550\n 12. The presence of any of the following coexisting driver gene abnormalities:\n 1. Genetic mutations (excluding VUS): KRAS, NRAS, EGFR, or BRAF V600\n 2. Gene translocations: ALK, ROS1, or NTRK", "output": {"inclusion_biomarker": [["FGFR1 fusion"], ["FGFR2 fusion"], ["FGFR3 fusion"], ["FGFR1 P150S"], ["FGFR1 T340M"], ["FGFR1 R445W"], ["FGFR1 N546K"], ["FGFR1 K656E"], ["FGFR2 C62Y"], ["FGFR2 A67V"], ["FGFR2 N82K"], ["FGFR2 D101Y"], ["FGFR2 E160K"], ["FGFR2 E163K"], ["FGFR2 M186T"], ["FGFR2 R203H"], ["FGFR2 R210Q"], ["FGFR2 Q212K"], ["FGFR2 R251Q"], ["FGFR2 S252W"], ["FGFR2 P253R"], ["FGFR2 P253L"], ["FGFR2 A264T"], ["FGFR2 W290C"], ["FGFR2 K310R"], ["FGFR2 Y328N"], ["FGFR2 G364E"], ["FGFR2 Y375C"], ["FGFR2 C382R"], ["FGFR2 A389T"], ["FGFR2 V392A"], ["FGFR2 R399Q"], ["FGFR2 H416R"], ["FGFR2 I422V"], ["FGFR2 H544Q"], ["FGFR2 N549H"], ["FGFR2 N549K"], ["FGFR2 N549D"], ["FGFR2 N549S"], ["FGFR2 L560F"], ["FGFR2 K659E"], ["FGFR2 K659N"], ["FGFR2 R664W"], ["FGFR2 E718K"], ["FGFR2 S791T"], ["FGFR3 G380E"], ["FGFR3 G380R"], ["FGFR3 A391E"], ["FGFR3 K650T"], ["FGFR3 K650E"], ["FGFR3 K650Q"], ["FGFR3 K650N"], ["FGFR1 activating mutation"], ["FGFR2 activating mutation"], ["FGFR3 activating mutation"], ["FGFR1 amplification"], ["FGFR2 amplification"]], "exclusion_biomarker": [["FGFR1 V561"], ["FGFR2 V564"], ["FGFR2 V565"], ["FGFR3 V555"], ["FGFR3 V557"], ["FGFR4 V550"], ["KRAS mutation"], ["NRAS mutation"], ["EGFR mutation"], ["BRAF V600"], ["ALK translocation"], ["ROS1 translocation"], ["NTRK translocation"]]}}
{"input": "This is a phase I clinical trial to determine the maximum tolerated dose (MTD) of KK-LC-1\n TCR-T cells for the treatment of metastatic cancers that express KK-LC-1. Participants will\n receive a conditioning regimen, KK-LC-1 TCR-T cells, and aldesleukin. The safety profile and\n clinical response to treatment will be determined.\n ;\n ;\n 1. Signed, written informed consent obtained prior to any study procedures.\n 2. Age > 18 years at the time of informed consent.\n 3. Metastatic solid tumor with \u2265 25% of tumor cells positive for KK-LC-1 by IHC assay.\n Due to the low frequency of KK-LC-1 expression in most cancers, screening will focus\n on gastric, NSCLC, TNBC, and cervix cancers. The IHC test will be performed by the\n Rutgers Cancer Institute of New Jersey, Department of Biorepository Services.\n 4. HLA-A*01:01 allele by HLA haplotype test.\n 5. Measureable disease per RECIST Criteria Version 1.1 at time of enrollment.\n 6. Prior treatment with cancer type-specific stand of care systemic cancer therapy is\n required. Standard treatment options must be considered and declined. Documentation of\n rationale is required if a subject is deemed unsuitable for standard therapy.\n 7. Subjects with < 3 brain metastases that have been treated with surgery or stereotactic\n radiosurgery are eligible. Lesions that have been treated with stereotactic\n radiosurgery must be clinically stable for one month before protocol treatment.\n Patients with surgically resected brain metastases are eligible.\n 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening.\n 9. Negative pregnancy test for women under 55 and all women who have had a menstrual\n period in the last 12 months. A pregnancy tests is not required for women who have had\n a bilateral oophorectomy or hysterectomy.\n 10. Women of child-bearing potential must agree to use adequate contraception (i.e.,\n intrauterine device, hormonal barrier method of birth control; abstinence; tubal\n ligation or vasectomy) prior to study entry and for four months after treatment.\n Should a women become pregnant or suspect she is pregnant while she is participating\n in this study, she should inform her treating physician immediately.\n 11. Participants must have organ and marrow function as defined below:\n 1. Leukocytes > 3,000/mcL\n 2. Absolute neutrophil count > 1,500/mcL\n 3. Platelets > 100,000/mcL\n 4. Hemoglobin > 9.0 g/dL\n 5. Total bilirubin within normal institutional limits except in participants with\n Gilbert's Syndrome who must have a total bilirubin < 3.0 mg/dL.\n 6. Serum AST (SGOT)/ALT (SGPT) < 2.5 x ULN\n 7. Calculated creatinine clearance (CrCl) >50 mL/min/1.73 m2for participants with\n creatinine levels above institutional normal (by the Chronic Kidney Disease\n Epidemiology Collaboration (CKD-EPI) equation).\n 8. INR or a PTT \u22641.5 X ULN unless the subject is receiving anticoagulant therapy.\n Subjects on anticoagulant therapy must have a PT or PTT within therapeutic range\n and no history of severe hemorrhage.\n 12. Serology:\n - HIV antibody negative\n - Hepatitis B antigen negative\n - Hepatitis C antibody negative or HCV RNC negative (i.e., no current HCV\n infection)\n 13. More than four weeks must have elapsed since any prior systemic therapy or\n radiotherapy at the time the patient receives the KK-LC-1 TCR T cells. Adverse events\n from prior therapy must have resolved to\u2264 grade 1 according to CTCAE Version 5 or have\n demonstrated clinical stability and meet the eligibility criteria for the protocol.\n 14. Oxygen saturation \u2265 92% on room air.\n 15. Left ventricular ejection fraction \u226545% by echocardiogram or MUGA for patients 50\n years of age or older.", "output": {"inclusion_biomarker": [["KK-LC-1 expression", "HLA-A*01:01"]], "exclusion_biomarker": []}}
{"input": "Chemotherapy is an important means to prolong the survival time of advanced breast cancer. As\n a new type of microtubule inhibitor, eribulin has a unique mechanism of action. Compared with\n single drug chemotherapy, it can improve the overall survival time of 2.5 months, increase\n the clinical benefit rate by 5 times, and the tolerance of eribulin is good. Therefore, the\n guidelines at home and abroad recommend eribulin for the rescue of advanced breast cancer.\n However, up to now, there is no large sample data on the efficacy of eribulin combined with\n anti HER2 targeted therapy in HER2 + metastatic breast cancer, and the efficacy of combined\n immunotherapy in triple negative metastatic breast cancer. Moreover, as a newly marketed\n chemotherapy drug in China, the efficacy and safety data of eribulin in Chinese population\n are relatively lacking. Therefore, we plan to include different types and line numbers of\n advanced breast cancer patients based on the Chinese population through real-world research,\n and receive the treatment regimen containing eribulin respectively. In HR + / her2-mbc, we\n use eribulin monotherapy; in HER2 + MBC, we use eribulin + anti HER2 targeted therapy; in\n TNBC, we use eribulin + immunotherapy / chemotherapy, The efficacy and safety of eribulin\n were evaluated.\n ;NA;\n Inclusion Criteria:\n 1. Adult female patients (aged 18-80 years, including 18 and 80 years) with metastatic\n breast cancer confirmed by pathology or imaging are not suitable for surgical\n resection or radiotherapy for the purpose of cure;\n 2. The starting time of eribulin treatment was between January 2021 and December 2021;\n 3. They received no more than 2-line chemotherapy in the past;\n 4. In HR + / her2-mbc, patients were treated with eribulin monotherapy; in HER2 + MBC,\n patients were treated with eribulin + anti HER2 targeted therapy; in TNBC, patients\n were treated with eribulin + immunotherapy / chemotherapy; in patients with HER2 +\n MBC, patients were treated with eribulin + immunotherapy /chemotherapy;\n Exclusion Criteria:\n 1. Patients without pathological diagnosis;\n 2. Patients with central nervous system metastasis;\n 3. She has received more than two chemotherapy regimens for metastatic breast cancer;\n 4. Participating in any intervention drug clinical trials.\n 5. Those who have been known to have allergic history to the components of this regimen;\n 6. The patient, the patient, or the person with serious harm to the safety of the study.\n 7. Any other situation in which the researcher considers that the patient is not suitable\n for the study may interfere with the concomitant diseases or conditions involved in\n the study, or there are any serious medical barriers that may affect the safety of the\n subjects (e.g., uncontrollable heart disease, hypertension, active or uncontrollable\n infection, active hepatitis B virus infection)", "output": {"inclusion_biomarker": [["HR positive", "HER2 negative"], ["HER2 positive"]], "exclusion_biomarker": []}}
{"input": "The purpose of this study is to further evaluate the efficacy and safety of niraparib in\n patients with locally advanced or metastatic solid tumors and a pathogenic or likely\n pathogenic tumor PALB2 (tPALB2) mutation.\n ;NA;\n Inclusion Criteria:\n - Participants must be at least 18 years of age or older.\n - Participants must have a histologically or cytologically confirmed diagnosis of\n locally advanced or metastatic solid tumor(s).\n - Participants must have tested positive for a pathogenic or likely pathogenic tPALB2\n gene mutation using a CLIA-certified laboratory as described in the Next-Generation\n Sequencing (NGS) Laboratory Manual.\n - Participants who have stable and asymptomatic Central Nervous System (CNS) disease\n must be receiving a stable (for at least 7 days) or decreasing corticosteroid dose at\n the time of study entry.\n - Participants must submit fresh or archived (collected within 24 months of enrollment)\n Formalin-Fixed Paraffin-Embedded (FFPE) tumor sample to the central laboratory for\n post-enrollment confirmation of tPALB2 status.\n - Participants must have received all standard therapies appropriate for their tumor\n type and stage of disease or, in the opinion of the Investigator, the patient would be\n unlikely to tolerate or derive clinically meaningful benefit from appropriate standard\n of care therapy, or the participant has no satisfactory alternative treatments.\n Exclusion Criteria:\n - Participants have other active concomitant malignancy that warrants systemic,\n biologic, or hormonal therapy.\n - Participants who have ovarian or prostate cancer.\n - Participants who have variants of undetermined significance (VUS), but not pathogenic\n variants of PALB2, at the time of screening.\n - Participants who relapsed while receiving platinum based therapy in the\n adjuvant/curative setting.\n - Participants progressing within 14-18 weeks while receiving platinum based therapy in\n the metastatic setting.\n - Participants who have received Poly (ADP-ribose) polymerase (PARP) inhibitor(s) in\n prior lines of treatment.\n - Participants with leptomeningeal disease, carcinomatous meningitis, symptomatic brain\n metastases, or radiologic signs of CNS hemorrhage.\n - Participants with germline or somatic BRCA1 or BRCA2 mutations.\n - Participant has systolic blood pressure (BP) over 140 mmHg or diastolic BP over 90\n mmHg, despite optimal medical therapy.\n - Participants have previously or are currently participating in a treatment study of an\n investigational agent within 3 weeks of the first dose of therapy preceding the study.\n - Participants have received prior systemic cytotoxic chemotherapy, biological therapy,\n or hormonal therapy for cancer, or received radiation therapy within 3 weeks of the\n first dose therapy preceding the study.", "output": {"inclusion_biomarker": [["PALB2 mutatuon"]], "exclusion_biomarker": [["PALB2 variants of undetermined significance"], ["BRCA1 mutation (germline)"], ["BRCA1 mutation (somatic)"], ["BRCA2 mutation (germline)"], ["BRCA2 mutation (somatic)"]]}}
{"input": "This is a Phase 1/2a, first-in-human, open-label study of JAB-8263, this study has two parts:\n solid tumor dose escalation and expansion study and hematology tumor dose escalation and\n expansion study.\n These two parts will determine the maximum tolerated dose (MTD), recommended Phase 2 dose\n (RP2D) and assess the DLT of JAB-8263 in treatment with patients with advanced solid tumors\n and hematology tumors separately. 30 subjects each will be enrolled.\n ;\n ;\n Inclusion Criteria:\n - Subjects must meet all the following criteria in order to be included in the research\n study:\n 1. Subject must be \u226518 years-of-age at the time of signature of the informed consent\n form (ICF).\n 2. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.\n 3. Subjects with histologically or cytologically confirmed advanced solid tumors\n which have progressed despite standard therapy(ies), or are intolerant to\n standard therapy(ies), or have a tumor for which no standard therapy(ies) exists.\n 4. Subjects with recurrent/refractory AML according to WHO 2016\n 5. Subjects with life expectancy \u22653 months.\n 6. Patients with solid tumor must have at least one measurable lesion as defined by\n RECIST v1.1.\n 7. Patients who have sufficient baseline organ function.\n Exclusion Criteria:\n 1. History (\u22643 years) of cancer that is histologically distinct from the cancer under\n study.\n 2. Known serious allergy to investigational drug or excipients\n 3. Active brain or spinal metastases\n 4. History of pericarditis or Grade \u22652 pericardial effusion\n 5. History of interstitial lung disease.\n 6. History of Grade \u22652 active infections within 2 weeks\n 7. Known human immunodeficiency virus (HIV) infection\n 8. Seropositive for hepatitis B virus (HBV)\n 9. Seropositive for hepatitis C virus (HCV), or HCV-RNA viral levels are not detectable.\n 10. Any severe and/or uncontrolled medical conditions\n 11. History of myocardial infarction, unstable angina pectoris, coronary artery bypass\n graft, or cerebrovascular accident\n 12. Impaired cardiac function or clinically significant cardiac diseases\n 13. QTcF >470 msec at screening\n 14. History of medically significant thromboembolic events or bleeding diathesis\n 15. Unresolved Grade >1 toxicity\n 16. History of malignant biliary obstruction\n 17. Pregnant or breast-feeding", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
{"input": "This is a single center, Phase I dose finding study of HCW9218 for the treatment of\n advanced/metastatic solid tumor cancer (except pancreatic and primary brain cancers). HCW9218\n is a novel bi-functional fusion protein complex administered by subcutaneous (SC) injection.\n It is comprised of a soluble fusion of two human TGF\u03b2RII domains, human tissue factor, and\n human IL-15, and a second soluble fusion of two human TGF\u03b2RII domains and a sushi domain of\n human IL-15R\u03b1. HCW9218 activates IL-15R signaling on effector immune cells and the dimeric\n TGF\u03b2RII functions as a \"trap\" for all three human TGF-\u03b2 isoforms.\n ;NA;\n Inclusion Criteria:\n - Histologically or cytologically confirmed advanced/metastatic solid tumor cancer\n (except pancreatic and primary brain cancers), has failed at least 2 prior lines of\n therapy given either in the recurrent or metastatic setting and must be refractory to\n or intolerant of existing therapy(ies) known to provide clinical benefit for their\n condition.\n - Measurable disease per RECIST v 1.1.\n - Acute effects of any prior therapy must have resolved to baseline or Grade \u22641 NCI\n CTCAE v5 except for AEs not constituting a safety risk by enrolling Investigator\n judgment.\n - Age 18 years or older at the time of consent.\n - ECOG Performance Status 0 or 1.\n - Evidence of adequate organ function within 14 days prior to enrollment as defined in\n Section 4.1.6.\n - Adequate pulmonary function with PFTs >50% FEV1 if symptomatic or known impairment.\n - Sexually active persons of child-bearing potential or with partners of childbearing\n potential must agree to use a highly effective form of contraception (refer to Section\n 4.1.10 for acceptable methods) for at least 28 days after the last dose of HCW9218.\n - Provides voluntary written consent prior to the performance of any research related\n activity.\n Exclusion Criteria:\n - Pregnant or breastfeeding.\n - History of clinically significant vascular disease, including any of the following\n within 6 months prior to start of study treatment: MI or unstable angina, percutaneous\n coronary intervention, bypass grafting, ventricular arrhythmia requiring medication,\n stroke or transient ischemic attack, symptomatic peripheral arterial disease.\n - Marked baseline prolongation of QT/QTc interval (e.g., demonstration of a QTc interval\n greater or equal to 470 milliseconds by Fridericia's correction).\n - Known or suspected untreated CNS metastases.\n - Anti-cancer treatment including surgery, radiotherapy, chemotherapy, other\n immunotherapy, or investigational therapy within 14 days before treatment start.\n - Other prior malignancy except for the following: adequately treated basal cell or\n squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II\n cancer from which the subject is currently in complete remission, or any other cancer\n from which the subject has been disease-free for 3 years after surgical treatment.\n - Known hypersensitivity or history of allergic reactions attributed to compounds of\n similar chemical or biologic composition to the agents used in the study.\n - Prior therapy with TGF-\u03b2 antagonist, IL-15 or analogs.\n - Concurrent use of St. John's wort and and/or other herbal CYP modulators within 7 days\n of Day 1. Must agree to not use during study treatment through the end of treatment\n visit to be eligible.\n - Known autoimmune disease requiring active treatment. Persons with a condition\n requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone\n equivalent) or other immunosuppressive medications within 14 days of enrollment.\n Inhaled or topical steroids, and adrenal replacement steroid doses \u2264 10 mg daily\n prednisone equivalent, are permitted in the absence of active autoimmune disease.\n - Active systemic infection requiring parenteral antibiotic therapy. All prior\n infections must have resolved following optimal therapy.\n - Prior organ allograft or allogeneic transplantation.\n - Known HIV-positive or AIDS.\n - Psychiatric illness/social situations that would limit compliance with study\n requirements.\n - Other illness or a medical issue that in the opinion of the Investigator would exclude\n the subject from participating in this study", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
{"input": "This research study is studying a targeted therapy as a possible treatment for Non-Small Cell\n Lung Cancer (NSCLC) with an EGFR mutation.\n The names of the study drug involved in this study is:\n - Osimertinib (Tagrisso)\n ;\n ;\n Inclusion Criteria:\n - Participants must have histologically confirmed stage IV NSCLC (per AJCC 7th edition)\n with either the L858R or exon 19 deletion activating EGFR mutation as identified in a\n CLIA-approved laboratory from tumor tissue.\n --Note: recurrent stage IV disease initially diagnosed at an earlier stage is\n considered eligible, provided prior treatment criteria is met.\n - Participants must have measurable disease at baseline, defined as at least one lesion\n that can be accurately measured in at least one dimension (longest diameter to be\n recorded for non-nodal lesions and short axis for nodal lesions) as \u226520 mm with\n conventional techniques or as \u226510 mm with spiral CT scan, MRI, or calipers by clinical\n exam.\n - Participants must be aged \u2265 18 years\n - Participants must have an ECOG performance status of 0-1 (Appendix A)\n - Participants must have normal organ and marrow function as defined below:\n - absolute neutrophil count \u22651,500/mcL\n - platelets \u2265100,000/mcL\n - hemoglobin >9.0 g/dL\n - total bilirubin < 1.5 times the ULN if no liver metastases or < 3 times the ULN\n in the presence of documented Gilbert's syndrome (unconjugated\n hyperbilirubinemia) or liver metastases\n - AST(SGOT)/ALT(SGPT) <2.5 \u00d7 institutional upper limit of normal or <5 times the\n ULN in the presence of liver metastases\n - creatinine \u2264 1.5 x institutional upper limit of normal\n --- OR\n - creatinine clearance \u226550 mL/min as determined by the Cockcroft-Gault formula.\n - Note: For participants entering study after starting commercial osimertinib,\n elevations in hepatic transaminases (AST/ALT) and/or total bilirubin < grade 2 at\n study entry are acceptable (see protocol Table 2).\n - Participants must have biopsy tissue at time of diagnosis available and sufficient for\n targeted next-generation sequencing. The sequencing can be performed at a commercial\n vendor such as Foundation Medicine. The testing does not have to be completed prior to\n study enrollment. If the specimen is insufficient a repeat biopsy will need to be\n performed.\n --Note: Cytology specimen may be acceptable for baseline NGS if tumor cellular content\n is sufficient and following PI approval. If there is no cytology specimen or tissue\n sample available for NGS, plasma-based NGS may be acceptable for enrollment following\n discussion with PI.\n - For participants entering study after starting commercial osimertinib: a tissue sample\n from the time of diagnosis must be available and sufficient for NGS testing.\n Participants who have had commercial tumor NGS testing performed on their\n pre-osimertinib treated specimen do not need NGS repeated as part of this study.\n - Participants must be willing to undergo a repeat tumor biopsy during study treatment\n between cycles 4 and 8 (if considered medically safe) and at the time of disease\n progression.\n - Participants must be \u22652 weeks since any major surgery (excluding vascular access\n placement, mediastinoscopy, or biopsies performed by an interventional service)\n - Male patients should be asked to use barrier contraceptives (i.e., by use of condoms)\n during sex with all partners who are women of child bearing potential, including\n pregnant women, during the trial and for a washout period of 4 months. Male patients\n should avoid procreation for 4 months after completion of trial treatment. Patients\n should refrain from donating sperm from the start of dosing until 4 months after\n discontinuing study treatment.\n - Female patients (women of child-bearing potential): Willing to use adequate\n contraception (barrier or abstinence) at least 2 weeks before receiving any study\n medication, while on treatment with study drug, and for 6 weeks after finishing\n treatment.\n - Female patients: Must not be pregnant or breast-feeding. Women of child-bearing\n potential must have a negative pregnancy test (urine or serum) prior to start of\n dosing or must have evidence of non-child-bearing potential by fulfilling one of the\n following criteria at screening:\n - a) Post-menopausal defined as aged more than 50 years and amenorrheic for at\n least 12 months following cessation of all exogenous hormonal treatments\n - b) Women under 50 years are considered postmenopausal if they have been\n amenorrheic for 12 months or more following cessation of exogenous hormonal\n treatments and with LH and FSH levels in the post-menopausal range for the\n institution.\n - c) Documentation of irreversible surgical sterilization by hysterectomy,\n bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation.\n - Ability to understand and the willingness to sign a written informed consent document.\n - Subjects may enter the study even if they have started their treatment using\n commercial osimertinib. Subjects may enter the study anytime during the first 3 months\n of receiving commercial osimertinib therapy (up to 84 days of commercial osimertinib\n before entering the study). In order to enter the study after starting commercial\n osimertinib, subjects must meet all eligibility criteria listed above, have baseline\n and follow up imaging available for review for response assessment, and must not have\n developed disease progression during the first 3 months of commercial osimertinib\n therapy.\n Exclusion Criteria:\n - Subjects should not enter the study if any of the following exclusion criteria are\n fulfilled:\n - Prior or ongoing treatment with any of the following:\n - EGFR targeted therapy (TKI or antibody) or any other targeted therapies targeting\n the ERBB family except for subjects receiving first line osimertinib during the\n first three months of therapy.\n - Any cytotoxic chemotherapy, investigational agents, immunotherapy or anticancer\n drugs for the treatment of metastatic NSCLC\n - Note: Patients who have completed adjuvant or neo-adjuvant chemotherapy > 6\n months ago are considered treatment na\u00efve\n - Prior radiotherapy, including CNS radiation, within 2 weeks of the first dose of study\n treatment.\n - Uncontrolled central nervous system (CNS) disease, including parenchymal brain\n metastases, leptomeningeal disease, or spinal cord compression. Patients with\n asymptomatic untreated brain metastases are eligible. Patients with treated CNS\n disease will be allowed to enroll provided they have asymptomatic clinically confirmed\n stable disease with \u22652 weeks since definitive CNS therapy (radiation or surgery) and\n \u22652 weeks without systemic steroids. Patients may undergo either whole brain radiation\n or stereotactic radiosurgery prior to study entry.\n - History of allergic reactions attributed to compounds, or any of its excipients, of\n similar chemical or biologic composition to osimertinib.\n - Patients currently receiving and unable to stop using medications or herbal\n supplements known to be potent inhibitors or inducers of CYP3A4. The full list of\n medications that would make a patient ineligible are provided in Appendix B, along\n with indicated washout times.\n - Any unresolved toxicities from prior therapy, including commercial osimertinib,\n greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the\n time of starting study treatment.\n - Malignancies within the past 3 years excluding adequately treated basal or squamous\n cell carcinomas of the skin without local or distant metastases.\n - Refractory nausea and vomiting, chronic gastrointestinal diseases, previous\n significant bowel resection, or any process that compromises the ability to swallow or\n absorb oral medication\n - Significant medical history or unstable medical comorbidities, including:\n - heart disease including congestive heart failure (NYHA Grade II or greater);\n unstable angina; prior myocardial infarction (NSTEMI or STEMI) within 6 months\n prior to study enrollment; hypertension with a systolic blood pressure of >150 mm\n Hg or diastolic blood pressure of >100 mm Hg while on antihypertensive medication\n - any clinically important abnormalities in rhythm, conduction or morphology of\n resting ECG, e.g. complete left bundle branch block, third-degree heart block,\n second-degree heart block, PR interval >250msec, have normal QT interval on ECG\n evaluation QT corrected Fridericia (QTcF) of \u2264 450 ms in males or \u2264 470 ms in\n females\n - any factors that increase the risk of QTc prolongation or risk of arrhythmic\n events such as heart failure, hypokalemia, congenital long QT syndrome, family\n history of long QT syndrome or unexplained sudden death under 40 years of age in\n first degree relatives, or any concomitant medication known to the prolong the QT\n interval and cause Torsades de Pointes and listed in Appendix B that a patient is\n unable to stop\n - past medical history of interstitial lung disease, drug-induced interstitial lung\n disease, radiation pneumonitis which required steroid treatment, or any evidence\n of clinically active interstitial lung disease\n - active bleeding diatheses, which in the investigator's opinion makes it\n undesirable for the patient to participate in the trial or which would jeopardize\n compliance with the protocol\n - known active infection or ongoing antiviral medication for viral infections\n including hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).\n Screening for chronic conditions is not required. HIV-positive participants on\n combination antiretroviral therapy are ineligible because of the potential for\n pharmacokinetic interactions with osimertinib.\n - cardiac ejection fraction of < 45%\n - Any evidence of severe or uncontrolled systemic diseases, including active\n bleeding diatheses, which in the investigator's opinion makes it undesirable for\n the patient to participate in the trial or which would jeopardize compliance with\n the protocol\n - Known to be T790M+ (on pre-treatment tumor or plasma) or known germline T790M. Note:\n testing is not required for study entry.\n - Males and females of reproductive potential who are not using an effective method of\n birth control and females who are pregnant or breastfeeding or have a positive (urine\n or serum) pregnancy test prior to study entry. Women of child-bearing potential must\n have a negative pregnancy test prior to start of dosing.\n - Pregnant women are excluded from this study because the effects of osimertinib on the\n development of the fetus are unknown, and there is potential for teratogenic or\n abortifacient effects. Because there is an unknown but potential risk for adverse\n events in nursing infants secondary to treatment of the mother with osimertinib,\n breastfeeding should be discontinued if the mother is treated with osimertinib.", "output": {"inclusion_biomarker": [["EGFR mutation"], ["EGFR L858R"], ["EGFR exon 19 deletion"]], "exclusion_biomarker": [["EGFR T790M"], ["EGFR T790M (germline)"]]}}
{"input": "The aim of this trial is to identify the maximum tolerated dose (MTD)/recommended phase II\n dose (RP2D), to define pharmacokinetic (PK) parameters and the preliminary efficacy of a\n continuous treatment with EGF816 and trametinib in locally advanced or metastatic (stage IIIB\n or IV) lung cancer patients with activating mutations in the epithelial growth factor\n receptor (EGFR).\n ;\n ;\n Inclusion Criteria:\n 1. Written informed consent must have been obtained prior to any screening procedures.\n 2. Patients (male or female) \u2265 18 years of age.\n 3. Histologically documented, locally advanced or recurrent (stage IIIB who are not\n eligible for combined modality treatment) or metastatic (stage IV) non-small cell lung\n cancer.\n 4. Presence of at least one measurable lesion according to RECIST v.1.1.\n 5. ECOG performance status \u2264 2\n 6. Patients must have NSCLC harbouring EGFR p.L858R or EGFR del19 as assessed by local\n testing.\n 7. Patients must be EGFR TKI treatment na\u00efve (prior chemotherapy treatment is allowed) or\n must have progressed while on continuous treatment with a first- or second-generation\n EGFR TKI (EGFR p.T790M-negative or -positive) or must have progressed while on\n continuous treatment with osimertinib (EGFR p.T790M-negative or -positive)\n 8. In patients who have received no prior EGFR TKI treatment, an archival biopsy sample,\n defined as a sample being obtained prior to any anti-cancer treatment is mandatory. If\n an archival biopsy fulfilling this criterion is not available, patients must be\n suitable and willing to undergo baseline biopsy according to the local institution's\n guidelines (newly obtained biopsy).\n 9. In patients who have received prior EGFR TKI treatment, an archival biopsy sample,\n defined as a sample being obtained after or during progression upon the last\n anti-cancer treatment is mandatory. No consecutive line of treatment must have been\n given after collection of the rebiopsy and inclusion into this trial. If an archival\n rebiopsy fulfilling these criteria is not available, patients must be suitable and\n willing to undergo baseline biopsy according to the local institution's guidelines\n (newly obtained biopsy).\n 10. In patients who have received prior EGFR TKI treatment, EGFRp.T790M mutation status\n must have been assessed by local testing in the tumour sample fulfilling the\n requirements of inclusion criterion 9.\n 11. Patients who have received prior osimertinib treatment, may only be eligible if no\n standard treatment approach outside this trial is available or feasible (e.g.\n chemotherapy)\n 12. Patients who have progressed while on continuous treatment with a first- or\n second-generation EGFR inhibitor and whose tumour has been tested EGFR\n p.T790M-negative may only be eligible if no standard treatment approach outside this\n trial is available or feasible (e.g. chemotherapy).\n 13. In patients who have received prior EGFR TKI treatment, progression of disease\n according to RECIST v1.1 while on continuous treatment with an EGFR TKI (e.g.\n erlotinib, gefitinib, afatinib or osimertinib) must be documented.\n Exclusion Criteria:\n 1. History of allergic reactions or hypersensitivity to one of the study drugs or to any\n component of the study drugs\n 2. Prior treatment with any investigational agent known to inhibit EGFR (mutant or\n wild-type)\n 3. Prior treatment with any agent known to inhibit MEK/ERK or other mediators of RAS\n pathway.\n 4. Patients with high level MET amplification in the archival or newly obtained biopsy\n sample as determined by local testing. High-level MET amplification is defined as: a)\n a MET/CEN7 ratio \u22652.0 and/or b) an average MET gene copy number per cell of \u22656.0\n [modified Schildhaus et al., 2015].\n 5. Patients with EGFR mutations other than EGFR del19, p.L858R or p.T790M.\n 6. Patients with brain metastases. However, if radiation therapy and/or surgery has been\n completed at least 4 weeks prior to screening for the trial and evaluation by CT (with\n contrast enhancement) or MRI at study baseline demonstrates the disease to be stable\n and if the patient remains asymptomatic and off steroids, then patients with brain\n metastases may be enrolled.\n 7. Patients with presence or history of carcinomatous meningitis.\n 8. Any acute or chronic medical, mental or psychological condition, which in the opinion\n of the investigator would not permit the patient to participate or complete the study\n or understand the patient information\n 9. History of hepatitis B (HBV) or hepatitis C (HCV) or positive result in mandatory\n testing for acute or chronic hepatitis B or hepatitis C\n 10. Known HIV infection or history of HIV infection independent from the cellular immune\n status\n 11. Patients who receive any continuous, long term immunosuppressive treatment, including\n long term treatment with steroids at immunosuppressive doses at the time of study\n entry\n 12. Patients who underwent bone marrow or solid organ transplantation, including patients\n who do not receive any immunosuppressive treatment.\n 13. Presence or history of any other primary malignancy other than NSCLC within 5 years\n prior to enrolment into the trial. Except from this: Adequately treated basal or\n squamous cell carcinoma of the skin or any adequately treated in situ carcinoma\n 14. Any of the following within 6 months prior to first trial drug administration:\n Myocardial infarction (NSTEMI or STEMI), severe/unstable angina pectoris, symptomatic\n congestive heart failure (> NYHA II), uncontrolled hypertension, coronary/peripheral\n artery bypass graft, cerebrovascular accident or transient ischemic attack, atrial\n fibrillation of CTCAE Grade \u2265 2, ongoing cardiac dysrhythmias of CTCAE Grade \u2265 2,\n including corrected QTcF prolongation of > 480 ms,\n 15. Aortic valve stenosis with mean gradient \u2265 25 mmHg and aortic valve area of \u2264 1.5 cm2\n 16. Any other cardiac valve abnormality of more than mild degree/stage\n 17. Left ventricular ejection fraction (LVEF) of < 50 %\n 18. History of congenital long QT-syndrome or Torsades de Pointes\n 19. History of retinal vein occlusion (RVO) or retinal pigment epithelial detachment\n (RPED)\n 20. Unable or unwilling to swallow tablets or capsules\n 21. Patients with impaired gastrointestinal function or gastrointestinal disease that may\n significantly alter the absorption of EGF816 (e.g., ulcerative diseases, uncontrolled\n nausea, vomiting diarrhoea, or malabsorption syndromes\n 22. Patients have received anticancer treatment within the following time frames prior to\n the first dose of study treatment:\n 1. Conventional cytotoxic chemotherapy: \u2264 4 weeks (\u2264 6 weeks for nitrosoureas,\n mitomycin-C and suramin)\n 2. Biological therapy (e.g., antibodies, excluding PD-1 or PD-L1 antibodies): \u2264 4\n weeks\n 3. PD-1/PD-L1 antibodies (e.g., nivolumab, pembrolizumab): \u2264 5 half-times\n 4. Non-cytotoxic anti-cancer therapeutic (e.g., tyrosine kinase inhibitors): \u2264 5\n half-times or \u2264 1 weeks (whichever is longer)\n 5. Other investigational agent: \u2264 4 weeks\n 6. Radiation therapy (excluding palliative radiation, e.g., of bone metastases): \u2264 4\n weeks\n 7. Major surgery (excluding minor surgical interventions, e.g., vascular device\n implantation): \u2264 2 weeks\n 23. Laboratory values as listed below, that cannot be corrected to normal limits within\n screening :\n 1. Absolute Neutrophil Count (ANC) < 1.5 x 10^9/L\n 2. Haemoglobin (Hb) < 9 g/dL\n 3. Platelets (PLT) < 100 x 10^9/L\n 4. Total bilirubin > 1.5 x upper limit of normal (ULN). For patients with confirmed\n Gilbert's disease total bilirubin > 2.5 x ULN\n 5. AST and/or ALT > 3 x ULN\n 6. AST and/or ALT > 5 x ULN in patients with liver involvement\n 7. Serum creatinine > 1.5 x ULN\n 8. Measured or calculated creatinine clearance \u2264 45 mL/min\n 9. Serum amylase and/or lipase CTCAE Grade > 2\n 10. Potassium, magnesium, phosphorus, total calcium (corrected from serum albumin) >\n ULN\n 24. Patients receiving treatment with any medication that are known to be\n 1. Strong inhibitors or inducers of CYP3A4/5\n 2. Substrates of CYP2D6 with narrow therapeutic index\n 3. and that cannot be discontinued at least 7 days prior to the first dose of the\n study drugs.\n 4. For further information please refer to Section 11.7 and the Concomitant\n Medication Manual.\n 25. Patients with a history of or presence of interstitial lung disease or interstitial\n pneumonitis, including clinically significant radiation pneumonitis\n 26. Pregnancy or breastfeeding/nursing women\n 27. Women of child-bearing potential (for definition see Section 8.3.3) unless they use\n highly effective methods of contraception during treatment and for four months after\n withdrawal of study treatment (for methods of contraception see Section 8.3.4)\n 28. Sexually active males unless they use a condom during intercourse for the time of\n study treatment and for four months after the withdrawal of study treatment.", "output": {"inclusion_biomarker": [["EGFR p.L858R"], ["EGFR del19"], ["EGFR p.T790M"]], "exclusion_biomarker": [["MET amplification"], ["EGFR mutation"]]}}
{"input": "This study will evaluates the safety and efficacy of Chimeric antigen receptor T cells\n (CAR-T) in treating central nervous system B-cell acute lymphocytic leukemia.\n ;\n ;\n Inclusion Criteria:\n 1. Patients with CD19 positive central nervous system B-cell acute lymphocytic leukemia\n 2. ALT/ AST \u300a 3x normal\n 3. Creatinine \u300a 3x normal\n 4. Age:10-60.\n 5. Signed informed consent\n Exclusion Criteria:\n 1. Active hepatitis B , hepatitis C or HIV infection\n 2. Uncontrolled active infection\n 3. Pregnancy or breast-feeding women\n 4. Survival less than four weeks", "output": {"inclusion_biomarker": [["CD19 positive"]], "exclusion_biomarker": []}}
{"input": "The purpose of this study is to find out what effects, a drug called ado-trastuzumab\n emtansine has on the patient and their cancer which is thought to be controlled by the\n abnormal HER2 gene.\n ;NA;\n Inclusion Criteria:\n - Adults who are \u226518 years old.\n - Pathologically confirmed advanced solid tumor cancers\n - For Cohort 1, documented activating HER2 mutation in lung cancer by CLIA laboratory,\n specifically exon 20 insYVMA (Y772_A775dup), insGSP (G778_P780dup), insTGT\n (G776delinsVC), single base pair substitutions L755A, L755S, V777L, V659E, S310F, or\n another HER2 mutation approved by the Principal Investigator\n - For Cohorts 2, 3, 4, 5, 6 documented HER2 amplification identified through next\n generation sequencing by MSK-IMPACT or at another Clinical Laboratory Improvement\n Amendments (CLIA) laboratory, or documented HER2 amplification by in-situ\n hybridization (ISH) with HER2/CEP17 ratio \u22652.0 at a CLIA laboratory. Patients with\n HER2 amplification identified by another method or criteria must be approved by the\n Principal Investigator and may enroll in the \"Other\" Cohort 4.\n - Measurable or evaluable indicator lesion(s) as defined by RECIST v1.1. Patients\n without RECIST measurable disease will be eligible for enrollment to \"Other\" cohort\n provided their disease can be evaluated using another accepted response criteria (e.g.\n Gynecologic Cancer InterGroup (GCIG) CA125 Response Criteria, modified PET Response\n Criteria in Solid Tumors (PERCIST)). Patients with salivary gland cancers (Cohort 5)\n may be eligible on the basis of evaluable disease on modified PET.\n - Karnofsky Performance Status 70% or above.\n - Left ventricular ejection fraction (LVEF) \u226550% measured by echocardiogram (ECHO) or\n multiple gated acquisition scan (MUGA).\n - Negative \u03b2-human chorionic gonadotropin (hCG) pregnancy test within 2 weeks before\n enrollment for premenopausal women of reproductive capacity and for women less than 12\n months after menopause. Pregnancy screening will be conducted for women up to the age\n of 50 years per institutional standard.\n - Women of childbearing potential must agree to use of a highly effective method of\n contraception. Effective contraception is required during treatment and for 7 months\n following the last dose for female participants of reproductive potential and during\n treatment and for 4 months following the last dose for male participants with female\n sexual partners of reproductive potential. Male participants should also refrain from\n donating sperm during treatment and for 4 months following the last dose.\n - Absolute neutrophil count \u2265 1,000/\u00b5L within 30 days prior to C1D1\n - Platelet count \u2265 100,000/\u00b5L within 30 days prior to C1D1\n - Total bilirubin \u2264 1.5 x institutional upper limit of normal (ULN), in case of\n Gilbert's syndrome, \u2264 2x ULN within 30 days prior to C1D1\n - Aspartate aminotransferase and/or alanine aminotransferase \u2264 3 x ULN (\u2264 5 x ULN if\n liver metastases are present) within 30 days prior to C1D1\n - Provide written, informed consent to participate in the study and follow the study\n procedures\n Exclusion Criteria:\n - Prior therapy resulting in cumulative epirubicin dose \u2265 900mg/m2 or cumulative\n doxorubicin dose \u2265 500mg/m2 or equivalent dose of another anthracycline.\n - Prior therapy with ado-trastuzumab emtansine (patients who had prior trastuzumab or\n other HER2 targeted agents are eligible).\n - Symptomatic congestive heart failure (New York Heart Association Classification\n II-IV).\n - Myocardial infarction or unstable angina within 6 months of enrollment.\n - Unstable ventricular arrhythmia requiring treatment.\n - Grade 3 or worse peripheral neuropathy as defined by CTCAE v4.1.\n - Women who are pregnant or breast-feeding.\n - Known hypersensitivity to any component of ado-trastuzumab emtansine.\n - History of interstitial lung disease or pneumonitis.", "output": {"inclusion_biomarker": [["HER2 mutation"], ["HER2 exon 20 insYVMA"], ["HER2 exon 20 insGSP"], ["HER2 exon 20 insTGT"], ["HER2 L755A"], ["HER2 L755S"], ["HER2 V777L"], ["HER2 V659E"], ["HER2 S310F"], ["HER2 amplification"]], "exclusion_biomarker": []}}
{"input": "LVGN6051 is a humanized monoclonal antibody that specifically binds to CD137, and acts as an\n agonist against CD137.\n This first in human study of LVGN6051 is designed to establish the maximum tolerated dose\n (MTD) and/or the recommended dose for expansion (RDE) as well as the recommended Phase 2\n dose(s) (RP2D) of LVGN6051, both as a single agent (monotherapy) and in combination with a\n fixed dose of anti-PD-1 antibody (Pembrolizumab/MK-3475) in the treatment of advanced or\n metastatic malignancy.\n ;\n ;\n Inclusion Criteria:\n - Males or females aged \u2265 18 years.\n - Ability to understand and willingness to sign a written informed consent document.\n - Patients must have a histologically or cytologically confirmed metastatic or\n unresectable malignancy.\n - Estimated life expectancy, in the judgment of the Investigator, of at least 90 days.\n - Adequate bone marrow, liver, and renal functions.\n - Men and women of childbearing potential must agree to take highly effective\n contraceptive methods.\n - Patients should recover from all reversible AEs of previous anticancer therapies to\n baseline.\n - Patients infected with the HIV virus will be eligible if the disease is under control\n of effective therapy.\n Exclusion Criteria:\n - Receipt of systemic anticancer therapy including investigational agents or devices\n within 5 half-lives of the first dose of study treatment.\n - Previous radiotherapy within 14 days of the first dose of study treatment.\n - Known active CNS metastasis and/or carcinomatous meningitis.\n - Has received a live-virus vaccine within 30 days.\n - Has had a Grade \u2265 3 allergic reaction to treatment with a monoclonal antibody.\n - Abnormality of QT interval or syndrome.\n - Patients with history of Grade \u2265 3 immune-related AEs (irAEs) or irAE.\n - Patients who are receiving an immunologically-based treatment for any reason.\n - Treatment with systemic immune-stimulatory agents within 4 weeks prior to the first\n dose of study drug.\n - Active or chronic autoimmune disease that has required systemic treatment in the past\n 2 years or who are receiving systemic therapy for an autoimmune or inflammatory\n disease.\n - Has a clinically significant cardiac condition, including unstable angina, acute\n myocardial infarction within 6 months.\n - Has an active infection requiring intravenous (i.v.) anti-infectives within 14 days\n before the first dose of study treatment.\n - Current evidence or history of interstitial lung disease or active, noninfectious\n pneumonitis requiring treatment such as oral or intravenous glucocorticoids to assist\n with management.\n - Female patients who are pregnant or breastfeeding.\n - Any evidence of severe or uncontrolled systemic disease.\n - Any other disease or clinically significant abnormality in laboratory parameters.\n - Has previously had a stem cell or bone marrow or solid organ transplant.", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
{"input": "This is a US, multicenter, open-label expanded access program to provide access to\n avapritinib until such time that avapritinib becomes available through other mechanisms or\n the Sponsor chooses to discontinue the program.\n ;NA;\n Inclusion Criteria:\n 1. Patient is \u2265 16 years of age.\n 2. Diagnosis of unresectable or metastatic GIST\n 3. The patient is not eligible for an ongoing study of avapritinib or cannot access an\n ongoing study of avapritinib.\n 4. Patient has received 3 or more TKI therapies including imatinib, or the patient has\n GIST that carries a mutation in exon 18 of the PDGFRA gene (such as D842V).\n 5. The patient has adequate vital organ function, including heart, lungs, liver, kidneys,\n bone marrow and endocrine, and is expected to tolerate therapy with a TKI.\n 6. Patient or legal guardian, if permitted by local regulatory authorities, provides\n informed consent.\n Exclusion Criteria:\n 1. Patients who have poor organ function as defined by one or more of the following\n laboratory parameters;\n 1. Total bilirubin > 2 \u00d7 ULN; or > 3 \u00d7 ULN in the presence of Gilbert's Disease;\n 2. Platelet count < 75 \u00d7 10^9/L.\n 2. Patient requires therapy with a concomitant medication that is a strong inhibitor or\n strong inducer of cytochrome P450 (CYP) 3A4\n 3. Patient has had a major surgical procedure (minor surgical procedures such as central\n venous catheter placement, tumor needle biopsy, and feeding tube placement are not\n considered major surgical procedures) within 14 days of the first dose of avapritinib.\n 4. Patient has a history of a cerebrovascular accident or transient ischemic attacks\n within 1 year prior to the first dose of program drug.\n 5. Patient has a known risk of intracranial bleeding, such as a brain aneurysm or history\n of subdural or subarachnoid bleeding.\n 6. Women who are unwilling, if not postmenopausal or surgically sterile, to abstain from\n sexual intercourse or employ highly effective contraception from the time of\n randomization and for at least 30 days after the last dose of avapritinib. Men who are\n unwilling, if not surgically sterile, to abstain from sexual intercourse or employ\n highly effective contraception from the time of first dose and for at least 90 days\n after the last dose of avapritinib.\n 7. Women who are pregnant, as documented by a serum beta human chorionic gonadotropin\n (\u03b2-hCG) pregnancy test consistent with pregnancy, obtained within 7 days before the\n randomization. Females with \u03b2-hCG values that are within the range for pregnancy but\n are not pregnant (false-positives) may be enrolled with written consent of the\n Sponsor, after pregnancy has been ruled out. Females of non- childbearing potential\n (postmenopausal for more than 1 year; bilateral tubal ligation; bilateral\n oophorectomy; hysterectomy) do not require a serum \u03b2-hCG test.\n 8. Women who are breast feeding.", "output": {"inclusion_biomarker": [["PDGFRA exon 18 mutation"], ["PDGFRA D842V"]], "exclusion_biomarker": []}}
{"input": "This is a Phase 2 open-label, multicenter study to evaluate the clinical activity, safety,\n pharmacokinetics (PK), and biomarker profile of ZN-c3 in subjects with Cyclin E driven\n High-Grade Serous Ovarian, Fallopian Tube, Or Primary Peritoneal Cancer\n ;NA;\n Inclusion Criteria:\n 1. Age \u226518 years at the time of informed consent.\n 2. Histologically or cytologically confirmed recurrent, high-grade serous ovarian,\n fallopian tube, or primary peritoneal cancer with copy number amplification in the\n CCNE1 gene\n 3. Prior therapy:\n 1. Documented progressive disease \u22646 months\n 2. One to 3 prior lines or regimens are allowed\n 3. Prior bevacizumab treatment is required\n 4. Subjects must have at least one measurable lesion as defined by RECIST Guideline\n Version 1.1.\n 5. Performance Status: Eastern Cooperative Oncology Group (ECOG) score of \u22641.\n 6. Adequate hematologic and organ function\n 7. Females of childbearing potential and male subjects must agree to use an effective\n method of contraception prior to the first dose and for 6 months after the last dose\n of ZN-c3. Male subjects must agree to use an effective method of contraception prior\n to the first dose and for at least 3 months after the last dose of ZN-c3.\n 8. Willingness and ability to comply with scheduled visits, treatment plan, laboratory\n tests, and other study procedures.\n Exclusion Criteria:\n 1. 1. Any of the following treatment interventions within the specified time frame prior\n to C1D1:\n 1. Major surgery within 28 days (any surgical incision should be fully healed prior\n to study drug administration);\n 2. Any chemotherapy or targeted tumor therapy within 14 days or 5 half-lives\n (whichever is shorter);\n 3. Radiation therapy within 21 days; however, if the radiation portal covered \u22645% of\n the bone marrow, the subject is eligible irrespective of the end date of\n radiotherapy.\n 4. Autologous or allogeneic stem cell transplant within 3 months.\n 5. Current use of any other investigational drug therapy <28 days or 5 half-lives\n (whichever is shorter).\n 6. Inability to discontinue treatment prescription or non-prescription drugs, or to\n discontinue consumption of food and herbal supplements, that are strong/ and\n moderate CYP3A4 inhibitors and inducers, or P-gp inhibitors at least 14 days\n prior to C1D1.\n 2. Prior therapy with ZN-c3 or any other WEE1 inhibitor, ATR inhibitor, or CHK1/2\n inhibitor.\n 3. Known hypersensitivity to any inactive ingredients present in ZN-c3.\n 4. A serious illness or medical condition(s)\n 5. Unresolved toxicity of Grade >1 attributed to any prior therapies (excluding Grade \u22642\n neuropathy, alopecia or skin pigmentation).\n 6. Pregnant or lactating females or females of childbearing potential who has a positive\n serum pregnancy test within 14 days prior to C1D1.\n 7. Subjects with active (uncontrolled, metastatic) second malignancies or requiring\n therapy.\n 8. Individuals who are judged by the Investigator to be unsuitable as study subjects.\n 9. 12-lead ECG demonstrating a corrected QT interval using Fridericia's formula (QTcF) of\n >470 ms, except for subjects with atrioventricular pacemakers or other conditions\n (e.g., right bundle branch block) that render the QT measurement invalid.\n 10. History or current evidence of congenital or family history of long QT syndrome or\n Torsade de Pointes (TdP).", "output": {"inclusion_biomarker": [["CCNE1 copy number amplification"]], "exclusion_biomarker": []}}
{"input": "This is a phase I, multi-center, open-label, dose-escalation study to evaluate the safety,\n tolerability, pharmacokinetics and clinical activity of LP-168 in subjects with relapsed or\n refractory B-cell malignancies. LP-168 is a small molecule inhibitor.\n ;\n ;\n Inclusion Criteria:\n A subject will be eligible for study participation if he/she meets the following criteria:\n - Subjects are eligible with B-cell malignancies, WM, FL, MCL, MZL, DLBCL, HCL, CLL,\n SLL, based upon 2016 updated WHO classification. Those subjects with WM, FL, MCL,\n DLBCL, or HCL must have received at least 2 prior systemic therapies.\n - Low-grade B-cell lymphomas as follicular Grade 1, 2, or 3A, marginal zone or small\n lymphocytic lymphoma.\n - Subject must have adequate coagulation, renal, and hepatic function, per local\n laboratory reference ranges at Screening as follows:\n - Activated partial thromboplastin time (APTT) and prothrombin time (PT) not to\n exceed 1.5 \u00d7 ULN\n - Calculated creatinine clearance (CrCl) \u2265 60 mL/min using 24-hour CrCl OR\n Cockcroft-Gault formula.\n - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \u2264 1.5 \u00d7ULN;\n Bilirubin \u2264 1.5 \u00d7 ULN (except subjects with Gilbert's Syndrome, who may have a\n bilirubin > 1.5 \u00d7 ULN, per discussion between the Investigator and the Medical\n Monitor).\n - Subjects must have adequate bone marrow independent of growth factor support per local\n laboratory reference range at screening as follows:\n - Absolute Neutrophil Count (ANC) \u22651000/uL;\n - An exception is for subjects with an ANC<1000/uL and bone marrow heavily\n infiltrated with underlying disease (approximately 60% or more) may use growth\n factor to achieve the ANC eligibility criteria per discussion between the\n Investigator and the Medical Monitor.\n - Platelet count \u2265 50,000/\u00b5L - OR - Platelet count \u2265 20,000/ \u00b5L if thrombocytopenia\n is clearly due to CLL disease under study (per Investigator discretion)\n - Hemoglobin \u22658.0g/dL, and can be achieved by transfusion\n Exclusion Criteria:\n A subject will not be eligible for study participation if he/she meets any of the following\n criteria.\n - Subject has received any of the following therapies within 14 days or 5 half-lives\n (whichever is shorter) prior to the first dose of study drug, or has not recovered to\n \u2264 Grade 1 clinically significant adverse effect(s)/toxicity(s) of the previous therapy\n (other than alopecia):\n - Any anti-cancer therapy including chemotherapy, biologic or immunotherapy,\n radiotherapy, etc;\n - Any investigational therapy, including targeted small molecule agents.\n - For CLL subjects who come off BCR antagonists (BTK inhibitors, PI3K inhibitors,\n etc.) treatment, allow washout for 2 days as these subjects progress quickly\n after treatment discontinuation and then remain eligible (steroids may be given\n during these two days to allow disease control).\n - Subjects who require immediate cytoreduction. However, subjects may receive up to two\n days of steroids for symptoms of impending organ impairment and remain eligible.\n - Subject has received the following medications or therapies within 7 days prior to the\n first dose of study drug:\n - Steroid therapy (at dosages equivalent to prednisone >20 mg/day) for\n anti-neoplastic intent (except as noted in exclusion criteria #3);\n - Cytochrome P450, family 3, subfamily A (CYP3A4) strong inhibitors and strong\n CYP2C8 inducers/inhibitors.\n - Potent CYP3A4 inducers such as rifampin, carbamazepine, phenytoin, and St. John's\n wort.\n - Subjects require treatment with systemic acid-reducing agents including H-2-receptor\n antagonists and proton pump inhibitors with the following exceptions:\n - Proton pump inhibitors should be discontinued at least 7 days prior and held\n throughout the study\n - If concurrent use of an H2 blocking agent is necessary, it must be administered\n only between 2 and 3 hours after the dose of LP-168. If not taken during this\n time, the dose of H2 blocking agents should not be taken again until 2-3 hours\n after the next dose of LP-168.\n - If concurrent use of a local antacid is necessary, it must be administered 2 or\n more hours before and/or 2 or more hours after the dose of LP-168.\n - Subject has significant screening electrocardiogram (ECG) abnormalities including. 2nd\n degree AV block type II 3rd degree block, Grade 2 or higher bradycardia, and corrected\n QT interval (QTc) \u2265 480ms.\n - Serum amylase > 1.5 \u00d7 ULN or serum lipase > 1.5 \u00d7 ULN.\n - Subject has any history of Richter's transformation for Phase 1a portion of the trial.\n - Subjects who have undergone autologous/allogeneic hematopoietic stem cell\n transplantation (HSCT) therapy within 90 days of the first dose of LP-168, or patients\n on immunosuppressive therapy post-HSCT at the time of Screening, or currently with\n clinically significant graft-versus-host disease (GVHD) as per treating physician\n (Patients in relapse after allogeneic transplantation must be off treatment with\n systemic immunosuppressive agents for at least 4 weeks. The use of topical steroids\n and/or up to 20 mg/day prednisone or equivalent systemic steroids for ongoing GVHD is\n permitted.\n - Subject has a history of other active malignancies other than B-cell malignancies\n within the past 3 years prior to study entry, with the exception of:\n - Adequately treated in situ carcinoma of the cervix uteri;\n - Basal cell carcinoma of the skin or localized squamous cell carcinoma of the\n skin;\n - Previous malignancy confined and surgically resected (or treated with other\n modalities) with curative intent.\n - Subject requires anticoagulation with Warfarin.", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
{"input": "Flonoltinib Maleate (FM) targets Janus kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3).\n FM is a dual target inhibitor of JAK2/FLT3.FM has the activity of inhibiting JAK2 signaling\n pathway, and pharmacodynamics evaluation also confirmed that FM has a good therapeutic effect\n on the primary splenomegaly model of mice induced by JAK2V617 mutation.Therefore, FM has the\n potential to treat bone marrow proliferative tumors.The drug is intended to be used in\n patients with MPN, mainly including medium-risk or high-risk myelofibrosis (FM) (including\n primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PostPV-MF) and\n post-primary thrombocythemia myelofibrosis (postET-MF)), Polycythemia vera (PV) and essential\n thrombocythemia (ET) were the primary causes of thrombocythemia and thrombocythemia.\n FM has high inhibitory activity against JAK family and FLT3 kinase, suggesting that FM may\n have a certain therapeutic effect on AML disease.The IC50 of JAK2 kinase inhibition by FM was\n as low as 0.8 nM, while the IC50 of JAK1, JAK3 and Tyk2 kinase inhibition was 690 nM, 557 nM\n and 65nM, respectively. The selectivity of JAK2 kinase inhibition by FM was 862.5, 696.3 and\n 81.3 times, respectively. Therefore, FM showed highly selective inhibition of JAK2 kinase.The\n IC50 for FLT3 kinase was 15 nM. FM has better inhibitory activity against JAK2 kinase than\n the listed Ruxolitinib and Fedratinib, and has better selectivity against JAK family.In order\n to determine whether FM has targets other than JAK2 and Flt3 kinases, we tested FM's\n inhibitory activity against 100 human kinases that are highly associated with tumors,\n including some common drug-resistant mutant kinases.The results showed that, except for\n CDK4/6, LCK and LN, FM had no obvious inhibitory activity against the screened kinases at 0.1\n \u03bcm, and no other targets were found.\n In vitro experiments on the proliferation of JAK2-dependent and Flt3-related tumor cell lines\n with FM showed that the tumor cell lines had a significant inhibitory effect. The IC50 of\n half of the tumor cell lines was less than 0.5 \u03bcm, which was better than or equal to the\n similar drugs Ruxolitinib and Fedratinib.\n The effect of FM on tumor cells from MPN patients indicated that FM has the potential to\n treat MPN disease.\n In multiple animal models of bone marrow proliferative tumors with JAK2V617F mutations, FM\n showed superior efficacy and low toxicity (no obvious VISCAL toxicity) than existing drugs on\n the market, and the tumor inhibition effect of FM showed a good dose-dependent relationship.\n Objectives of Study\n Main Purpose:\n 1. Tolerance and safety of flonoltinib maleate Tablets tablets in patients with bone marrow\n proliferative tumors;\n 2. To observe the possible dose-limiting toxicity(DLT) of flonoltinib maleate tablets in\n patients with bone marrow proliferative tumors,To determine the maximum tolerated\n dose(MTD) of flonoltinib maleate tablets,To provide the basis for the recommended dose\n and design scheme of the later clinical trial.\n Secondary Purpose:\n 1. To evaluate the pharmacokinetic characteristics of single and repeated oral\n administration of flonoltinib maleate tablets in patients with bone marrow proliferative\n tumors;\n 2. To evaluate the primary efficacy of single and multiple oral flonoltinib maleate tablets\n in patients with bone marrow proliferative tumors.\n ;NA;\n Inclusion Criteria:\n 1. Age \u226518, gender unlimited;\n 2. Patients diagnosed as PMF, PV (PV at least 24 weeks), ET according to WHO criteria\n (2016 edition), or post-PV-MF or post-ET-MF according to IWG-MRT criteria;\n 3. Any of the following criteria is met :(1) Patients receiving treatment for myeloid\n fibrosis must be at least medium-risk -1 or high risk as assessed according to the\n DIPSS risk grouping criteria; (2) PV and ET patients who are resistant or intolerant\n to hydroxyurea and/or interferon therapy;\n 4. No immediate plans for a stem cell transplant;\n 5. At least 4 weeks or more than 5 half-lives (whichever is longer) after receiving the\n last antitumor therapy (chemotherapy, radiotherapy, biotherapy or immunotherapy)\n before enrollment;\n 6. Expected survival \u226512 weeks;\n 7. ECOG\u22642;\n 8. Splenomegaly: palpate the margin of the spleen (the farthest point of the spleen) at\n least 5 cm below the costal margin; Or not accessible due to body type (obesity), but\n confirmed by MRI (CT scan if necessary) spleen assessment at screening time, the\n volume is \u2265450 cm3;\n 9. Bone marrow primitive cells and peripheral blood primitive cells \u226410%;\n 10. PLT\u226575\u00d7109 /L, ANC\u22651.0\u00d7109 /\u03bcL, HGB> without the assistance of colony stimulating\n factor, growth factor, thrombogenic factor or platelet infusion; 80 g/L. Subjects did\n not receive growth factor, colony-stimulating factor, thrombogenic factor or platelet\n transfusions within 2 weeks before examination.\n 11. Heart, lung, liver, kidney, pancreas without serious organic lesions (LVEF (left\n ventricular ejection fraction) \u226545%; Total bilirubin \u22641.5\u00d7ULN; Serum creatinine\n \u22641.5\u00d7ULN or CCR> 40 ml/min. Alanine aminotransferase (ALT) \u22642\u00d7ULN; Aspartate\n aminotransferase (AST) \u22642\u00d7ULN;\n 12. No severe coagulation abnormalities (PT\u22641.5\u00d7ULN, APTT\u22641.5\u00d7ULN, TT\u22641.5\u00d7ULN);\n 13. Those who agree to participate in the study and sign the informed consent;\n 14. Agree to comply with the regulations of the hospital and research institution.\n Exclusion Criteria:\n 1. The toxicity of previous anticancer therapy does not recover to grade I or below\n (except for hair loss), or does not fully recover from previous surgery (major surgery\n within 4 weeks);\n 2. Allergic constitution, allergy to test drugs and their excipients;\n 3. Any significant clinical or laboratory abnormalities that the investigator considers\n to affect the safety reviewer, such as: A. Uncontrolled diabetes - fasting glucose >\n 250 mg/dL (13.9 mmol/L), b. Patients with hypertension who cannot be reduced to the\n following range after treatment with two or less antihypertensive drugs (systolic\n blood pressure < 160 mmHg, diastolic blood pressure < 100 mmHg), c. Peripheral\n neuropathy (NCI-CTC AE V5.0 Grade 2 or above);\n 4. Patients with a history of congestive heart failure, unstable angina pectoris or\n myocardial infarction, cerebrovascular accidents, or pulmonary embolism within the\n first 6 months were screened;\n 5. Patients with impaired heart function (Ejection fraction measured by ultrasonic\n electrocardiogram; ST segment descending in two or more channels in 45% or complete\n left bundle branch block > 1 mm or T wave inverted; Congenital ventricular arrhythmia,\n clinically significant tachycardia (>; 100 beats/min), bradycardia (lt; 50 times/min),\n ECG QTc > 450 ms (male), QTc > 480 MS (female) or clinically significant heart disease\n (such as unstable angina pectoris, congestive heart failure, myocardial infarction\n within 6 months);\n 6. Arrhythmic disease requiring treatment, or QTC interphase (QTCB) > 480 ms;\n 7. Any active infections requiring treatment at the time of screening;\n 8. Patients who had previously undergone splenectomy or who had received radiotherapy in\n the splenic region within 12 months prior to screening;\n 9. Positive HIV antibody, positive active hepatitis B virus (HBsAg positive, HBV-DNA\n positive or \u22651000 copies/mL), positive anti-HCV antibody or HCV-RNA at screening time;\n 10. Screening patients with epilepsy or using psychotropic drugs or sedatives;\n 11. Pregnant or lactating women, fertile women/men who refuse to use contraceptives during\n the trial and within 6 months after the trial;\n 12. Patients who have had malignant tumors (except cured basal cell carcinoma of the skin\n and carcinoma in situ of the cervix) in the past 5 years;\n 13. Concomitant with other serious diseases that the investigator believes may affect\n patient safety or compliance;\n 14. Screening patients who participated in other new drugs or medical devices and took\n study drugs or used study devices within the previous 1 months;\n 15. Within 2 weeks before randomization and into the group to use any drug for MF (JAK\n inhibitor, hydroxyurea), any immune modulators (such as Sally degree amine), any\n immune inhibitors, 10 mg/day or prednisone or equivalent strength of biological effect\n of glucocorticoid, growth factors, such as EPO therapy, or within six drug half-life\n of patients;\n 16. Intravenous use of either a potent or moderate CYP3A inhibitor (such as ketoconazole,\n clarithromycin, itraconazole, nefazoldone, telimycin) or a potent CYP3A4 inducer\n (rifampicin perforatum) within two weeks prior to initial administration;\n 17. Patients with a history of congenital or acquired bleeding diseases;\n 18. Alcohol dependence or drug abuse;\n 19. People who use grapefruit, star fruit or its products within 48 hours before taking\n the study drug for the first time, or who do not agree to prohibit the consumption of\n the above-mentioned food, drink or other special diet, which may affect the\n absorption, distribution, metabolism and excretion of the study drug;\n 20. Other factors considered by the investigator to be unsuitable for participation in the\n study.", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
{"input": "Depending on the variant of the disease, patients are divided into 3 groups: A, B and C.\n Group A include patients with acute myeloid leukemia (AML) inv(16)(p13.1q22) or\n t(16;16)(p13.1;q22); CBFB-MYH11, group B - AML with t(8;21)(q22;q22.1); RUNX1-RUNX1T1, AML\n with normal karyotype with or without gene mutations (FLT3, NPM1, CEBPa) regardless of the\n allele ratio, and also AML with cytogenetic abnormalities not classified as those within\n groups A/C, group C - AML with myelodysplasia-related changes. Patients from group A receive\n treatment according to the scheme: 2 courses \"7+3\", 2 courses \"FLAG\", then - 6 courses of\n maintenance therapy according to the scheme \"5+5\". Patients from group B are given one course\n of \"7+3\". After that, their minimal residual disease (MRD) status is assessed. In case MRD\n negativity is achieved after the 1st course of \"7 +3\", randomization is carried out: branch 1\n - therapy is similar to therapy for patients from group A (4 courses of induction and\n consolidation + 6 courses of maintenance chemotherapy (CT), allogeneic hematopoietic stem\n cell transplantation (allo-HSCT) is not planned), branch 2 - performing allo-HSCT should be\n done as soon as possible (before the start of maintenance CT is most desirable). If MRD\n negativity is not achieved after the 1st course of \"7+3\", the patient is given CT according\n to the standard program, followed by mandatory allo-HSCT. Patients from group C are treated\n either according to the \"Aza-Ida-Ara-C\" scheme, or according to the \"Ven-DAC /AZA\" scheme,\n followed by mandatory allo-HSCT.\n ;\n ;\n Inclusion Criteria:\n 1. Newly diagnosed, previously untreated AML;\n 2. Age from 18 to 59 years;\n 3. Somatic status - ECOG < 3.\n Exclusion Criteria:\n 1. previous chemotherapy for AML;\n 2. pregnancy;\n 3. relapses and refractory forms of AML;\n 4. acute promyelocytic leukemia;\n 5. blast crisis of chronic myeloid leukemia;\n 6. de novo AML with t(9;22);\n 7. AML transformed from MDS or MPN after treatment, for which a different protocol is\n provided;\n 8. Blastoid plasmacytoid dendritic cell neoplasia (with the exception of cases when a\n small population of plasmacytoid dendritic progenitors is detected in the leukemic\n neoplasia).\n 9. Undifferentiated acute leukemia", "output": {"inclusion_biomarker": [["inv(16)(p13.1q22)"], ["t(16;16)(p13.1;q22)"], ["CBFB-MYH11"], ["t(8;21)(q22;q22.1)"], ["RUNX1-RUNX1T1"], ["FLT3 mutation"], ["NPM1 mutation"], ["CEBPa mutation"]], "exclusion_biomarker": [["t(9;22)"]]}}
{"input": "This phase II trial studies the effect of ASTX727 and dasatinib in treating patients with\n newly diagnosed Philadelphia chromosome or BCR-ABL positive chronic myeloid leukemia in\n chronic phase. Philadelphia chromosome positive and BCR-ABL positive are types of genetic\n mutations (changes). Chemotherapy drugs, such as ASTX727, work in different ways to stop the\n growth of cancer cells, either by killing the cells, by stopping them from dividing, or by\n stopping them from spreading. Dasatinib may stop the growth of cancer cells by blocking some\n of the enzymes needed for cell growth. ASTX727 and dasatinib may help to control Philadelphia\n chromosome-positive chronic myeloid leukemia or BCR-ABL positive chronic myeloid leukemia in\n chronic phase.\n ;\n ;\n Inclusion Criteria:\n - Diagnosis of Philadelphia chromosome (Ph)-positive or BCR-ABL positive CML in early\n chronic phase CML (i.e., time from diagnosis =< 12 months). Except for hydroxyurea\n and/or 1 to 2 doses of cytarabine patients must have received no or minimal prior\n therapy, defined as < 1 month (30 days) of prior Food and Drug Administration (FDA)\n approved tyrosine kinase inhibitor (TKI)\n - Clonal evolution defined as the presence of additional chromosomal abnormalities\n other than the Ph chromosome has historically been included as a criterion for\n accelerated phase. However, patients with clonal evolution as the only criterion\n of accelerated phase have a significantly better prognosis, and when present at\n diagnosis may not impact the prognosis at all. Thus, patients with clonal\n evolution and no other criteria for accelerated phase will be eligible for this\n study\n - Eastern Cooperative Oncology Group (ECOG) performance of 0-2\n - Total bilirubin < 1.5 x upper limit of normal (ULN) (unless secondary to Gilbert's\n disease, in which case should be < 2.5 x ULN)\n - Serum glutamic pyruvic transaminase (SGPT) < 3 x ULN\n - Creatinine < 1.5 x ULN\n - Patients must sign an informed consent indicating they are aware of the\n investigational nature of this study, in keeping with the policies of the hospital\n Exclusion Criteria:\n - New York Heart Association (NYHA) cardiac class 3-4 heart disease\n - Cardiac Symptoms: Patients meeting the following criteria are not eligible unless\n cleared by Cardiology:\n - Uncontrolled angina within 3 months\n - Diagnosed or suspected congenital long QT syndrome\n - Any history of clinically significant ventricular arrhythmias (such as\n ventricular tachycardia, ventricular fibrillation, or Torsades de pointes).\n - Prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (> 460 msec)\n - History of significant bleeding disorder unrelated to cancer, including:\n - Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)\n - Diagnosed acquired bleeding disorder within one year (e.g., acquired\n anti-factor VIII antibodies)\n - Patients with active, uncontrolled psychiatric disorders include: psychosis, major\n depression, and bipolar disorders\n - Subject is known to be positive for human immunodeficiency virus (HIV) (HIV testing is\n not required)\n - Evidence of other clinically significant uncontrolled condition(s) including, but not\n limited to:\n - Uncontrolled and/or active systemic infection (viral, bacterial or fungal)\n - Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note:\n subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B\n surface [HBs] antigen negative-, anti-HBs antibody positive and anti-hepatitis B\n core [HBc] antibody negative) or positive anti-HBc antibody from intravenous\n immunoglobulins (IVIG) may participate\n - Women of pregnancy potential must practice an effective method of birth control during\n the course of the study, in a manner such that risk of failure is minimized. Prior to\n study enrollment, women of childbearing potential (WOCBP) must be advised of the\n importance of avoiding pregnancy during trial participation and the potential risk\n factors for an unintentional pregnancy. Postmenopausal women must be amenorrheic for\n at least 12 months to be considered of non-childbearing potential. Women must continue\n birth control for the duration of the trial and at least 3 months after the last dose\n of study drug. Pregnant or breast-feeding women are excluded. All WOCBP must have a\n negative pregnancy test prior to first receiving investigational product. If the\n pregnancy test is positive, the patient must not receive study drug and must not be\n enrolled in the study\n - Patients in late chronic phase (i.e., time from diagnosis to treatment > 12 months),\n accelerated (except as noted in inclusion criteria) or blast phase are excluded. The\n definitions of CML phases are as follows:\n - Early chronic phase: time from diagnosis to therapy =< 12 months\n - Late chronic phase: time from diagnosis to therapy > 12 months\n - Blastic phase: presence of 30% blasts or more in the peripheral blood or bone\n marrow\n - Accelerated phase CML: presence of any of the following features:\n - Peripheral or marrow blasts 15% or more\n - Peripheral or marrow basophils 20% or more\n - Thrombocytopenia < 100 x 10^9/L unrelated to therapy\n - Documented extramedullary blastic disease outside liver or spleen", "output": {"inclusion_biomarker": [["Philadelphia chromosome positive"], ["BCR-ABL positive"]], "exclusion_biomarker": []}}
{"input": "The purpose of this Cohort Treatment Plan is to allow access to ceritinib for eligible\n patients diagnosed with ALK positive tumors, previously pre-treated with ALK inhibitors or\n naive. The patient's Treating Physician should follow the suggested treatment guidelines and\n comply with all local health authority regulations.\n ;NA;\n Inclusion Criteria:\n Patients eligible for inclusion in this Treatment Plan have to meet all of the following\n criteria:\n 1. The patient is diagnosed with ALK-positive tumor.\n 2. The patient has been previously pre-treated with ALK inhibitor or naive.\n 3. The patient has progression of disease at screening or is intolerant to prior therapy\n and does not qualify or have access to LDK378 through a clinical trial.\n 4. The patient has a performance status (WHO) of 0-2.\n 5. The following laboratory criteria have been met:\n - Absolute neutrophil count (ANC) \u22651.5 x 10^9/L\n - Hemoglobin (Hgb) \u2265 8 g/dL\n - Platelets \u226575 x 10^9/L\n - Serum total bilirubin \u2264 1.5 x upper limit of normal (ULN), except for patients\n with Gilbert's syndrome who may be included if total bilirubin \u2264 3.0 x ULN or\n direct bilirubin \u2264 1.5 x ULN\n - Aspartate transaminase (AST) \u2264 3.0 x ULN, except for patients with liver\n metastasis, who are only included if AST \u2264 5.0 x ULN;\n - Alanine transaminase (ALT) \u22643.0 x ULN, except for patients with liver metastasis,\n who are only included if ALT \u2264 5.0 x ULN;\n - alkaline phosphatase (ALP) \u2264 5.0 x ULN\n - Serum creatinine <1.5 mg/dL and or Calculated creatinine clearance (CrCL) (using\n Cockcroft-Gault formula) \u2265 30 mL/min\n - Serum amylase \u2264 2 x ULN\n - Serum lipase \u2264 ULN\n - Fasting plasma glucose \u2264175 mg/dL (\u22649.8 mmol/L)\n 6. Patient must have the following laboratory values within normal limits or corrected to\n within normal limits with supplements before the first dose of ceritinib:\n - Potassium\n - Magnesium\n - Phosphorus\n - Total calcium (corrected for serum albumin) Written patient informed consent must\n be obtained prior to start of treatment.\n Exclusion Criteria:\n Patients eligible for this Treatment Plan must not meet any of the following criteria:\n 1. A history of pancreatitis or history of increased amylase or lipase that was due to\n pancreatic disease.\n 2. Other concurrent severe, acute, or chronic and/or uncontrolled medical conditions\n (e.g. diabetes mellitus or psychiatric conditions or laboratory abnormalities\n uncontrolled heart disease in the last 6 months, active or uncontrolled infection)\n that, in the opinion of the treating physician, could cause unacceptable safety risks,\n interfere with the interpretation of the results or compromise compliance with the\n treatment plan.\n 3. Patient who has received thoracic radiotherapy to lung fields \u22644 weeks prior to\n starting the study treatment or patients who have not recovered from\n radiotherapy-related toxicities. For all other anatomic sites (including radiotherapy\n to thoracic vertebrae and ribs) radiotherapy \u22642 weeks prior to starting the study\n treatment or has not recovered from radiotherapy-related toxicities. Palliative\n radiotherapy for bone lesions \u22642 weeks prior to starting study treatment is allowed.\n 4. Known history of interstitial lung disease or interstitial pneumonitis including\n clinically significant radiation pneumonitis (i.e. affecting activities of daily\n living or requiring therapeutic intervention).\n 5. Clinically significant, uncontrolled heart disease and/or recent cardiac event (within\n 6 months), such as:\n - Unstable angina within 6 months prior to screening.\n - Myocardial infarction within 6 months prior to screening.\n - History of documented congestive heart failure (New York Heart Association\n functional classification III-IV).\n - Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) \u2265160 mm Hg\n and/or Diastolic Blood Pressure (DBP) \u2265100 mm Hg, with or without\n antihypertensive medication. Initiation or adjustment of antihypertensive\n medication (s) is allowed prior to screening.\n - Ventricular arrhythmias\n - Supraventricular and nodal arrhythmias not controlled with medication.\n - Other cardiac arrhythmia not controlled with medication.\n - Corrected QT (QTcF) >470 ms using Fridericia's correction on the screening ECG\n (as mean of triplicate ECGs).\n 6. Known hypersensitivity to any excipients of LDK378 (microcrystalline cellulose,\n mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate)\n 7. Impaired GI function or GI disease that may significantly alter absorption of LDK378\n (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption\n syndrome).\n 8. Patient must not be participating in other ongoing trials, or ALK inhibitors trials or\n other compassionate use programs. Patients eligible for this program are also\n ineligible for other ALK inhibitors trials.\n 9. Receiving medications that meet one of the following criteria and that cannot be\n discontinued at least 1 week prior to the start of treatment with LDK378 and for the\n duration of the program:\n - Strong inhibitors or strong inducers of CYP3A4/5\n - Medications with a low therapeutic index that are primarily metabolized by\n CYP3A4/5 and/or CYP2C9\n - Medications with a known risk of prolonging the QT interval or inducing Torsades\n de Pointes.\n - Receiving treatment with warfarin sodium (Coumadin) or any other coumadinderived\n anti-coagulant\n - Receiving unstable or increasing doses of corticosteroids. If patients are on\n corticosteroids for endocrine deficiencies or tumor-associated symptoms (non-\n CNS), dose must have been stabilized (or decreasing) for at least 5 days before\n first dose of treatment.\n - Patient has had major surgery (e.g., intra-thoracic, intra-abdominal or\n intra-pelvic) within 4 weeks prior to starting treatment or has not recovered\n from side effects of such procedure. Video-assisted thoracic surgery (VATS) and\n mediastinoscopy will not be counted as major surgery and patients can receive\n treatment \u22651 week after these procedures\n - Receiving enzyme-inducing anticonvulsives that cannot be discontinued at least 1\n week before first dose of treatment, and for the duration of the treatment.\n Patients on non-enzyme-inducing anticonvulsants are eligible.\n 10. Sexually active males unless they use a condom during intercourse while taking the\n drug and for 3 months after the last dose of program drug. Patient should not father a\n child in this period. A condom is required to be used also by vasectomized men in\n order to prevent delivery of the drug via seminal fluid.\n 11. Pregnant or nursing (lactating) women\n 12. Women of child-bearing potential, defined as all women physiologically capable of\n becoming pregnant, unless they are using highly effective methods of contraception\n during dosing and for 3 months after stopping medication. Highly effective\n contraception methods include:\n - Total abstinence (no sexual relations), when this is in line with your preferred\n and usual lifestyle. Periodic abstinence like calendar, ovulation, symptothermal,\n postovulation methods, and withdrawal are not acceptable methods of\n contraception.\n - Female sterilization, when you have been already surgically sterilized prior to\n the program by surgical removal of both ovaries (woman's reproductive system that\n stores and releases eggs for fertilization and produces female sex hormones),\n total hysterectomy (surgical removal of the uterus and cervix), or tubal ligation\n (getting your \"tubes tied\") at least six weeks before taking program treatment.\n - Your male partner has already been sterilized at least 6 months prior to\n screening with the appropriate documentation. The sterilized male partner should\n be your sole partner.\n - Use of oral, injected, or implanted hormonal methods of contraception or\n placement of an intrauterine device (IUD) or intrauterine system (IUS) or other\n forms of hormonal contraception that have comparable efficacy (failure rate <1%),\n for example hormone vaginal ring or transdermal hormone contraception (in case of\n oral contraception you should have been using the same pill on a stable dose for\n a minimum of 3 months before taking program treatment).\n In case of use of oral contraception, women should have been stable on the same pill for a\n minimum of 3 months before taking study treatment.", "output": {"inclusion_biomarker": [["ALK positive"]], "exclusion_biomarker": []}}
{"input": "This is a phase 1, open-label, dose escalation and cohort expansion study and conducted in\n China and the United States to investigate the safety, tolerability and preliminary efficacy\n of QLH11811 in advanced or metastatic NSCLC patients who have progressed after prior EGFR-TKI\n treatment. The study consists of the following 2 phases: phase 1: dose escalation (1a) and\n phase 2: cohort expansion (1b).\n ;NA;\n Inclusion Criteria:\n 1. Patients who participate voluntarily, sign informed consent form (ICF), and will be\n able to follow the study procedures;\n 2. Aged \u2265 18 years;\n 3. Patients who are histologically or cytologically diagnosed with EGFR mutation and have\n unresectable locally advanced or recurrent/metastatic NSCLC;\n 4. EGFR mutation requirements:\n Dose escalation phase (phase 1a): NSCLC patients who have progressed after standard\n EGFR-TKI treatment or cannot tolerate standard of care;\n Cohort expansion phase (phase 1b):\n 1. Cohort 1: advanced NSCLC patients who have progressed after treatment with\n third-generation EGFR-TKIs and have EGFR C797S mutation.\n 2. Cohort 2: advanced NSCLC patients who have progressed after standard EGFR-TKI\n treatment but have no other additional driver gene mutation(s).\n 3. Cohort 3: advanced NSCLC patients who have progressed after EGFR-TKI treatment\n and have T790M mutation.\n 4. Cohort 4: patients with locally progressed, unresectable or recurrent metastatic\n NSCLC who are naive to EGFR-TKI treatment and have 19del or 21L858R mutation\n among EGFR sensitive mutations.\n 5. Patients who agree to provide tumor samples (fresh tissues or archived samples) for\n analysis of EGFR gene.\n Dose escalation phase: tumor samples collected from the progression site of disease\n during or after PD after the last TKI treatment should be provided for new genetic\n testing The subjects who fail to provide tumor samples will be allowed to enroll only\n after communication and consultation with the sponsor.\n Cohort expansion phase:\n Cohort1: tumor samples collected from the progression site of disease during or after\n PD after the last TKI treatment should be provided for genetic testing at central\n laboratory.\n Cohorts 2 and 3: tumor samples collected from the progression site of disease during\n or after PD after the last TKI treatment should be provided for genetic testing. The\n genetic testing will be exempted if subjects have the test results meeting the above\n requirements before their enrollment.\n Cohort 4: tumor samples collected from the progression site of disease during or after\n PD after the last treatment should be provided for genetic testing (of EGFR mutation);\n and if subjects are treatment-naive, they will be required to provide the tumor\n samples only during the screen period. The genetic testing will be exempted if\n subjects have the test results meeting the above requirements before their enrollment.\n 6. ECOG \u2264 1 point (for details, refer to Appendix 2 ECOG performance status score);\n 7. Life expectancy \u2265 12 weeks;\n 8. Patients who have been diagnosed according to RECIST v1.1 and have measurable lesions\n as documented by computed tomography (CT) and/or magnetic resonance imaging (MRI)\n (note: subjects who do not have measurable lesions are allowed to be enrolled in phase\n 1a study). Note: a measurable lesion for response evaluation has to meet the following\n criteria: a) it is not in an area that has been involved in prior radiotherapy, or b)\n there is notable radiographic evidence of progression after the completion of\n radiotherapy and before study enrollment;\n 9. Patients who have adequate organ functions and meet the following criteria:\n 1. Hematology:\n Absolute neutrophil count \u2265 1.5 \u00d7 109/L; platelet count \u2265 100 \u00d7 109/L; hemoglobin\n \u2265 90 g/L (no blood transfusion and no use of granulocyte colony stimulating\n factor in the 14 days prior to the screening);\n 2. Coagulation:\n For patients who have not received anticoagulant therapy: international\n normalized ratio (INR) of prothrombin time and partial thromboplastin time \u2264 1.5\n \u00d7 ULN;\n 3. Liver:\n Alanine aminotransferase (AST) or alanine aminotransferase (ALT) \u2264 3.0 \u00d7 ULN. For\n patients with liver metastases: ALT and AST \u2264 5 \u00d7 ULN, total bilirubin \u2264 1.5 \u00d7\n ULN. For patients with Gilbert syndrome: conjugated bilirubin within normal\n range;\n 4. Kidney:\n Serum creatinine \u2264 1.5 \u00d7 ULN, or creatinine clearance \u2265 50 mL/min (calculated\n according to Cockcroft-Gault formula, refer to Appendix 4 Creatinine clearance\n calculation formula).\n 10. All acute toxic reactions arising from prior antineoplastic therapy or surgery have\n resolved to baseline or reduced in severity to \u2264 Grade 1 according to NCI CTCAE V5.0\n (except for alopecia or other toxicities which, in the opinion of the investigator,\n pose no safety risk to the patient);\n 11. Patients (both female and male) who agree to take effective contraceptive measures\n from their signing of ICF to 6 months after the last dose of the study drug. For women\n of childbearing potential: negative serum pregnancy test result in 7 days prior to the\n start of treatment is required.\n Exclusion Criteria:\n 1. Patients who have received systemic anticancer therapies (e.g., chemotherapy,\n molecularly targeted therapy, radiotherapy, biotherapy, hormone therapy, vaccine\n therapy), or antineoplastic TCM therapy in the 2 weeks prior to the first dose of\n study treatment; or who have received immune-checkpoint inhibitor therapy in the 4\n weeks prior to the first dose of study treatment;\n 2. Patients who have received radical radiotherapy (including radiotherapy of more than\n 25% of bone marrow) in the 4 weeks prior to the first dose, or who have received local\n palliative radiotherapy for bone metastatic lesions in the 1 week prior to the first\n dose;\n 3. Patients who have received strong or moderate CYP3A, P-gp inhibitors in the 1 week\n prior to the first dose or in 5 half-lives of these drugs (whichever is longer), or\n need to continue to receive these drugs during the study; and who have received strong\n or moderate CYP2B6, CYP1A2 and CYP3A inducers in the 4 weeks prior to the first dose;\n 4. Patients who are in the treatment period of other interventional clinical studies in\n the 4 weeks prior to the first dose. However, participants of non-interventional\n clinical studies (e.g., epidemiologic studies) are eligible for enrollment in this\n study. Patients in the survival follow-up period of interventional clinical studies\n are also eligible for enrollment in this study;\n 5. Patients who have active bacterial, fungal or viral infection requiring systemic\n therapies within the 1 week prior to the first dose;\n 6. Patients who have underwent a major operation (e.g., a surgical operation requiring\n local or general anesthesia and hospitalization) in the 3 weeks prior to the start of\n study treatment;\n 7. Patients with a history of chronic diarrhea, including but not limited to Crohn's\n disease, irritable bowel syndrome, etc.;\n 8. Patients who have experienced > CTCAE Grade 1 continuous diarrhea within the 1 week\n prior to the first dose;\n 9. Patients with serious respiratory disorders, e.g. interstitial lung disease, radiation\n pneumonitis, drug-induced pneumonia (however, patients whose conditions have resolved\n and stabilized for 3 months or more are eligible for enrollment);\n 10. Patients with symptomatic metastasis to central nervous system (CNS) and/or with\n meningitis carcinomatosa.\n Note: patients with brain metastases whose clinical symptoms have stabilized after\n treatment are eligible for participation in the study, provided that their conditions\n are radiographically stabilized (defined as stability demonstrated by 2 brain images\n acquired by the same imaging technique after treatment of brain metastases). These\n imaging scans should be carried out at an interval of at least 4 weeks, and show no\n signs of intracranial progression. Furthermore, brain metastases or its treatment\n induced neurologic symptoms need to regress to baseline level or resolve. All steroids\n administered as a part of the treatment must be completed \u2265 3 days prior to the\n administration of study treatment.\n 11. Patients with clinically significant cardiovascular and cerebrovascular diseases,\n including but not limited to:\n 1. Myocardial infarction or unstable angina in the 6 months prior to the first dose;\n 2. Stroke or transient ischemic attack in the 6 months prior to the first dose;\n 3. Any clinically significant abnormalities in resting ECG in terms of cardiac\n rhythm, heart rate, conduction or morphology, e.g. complete left bundle branch\n block, third-degree conduction block, second-degree conduction block, PR interval\n > 250 ms, etc.;\n 4. Uncontrolled hypertension after active treatment: systolic pressure > 180 mmHg or\n diastolic pressure > 100 mmHg;\n 5. Congestive cardiac failure (NYHA functional class III-IV);\n 6. Pericarditis or clinically significant pericardial effusion;\n 7. Myocarditis;\n 8. 12-lead ECG shows that mean QT interval (QTcF) > 450 ms (male) or > 470 ms\n (female) before the first dose of investigational drug;\n 9. Failure to discontinue the drugs that may cause QTc prolongation or torsades de\n pointes (e.g., antiarrhythmics) during the study.\n 12. Patients with clinically uncontrolled serous effusion(e.g., pleural fluid that cannot\n be controlled by drainage or other methods).\n 13. Patients with active gastrointestinal disorders or other conditions that have serious\n interference with the drug absorption.\n 14. Patients with any condition that have an adverse impact on the swallowing of the drug\n or on the absorption or PK parameters of the investigational drug;\n 15. Patients with known serious allergy to the study drug or any excipient of the drug;\n 16. Patients with known HIV test positive result and/or treponema pallidum antibody test\n positive result (except for those whose infection has been cured after treatment).\n 17. Patients with HBsAg positive result and HBV DNA > 2000 IU/mL or 104 copies/mL (for\n sites which only provide the qualitative testing, HBV DNA test result is positive or\n higher than lower limit of detection); or with HCV antibody positive and HCV RNA\n positive results.\n 18. Patients who experienced other malignancies (with the exceptions of Bowen's disease;\n cured basal cell or squamous cell skin cancer; prostate cancer with a Gleason score of\n 6; treated cervical carcinoma in situ) in the 2 years prior to the study enrollment.\n 19. Pregnant or lactating women. Lactating female subjects need to stop breast-feeding\n before the first dose of study treatment, which cannot be resumed throughout the study\n and in the 6 months after the last dose of study treatment.\n 20. Patients with any existing serious or unstable diseases (except for the\n above-mentioned malignancies), psychiatric disorders or any disease or medical\n condition which, in the investigator's opinion, may have an adverse impact on the\n subject safety, the signing of ICF or the compliance with the study procedures.\n 21. Patients who are currently participating in a clinical study of other investigational\n therapies.", "output": {"inclusion_biomarker": [["EGFR mutation"], ["EGFR C797S"], ["EGFR T790M"], ["EGFR 19del"], ["EGFR 21L858R"]], "exclusion_biomarker": []}}
{"input": "This is a Phase 1 dose-finding study of FT538 in combination with monoclonal antibodies.\n ;\n ;\n Inclusion Criteria:\n Subjects with locally advanced or metastatic disease who have progressed after at least one\n line of therapy and diagnosis of one of the following by treatment cohort:\n - Cohort A: The following solid tumor malignancies where anti-PD-1/PD-L1 antibodies are\n approved: cutaneous melanoma, non-small cell/small cell lung cancer, renal cell\n carcinoma, head and neck squamous cell cancer, microsatellite instability-high/\n mismatch repair deficient cancer, gastric cancer, esophageal cancer, cervical cancer,\n merkel cell carcinoma, endometrial carcinoma, tumor mutation burden-high \u2265 10\n mutations/megabase], cutaneous squamous cell carcinoma, triple-negative breast cancer.\n - Cohort B: HER2+ breast cancer that has relapsed or progressed on trastuzumab and\n progressed on either pertuzumab or HER2-targeting antibody drug conjugate; HER2+\n gastric cancer that has relapsed or progressed on trastuzumab-containing therapy; OR\n any other HER2+ solid tumor having progressed on at least one line of standard-of-care\n therapy. For any tumor type in this cohort, HER2 status must be documented by a U.S.\n Food and Administration (FDA) approved test to be \u22652+ IHC or Average HER2 copy number\n \u22654 signals per cell by in situ hybridization.\n - Cohort C: CRC having progressed following prior cetuximab treatment or has KRAS/NRAS\n mutation; HNSCC having progressed following prior cetuximab.\n Capable of giving signed informed consent\n Aged ~ 18 years old\n Willingness to comply with study procedures and duration\n Measurable disease per RECIST v1.1\n For subjects with >1 measurable lesion by RECIST v1.1 that can be safely accessed,\n willingness to undergo tumor biopsy\n Contraceptive use for women and men as defined in the protocol\n Exclusion Criteria:\n Pregnant or breast-feeding women\n ECOG performance status greater than or equal to 2\n Evidence of insufficient organ function\n Clinically significant cardiovascular disease including left-ventricular ejection fraction\n < 45%\n Receipt of therapy within 2 weeks prior to Day 1 or five half-lives, whichever is shorter\n or any investigational therapy within 28 days prior to Day 1\n Known active central nervous system (CNS) involvement by malignancy that hasn'thas not\n remained stable for at least 3 months following effective treatment for CNS disease\n Non-malignant CNS disease such as stroke, epilepsy, CNS vasculitis or neurodegenerative\n disease or receipt of medications for these conditions\n Currently receiving or likely to require immunosuppressive therapy Active bacterial,\n fungal, or viral infections including hep B, Hep C or HIV Live vaccine within 6 weeks prior\n to start of lympho-conditioning\n Known allergy to albumin (human) or DMSO", "output": {"inclusion_biomarker": [["microsatellite instability-high"], ["mismatch repair deficient"], ["HER2 positive"], ["KRAS mutation"], ["NRAS mutation"]], "exclusion_biomarker": []}}
{"input": "This is a multicenter, open label, pilot phase II study of the PI3K inhibitor copanlisib in\n combination with a ketogenic diet in the treatment of patients with one of the following\n malignancies: (a) relapsed or refractory (R/R) follicular lymphoma (FL), (b) R/R endometrial\n cancer (EC) with a documented activating mutation in PIK3CA or loss of phosphatase and tensin\n homolog (PTEN).\n ;\n ;\n Inclusion Criteria:\n - Be willing and able to provide written informed consent for the trial.\n - Be 18 years of age or older on day of signing informed consent.\n - For lymphoma, patients should have measurable disease based on the Lugano Criteria.\n - For FL patients must have received at least two lines of prior therapy. There is no\n upper limit for the number of prior therapies. Tumor tissues of all patients are\n encouraged to be submitted (optional) prospectively for whole or targeted exome\n sequencing of key cancer related genes, using the Columbia Combined Cancer Panel\n (CCCP) or a comparable sequencing platform, such as the MSK-IMPACT 468-gene oncopanel.\n - For EC the patients must have recurrent/advanced tumor for which surgical or the\n systemic curative treatments, or standard therapeutic approaches are not available.\n The following histologic subtypes are eligible: endometrioid, serous, clear cell,\n undifferentiated /dedifferentiated, mucinous, squamous, transitional, not-otherwise\n specified, and mixed celltype.\n - Fresh and or archived tumor tissues must be available to (a) establish the diagnosis\n of the respective malignancies as described in Inclusion Criteria, and (b) be\n investigated for biomarkers. Patients without historical material or fresh tissue\n biopsy that is adequate for both diagnosis and correlative studies will not be\n eligible for the clinical trial.\n - Left Ventricular Ejection Fraction (LVEF) > 50%.\n - A performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG)\n Performance Scale.\n - Demonstrate adequate organ function. All screening labs should be performed within 14\n days of treatment initiation.\n - HIV positive patients will be eligible as long as the viral load by polymerase chain\n reaction (PCR) testing is undetectable.\n - Female patients of childbearing potential must have a negative pregnancy test within 7\n days prior to treatment start.\n - Adequate contraception.\n Exclusion Criteria:\n - The following treatments are prohibited: (a) Chemotherapy (including PI3K inhibitors\n and other approved or investigational drugs) and monoclonal antibody within 3 weeks;\n (b) radiotherapy within 2 weeks prior to entering the study; (c) systemic steroids\n that have not been stabilized (\u2265 5 days) to the equivalent of \u226410 mg/day prednisone\n prior to the start of the study drugs.\n - Patients that have not recovered from adverse events due to chemotherapy agents\n administered more than 3 weeks earlier.\n - Hypersensitivity to copanlisib or any of its excipients.\n - Type I diabetes\n - Uncontrolled Type II diabetes mellitus (HbA1c> 7.5%).\n - Type II diabetes requiring treatment with a sulfonylurea, meglitinide, or insulin.\n - Patients that received major surgery and have not recovered adequately from the\n toxicity and/or complications from the intervention prior to starting therapy.\n - Patients with active, clinically serious infections > CTCAE version 5 Grade 2.\n - Patients with known active concurrent malignancy with the following exception:\n nonmelanoma skin cancer, prostatic intraepithelial neoplasia, or carcinoma in situ of\n the cervix, prostate cancer that responds to androgen deprivation therapy and has no\n progression of disease for at least 12 months. If there is a history of prior\n malignancy, the patient must be disease-free for \u2265 3 years.\n - Uncontrolled hypertension, i.e., blood pressure (BP) of \u2265 150/90; patients who have a\n history of hypertension controlled by medication must be on a stable dose (for at\n least one month) and meet all other inclusion criteria.\n - Concomitant use of strong CYP3A4 inhibitors (defined in the protocol).\n - Uncontrolled moderate to severe hypertriglyceridemia (TG>300 mg/dL).\n - Myocardial infarction within 6 months of cycle 1, day 1.\n - Symptomatic coronary artery disease (CAD), e.g., angina Canadian Class II-IV (see\n Appendix 5).\n - An ECG recorded at screening showing evidence of cardiac ischemia.\n - Congestive heart failure (CHF) that meets New York Heart Association (NYHA) Class II\n to IV definitions and/or ejection fraction < 40% by multigated acquisition (MUGA) scan\n or < 50% by echocardiogram and/or magnetic resonance imaging (MRI);\n - Arterial or venous thrombotic or embolic events such as cerebrovascular accident\n (including transient ischemic attacks) within 6 months before the start of study\n medication.\n - Patients who are pregnant or breastfeeding, or expecting to conceive or father\n children within the projected duration of the trial, starting with the pre-screening\n or screening visit through at least 30 days after the last dose of trial treatment.\n - History of nephrolithiasis or nephrolithiasis incidentally discovered during CT\n screening. *Known selenium deficiency.\n - Body mass index (BMI) less than 20.\n - An allergy or intolerance to egg, gluten or milk protein.\n - History of serious or uncontrolled gout or hyperuricemia.\n - Pregnancy, lactation, or breastfeeding.\n - Any other disease, metabolic dysfunction, physical examination finding, or clinical\n laboratory finding that, in the investigators' opinion, gives reasonable suspicion of\n a disease or condition that contraindicates the use of an investigational drug or that\n may affect the interpretation of the results or render the patient at high risk from\n treatment complications.\n - Major surgical procedure or significant traumatic injury within 28 days prior to Day 1\n or anticipation of the need for major surgery during the course of study treatment.", "output": {"inclusion_biomarker": [["PIK3CA activating mutation"], ["PTEN loss"]], "exclusion_biomarker": []}}
{"input": "Imatinib has revolutionized the treatment of chronic myeloid leukemia (CML) and is the\n current standard of care in the treatment of patients with newly diagnosed CML. However,\n about 30% of patients still show drug resistance or disease progression. Currently, the most\n widely studied mechanism of TKI resistance in CML patients is mutations in the ABL kinase\n region. So far, more than 100 kinase domain mutations have been found in disease progression\n and imatinib resistance. It is estimated that more than 25% of CML patients will change TKI\n at least once in their lifetime due to drug resistance or intolerance. The 2020 edition of\n the \"Guidelines for the Diagnosis and Treatment of Chronic Myelogenous Leukemia in China\"\n proposes that patients with F317L/V/I/C, V299L and T315A mutations are more likely to obtain\n clinical efficacy by switching to the second-generation TKI nilotinib; patients with Y253H,\n E255K/V and F359C/V/I mutations are more likely to obtain clinical efficacy by switching to\n the second-generation TKI dasatinib; patients with T315I mutations are resistant to both\n nilotinib and dasatinib. Flumatinib has been shown to be a more potent inhibitor of BCR-ABL1\n tyrosine kinase than imatinib. In vitro studies, it has shown that flumatinib inhibits\n wild-type and common BCR-ABL mutations(Q252H, V299L, F317L/I, M351T, H396P, etc.) more\n potently, and the anti-mutation spectrum of flumatinib is similar to nilotinib. Therefore,\n this study is designed to provide clearer guidance for patients with suboptimal response or\n failure in the treatment of TKI as well as those who have specific ABL kinase domain\n mutations during CML treatment.\n ;NA;\n Inclusion Criteria:\n 1. Male or female patients \u226518 years of age;\n 2. CML-CP patients when enrolled\n Definition of diagnosis:\n Bone marrow cytogenetic confirmation of Philadelphia chromosome of t (9;22)\n translocations and/or the presence of P210 BCR-ABL1 transcripts via molecular\n assessment;\n Documented chronic phase CML will meet all the criteria defined as:\n < 15% blasts in peripheral blood and bone marrow < 30% blasts plus promyelocytes in\n peripheral blood and bone marrow < 20% basophils in the peripheral blood\n \u2265 100 x 109/L (\u2265 100,000/mm3) platelets No evidence of extramedullary leukemic\n involvement, with the exception of hepatosplenomegaly\n 3. CML-CP patients without optimal response(warning or failure) when treated with\n imatinib or dasatinib.\n 4. Female patients of childbearing potential must have a negative serum pregnancy test;\n 5. Ability to provide written informed consent prior to any study related screening\n procedures being performed.\n Exclusion Criteria:\n 1. Treatment with other tyrosine kinase inhibitor(s) except imatinib and dasatinib prior\n to study entry;\n 2. With any mutations as follows :T315I\u3001Y253F/H\u3001E255K/V\u3001F359C/V/I (if there are any other\n mutations,at physicians' discretion );\n 3. Entry into another therapeutic clinical trial;\n 4. Concomitant diseases that, according to the investigator's judgment, pose a serious\n risk to the patient's safety or completion of the study;\n 5. History of neurological or psychiatric disorders, including epilepsy or dementia;\n 6. Major surgery within 4 weeks prior to Day 1 of study;\n 7. Patients with another primary malignancy,unless the other primary malignancy is\n currently stable or does not need active intervention;\n 8. Women of reproductive age or men who are unable to use adequate methods of\n contraception, including women who are pregnant or breastfeeding;\n 9. ECOG\u22653;\n 10. Patients who are unable to compliance with study or follow-up procedures;\n 11. Allergic to any of the components in this trial;\n 12. Not appropriate to attend this trial judged by the investigator.", "output": {"inclusion_biomarker": [["Philadelphia chromosome of t (9;22) translocation"], ["BCR-ABL1 P210"]], "exclusion_biomarker": [["ABL T315I"], ["ABL Y253F"], ["ABL Y253H"], ["ABL E255K"], ["ABL E255V"], ["ABL F359C"], ["ABL F359V"], ["ABL F359I"]]}}
{"input": "Evaluate the safety and tolerability of RMC-6236 in adults with KRAS p.G12 mutant advanced\n solid tumors, KRAS p.G12C excluded.\n ;\n ;\n Inclusion Criteria:\n - Histologically confirmed advanced solid tumor with KRAS p.G12A, KRAS p.G12D, KRAS\n p.G12R, KRAS p.G12S, or KRAS p.G12V mutations identified through deoxyribonucleic acid\n (DNA) sequencing.\n - Received prior standard therapy appropriate for tumor type and stage\n - Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1\n - Adequate organ function\n Exclusion Criteria:\n - Tumor harboring the KRAS p.G12C mutation\n - Primary central nervous system (CNS) tumors\n - Known or suspected leptomeningeal or brain metastases or spinal cord compression\n - Known or suspected impairment of gastrointestinal function that may prohibit ability\n to swallow or absorb an oral medication\n - History of any other unstable or clinically significant concurrent medical condition\n that would, in the opinion of the investigator, jeopardize the safety of a\n participant, impact their expected survival through the end of the study\n participation, and/or impact their ability to comply with the protocol\n prior/concomitant therapy", "output": {"inclusion_biomarker": [["KRAS p.G12A"], ["KRAS p.G12D"], ["KRAS p.G12R"], ["KRAS p.G12S"], ["KRAS p.G12V"]], "exclusion_biomarker": [["KRAS p.G12C"]]}}
{"input": "This study will collect medical records, scan results, and complete surveys to create a\n registry about people with a neurofibromatosis type 1-associated brain tumor (NF1-associated\n glioma). A registry is a collection of health information about individuals, and it is\n usually focused on a specific diagnosis or condition.\n This registry study will help the researchers learn more about the diagnosis, treatment, and\n quality of life of people with NF1-associated glioma. The researchers want to understand what\n happens as a result of different treatments for NF1-associated glioma and how these\n treatments and the disease itself affect people's lives over a period of time. Information\n collected during this study could affect how doctors diagnose, test, and treat NF1-associated\n glioma, and the study could help future patients with this type of cancer.\n ;NA;\n Inclusion Criteria:\n - Clinical diagnosis that meets NIH criteria for NF1 disease by either 1) documented\n clinical record establishing NF1 or 2) self-reported with supported documentation upon\n medical record collection.\n - Willing to have historical and future NF1 related health records sent to registry for\n review.\n - Radiologic or pathologically confirmed glioma.\n - Individuals \u226518 years of age on the date of informed consent.\n Exclusion Criteria:\n - Unwillingness to sign informed consent.\n - No proficiency in English or Spanish as determined by the Investigator.", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
{"input": "This is an expanded access program (EAP) for eligible participants designed to provide access\n to ACE-011.\n ;NA;\n Inclusion Criteria:\n -\n Exclusion Criteria:\n -", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
{"input": "This study is open to adults with different types of advanced or metastatic cancer (including\n lung cancer, colorectal cancer, pancreatic cancer, and bile duct cancer). This study is for\n people for whom previous treatment was not successful or no treatment exists.\n People who have a tumour with a KRAS mutation can participate in the study. A KRAS mutation\n makes tumours grow faster. BI 1823911 and BI 1701963 are medicines that may turn off KRAS,\n each in a different way. In this study, BI 1823911 is given to people for the first time.\n The purpose of this study is to find the highest dose of BI 1823911 that people can tolerate\n when taken alone and together with BI 1701963. The most suitable dose is used to find out\n whether BI 1823911 alone and in combination with BI 1701963 can make tumours shrink.\n Participants can stay in the study as long as they benefit from treatment and can tolerate\n it.\n During this time, participants take tablets of BI 1823911 alone or in combination with BI\n 1701963 once a day. The doctors regularly monitor the size of the tumour. Doctors also\n regularly record any unwanted effects and check participant's health.\n ;NA;\n Inclusion Criteria:\n - Pathologically confirmed diagnosis of locally advanced or metastatic solid tumours,\n e.g. adenocarcinoma of the lung, colorectal cancer, pancreatic cancer or\n cholangiocarcinoma. Non-small cell lung cancer (NSCLC) patients with mixed histology\n are eligible if adenocarcinoma is the predominant histology.\n - Documented disease progression despite appropriate prior standard therapies or for\n whom no standard therapy exists for their tumour type and disease stage.\n - KRAS mutation status: Kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine\n (G12C) mutation in tumour tissue or blood based on previously performed local testing\n using a validated test.\n - Provision of archival tumour tissue, if available, to confirm retrospectively KRAS\n G12C mutation status and for biomarker assessment.\n - At least one target lesion that can be measured per Response Evaluation Criteria In\n Solid Tumours (RECIST) version 1.1 (radiated lesions do not qualify as target\n lesions). In patients who only have one target lesion, and a biopsy of the lesion is\n required, the baseline imaging must be performed before the biopsy or at the earliest\n two weeks after the biopsy.\n - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n - Adequate organ function as follows:\n - Absolute neutrophil count (ANC) \u22651.5 x 10^9/L (equivalent values: \u2265 1.5 x 10\u00b3/\u03bcL\n or \u2265 1500/mm\u00b3); hemoglobin \u22659.0 g/dL (equivalent values: \u2265 90 g/L or \u2265 5.6\n mmol/L); platelets \u2265100 x 10^9/L (equivalent values: \u2265 100 x 10\u00b3/\u03bcL or \u2265 100 x\n 10\u00b3/mm\u00b3) without the use of haematopoietic growth factors.\n - Total bilirubin \u22641.5 times the upper limit of normal (ULN), or \u22644 x ULN for\n patients who are known to have Gilbert's syndrome.\n - Creatinine \u22641.5 x ULN. If creatinine is >1.5 x ULN, patient is eligible if\n concurrent creatinine clearance \u226550 mL/min (equivalent value: 0.84mL/s) (measured\n or calculated by Cockcroft-Gault formula).\n - Aspartate transaminase (AST) and alanine transaminase (ALT) \u22643 x ULN, for\n patients with liver metastases \u22645 x ULN.\n - Age \u226518 years of age, or over the legal age of consent as required by local\n legislation.\n Further inclusion criteria apply.\n Exclusion Criteria:\n - Previous anticancer chemotherapy within 3 weeks of the first administration of trial\n drug. Previous anticancer hormonal treatment or anticancer immunotherapy within 2\n weeks of the first administration of trial drug.\n - Previous treatment with Rat Sarcoma (RAS), Mitogen-activated protein kinase (MAPK) or\n Son of sevenless 1 (SOS1) targeting agents (only for monotherapy Parts A, B, and C).\n - Radiotherapy within 2 weeks prior to start of treatment, provided recovery from\n related toxicity.\n - Major surgery (major according to the investigator's assessment) performed within 4\n weeks prior to start of treatment or planned during the projected course of the trial,\n e.g. hip replacement.\n - Previous treatment with any investigational agent(s) or targeted treatment within 28\n days prior to start of treatment or 5 half-lives, whichever is shorter.\n - Known history of hypersensitivity to any of the excipients of BI 1823911 tablets, or\n any contraindication to Midazolam (for Monotherapy Part B only).\n - History or presence of cardiovascular abnormalities such as congestive heart failure\n New York Heart Association (NYHA) classification of \u22653, unstable angina or poorly\n controlled arrhythmia which are considered clinically relevant by the Investigator.\n Myocardial infarction within 6 months prior to start of treatment. Uncontrolled\n hypertension defined as: Blood pressure (BP) measured in a rested and relaxed\n condition, where systolic BP >=140 mmHg, or diastolic BP >= 90 mmHg, with or without\n medication.\n - Left ventricular ejection fraction (LVEF) <50%. Further exclusion criteria apply.", "output": {"inclusion_biomarker": [["KRAS G12C"]], "exclusion_biomarker": []}}
{"input": "This is a single center and exploratory study, aiming to analyze the efficacy and safety of\n dacomitinib-a pan-HER and irreversible TKI in subjects with diagnosed stage IIIB/IV or\n recurrent NSCLC. All subjects will have tumors that test positive for at least one uncommon\n EGFR activating mutation (do not have drug-resistant pattern, e.g. 20 insertion or 20T790M).\n All patients will be of histo- and/or cytopathology confirmed. Determination of the EGFR\n mutation type will be performed in the pathological department of Shanghai Chest Hospital.\n Both ARMS method or targeted sequencing are acceptable. It is not acceptable for subjects\n with the presence of the exon 20T790M mutation or insertion together with either EGFR\n activating mutations (exon 19 deletion or the L858R mutation in exon 21) or uncommon EGFR\n mutations. 10ml peripheral blood must be available for concomitant study. All eligible\n subjects must have adequate renal, hepatic, and hematologic function, as defined in\n \"inclusion criteria\".\n Patients will receive continuous oral therapy with the study drugs (dacomitinib 45 mg) until\n progressive disease as defined by RECIST version 1.1 or judged by investigator that the\n patient no longer derives clinical benefit from study treatment. At the time of progression\n and removal from study treatment, the subject may receive any regulatory approved therapy at\n the judgment of the investigator. Timely and complete disease assessments in this study are\n important. Every effort should be made to ensure disease assessments performed as scheduled\n to prevent the introduction of bias into the assessment of efficacy. Failure to perform any\n of the required disease assessments will result in the inability to determine disease status\n for that time point. Frequent off schedule or incomplete disease assessments have the\n potential to weaken the study conclusion.\n Subjects who have progressive disease per RECIST version 1.1 confirmed by the investigator\n believes it is in their best interest to continue on their study therapy, will be allowed to\n continue on their therapy with or without local therapy (e.g. surgical removal and/or\n radiation of a single lesion), at the discretion of the investigator until any alternate or\n additional systemic anti-cancer therapy regimen is implemented. The subsequent new cancer\n therapy (including, for systemic therapy, drugs administered, date of initiation and\n discontinuation of each drug) and OS will be recorded. Each subject will be followed for\n survival status and subsequent cancer therapies up to 48 months from the date of first\n dosing. This data may be collected from subjects by telephone, and if collected should be\n entered into the CRF.\n ;NA;\n Inclusion criteria: Only patients who meet all of the following criteria will be enrolled\n into this study:\n 1. According to the 8th edition of the AJCC/UICC TNM staging system for NSCLC, patients\n with locally advanced (stage III B/III C), metastatic or recurrent (stage IV) NSCLC\n confirmed by histology or cytology who are unable to undergo surgery and radical\n concomitant radiochemotherapy and are confirmed to have at least one measurable lesion\n according to RECIST 1.1.\n 2. Patients harboring uncommon EGFR mutations. Uncommon EGFR mutations were defined as\n mutations in exon 18-21 but except for 19del, 21L858R and well-established drug\n resistant type (20 insertion, 20T790M, 19L747S, 19L747P, D761Y, 21T854A). Mutations\n should be previously reported that it was sensitive to first- or second-generation\n TKIs. Detailed mutation type including:\n Mutation in exon 18:\n G719X(X=A/C/S/D/E), 18del, E709X(X=G/M/V/H/DA/K), V689M, S720P/F, P699S, N700D, E709Q,\n G721A, V740A, L718P;\n Mutation in exon 19:\n Few exon 19 point mutations with unknown structure and kinase activity have been found\n in EGFR-TKI responders, however, a new class of sensitizing mutations, exon 19\n insertions, were recently found, these patients were also eligible for this study:\n I744_K745insKIPVAI, K745_E746insIPVAIK, K745_E746insVPVAIK, K745_E746insTPVAIK.\n Mutation in exon 20:\n Including S768I, V765A, T783A, V774A, S784P, R776C, R776H, V765M, G779C, G779F, G779S,\n T783A, T783I, L798F, L798H, K806E, Q812R, L814P\n Mutation in exon 21:\n L861Q, R831H, V834I, L838P, L861R.\n Others:\n Patients with complex mutation but do not have drug-resistant pattern (e.g.\n 18G719A+20S768I, 18 E709X+21L861Q) are also eligible. However, individuals who have\n common mutation (e.g. 19del+21L861Q, 18G719X+21L858R) were not eligible.\n 3. Age \u226518 years and \u226475 years;\n 4. ECOG PS score: 0 to 2\n 5. Previously untreated with EGFR-TKIs including first-, second- or third generation\n agents. Subjects who were only treated with chemotherapy were eligible. Patients who\n have received adjuvant chemotherapy but disease recurrence must have happened at least\n 6 months after the last dose of chemotherapy. Palliative radiotherapy must be\n completed 7 days before the first dose of study drugs;\n 6. The main organs function is normal, that is, the following criteria met:\n - Good hematopoietic function, defined as absolute neutrophil count \u22651.5\u00d7109 /L,\n platelet count\u2265100 \u00d7109 /L, hemoglobin \u226590g/L [no blood transfusion or no\n erythropoietin (EPO) dependence within 7 days before enrollment]\n - Biochemical test results should meet the following criteria: BIL < 1.25 times the\n upper limit of normal value (ULN); ALT and AST < 2.5 \u00d7 ULN; in case of liver\n metastases, ALT and AST < 5 \u00d7 ULN; Cr \u22641.5\u00d7ULN or creatinine clearance (CCr)\n \u226560ml/min; Coagulation function is good, INR and PT \u22641.5 times ULN; if the\n subject is receiving anticoagulant treatment, PT should be within the prescribed\n range of use of anticoagulant drugs;\n 7. Women of child-bearing age should agree to take contraceptive measures (such as\n intrauterine devices, contraceptives or condoms) during the study and within 6 months\n after the study; non-breast-feeding patients whose serum or urinary pregnancy test\n should be negative; male patients should agree to take contraceptive measures during\n the study and within 6 months after the study.\n 8. Patients are voluntarily enrolled into the study, sign the informed consent form and\n have good compliance.\n Exclusion criteria\n Patients who meet any of the following criteria will be excluded:\n 1. Small cell lung cancer (including mixed small cell and non-small cell lung cancer);\n 2. Patients who have received EGFR-TKIs as adjuvant or salvaged treatment;\n 3. Patients with 19del or 21L858R or well-established drug resistant type (20 insertion,\n 20T790M, L747S, L747P, D761Y, T854A).\n 4. Patients with many factors affecting oral medication, such as dysphagia,\n gastrointestinal resection, chronic diarrhea and intestinal obstruction;\n 5. Patients who are known to have brain metastases including asymptomatic metastasis,\n spinal cord compression, carcinomatous meningitis, or brain or leptomeningeal disease\n diagnosed by CT or MRI at the time of screening;\n 6. Patients with severe and / or uncontrolled diseases, such as:\n - Unstable angina pectoris, symptomatic congestive heart failure, myocardial\n infarction within 6 months before randomization, severe uncontrolled arrhythmias;\n uncontrolled blood pressure (systolic blood pressure > 140 mmHg, diastolic blood\n pressure > 90 mmHg);\n - Active or uncontrolled serious infection;\n - Liver diseases such as cirrhosis, decompensated liver disease, acute or chronic\n active hepatitis;\n - Not completely controlled eye inflammation or eye infection, or any condition\n that may lead to the above-mentioned ocular diseases\n - Poorly controlled diabetes (fasting blood glucose (FBG) > 10mmol/L);\n - Routine urine test result indicates that urine protein \u2265++, and 24-hour urine\n protein quantitation is confirmed to be > 1.0 g;\n - Active tuberculosis, etc.;\n - Uncontrolled hypercalcemia (> 1.5 mmol/L calcium ion or calcium > 12 mg/dL or\n corrected serum calcium > ULN), or symptomatic hypercalcemia requiring continued\n diphosphate therapy;\n - Long-term unhealed wounds or fractures;\n 7. Patients who have a history of psychotropic drug abuse and cannot abstain from it or\n have mental disorders;\n 8. Patients who are known to have severe allergies (\u2265 grade 3) to active ingredients and\n any excipients of dacomitinib\n 9. Patients who have other malignant tumors (except radical cervical carcinoma in situ,\n non-melanoma skin cancer, etc.) at the same time; patients who are evaluated by the\n investigator to have concomitant diseases that seriously endanger the safety of the\n patients or affect the patients completing the study.\n 10. The subjects or their sexual partners cannot or refuse to take effective contraceptive\n measures during the clinical trial\n 11. Pregnant or breast-feeding women\n 12. Patients in other situations who are evaluated by the investigator to be ineligible to\n be enrolled", "output": {"inclusion_biomarker": [["EGFR activating mutation"], ["EGFR uncommon mutation"], ["EGFR exon 18 mutation"], ["EGFR exon 19 mutation"], ["EGFR exon 20 mutation"], ["EGFR exon 21 mutation"], ["EGFR G719A"], ["EGFR G719C"], ["EGFR G719S"], ["EGFR G719D"], ["EGFR G719E"], ["EGFR 18del"], ["EGFR E709G"], ["EGFR E709M"], ["EGFR E709V"], ["EGFR E709H"], ["EGFR E709DA"], ["EGFR E709DK"], ["EGFR V689M"], ["EGFR S720P"], ["EGFR S720F"], ["EGFR P699S"], ["EGFR N700D"], ["EGFR E709Q"], ["EGFR G721A"], ["EGFR V740A"], ["EGFR L718P"], ["EGFR I744_K745insKIPVAI"], ["EGFR K745_E746insIPVAIK"], ["EGFR K745_E746insVPVAIK"], ["EGFR K745_E746insTPVAIK"], ["EGFR S768I"], ["EGFR V765A"], ["EGFR T783A"], ["EGFR V774A"], ["EGFR S784P"], ["EGFR R776C"], ["EGFR R776H"], ["EGFR V765M"], ["EGFR G779C"], ["EGFR G779F"], ["EGFR G779S"], ["EGFR T783I"], ["EGFR L798F"], ["EGFR L798H"], ["EGFR K806E"], ["EGFR Q812R"], ["EGFR L814P"], ["EGFR L861Q"], ["EGFR R831H"], ["EGFR V834I"], ["EGFR L838P"], ["EGFR L861R"], ["EGFR 18G719A+20S768I"], ["EGFR 18 E709X+21L861Q"]], "exclusion_biomarker": [["EGFR 19del+21L861Q"], ["EGFR 18G719X+21L858R"], ["EGFR exon 19 deletion"], ["EGFR exon 21 L858R"], ["EGFR 20 insertion"], ["EGFR exon 20 T790M"], ["EGFR L747S"], ["EGFR L747P"], ["EGFR D761Y"], ["EGFR T854A"]]}}
{"input": "This clinical trial is the first-in-human study of BBT-176. The purpose of this trial is to\n investigate the safety and tolerability of BBT-176 (Part 1) and to evaluate the anti-tumor\n activity of BBT-176 (Part 2).\n ;NA;\n Key Inclusion Criteria:\n - Provision of signed and dated, written informed consent before any study specific\n procedures, sampling and analyses\n - Histological or cytological confirmation of advanced and/or metastatic stage IIIB/IV\n NSCLC\n - Radiological documentation of disease progression while on a previous continuous (at\n least 30 days) treatment with an EGFR TKI monotherapy (including, but not limited to,\n osimertinib, afatinib, gefitinib, or erlotinib)\n - Patients must fulfill one of the following:\n - Confirmation that the tumor harbors an EGFR mutation known to be associated with\n EGFR TKI sensitivity (including, but not limited to, exon 19 deletion, L858R, or\n L861Q)\n - Documented partial or complete response or a significant and durable stable\n disease (at least 6 months), based on the RECIST or WHO criteria, after treatment\n of an EGFR TKI\n Key Exclusion Criteria:\n - Treatment with any of the following:\n - An EGFR TKI, including but not limited to osimertinib, afatinib, gefitinib, or\n erlotinib within 8 days of the first dose of study treatment.\n - Any cytotoxic chemotherapy, investigational agents, or anticancer drugs for the\n treatment of advanced NSCLC, between prior EGFR TKI treatment and BBT-176\n treatment\n - Major surgery (excluding placement of vascular access) within 4 weeks of the\n first dose of study treatment\n - Radiotherapy with a limited field of radiation for palliation within 1 week of\n the first dose of study treatment\n - Patients receiving radiation to more than 30% of the bone marrow or with a wide\n field of radiation within 6 weeks of the first dose of study treatment\n - Any unresolved toxicities from prior therapy greater than NCI Common Terminology\n Criteria for Adverse Events (CTCAE v5.0) Grade 1 at the time of starting study\n treatment, with the exception of alopecia and Grade 2 neuropathy related to prior\n platinum-therapy\n - Spinal cord compression or brain metastases, unless asymptomatic and stable", "output": {"inclusion_biomarker": [["EGFR mutation"], ["EGFR exon 19 deletion"], ["EGFR L858R"], ["EGFR L861Q"]], "exclusion_biomarker": []}}
{"input": "This phase II trial studies the effect of polatuzumab vedotin, venetoclax, and rituximab and\n hyaluronidase human in treating patients with mantle cell lymphoma that has come back\n (relapsed) or does not respond to treatment (refractory). Polatuzumab vedotin is a monoclonal\n antibody, polatuzumab, linked to a toxic agent called vedotin. Polatuzumab attaches to CD79B\n positive cancer cells in a targeted way and delivers vedotin to kill them. Venetoclax may\n stop the growth of cancer cells by blocking Bcl-2, a protein needed for cell growth.\n Rituximab hyaluronidase is a combination of rituximab and hyaluronidase. Rituximab binds to a\n molecule called CD20, which is found on B cells (a type of white blood cell) and some types\n of cancer cells. This may help the immune system kill cancer cells. Hyaluronidase allows\n rituximab to be given by injection under the skin. Giving rituximab and hyaluronidase by\n injection under the skin is faster than giving rituximab alone by infusion into the blood.\n Giving polatuzumab vedotin, venetoclax, and rituximab and hyaluronidase human may work better\n than standard therapy in treating patients with mantle cell lymphoma.\n ;\n ;\n Inclusion Criteria:\n - Pathologically confirmed relapsed or primary refractory mantle cell lymphoma with\n concurrent or prior tissue sample immunohistochemistry (IHC) positive for cyclin D1 or\n that is positive for fluorescence in situ hybridization (FISH) or cytogenetics for\n t(11;14)\n - NOTE: Safety Portion only: MCL or indolent B cell non-Hodgkin lymphoma (NHL)\n (follicular lymphoma [FL] [grades I-IIIa] marginal zone lymphoma [MZL]), or,\n small lymphocytic lymphoma (SLL) stratified as low risk for tumor lysis syndrome\n (TLS), relapsed or progressed after at least two lines of therapy (or one BTK\n inhibitor containing line of therapy). No limit to prior lines of therapy\n - NOTE: Expansion Portion only: MCL relapsed or progressed after at least two lines\n of therapy or one BTK inhibitor line of therapy. Prior autologous stem cell\n transplant (AutoSCT) is allowed. No limit to number of prior therapies. May have\n received prior BTK inhibitor therapy\n - Measurable disease as defined with at least one lesion measuring >= 1 x 1.5 cm\n - Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2\n - Absolute neutrophil count (ANC) >= 1000/mm^3 (obtained =< 14 days prior to\n registration)\n - Platelet count >= 75,000/mm^3 (obtained =< 14 days prior to registration)\n - Hemoglobin >= 9.0 g/dL (obtained =< 14 days prior to registration)\n - International normalized ratio =< 1.5 x upper limit of normal (ULN) for patients not\n receiving therapeutic anticoagulation (obtained =< 14 days prior to registration)\n - Partial thromboplastin time (PTT) or activated PTT (aPTT) =< 1.5 x ULN (obtained =< 14\n days prior to registration)\n - Calculated creatinine (Cr) clearance >= 45 ml/min using the modified Cockcroft-Gault\n formula (obtained =< 14 days prior to registration)\n - Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 x ULN\n (obtained =< 14 days prior to registration)\n - Total bilirubin < 1.5 x ULN (or =< 3 x ULN for patients with documented Gilbert\n syndrome) (obtained =< 14 days prior to registration)\n - Negative serum pregnancy test done =< 7 days prior to registration, for women of\n childbearing potential only\n - Able to provide informed written consent, and ability to comply with study related\n procedures\n - Willing to return to enrolling institution for follow-up (during the Active Monitoring\n Phase of the study)\n - Willing to provide tissue samples for mandatory correlative research\n - For women of childbearing potential: agreement to remain abstinent (refrain from\n heterosexual intercourse) or use a contraceptive method with a failure rate of < 1%\n per year during the treatment period and for at least 30 days after the last dose of\n venetoclax or 18 months after the last dose of rituximab and hyaluronidase human,\n whichever is longer. For men: agreement to remain abstinent (refrain from heterosexual\n intercourse) or use contraceptive measures, and agreement to refrain from donating\n sperm, as defined below:\n - With female partners of childbearing potential, men must remain abstinent or use\n a condom plus an additional contraceptive method that together result in a\n failure rate of < 1% per year during the treatment period and for at least 6\n months after the last dose. Men must refrain from donating sperm during this same\n period.\n - With pregnant female partners, men must remain abstinent or use a condom during\n the treatment period and for at least 6 months after the last dose to avoid\n exposing the embryo\n Exclusion Criteria:\n - Any of the following because this study involves an investigational agent whose\n genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are\n unknown:\n - Pregnant women\n - Nursing women\n - Men or women of childbearing potential who are unwilling to employ adequate\n contraception\n - Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment\n of the investigator, would make the patient inappropriate for entry into this study or\n interfere significantly with the proper assessment of safety and toxicity of the\n prescribed regimens\n - Uncontrolled intercurrent illness including, but not limited to, ongoing or active\n infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac\n arrhythmia, or psychiatric illness/social situations that would limit compliance with\n study requirements\n - Receiving any other investigational or chemotherapeutic agent which would be\n considered as a treatment for the primary neoplasm\n - Known CD20-negative status at relapse or progression\n - Prior allogeneic SCT\n - Completion of autologous SCT =< 100 days prior to registration\n - Radioimmunoconjugate =< 12 weeks prior to registration\n - Monoclonal antibody or antibody-drug conjugate (ADC) therapy within 5 half-lives or 4\n weeks prior to registration, whichever is longer\n - Radiotherapy, chemotherapy, hormonal therapy, or targeted small-molecule therapy\n within 2 weeks prior to registration (with the exception of ibrutinib to prevent tumor\n flare, patients taking ibrutinib who are progressing must discontinue ibrutinib 2\n half-lives or 2 days prior to initiating protocol therapy)\n - Clinically significant toxicity (other than alopecia) from prior therapy that has not\n resolved to grade =< 2 (per National Cancer Institute [NCI] Common Terminology\n Criteria for Adverse Events [CTCAE] version [v]5.0) prior to registration\n - Current grade > 1 peripheral neuropathy\n - Any history of central nervous system (CNS) lymphoma or leptomeningeal infiltration\n - Treatment with systemic corticosteroids > 20 mg/day prednisone or equivalent Patients\n who are receiving corticosteroids =< 20 mg/day, prednisone or equivalent, for\n non-lymphoma treatment reasons must be documented to be on a stable dose for at >= 4\n weeks prior to registration. If corticosteroid treatment is urgently required for\n lymphoma symptom control prior to the start of study treatment, up to 100 mg/day of\n prednisone or equivalent can be given for a maximum of 5 days, but all tumor\n assessments must be completed prior to start of corticosteroid treatment\n - History of severe allergic or anaphylactic reaction or known sensitivity to humanized\n or murine monoclonal antibodies rituximab, polatuzumab vedotin, and venetoclax\n - Active bacterial, viral, fungal, or other infection\n - Requirement for warfarin treatment (because of potential drug-drug interactions [DDIs]\n that may increase the exposure of warfarin)\n - Treatment with the following agents =< 7 days prior to registration\n - Strong and moderate CYP3A inhibitors such as fluconazole, ketoconazole, and\n clarithromycin\n - Strong and moderate CYP3A inducers such as rifampin and carbamazepine. If taking\n proton pump inhibitors willing to avoid co-administration and stagger venetoclax\n dosing\n - Consumption of grapefruit, grapefruit products, Seville oranges (including marmalade\n that contains Seville oranges), or star fruit =< 3 days prior to registration\n - Clinically significant history of liver disease, including viral or other hepatitis,\n current alcohol abuse, or cirrhosis\n - Active hepatitis B or hepatitis C infection. Patients who have been successfully\n treated and cleared their virus as evidenced a negative hepatitis (Hep) B or Hep C\n polymerase chain reaction (PCR) are eligible\n - Known history of human immunodeficiency virus (HIV) positive status or known infection\n with human T-cell leukemia virus 1. For patients with unknown HIV status, HIV testing\n will be performed at screening if required by local regulations\n - History of PML (progressive multifocal leukoencephalopathy)\n - Vaccination with a live virus vaccine =< 28 days prior to registration\n - History of other malignancy that could affect compliance with the protocol or\n interpretation of results, with the exception of the following: curatively treated\n carcinoma in situ of the cervix, good-prognosis ductal carcinoma in situ of the\n breast, basal- or squamous-cell skin cancer, stage I melanoma, or low-grade,\n early-stage localized prostate cancer\n - Any previously treated malignancy that has been in remission without treatment for =<\n 3 years prior to registration\n - Evidence of any significant, uncontrolled concomitant disease that could affect\n compliance with the protocol or interpretation of results, including significant\n cardiovascular disease (such as New York Heart Association class III or IV cardiac\n disease, myocardial infarction within the previous 6 months, unstable arrhythmia, or\n unstable angina) or significant pulmonary disease (such as obstructive pulmonary\n disease or history of bronchospasm)\n - Major surgical procedure other than for diagnosis =< 28 days prior to day 1 of cycle\n 1, or anticipation of a major surgical procedure during the course of the study\n - Inability or unwillingness to swallow pills\n - History of malabsorption syndrome or other condition that would interfere with enteral\n absorption\n - History of inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis) or\n active bowel inflammation (e.g., diverticulitis)", "output": {"inclusion_biomarker": [["cyclin D1 positive"], ["t(11;14) positive"]], "exclusion_biomarker": [["CD20 negative"]]}}
{"input": "The objective of this study is to evaluate the safety, tolerability and PK profile of\n HMPL-295S1 and determine MTD and/or RP2D in patients with advanced malignant solid tumor. It\n will be extended to enroll 10-15 patients at this dose after RP2D is determined, as to\n further evaluate the safety of RP2D and the preliminary efficacy of HMPL-295S1. In addition,\n an exploratory study on the pharmacokinetic biomarkers of HMPL-295S1 is planned in this\n study.\n ;\n ;\n Inclusion Criteria:\n All the following conditions must be met for enrollment:\n 1. Having understood this study adequately and being voluntary to sign the informed\n consent form;\n 2. Aged 18~75 years (inclusive);\n 3. Patients with histopathologically or cytologically confirmed advanced malignant solid\n tumors who have failure of standard of care or can not tolerate standard of care, or\n can not obtain standard of care for various reasons, or have no standard of care\n (regardless of previous surgery);\n 4. Having at least one measurable lesion (in accordance with the RECIST 1.1 criteria);\n note: the lesion previously irradiated can not be regarded as target lesion, unless\n unequivocal progression of disease is shown in radiological evidence after\n radiotherapy;\n 5. United States Eastern Cooperative Oncology Group (ECOG) Performance Status score \u2264 1;\n 6. Life expectancy \u226512 weeks based on investigator's judgment;\n 7. Having adequate bone marrow, hepatic and renal function (no transfusion of whole\n blood, blood components, blood products, no use of granulocyte colony-stimulating\n factor or other hematopoietic stimulator or drug for correction within two weeks prior\n to blood collection):\n - Absolute neutrophil count \u22651.5\u00d7109/L;\n - HGB\u226590 g/L;\n - Platelet count \u2265 100\u00d7109/L;\n - Serum total bilirubin \u2264 1.5 \u00d7 upper limit of normal (ULN) [alanine\n aminotransferase (ALT) and aspartate aminotransferase (AST) need to be normal,\n serum total bilirubin needs to be \u22643 \u00d7 ULN in the patients with Gilbert disease];\n - Serum ALT and/or AST \u22642.5 \u00d7 ULN in the patients without hepatic metastasis (ALT\n and AST \u22645 \u00d7ULN for those with liver metastasis);\n - Creatinine clearance \u2265 60 mL/min (calculated according to Cockcroft-Gault\n formula, see Appendix 11);\n - International normalized ratio (INR) \u22641.5, and activated partial thromboplastin\n time (aPTT) \u2264 1.5 ULN.\n 8. A man of childbearing potential and his heterosexual partner of childbearing age must\n agree to use effective contraceptive methods from the signature of informed consent\n form to 90 days after the last dose; any female of childbearing potential (including\n those who have received tubal ligation) must receive serum or urine pregnancy test and\n the result is negative within 7 days prior to the first dose of study drug; and she\n must agree to use effective contraceptive methods, for example, dual barrier\n contraceptive method, intrauterine device, etc., from the signature of informed\n consent form to 30 days after the last dose of study drug. Postmenopausal woman (age >\n 50 years and menopause for 1 year or above, in the absence of other biological or\n physiological reasons) and the woman receiving irreversible sterilization operation\n (including hysterectomy, bilateral ovariectomy or bilateral salpingectomy, but\n excluding tubal ligation) who is regarded as infertile, will not be restricted by this\n condition.\n Exclusion Criteria:\n - The patients can not participate in this study if any of the following conditions is\n met:\n 1. Previous antitumor therapy meeting any of the following:\n 1. Previous treatment with a ERK inhibitor and having PD;\n 2. Receiving approved systematic antitumor therapy within 4 weeks prior to the\n first dose, including chemotherapy, targeted therapy, immunotherapy,\n biotherapy, etc. (elution for two weeks for hormone therapy or treatment\n with traditional Chinese medicine and Chinese patent drug with clear\n antitumor indication);\n 3. In the treatment period of other interventional clinical study (including\n small molecular chemical drug and macromolecular antibody) within 4 weeks\n prior to the first dose. Patients can be enrolled in this study if they are\n involved in non-interventional clinical study (e.g., epidemiological study);\n and can also be enrolled if they stay in the survival follow-up period of\n one interventional clinical study.\n 4. Having received major surgery or radical radiotherapy (except for the\n palliative radiotherapy for bone metastasis) within 4 weeks prior to the\n first dose.\n 2. Toxicity associated with previous antitumor therapy (including surgery,\n chemotherapy, radiotherapy, targeted therapy and immunotherapy) not recovered to\n \u2264 CTCAE grade 1, except for alopecia and peripheral neuropathy. The peripheral\n neurotoxicity needs to be recovered to \u2264 CTCAE grade 2 in the patients who have\n been previously treated with platinum;\n 3. Patients with central nervous system (CNS) malignant tumor or malignant solid\n tumor with known CNS metastasis;\n 4. Combined with other malignant tumor or having a history of other malignant tumor\n within 2 years prior to study screening (not including the basal or squamous cell\n carcinoma of skin, non-melanoma skin cancer, papillary thyroid carcinoma that\n have been appropriately treated, or radically resected cervical carcinoma in situ\n and ductal carcinoma in situ);\n 5. Known history of clinically significant liver disease, including viral or other\n hepatitis, except the following patients:\n - HBsAg positive patients can be enrolled if the polymerase chain reaction\n (PCR) test of hepatitis B virus (HBV) DNA is negative. The investigator can\n provide preventive or therapeutic antiviral therapy based on patient's\n condition and diagnostic routines during study treatment;\n - Patients with positive hepatitis C virus (HCV) antibody can be enrolled if\n the PCR test of HCV RNA is negative.\n 6. Patients infected by human immunodeficiency virus (HIV);\n 7. Presence of active bacterial, fungal or viral infection requiring systematic\n treatment within one week prior to the first dose;\n 8. Use of CYP3A potent inducer within 2 week or 5 half-lives (whichever is longer, 3\n weeks needed for St. John's wort) prior to the first dose, see (Appendix 5);\n 9. Use of CYP3A, P-gp potent inhibitor or sensitive substrate of P-gp, BCRP, MATE\n 2-K, CYP3A, CYP2C8/OATP1B1 and CYP2D6/CYP3A within one week or three half-lives\n (whichever is longer) prior to the first dose, this exclusion criterion will be\n adjusted in accordance with the actual dose of HMPL-295S1 and determined plasma\n concentration during the clinical study (see Appendix 5);\n 10. Meeting any of the following criteria for cardiac examination:\n - Hereditary long QT syndrome or QTcF>480 msec (the formula is seen in\n Appendix 10), or currently taking the drugs that are known to prolong QT\n interval or lead to torsade de pointe arrhythmia (Appendix 6);\n - Serious arrhythmia or conduction abnormality requiring clinical\n intervention;\n - Impaired cardiac function or clinically significant cardiac disease,\n including but not limited to the acute myocardial infarction, unstable\n angina pectoris, coronary artery bypass grafting, New York Heart Association\n (NYHA, see Appendix 9) evaluated Grade III/IV congestive heart failure, left\n ventricular ejection fraction (LVEF) <50%, or uncontrollable hypertension\n within 6 months prior to enrollment.\n 11. Pregnant or lactating women;\n 12. Having multiple factors affecting absorption, distribution, metabolism or\n excretion of oral drugs, e.g., inability to swallow, frequent vomiting, chronic\n diarrhea, etc.;\n 13. Currently known or previous retinopathy;\n 14. Any other disease, metabolic abnormality, physical examination abnormality or\n clinically significant laboratory examination abnormality, one disease or state\n that may affect patient's compliance or provides a reason to suspect that the\n patient is not suitable to use the study drug, or will affect interpretation of\n the study results, or bring the patient at a high risk, according to\n investigator's judgment.", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}
{"input": "Patients with refractory and/or recurrent solid tumor have poor prognosis despite complex\n multimodel therapy and therefore, novel approaches are urgently needed. This study attempts\n to treat these diseases using T cells genetically modified with a 4th generation lentiviral\n chimeric antigen receptor (4SCAR fused with an inducible apoptotic caspase 9 domain)\n targeting CD276 (B7-H3). The 4SCAR-CD276-modified T cells (4SCAR-276) can recognize and kill\n tumor cells through the recognition of CD276, a surface protein expressed at high levels on\n many types of tumors but at low levels on normal tissues. This study will evaluate the side\n effects and effective doses of 4SCAR-276 in treating refractory and/or recurrent tumors.\n ;\n ;\n Inclusion Criteria:\n - Patients with tumors have received standard first-line therapy and have been judged to\n be non-resectable, metastatic, progressive or recurrent.\n - The CD276 antigen status of the tumor is determined for eligibility. Positive\n expression is defined by antibody staining results based on immunohistochemistry or\n flow cytometry analysis.\n - Body weight greater than or equal to 10 kg.\n - Age: \u22651 year and \u2264 75 years of age at the time of enrollment.\n - Life expectancy: at least 8 weeks.\n - Prior Therapy: 1) There is no limit to the number of prior treatment regimens. Any\n grade 3 or 4 non-hematologic toxicity of any previous therapy must have resolved to\n grade 2 or less. 2) Must not have received hematopoietic growth factors for at least 1\n week prior to mononuclear cells collection. 3) At least 7 days must have elapsed since\n the completion of therapy with a biologic agent, targeted agent, tyrosine kinase\n inhibitor or a metronomic nonmyelosuppressive regimen. 4) At least 4 weeks must have\n elapsed since prior therapy that included a monoclonal antibody. 5) At least 1 week\n since any radiation therapy at the time of study entry.\n - Karnofsky/jansky score of 60% or greater.\n - Cardiac function: Left ventricular ejection fraction greater than or equal to 40/55\n percent .\n - Pulse Ox greater than or equal to 90% on room air.\n - Liver function: defined as alanine transaminase (ALT) <3x upper limit of normal (ULN),\n aspartate aminotransferase (AST) <3x ULN; serum bilirubin and alkaline phosphatase <2x\n ULN.\n - Renal function: Patients must have serum creatinine less than 3 times upper limit of\n normal.\n - Marrow function: White blood cell count \u22651000/ul, Absolute neutrophil count \u2265500/ul,\n Absolute lymphocyte count \u2265500/ul, Platelet count \u226525,000/ul (not achieved by\n transfusion).\n - Patients with known bone marrow metastatic disease will be eligible for study as long\n as they meet hematologic function criteria, and the marrow disease not evaluable to\n have hematologic toxicity.\n - For all patients enrolled in this study, themselves or their parents or legal\n guardians must sign an informed consent and assent.\n Exclusion Criteria:\n Existing severe illness (e.g. significant cardiac, pulmonary, hepatic diseases, etc.) or\n major organ dysfunction, or grade 3 hematologic toxicity.\n - Untreated central nervous system (CNS) metastasis: Patients with CNS tumor involvement\n that has been treated and/or is stable for at least 6 weeks following completion of\n therapy are eligible.\n - Previous treatment with other genetically engineered CD276-CAR T cells or CD276\n antibody therapy.\n - Active HIV, Hepatitis B virus (HBV), Hepatitis C virus (HCV) infection or uncontrolled\n infection.\n - Patients who require systemic corticosteroid or other immunosuppressive therapy.\n - Evidence of tumor potentially causing airway obstruction.\n - Inability to comply with protocol requirements.\n - Insufficient CAR T cells availability.", "output": {"inclusion_biomarker": [["CD276 expression"]], "exclusion_biomarker": []}}
{"input": "This intermediate-size IND will treat participants with incurable, advanced or metastatic\n cancer, harboring KRAS G12V mutation and appropriate HLA class II match (HLA-DRB1*07:01).\n ;\n ;\n Patients with incurable, advanced or metastatic cancer, harboring KRAS G12V mutation, and\n appropriate HLA class II match (HLA-DRB1*07:01)", "output": {"inclusion_biomarker": [["KRAS G12V", "HLA class II match"]], "exclusion_biomarker": []}}
{"input": "This is an open-label, multi-center study to evaluate the safety, tolerability, and\n anti-tumor activity of SNK01 in combination with AFM24 in subjects with advanced or\n metastatic EGFR-expressing cancers.\n ;\n ;\n Key Inclusion Criteria:\n 1. Capable of giving signed informed consent\n 2. Males and females age \u2265 18 years\n 3. Phase 1/Dose Escalation : any histologically confirmed advanced or metastatic\n EGFR-positive malignancy for which all standard of care treatment options have been\n received and are no longer effective or are considered inappropriate at the discretion\n of the investigator.\n 4. Phase 2a/Expansion : histologically confirmed advanced or metastatic EGFR positive\n malignancy of mCRC (EXP-1 cohort), SCCHN (EXP-2 cohort) or NSCLC (EXP-3 cohort).\n 5. Additional Criteria for Phase 2a/Expansion: subjects must have a disease history\n specific to their disease as listed below:\n 1. EXP-1: mCRC. Metastatic colorectal cancer (mCRC) MSI low/DNA mismatch repair\n proficient. Subjects must have received \u2265 1 lines of previous combination therapy\n and must have been exposed to oxaliplatin, irinotecan, a fluoropyrimidine, a VEGF\n targeting agent and, if considered appropriate by the treating physician, an EGFR\n targeted antibody.\n 2. EXP-2: SCCHN. Subjects with advanced or metastatic SCCHN whose disease has\n progressed after having received \u2265 1 prior lines of therapy for advanced disease,\n which must have included platinum-based therapy, fluoropyrimidine, and an anti PD\n 1/PD-L1 antibody.\n 3. EXP-3: NSCLC. Subjects with advanced or metastatic EGFR-expressing NSCLC (EGFR\n WT) whose disease has progressed after having received \u2265 1 prior lines of therapy\n for advanced disease. Subjects must have received at least a platinum-based\n doublet in combination with anti-PD1/PD-L1 antibody or must have received a\n platinum-based doublet followed by an anti-PD1/PD-L1 antibody.\n 6. One or more measurable tumors lesions per RECIST v1.1\n 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1\n 8. Adequate bone marrow, hepatic and renal function.\n Key Exclusion Criteria:\n 1. Superior vena cava syndrome contra-indicating hydration\n 2. Untreated or symptomatic central nervous system (CNS) metastases\n 3. No resolution of specific toxicities related to any prior anti-cancer therapy to Grade\n \u2264 1 according to the NCI-CTCAE v.5.0 (except peripheral or motor neuropathy,\n lymphopenia and alopecia)\n 4. Treatment with systemic anticancer therapy or an investigational device within 4 weeks\n (6 weeks if therapy was mitomycin C and/or nitrosoureas), or within 5 half-lives of\n the agent (if half-life is known and it is shorter) before the first dose of study\n treatment.\n 5. Radiation therapy within 2 weeks before first dose of any study treatment or\n unresolved (NCI CTCAE v5.0 Grade > 1) toxicity from previous radiotherapy\n 6. Clinically significant cardiovascular disease\n 7. Major surgery within 4 weeks prior to any study treatment administration\n 8. Any pulmonary, thyroid, renal, hepatic severe/uncontrolled concurrent medical disease\n that in the opinion of the Investigator could cause unacceptable safety risks or\n compromise compliance with the protocol\n 9. Active uncontrolled viral, fungal, or bacterial infection requiring systematic therapy\n within 14 days prior to first dose of study treatment.\n 10. Known history of testing positive for human immunodeficiency virus (HIV), and/or\n positive test for Hepatitis B virus surface antigen (HBsAg) and/or positive Hep C\n antibody result with detectable hepatitis C virus (HCV) ribonucleic acid (RNA)\n indicating acute or chronic infection.\n 11. Autoimmune disease requiring therapy; immunodeficiency, or any disease process\n requiring systemic immunosuppressive therapy\n 12. A serious nonmalignant disease that could compromise protocol objectives in the\n opinion of the Investigator and/or the Sponsor\n 13. Any other condition that, in the opinion of the Investigator, would prohibit the\n subject from participating in the study", "output": {"inclusion_biomarker": [["EGFR expression"], ["MSI low"], ["DNA mismatch repair proficient"]], "exclusion_biomarker": []}}
{"input": "The objectives of this study are to evaluate the safety, tolerability, and pharmacokinetic\n profile of HB002.1T in combination with different chemotherapy regimens administered to\n patients with advanced solid tumors.\n ;\n ;\n Inclusion Criteria:\n 1. 18 years\u2264Age\u226475 years\n 2. Histologically or cytologically confirmed advanced malignant solid tumor , including\n gastric cancer, ovarian cancer, cervical cancer, head and neck cancer, lung cancer,\n biliary tract tumor, pancreatic cancer, bladder cancer and nasopharyngeal carcinoma\n (not limited to the above tumor types) . And be suitable for the treatment of HB0021.T\n combined with 3 different chemotherapy regimen assessed by the investigators.\n 3. No prior radiotherapy, chemotherapy, targeted therapy, endocrine therapy or\n immunotherapy within 4 weeks before the first administration of HB002.1T. And no\n traditional herb medicines for anti-tumor within 2 weeks .\n 4. No prior antiangiogenic therapy such as bevacizumab, ramucirumab, apatinib or\n regofinib, et al.\n 5. At least one measurable tumor lesion as per RECIST criteria v1.1\n 6. ECOG performance status of 0 or 1\n 7. Life expectancy of at least 12 weeks\n 8. Meet following organ functions:\n 1. Absolute neutrophil count \u22652.0 x 10^9/L(no Recombinant human granulocyte colony\n stimulating factor support therapy with 14 days)\n 2. Hemoglobin \u2265100g/L(no blood transfusion or erythropoietin support treatment was\n received within 14 days)\n 3. Platelet count \u2265100\u00d710^9/L (No Recombinant human thrombopoietin and other\n supportive therapies within 14 days prior to screening phase)\n 4. Serum creatinine\u22641.5\u00d7ULN or creatinine clearance of\u226560ml/min (based on the\n Cockcroft Gault formula).\n 5. Serum total bilirubin\u22641.5\u00d7ULN.\n 6. ALT and AST \u22642.5\u00d7ULN, with the following exceptions: Patients with liver\n metastases assessed by investigators: AST and/or ALT\u22645\u00d7ULN\n 7. Blood potassium\u22653.0 mmol/L, blood calcium\u22652.0 mmol/L\n 8. Prothrombin time (PT)\u22641.2\u00d7ULN, partial prothrombin kinase time (APTT)\u22641.2\u00d7ULN\n 9. Urine protein < 1+showed by urine test paper, or urine protein <1g for 24 hours\n 9. Previous treatment toxicity returned to grade 1 as per NCI CTCAE 5.0, with the\n following exceptions :Hair loss or other with no safety risk judged by investigators.\n 10. Subjects of childbearing potential must be willing to take effective contraceptive\n measures throughout the study and for 3 months after the last dose of HB002.1T.And\n females must have a negative pregnancy test during the screening period .\n 11. Ability to understand the patient information and informed consent form and signed and\n dated written informed consent form.\n Exclusion Criteria:\n - Patients who meet any of the following criteria will be excluded from study entry:\n 1. Confirmed active CNS metastasis and /or cancerous meningitis; For patients with\n stable clinical symptoms for brain metastasis for more than 3months can be\n enrolled.\n 2. Positive test for hepatitis B, hepatitis C, or HIV at screening.\n 3. History of organ transplantationHistory of severe allergy or known severe\n allergic reactions (greater than grade 3 in CTCAE V5.0) to macromolecular protein\n preparations / monoclonal antibodies and any components of the test drug;\n 4. Have received other clinical trial drugs within 4 weeks before the first\n treatment of HB002.1T;\n 5. Have undergone major surgery within 4 weeks prior to screening;\n 6. Have undergone minor surgical procedures (including catheterization, except for\n PICC) within 2 days prior to screening;\n 7. Systolic blood pressure\u2265140mmHg and/or diastolic blood pressure\u226590mmHg after\n antihypertensive treatment (one antihypertensive drug is allowed in the baseline\n period, and the compound preparation is recognized as two);\n 8. An active infection requiring antibiotics treatment during the screening period,\n or an unexplained fever > 38.5 \u00b0C occurs before the first dose;\n 9. Hemoptysis within 4 weeks before screening (defined as coughing with \u22651 teaspoon\n of blood), but do not rule out cough only with sputum or small blood clot;\n 10. Suffering from the following serious complications:\n 1. Prior arterial thromboembolic events, venous thrombosis great than grade 3\n or higher in NCI CTCAE5.0\n 2. Previous or current persistent bleeding or coagulation disorders\n 3. Dominant jaundice and/or coagulopathy caused by abnormal liver function\n 4. Chronic Obstructive Pulmonary Disease (COPD) or other respiratory illness\n requiring hospitalization within 4 weeks prior to screening;\n 5. History of abdominal hernia, gastrointestinal perforation abscess or acute\n bleeding within 6 months prior to screening;\n 6. Esophageal varices, unhealed ulcer, wounds or fractures within 6 months\n prior to screening;\n 7. Active cardiovascular diseases including but not limited to transient\n ischemic attack (TIA), cerebral vascular accident (CVA), transmural\n Myocardial infarction), transmural myocardial infarction, myocardial\n infarction (MI), hypertensive crisis or encephalopathy within 6 months prior\n to screening;\n 8. Gastrointestinal disorders or conditions that may cause gastrointestinal\n bleeding or perforation (e.g., duodenal ulcer, intestinal obstruction, acute\n Crohn's disease, ulcerative colitis, massive gastrectomy and small bowel\n resection). Patients with chronic Crohn's disease and ulcerative colitis\n (except those with total colectomy and rectal resection) should be excluded\n even in the inactive stage\n 9. Patients with hereditary nonpolyposis colorectal cancer or familial\n adenomatous polyposis syndrome;\n 10. Previous intestinal perforation and intestinal fistula, still not recover\n after surgical treatment\n 11. Absorption of oral drug will be significantly affected assessed by\n investigators (Cohort1 only)\n 11. Subjects who are in use of warfarin, heparin , aspirin (>325 mg/day) or other\n drugs known to inhibit platelet function within 10 days prior to the first study\n treatment;\n 12. Subjects receiving dipyridamole, ticlopidine, clopidogrel or cilostazol\n treatment;\n 13. Subjects with a clear history of neurological or dysfunction, such as poor\n adherence to epilepsy;\n 14. Pregnant or nursing women;\n 15. Any other reasons assessed by the investigator that are not suitable for\n participation in the trial.", "output": {"inclusion_biomarker": [], "exclusion_biomarker": []}}