Input:
This phase Ib trial studies the side effects and possible benefits of AL101 before surgery in
 treating patients with notch activated adenoid cystic cancer. AL101 may stop the growth of
 tumor cells by blocking some of the enzymes needed for cell growth. Giving AL101 before
 surgery may help to control adenoid cystic cancer that has a NOTCH pathway activation.
 ;
 ;
 Inclusion Criteria:
 - Capable of giving signed informed consent which includes compliance with the
 requirements and restrictions listed in the informed consent and in this protocol
 - Age >= 18 years old
 - Histologically/cytological confirmed adenoid cystic carcinoma (ACC) of any primary
 site
 - Evidence of NOTCH1 pathway activation as determined by NICD1 IHC nuclear staining in
 >= 70% of tumor cells
 - Patients must have surgically resectable disease, either with a curative intent or for
 local control in the setting of metastatic disease, in the opinion of the treating
 physician
 - Patients must be willing to undergo baseline biopsy to obtain tumor material
 - Disease must be measurable by RECIST 1.1
 - Performance status Eastern Cooperative Oncology Group (ECOG) 0 or 1
 - Neutrophils < 1500/mm^3
 - Platelet count < 100,000/mm^3
 - Hemoglobin < 9 g/dL
 - Total bilirubin > 1.5 upper limit of normal (ULN) (except known Gilbert's syndrome)
 - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 2.5 of upper
 limit of normality (ULN) OR > 5 ULN for patients with liver metastases
 - Creatinine clearance < 40 mL/min (Calculation of creatinine clearance [CrCl] will be
 based on acceptable institution standard)
 - Female patients with reproductive potential must practice two effective contraceptive
 measures for the duration of study drug therapy and for at least 90 days after
 completion of AL101 therapy. The two birth control methods can be either two barrier
 methods or a barrier method plus a hormonal method to prevent pregnancy. The following
 are considered adequate barrier methods of contraception: diaphragm, condom, copper
 intrauterine device, sponge, or spermicide. Appropriate hormonal contraceptives will
 include any registered and marketed contraceptive agent that contains an estrogen
 and/or a progestational agent (including oral, subcutaneous, intrauterine, or
 intramuscular agents)
 - Male patients who are sexually active with women with reproductive potential must
 agree to use contraception for the duration of treatment and for at least 90 days
 after completion of AL101 therapy
 Exclusion Criteria:
 - Prior radiotherapy, chemotherapy, or biologic therapy is allowed in patients with
 loco-regional recurrent disease, if administered at least 4 weeks prior to study
 enrollment
 - Prior treatment with gamma-secretase inhibitor
 - History of previous malignancy other than malignancy treated with curative intent and
 with no evidence of active disease >= 2 years before the first dose of study drug and
 of low potential risk for recurrence. Patients with the following diagnoses represents
 an exception and may enroll:
 - Non-melanoma skin cancers with no current evidence of disease
 - Melanoma in situ with no current evidence of disease
 - Localized cancer of the prostate with prostate-specific antigen of < 0.1 ng/mL
 - Treated or localized well-differentiated thyroid cancer
 - Treated cervical carcinoma in situ
 - Treated ductal/lobular carcinoma in situ of the breast
 - Current or recent (within 2 months of investigational product administration)
 gastrointestinal disease such as disorders that increase the risk of diarrhea (e.g.:
 inflammatory bowel disease). Non-chronic conditions (e.g., infectious diarrhea) that
 are completely resolved for at least 2 weeks prior to starting investigational product
 are not exclusionary
 - Evidence of clinically significant bleeding diathesis or coagulopathy (in the absence
 of therapeutic anticoagulation)
 - Evidence of uncontrolled, active infection, requiring systemic anti-bacterial,
 anti-viral or anti-fungal therapy =< 7 days prior to administration of investigational
 product such as known active infection with hepatitis B and hepatitis C (HCV) at
 Screening
 - Symptomatic central nervous system (CNS) metastases. Patients with asymptomatic CNS
 metastases as well as those with previously treated CNS metastases are eligible for
 enrollment in the study if at least four weeks has elapsed since last whole brain
 radiation treatment or at least two weeks has elapsed since last focal radiation
 treatment and the patient is deemed clinically stable by the investigator
 - Unstable or severe uncontrolled medical condition (e.g., unstable cardiac or pulmonary
 function or uncontrolled diabetes) or any important medical illness or abnormal
 laboratory finding that would, in the investigator's judgment, increase the risk to
 the patient associated with his or her participation in the study
 - Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) >= 480
 msec
 - Female subjects who are pregnant or breast-feeding
 - Hypersensitivity and/or history of allergy to the investigational product excipients


Input:
The purpose of the study is to learn from the real world practice of prescribing targeted
 therapies to patients with advanced cancer whose tumor harbors a genomic variant known to be
 a drug target or to predict sensitivity to a drug.
 NOTE: Due to character limits, the arms section does NOT include all TAPUR Study relevant
 biomarkers. For additional information, contact TAPUR@asco.org, or if a patient, your nearest
 participating TAPUR site (see participating centers).
 *********************************************************************************************
 *********************************************************************************
 Results in publication or poster presentation format are posted as they become available for
 individual cohorts at www.tapur.org/news. The results may be accessed at any time. All
 results will be made available on clinicaltrials.gov at the end of the study. Indexing of
 available results on PubMed is in progress.
 *********************************************************************************************
 *********************************************************************************
 ;
 ;
 Inclusion Criteria:
 - 12 years of age or older (*Restrictions apply. Not all therapies are available for
 patients <18)
 - Histologically-proven locally advanced or metastatic solid tumor, multiple myeloma or
 B cell non-Hodgkin lymphoma who is no longer benefiting from standard anti-cancer
 treatment or for whom, in the opinion of the treating physician, no such treatment is
 available or indicated
 - Performance status 0-2 (Per Eastern Cooperative Oncology Group (ECOG) criteria)
 - Patients must have acceptable organ function as defined below. However, as noted
 above, drug-specific inclusion/exclusion criteria specified in the protocol appendix
 for each agent will take precedence for this and all inclusion criteria:
 1. Absolute neutrophil count ≥ 1.5 x 106/µl
 2. Hemoglobin > 9.0 g/dl
 3. Platelets > 75,000/µl
 4. Total bilirubin < 2.0 mg/ dl, except in patients with Gilbert's Syndrome
 5. Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)
 and alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT) <
 2.5 x institutional upper limit of normal (ULN) (or < 5 x ULN in patients with
 known hepatic metastases)
 6. Serum creatinine ≤ 1.5 × ULN or calculated or measured creatinine clearance ≥ 50
 mL/min/1.73 m2
 - Patients must have disease that can be objectively measured by physicial or
 radiographic exam or evaluable disease (per RECIST v1.1 for solid tumor, Lugano
 criteria for non Hodgkin lymphoma or International Myeloma Working Group criteria for
 multiple myeloma), defined as at least one lesion that can be accurately measured in
 at least one dimension (longest diameter to be recorded for non-nodal lesions and
 short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with
 spiral computed tomography (CT) scan, Magnetic Resonance Imaging (MRI), or a
 subcutaneous or superficial lesion that can be measured with calipers by clinical
 exam. For lymph nodes, the short axis must be ≥15 mm. Patients who have assessable
 disease by physical or radiographic examination but do not meet these definitions of
 measurable disease are eligible and will be considered to have evaluable disease.
 Patient's whose disease cannot be objectively measured by physical or radiographic
 examination (e.g., elevated serum tumor marker only, bone-only disease without an
 identifiable soft tissue component, or patients with only assessable non-measurable
 disease) are NOT eligible.
 - Results must be available from a genomic test or immunohistochemistry (IHC) test for
 protein expression performed in a Clinical Laboratory Improvement Amendments
 (CLIA)-certified and College of American Pathologists (CAP)-accredited or New York
 State accredited (for labs offering services to residents of NY) laboratory. Labs that
 have registered the test with the NIH Genetic Testing Registry or that provide a
 report that has been designated as optimized for TAPUR participation are preferred,
 but not required. The genomic or IHC test used to qualify a patient for participation
 in TAPUR may have been performed on any specimen of the patient's tumor obtained at
 any point during the patient's care at the discretion of the patient's treating
 physician. Genomic assays performed on cell-free DNA in plasma ("liquid biopsies")
 will also be acceptable if the genomic analysis is performed in a laboratory that
 meets the criteria described above.
 - Ability to understand and the willingness to sign a written informed consent/assent
 document.
 - Have a tumor genomic profile for which single agent treatment with one of the FDA
 approved targeted anti-cancer drugs included in this study has potential clinical
 benefit based on the criteria described in protocol.
 - For orally administered drugs, the patient must be able to swallow and tolerate oral
 medication and must have no known malabsorption syndrome.
 - Because of the risks of drug treatment to the developing fetus, women of child-bearing
 potential and men must agree to use adequate contraception (hormonal or barrier method
 of birth control; abstinence) for the duration of study participation, and for four
 months following completion of study therapy. Should a woman become pregnant or
 suspect she is pregnant while participating in this study or if she is the partner of
 a male participant in this study and becomes pregnant while he is participating in
 this study, she should inform her or her partner's treating physician immediately as
 well as her obstetrician. Female study patients who become pregnant must immediately
 discontinue treatment with any study therapy. Male patients should avoid impregnating
 a female partner. Male study patients, even if surgically sterilized, (i.e.
 post-vasectomy) must agree to one of the following: practice effective barrier
 contraception during the entire study treatment period and for a specified amount of
 time the last dose of study drug, or completely abstain from sexual intercourse.
 Note: TAPUR does not explicitly exclude any type of solid tumor, but the patient must have
 measurable and evaluable disease per RECIST v1.1.
 Exclusion Criteria:
 - Patients whose disease is not measurable or cannot be assessed by radiographic imaging
 or physical examination (e.g., elevated serum tumor marker only) are not eligible
 - Patients with primary brain tumors or leptomeningeal metastases are excluded.
 - Patients with previously treated brain metastases are eligible, provided that the
 patient has not experienced a seizure or had a clinically significant change in
 neurological status within the 3 months prior to registration. All patients with
 previously treated brain metastases must be clinically stable for at least 1 month
 after completion of treatment and off steroid treatment for one month prior to study
 enrollment.
 - Patients with known progressive brain metastases are eligible but additional
 eligibility criteria apply.
 Note: there are additional exclusion criteria that may apply


Input:
The application of ALK inhibitors in the first-line cancer treatment can significantly
 increase the PFS and ORR of patients those with EML4-ALK fusion. The contemporary clinical
 ALK fusion detection are mainly via FISH and ICH while biopsies are needed. For locations
 where are difficult to take biopsies, these routine examinations can hardly been adopted.
 Apart from these, part of ALK fusion patients are resistant to ALK inhibitors, also making an
 accurate and efficient prognostic indicator for efficacy evaluation and identifying high-risk
 recurrent population an urgent priority.
 The bilayer membrane structure of exosome helps maintain its internal genetic stability,
 making detection of EML4-ALK fusion via plasma exosomes in advanced NSCLC patients a feasible
 way, which might provide a non-invasive and more convenient approach for NSCLC diagnosis and
 efficacy monitoring. Firstly, this study will evaluate the performance of exosome EML4-ALK
 fusion detection in NSCLC diagnosis, which sensitivity and specificity would be compared with
 the FDA approved IHC (ALK [D5F3] CDx Assay) test. Subsequently, this study would monitor the
 dynamic changes of EML4-ALK fusion in exosome examination diagnosed ALK fusion positive NSCLC
 patients both before and after treatment. It aims to prospectively evaluate the potential
 value of this approach on efficacy and prognosis prediction in NSCLC therapy and determining
 whether exosome ALK fusion could assess the curative effect more accurately than imaging
 examination and tumor markers. Thirdly, FISH diagnosed EML4-ALK positive NSCLC patients will
 be divided into the positive or negative subgroup according to their post-treatment exosome
 ALK fusion expression which were determined at 2-3 months after ALK inhibitor were adopted.
 The prognostic value of monitoring exosome EML4-ALK fusion expression is assessed through the
 comparison of patients PFS and OS.
 ;NA;
 Inclusion Criteria:
 - All eligible patients must have histologically or cytologically confirmed stage
 IIIB-IV unresectable NSCLC positive or negative for EML4-ALK4 fusion as defined by
 FISH. Patients must have an ECOG PS of 0- 1 and have at least 1 measurable lesions
 (RECIST 1.1 standard). For eligible patients, prior ALK inhibitor therapy or previous
 systemic anticancer therapy is not allowed or has been completed over 12 months.
 Patients with brain metastasis are eligible only in a stable central nervous system
 condition and treatment outcome, cannot receive glucocorticoids and drugs prohibited
 in the exclusion criteria ≤14 days before the first dose of study drug.
 Exclusion Criteria:
 - Eligible patients must not have received any major surgery ≤28 days before the first
 dose of study drug and must not have received any minor surgery or radiotherapy ≤14
 days before the first dose of study drug. Any acute toxic reaction must have recovered
 to ≤ Grade 1 (except for hair loss). Patients with carcinomatous meningitis,
 leptomeningeal disease or spinal cord compression must be excluded.


Input:
The purpose of this study was to assess efficacy, safety and PK in anaplastic thyroid cancer
 (ATC) given HLX208 (BRAF V600E inhibitor).
 ;NA;
 Inclusion Criteria:
 1. Age>=18Y;
 2. Good Organ Function;
 3. Expected survival time ≥ 3 months;
 4. Advanced BRAF V600 ATC that have been diagnosed histologically;
 5. At least one measurable lesion as per RECIST v1.1;
 6. ECOG score 0-1.
 Exclusion Criteria:
 1. Pregnant or lactating women;
 2. Previous treatment with BRAF inhibitors or MEK inhibitors;
 3. A history of other malignancies within two years, except for cured cervical carcinoma
 in situ, basal cell carcinoma of the skin;
 4. Severe active infections requiring systemic anti-infective therapy.


Input:
This single-arm, Phase II study was designed to evaluate the safety and efficacy of
 Camrelizumab (anti-programmed death-receptor 1 [PD-1] antibody) combination with Apatinib in
 participants with ES-SCLC who was response or stable disease after firstline standard
 chemotherapy. Participants will be receive camrelizumab +apatinib on 21-day cycles until
 progressive disease (PD) as assessed by the investigator using Response Evaluation Criteria
 in Solid Tumors Version 1.1 (RECIST v1.1). Treatment can be continued until persistent
 radiographic PD or symptomatic deterioration.
 ;NA;
 Inclusion Criteria:
 - Male or female patients aged 18 and 75 years old;
 - Signed the informed consent form prior to patient entry;
 - Eastern Cooperative Oncology Group performance status of 0 or 1;
 - Expected Survival Time: Over 3 months;
 - Pathological or cytologically proven extensive-Stage small cell lung cancer(according
 to Veterans Administration Lung Study Group)and without progression after Cycles 4-6
 21-day cycles of first-line Standard chemotherapy(Evaluation was CR /PR/SD based on
 RECIST1.1);
 - If prophylactic cranial irradiation (PCI) was not planned,informed consent was
 required to be written between 3 weeks and 5 weeks after day 1 of the last cycle of
 chemotherapy. If PCI was planned or already performe, informed consent was required to
 be written between 3 weeks and 8 weeks after day 1 of the last cycle of chemotherapy.
 Exclusion Criteria:
 - Has prior therapy with anti-programmed cell death (PD)-1, anti-PD-L1,anti Cytotoxic T
 lymphocyte-associated Antigen(CTLA)-4 or other Drugs that target T cells;
 - Has prior therapy with angiogenesis inhibitors,Such as sunitinib, bevacizumab,
 apatinib, anlotinib;
 - Has active or untreated central nervous system (CNS) metastases and/or cancerous
 meningitis;
 - Imaging (CT or MRI) shows that tumor invades large blood vessels or the boundary with
 blood vessels is unclear;
 - Has spinal cord compression which was not cured or relieved through surgery and/or
 radiotherapy, or diagnosed spinal cord compression after treatment showed no clinical
 evidence of disease stabilization prior to allocation ≥1 week;
 - Within the past 2 weeks have used high dose antibiotics;
 - According to the judgement of the researchers, there are other factors that may lead
 to the termination of the study.


Input:
Open-label, multi-center, non-randomized, multiple dose, safety, tolerability,
 pharmacokinetic, and pharmacodynamics and clinical activity study of PF-06940434 (Integrin
 alpha-V/beta-8 Antagonist) in patients with SCCHN (Squamous Cell Carcinoma of the Head and
 Neck), renal cell carcinoma (RCC - clear cell and papillary), ovarian, gastric, esophageal,
 esophageal (adeno and squamous), lung squamous cell, pancreatic and biliary duct,
 endometrial, melanoma and urothelial tumors. This study contains two parts, single agent dose
 escalation (Part 1A), dose finding of PF 06940434 in combination with anti-PD-1 (Part 1B) and
 dose expansion (Part 2). Part 2 Dose Combination Expansion will enroll participants into 2
 cohorts at doses determined from Part 1B in order to further evaluate the safety of
 PF-06940434 in combination with anti-PD-1.
 ;NA;
 Inclusion Criteria:
 - Histological or cytological diagnosis of SCCHN, RCC (clear cell and papillary cell),
 ovarian, gastric, esophageal (adeno and squamous), lung squamous cell, pancreatic and
 biliary duct, endometrial, melanoma, or urothelial cancer.
 Part 2:
 - Arm A SCCHN:
 - Primary tumor location of the oral cavity, oropharynx, hypopharynx or larynx.
 - PDL-1 expression positive and CPS ≥1. No prior systemic therapy administered in
 the recurrent or metastatic setting (except for systemic therapy given as part of
 a multimodal treatment for locally advanced disease).
 - Arm B RCC (clear cell):
 - 1 or 2 prior lines of therapy including PD-L1/PD-1 immunotherapy in combination
 or sequentially with antiangiogenic directed treatment
 - Adequate bone marrow, kidney and liver function.
 - Performance status of 0 or 1.
 Exclusion Criteria:
 - Participant disease status is suitable for local therapy administered with curative
 intent.
 - Hypertension that cannot be controlled by medications.
 - Active or prior autoimmune disease
 - Active, uncontrolled bacterial, fungal, or viral infection, including (but not limited
 to) Hepatitis B, Hepatitis C, and known Human Immunodeficiency Virus infection or
 Acquired Immunodeficiency Syndrome-related illness


Input:
UP-NEXT is a double-blind, randomized, placebo-controlled study of the antibody-drug
 conjugate (ADC) XMT-1536 (upifitamab rilsodotin) administered as an intravenous infusion once
 every four weeks in patients with recurrent, platinum-sensitive high-grade serous ovarian
 cancer (HGSOC), including fallopian tube and primary peritoneal cancer, expressing high
 levels of NaPi2b.
 ;
 ;
 Inclusion Criteria:
 1. Participant must have a histological diagnosis of high grade serous ovarian cancer,
 which includes fallopian tube and primary peritoneal cancer, that is metastatic or
 recurrent.
 2. Participant must have platinum-sensitive recurrent disease, defined as having achieved
 either a partial or complete response to 4 or more cycles in their penultimate
 platinum- containing regimen and their disease progressing more than 6 months after
 completion of the last dose of platinum containing therapy in the penultimate regimen.
 3. Participant must have had 4 to 8 cycles of platinum-based chemotherapy in 2nd to 4th
 line setting in their most recent treatment regimen as defined below:
 1. Platinum-based chemotherapy regimens allowed immediately preceding enrollment to
 the study: carboplatin or cisplatin ±: paclitaxel, docetaxel, pegylated liposomal
 doxorubicin or gemcitabine.
 2. Participant must receive first study treatment infusion between 4 and 12 weeks
 after completing final dose of platinum in the most recent platinum-based
 regimen.
 4. Participant must have had as their best response to last line of treatment one of the
 following: No Evidence of Disease (NED); Complete Response (CR); Partial Response
 (PR); OR Stable Disease (SD)
 5. Participants with NED, CR, or PR as their best response to most recent line of
 treatment and who have not received treatment with a prior PARP inhibitor must have
 definitive BRCA1 and BRCA2 testing results that demonstrate no evidence of a
 deleterious BRCA1 or BRCA2 mutation. Somatic BRCA mutation testing is required for
 participants who are classified as not having a deleterious mutation by germline
 testing alone.
 6. Participant must provide either a tumor tissue block or fresh cut slides for
 measurement of NaPi2b expression by a central laboratory. If sufficient archival tumor
 tissue is not available, then a tumor tissue block or slides must be obtained from a
 fresh biopsy and provided to the central laboratory. Confirmation of a
 NaPi2b-H/positive tumor by the central laboratory is required prior to randomization.
 Exclusion Criteria:
 1. Participant has received prior treatment with mirvetuximab soravtansine or another ADC
 containing an auristatin or maytansinoid payload.
 2. Participant has received bevacizumab in combination with last platinum-based regiment
 or plans to receive maintenance therapy outside the study intervention.
 3. Participant has clinical signs or symptoms of gastrointestinal obstruction and/or
 requirement for parenteral hydration or nutrition.
 4. Participant has ascites or pleural effusion managed with therapeutic paracentesis or
 thoracentesis within 28 days prior to signing the principal study consent form.
 5. Participant has history of cirrhosis, hepatic fibrosis, esophageal or gastric varices,
 or other clinically significant liver disease. Testing beyond laboratory studies
 otherwise defined in the eligibility criteria, to diagnose potentially clinically
 significant liver disease based on risk factors such as hepatic steatosis or history
 of excessive alcohol intake, will be based on clinical judgement of the investigator.
 6. Participant has history of or suspected pneumonitis or interstitial lung disease.
 7. Participant has untreated CNS metastases (including new and progressive brain
 metastases), history of leptomeningeal metastasis, or carcinomatous meningitis.


Input:
An open-label, two-part Phase I/Ib study of RP12146 in adult patients with locally advanced
 or metastatic solid tumors. The first part (Part 1) is a Phase I dose-escalation, 3+3 design,
 open-label, MTD determination study and will enroll patients who have tumors known to harbour
 DNA repair deficiencies. The second part (Part 2) is a Phase Ib, dose-expansion at the MTD
 (or optimal dose) and will enroll patients with a confirmed deleterious HRR mutation in their
 tumor as identified by a central genomics testing laboratory.
 ;NA;
 Inclusion Criteria.
 1. Provision of full informed consent prior to any study-specific procedures.
 2. Patients must be ≥18 years of age, at the time of signing informed consent.
 3. Dose escalation phase, patients with histologically and/or cytologically confirmed
 malignant solid tumor whose disease has progressed following at least one standard
 therapy and who have no other acceptable standard treatment options. Tumor types will
 include breast, ovarian, fallopian tube, or peritoneal cancer, extensive-stage small
 cell lung cancer (ES-SCLC), prostate, pancreatic, colorectal gastric, biliary tract,
 and endometrial cancer.
 4. Dose-expansion phase patients with histologically and/or cytologically confirmed
 malignant solid tumor (breast, ovarian, fallopian tube, or peritoneal cancer,
 extensive-stage small cell lung cancer (ES-SCLC), with one of the documented
 deleterious mutations of specified HRR genes and whose disease has progressed
 following at least one standard therapy.
 5. Patients with at least one measurable lesion per RECIST version 1.1 at baseline that
 can be accurately assessed by CT-scan or MRI and is suitable for repeated assessment
 at follow up-visits.
 6. ECOG performance status 0 to 2.
 7. Use of contraception measures
 Exclusion Criteria:
 1. Patients with HER2 positive breast cancer
 2. Patients receiving anticancer therapy
 3. Patient who has not recovered from acute toxicities of previous therapy except
 treatment-related alopecia.
 4. Prior treatment with a PARP inhibitor
 5. Major surgery within 4 weeks of starting study treatment or any patient who has not
 recovered from the effects of major surgery.
 6. Patient with symptomatic uncontrolled brain metastasis.
 7. Pregnancy and lactation
 8. Patients with uncontrolled disease


Input:
This research study is done to test the safety, effectiveness and pharmacokinetic
 characteristics of SIM1803-1A in patients with locally advanced/metastatic solid tumors with
 NTRK, ROS1 or ALK gene fusion mutations. The cancer must have a change in a particular gene
 (NTRK1, NTRK2, NTRK3, ROS1 or ALK). SIM1803-1A is a drug that blocks the actions of these
 NTRK/ ROS1 /ALK genes in cancer cells and can therefore be used to treat cancer.
 ;NA;
 Inclusion Criteria:
 - Adult patients with a locally advanced or metastatic solid tumor that has progressed
 or was nonresponsive to available therapies, are unfit for standard chemotherapy or
 for which no standard or available curative therapy exists；Proof of a malignancy
 harboring a NTRK、ROS1 or ALK fusion；Eastern Cooperative Oncology Group (ECOG) score of
 0 or 1 and a life expectancy of at least 3 month；Adequate hematologic, hepatic, and
 renal function；Signed informed consent form；
 Exclusion Criteria:
 - Any contraindications as listed in the local approved product information；Patients
 with unstable primary central-nervous-system tumors or metastasis, exceptions
 possible；Pregnancy or lactation；Clinically significant active cardiovascular disease
 or history of myocardial infarction；Participation in an investigational program with
 interventions outside of routine clinical practice；Prior treatment with other kinase
 inhibitor with tropomyosin receptor kinase inhibition；Active uncontrolled systemic
 bacterial, viral, or fungal infection；Current treatment with a strong CYP3A4 inhibitor
 or inducer；


Input:
This is Phase Ib/II, multicenter, open-label adaptive platform study of JDQ443 with select
 therapies in patients with advanced solid tumors harboring the KRAS G12C mutation.
 ;
 ;
 Inclusion Criteria:
 Dose Escalation:
 - Patients with advanced (metastatic or unresectable) KRAS G12C mutant solid tumors who
 have received standard of care therapy or are ineligible to receive such therapy.
 Phase II:
 - Patients with advanced (metastatic or unresectable) KRAS G12C mutant non-small cell
 lung cancer who have received platinum-based chemotherapy regimen and immune
 checkpoint inhibitor therapy, unless patient was ineligible to receive such therapy
 - Patients with advanced (metastatic or unresectable) KRAS G12C mutant colorectal cancer
 who have received fluropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy,
 unless patient was ineligible to such therapy.
 All patients:
 - ECOG performance status of 0 or 1.
 - Patients must have a site of disease amenable to biopsy and be a candidate for tumor
 biopsy according to the treating institution's guidelines.
 Exclusion Criteria:
 - Tumors harboring driver mutations that have approved targeted therapies, with the
 exception of KRAS G12C mutations
 - Prior treatment with a KRAS G12C inhibitor is excluded for patients in a subset of
 groups in Phase II.
 - Active brain metastases, including symptomatic brain metastases or known
 leptomeningeal disease
 - Clinically significant cardiac disease or risk factors at screening
 - Insufficient bone marrow, hepatic or renal function at screening Other
 protocol-defined inclusion/exclusion criteria may apply


Input:
This first-time-in-human (FTIH) study will evaluate the safety, tolerability,
 pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of escalating
 doses of GSK6097608 given as monotherapy and in combination with dostarlimab in participants
 with advanced solid tumors. In addition, dostarlimab will be given as monotherapy and in
 combination with GSK6097608 and with GSK4428859A (EOS884448) in Japanese and Chinese
 participants. Drug name mentioned as GSK4428859A and EOS884448 are interchangeable for the
 same compound. In the rest of the document, the drug will be referred to as GSK4428859A
 (EOS884448).
 ;NA;
 Inclusion Criteria:
 - Adults 18 years of age or older (or >=20 years of age in Arm-A Japan, Arm-D Japan, Arm
 E-Japan, and Arm F-Japan);
 - Female participants of childbearing potential must agree to use a highly effective
 form of contraception;
 - Histological or cytological documentation of locally advanced, recurrent, or
 metastatic solid malignancy;
 - Disease that has progressed after standard therapy for the specific tumor type, or for
 which standard therapy has proven to be ineffective, intolerable, or is considered
 inappropriate, or if no further standard therapy exists;
 - Participants in a PK/PD cohort must provide fresh tumor biopsies.
 - Eastern cooperative oncology group (ECOG) performance status (PS) 0 to 1
 - Life expectancy of at least 12 weeks.
 - Adequate organ function as determined by laboratory assessments.
 - Adequate cardiac ejection fraction as measured by echocardiogram.
 - Arm A-Japan, Arm D-Japan, Arm E-Japan, and Arm F-Japan only: lives in Japan and is
 racially Japanese, defined as all biological grandparents being Japanese.
 - Arm A-China, Arm B-China, Arm D-China, Arm E-China and Arm F-China only: is of Chinese
 descent and lives in China.
 - Arm D, Arm E, and Arm F only: has been deemed suitable for assigned treatment based on
 assessment by the investigator.
 Exclusion Criteria:
 - Prior anti-cancer treatment including investigational agents, immune checkpoint
 inhibitors, chemotherapy, targeted therapy, and biological therapy: within 4 weeks or
 5 half-lives of the drug, whichever is shorter.
 - Prior allogenic or autologous bone marrow transplantation or other solid organ
 transplantation.
 - Toxicity from previous anticancer treatment, including; greater than or equal to Grade
 3 immune-mediated toxicity considered related to prior immunotherapy and that led to
 treatment discontinuation; or toxicity related to prior treatment that has not
 resolved; or myocarditis of any grade considered related to prior immuno-oncology
 therapy that led to treatment discontinuation.
 - Known additional malignancy that progressed or required active treatment within the
 last 2 years.
 - Uncontrolled or symptomatic central nervous system (CNS) metastases and/or
 carcinomatous meningitis.
 - Active autoimmune disease that has required systemic disease-modifying or
 immunosuppressive treatment within the last 2 years.
 - Concurrent medical condition requiring the use of systemic immunosuppressive
 treatment.
 - Cirrhosis or current unstable liver or biliary disease per investigator assessment.
 - Active infection requiring systemic treatment, known human immunodeficiency virus
 infection, or positive test for hepatitis B surface antigen (HBsAg) or hepatitis C
 virus (HCV)
 - Prolonged QT as measured by electrocardiogram.
 - Allergen desensitization therapy within 4 weeks of starting study intervention.
 - History of hypersensitivity to any of the study interventions or their excipients.
 - History or evidence of significant cardiovascular (CV) risk.
 - Recent history (within 6 months) of uncontrolled symptomatic ascites or pleural
 effusions.
 - History of idiopathic pulmonary fibrosis; interstitial lung disease; organizing
 pneumonia; noninfectious pneumonitis that required steroids, or evidence of active,
 noninfectious pneumonitis.
 - Pregnant or lactating woman.
 - Receipt of live vaccine within 30 days of the start of study intervention.
 - Receipt of transfusion of blood products or administration of colony-stimulating
 factors within 14 days before the first dose of study intervention.
 - Major surgery less than 4 weeks before the first dose of study intervention.
 - Known drug or alcohol abuse.


Input:
Over-expression of Epidermal Growth Factor Receptor (EGFR) on cells occurs in all aggressive
 cancers of epithelial origin. Existing tests for monitoring EGFR expression are invasive and
 not reliable. There needs to be a better way to measure EGFR expression in cancerous tumors
 to better tailor cancer treatments.
 This clinical trial aims to demonstrate the feasibility of imaging cancers that express EGFR
 using 89Zr-DFO-nimotuzumab and Positron Emission Tomography (PET)/Computerized Tomography
 (CT). By non-invasively imaging the status of EGFR, 89Zr-DFO-nimotuzumab could be used to
 assist in the identification of patients who are likely to respond to anti-EGFR treatments,
 including nimotuzumab. The hypothesis is that 89Zr-DFO-nimotuzumab will accumulate to tumors
 over-expressing EGFR making them visible when imaged with PET/CT. This hypothesis will be
 tested in this study, along with the optimal imaging time and diagnostic ability.
 ;NA;
 Inclusion Criteria:
 - Male or female between 18 and 80 years old.
 - EGFR-positive cancer defined by a board certified pathologist
 - Primary or metastatic lesion size >= 1.5 cm as determined by imaging studies
 (ultrasonography, mammography, CT or MRI) or physical examination.
 - Able to give informed consent.
 - Not currently pregnant or nursing: If female subject must be surgically sterile (has
 had a documented bilateral oophorectomy and/or documented hysterectomy),
 post-menopausal (cessation of menses for > 1 year), non-lactating, or of childbearing
 potential for whom a urine pregnancy test is negative when taken within the 24 h
 before administration of 89Zr-DFO-nimotuzumab.
 - WHO performance status of 0 - 2
 - Patients naïve to anti-EGFR antibodies treatment.
 Exclusion Criteria:
 - Unable to tolerate 60 min of PET imaging per session.


Input:
It is often impossible to find therapeutic target in intermediate-risk AML, so it is very
 important to select appropriate chemotherapy protocol to eliminate minimal residual disease
 (MRD) in these AML patients. Recent studies demonstrated that leukemia microenvironment is
 the shelter nich for leukemia stem cells and the essential reason for impossibly eliminating
 MRD. Demethylation drug not only prove the effect of chemotherapy, but also change leukemia
 microenvironment through epigenetics modification. Both of them will result in eliminating
 MRD in patients with AML. The investigators designed a multicenter randomized control
 clinical trail to evaluate the effect of demethylation drug combined with chemotherapy in AML
 patients with intermediate-risk factors after hematological complete remission. Efficacy will
 be evaluated through MRD detected by flow cytometry every 1 month. Continuous negative MRD
 indicates a good prognosis. The patients with continuous negative MRD can select auto-HSCT or
 consolidation chemotherapy, those with continuous positive MRD should be considered as
 candidates of allo-HSCT. Overall survival and relapse free survival will be recorded after
 follow-up every 3 months. It will provide a basis for precision therapy and a new way for
 designing a novel protocol for intermediate-risk AML. This clinical trail will benefit to the
 AML patients with intermediate-risk factors.
 ;NA;
 Inclusion Criteria:
 - AML patients with normal heart, lung, liver and renal function, or without serious
 infection. ECOG score is below 2
 Exclusion Criteria:
 - AML patients with abnormal heart, lung, liver and renal function, or with serious
 infection. ECOG score is over 2


Input:
Vorasidenib in combination with pembrolizumab in participants with recurrent or progressive
 enhancing isocitrate dehydrogenase-1 (IDH-1) mutant astrocytomas.
 ;
 ;
 Inclusion Criteria:
 1. Have Karnofsky Performance Status (KPS) of ≥ 70%.
 2. Have expected survival of ≥ 3 months.
 3. Have histologically confirmed Grade 2 or Grade 3 astrocytoma (per the 2016 World
 Health Organization [WHO] Classification of Tumors of the central nervous system)
 4. Have documented IDH1-R132H gene mutation and absence of 1p19q co-deletion (i.e.,
 non-co-deleted, or intact) by local testing.
 5. Have measurable, magnetic resonance imaging (MRI)-evaluable, unequivocal contrast
 enhancing disease as determined by institution radiologist/Investigator at Screening
 on either 2D T1 post-contrast weighted images or 3D T1 post-contrast weighted images.
 Per mRANO criteria, measurable lesion is defined as at least 1 enhancing lesion
 measuring ≥ 1 cm x ≥ 1 cm.
 6. Have recurrent or progressive disease and received prior treatment with chemotherapy,
 radiation, or both.
 7. Surgical resection is indicated for treatment, but surgery is not urgently indicated
 (e.g., for whom surgery within the next 6-9 weeks is appropriate). (NOTE: This
 criterion only applies to participants enrolled in the perioperative phase of the
 study. Participants in the Safety Lead-In should not require surgery).
 Exclusion Criteria:
 1. Have received prior systemic anti-cancer therapy within 1 month of the first dose of
 IMP, radiation within 12 months of the first dose of IMP, or an investigational agent
 < 14 days prior to the first dose of IMP. In addition, the first dose of IMP should
 not occur before a period of ≥ 5 half-lives of the investigational agent has elapsed.
 2. Have received 2 or more courses of radiation.
 3. Have received any prior treatment with an isocitrate dehydrogenase (IDH) inhibitor;
 anti-programmed cell death 1 (PD1), anti-programmed cell death ligand 1 (PD-L1), or
 anti-PD-ligand 2 (L2) agent, or with an agent directed to another stimulatory or
 co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137); any other checkpoint
 inhibitor; bevacizumab; or any prior vaccine therapy.
 Note: Other inclusion and exclusion criteria may apply.


Input:
Positron emission tomography (PET) molecular imaging provides a valuable tool for the
 diagnosis and differential diagnosis, staging of various tumors. Malignant tumor is composed
 of tumor cells and tumor stroma, which occupies the vast majority of the tumor.
 Cancer-associated fibroblasts (CAF) are an important part of the tumor stroma. Fibroblast
 activation protein (FAP) is over-expressed in CAF, which is closely related to tumor growth,
 invasion, metastasis, immunosuppression and prognosis; and the expression level of FAP in
 normal tissues and organs is very low. So it becomes an excellent target for cancer diagnosis
 and treatment. Radionuclide-labeled fibroblast activation protein inhibitors (FAPI) that
 specifically target to FAP as a tracer for PET imaging can be applied for targeted diagnosis
 and treatment of cancer. Recently, some studies have found that gallium-68 (68Ga) -FAPI as a
 new novel positron tracer has shown to be with good application potential. In this
 prospective study, the investigators will use integrated PET/MR, and PET/CT with the agent
 68Ga-FAPI and conventional imaging agent [F-18] fluorodeoxyglucose (18F-FDG) to diagnose and
 stage various cancers, the aim is to make up for the deficiency in FDG PET imaging in the
 diagnosis and staging of some cancers.
 ;
 ;
 Inclusion Criteria:
 - Patients with suspected or diagnosed or treated malignant tumors who have completed
 18F-FDG PET/CT imaging.
 - Subjects are able to understand and sign the informed consent voluntarily, with good
 compliance.
 Exclusion Criteria:
 - Acute systemic diseases and electrolyte disorders.
 - Pregnant or lactating women.
 - Patients refuse to sign the informed consent.


Input:
The purpose of this study is to examine the combination of osimertinib and carotuximab to
 assess the safety and find the recommended dose for treatment of advanced EGFR-mutated
 non-small cell lung cancer (NSCLC). Safety and tolerability will be measured by the number of
 dose-limiting toxicities, according to National Cancer Institute Common Toxicity Criteria for
 Adverse Events (NCI CTCAE) Version 5, to find the maximum tolerated dose. The secondary
 objectives include evaluating the rate of objective response rate, duration of response,
 progression-free survival, and disease control rate, along with assessing biomarkers through
 tumor tissue and circulating tumor DNA.
 ;NA;
 Inclusion Criteria:
 - Stage IV or recurrent/metastatic non-squamous NSCLC that harbors an EGFR activating
 mutation (Exon 21 L858R, Exon 19 deletion, Exon 18 G719X, Exon 21 L861Q, etc). Local
 testing for EGFR mutations is acceptable provided it was performed in a CLIA certified
 lab.
 - Part I: Progressive disease on at least one prior EGFR TKI
 - Part II, Cohort 1: Progressive disease on osimertinib or other prior EGFR TKIs
 - Part II, Cohort 2: Receiving osimertinib as front line treatment for less than 12
 weeks. Persistent ctDNA with EGFR mutation between weeks 6-12 from the start of
 osimertinib treatment.
 - Age at least 18
 - Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2
 - Archival tissue from a biopsy performed after progression of disease on previous EGFR
 TKI or willing to consent for a fresh tumor biopsy.
 - Measurable disease by RECIST 1.1.
 - Patients with untreated brain metastases are allowed provided that the patient is
 clinically asymptomatic and stable.
 - Patients must have completed prior chemotherapy ≥ 3 weeks or radiotherapy ≥ 2 weeks
 prior to receiving study drugs.
 - If the subject's most recent line of therapy is treatment with osimertinib, then all
 adverse events must be resolved to Grade 2 or better
 - If the subject's most recent line of therapy is any other treatment than osimertinib,
 then all Adverse Events must be resolved to grade 1 or better, with the exception of
 fatigue, alopecia and neuropathy (which must resolve to CTCAE grade 2).
 - Adequate organ function
 - Women of childbearing potential and men must agree to use adequate contraception while
 on study.
 - Written informed consent obtained from subject and ability for subject to comply with
 the requirements of the study.
 Exclusion Criteria:
 - Past medical history of interstitial lung disease, drug-induced interstitial lung
 disease, radiation pneumonitis requiring steroid treatment, or any evidence of
 clinically active interstitial lung disease.
 - Small cell lung cancer histology.
 - Other prior malignancy that might interfere with study endpoints per opinion of the
 investigator.
 - Prior exposure to carotuximab or any CD105 targeted antibody.
 - Any major surgical procedure within 2 weeks of starting therapy.
 - Patients must not have a history of uncontrolled or poorly-controlled hypertension
 defined as SBP > 150 mmHg or DBP > 90 mmHg within 28 days prior to enrollment.
 - Active bleeding or pathologic conditions that carries a high bleeding risk (e.g.
 gastric ulcers).
 - Use of thrombolytics within 10 days prior to the first day of carotuximab.
 - Known hypersensitivity to Chinese hamster ovary products or other recombinant human,
 chimeric, or humanized antibodies.
 - A known diagnosis of Osler-Weber-Rendu syndrome.
 - Ascites or pericardial or pleural effusion requiring external drainage procedures.
 - New evidence of leptomeningeal disease.
 - Acute cardiovascular event within the past 6 months.
 - Pregnancy or breastfeeding.


Input:
This is a Phase 1 study of JSI-1187 as monotherapy and in combination with dabrafenib for the
 treatment of advanced solid tumors with MAPK pathway mutations, including mutations that
 cause MAPK pathway hyperactivation.
 ;
 ;
 Inclusion Criteria:
 - Males and females ≥ 18 years of age
 - Have locally advanced or metastatic solid tumor malignancy with measurable disease and
 be an appropriate candidate for experimental therapy
 - Part A (JSI-1187 Monotherapy Dose Escalation): Histologically or cytologically
 confirmed MAPK pathway mutation, including hyperactivating pathway mutations or gene
 fusions, e.g., BRAF (Class I, II or III), RAS (H/K/N), MEK (MAP2K1), RAS-GAP (NF1
 loss, RASA1), RAS-GEF, refractory to or relapsed on prior therapy, and have received
 all available therapy known to confer clinical benefit
 - Part B (JSI-1187 Plus Dabrafenib Combination Dose Escalation): Histologically or
 cytologically confirmed BRAF V600E/K-mutated unresectable or metastatic melanoma, BRAF
 V600E-mutated metastatic NSCLC, BRAF V600E-mutated locally advanced or metastatic
 anaplastic thyroid cancer, or other BRAF V600E-mutated unresectable or metastatic
 solid tumors, excluding colorectal cancer, refractory to, or relapsed on, prior
 therapy, and have received all available therapy known to confer clinical benefit
 - Part C (JSI-1187 Plus Dabrafenib Expansion Cohorts): Histologically or cytologically
 confirmed:
 - Cohort 1: BRAF V600E/K-mutated unresectable or metastatic melanoma after 1-3
 prior therapies for metastatic disease, including anti-PD1 therapy, with or
 without ipilimumab, and BRAF/MEK inhibitor treatment
 - Cohort 2: BRAF V600E/K-mutated unresectable or metastatic melanoma after BRAF/MEK
 inhibitor adjuvant therapy for Stage 3 disease followed by 1-2 prior therapies
 for metastatic disease, including anti-PD-1 therapy, with or without ipilimumab,
 and excluding BRAF/MEK inhibitor treatment
 - Cohort 3: BRAF V600E-mutated metastatic NSCLC after 1 or 2 prior therapies for
 metastatic disease
 - MAPK mutation tumor status will be established prior to entry based on previous MAPK
 pathway mutation reports from a CLIA qualified laboratory, or, if a report is not
 available, the mutation analysis will be performed at Screening on archival tissue or
 newly biopsied tumor tissue.
 - Have discontinued previous treatments for cancer and have resolution, except where
 otherwise stated in the inclusion criteria, of all clinically significant toxic
 effects of prior cancer treatment, surgery, or radiotherapy to Grade ≤ 1. Subjects
 with prior immune checkpoint inhibitor endocrinopathies must have resolution to ≤
 Grade 2 and be stable on hormonal therapy (e.g., levothyroxine, hydrocortisone,
 insulin, etc.).
 - Adequate performance status: Eastern Cooperative Oncology Group (ECOG) ≤ 2
 - Life expectancy of ≥ 3 months
 - Subjects with asymptomatic stable, prior or currently treated brain metastases are
 allowed
 - Adequate hematologic parameters without ongoing transfusional support:
 - Hemoglobin (Hb) ≥ 9 g/dL
 - Absolute neutrophil count (ANC) ≥ 1.0 x 10^9 cells/L
 - Platelets ≥ 75 x 10^9 cells/L
 - Adequate renal and hepatic function:
 - Creatinine ≤ 1.5 times the upper limit of normal (ULN), or calculated creatinine
 clearance ≥ 50 mL/minute x 1.73 m^2 per the Cockcroft-Gault formula
 - Total bilirubin ≤ 1.5 times the (ULN) unless due to Gilbert's disease
 - ALT/AST ≤ 2 times the ULN, or < 3 times the ULN for subjects with liver
 metastases
 - Negative serum pregnancy test within 14 days prior to the first dose of study therapy
 for women of child-bearing potential (WCBP). Sexually active WCBP and male subjects
 must agree to use adequate methods to avoid pregnancy throughout the study and for 28
 days after the completion of study treatment.
 - Ability to provide written informed consent
 Exclusion Criteria:
 - Serious cardiac condition within the last 6 months, such as uncontrolled arrhythmia,
 myocardial infarction, unstable angina or heart disease defined by the New York Heart
 Association (NYHA) Class III or Class IV
 - QT interval corrected for rate (QTc) > 480 msec on the ECG obtained at Screening using
 Fridericia method for QTc calculation
 - Concomitant medication(s) that may cause QTc prolongation or induce Torsades de
 Pointes, with the exception of anti-microbials that are used as standard of care to
 prevent or treat infections and other such drugs that are considered by the
 Investigator to be essential for patient care.
 - Medications that are strong inhibitors of CYP3A4 are prohibited during study and for
 14 days prior to the first dose of study drug(s).
 - Medications that are strong inducers of CYP3A4 are prohibited during study and for 14
 days prior to the first dose of study drug(s).
 - Medications that are strong inhibitors of BCRP are prohibited during study and for 14
 days prior to the first dose of study drugs(s).
 - Subjects on dabrafenib (Parts B and C) also are advised to avoid concurrent
 administration of strong inhibitors of CYP2C8 as these medications may increase the
 concentration of dabrafenib
 - History of or current evidence/risk of retinal vein occlusion or central serous
 retinopathy, or has medically relevant abnormalities identified on screening
 ophthalmologic examination
 - Symptomatic central nervous system malignancy or metastasis
 - Gastrointestinal conditions that could impair absorption of study drug(s)
 - Current hematologic malignancies
 - Second, active primary solid tumor malignancy that, in the judgement of the
 investigator or Sponsor medical monitor, may affect the interpretation of results
 - Prior malignancies, with the exception of carcinoma in situ of any origin, non-muscle
 invasive bladder cancer, Gleason 3+3 prostate cancer and prior malignancies in
 remission whose likelihood of recurrence is very low, as judged by the Sponsor medical
 monitor.
 - Active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or
 hepatitis C virus (HCV) requiring treatment within the last week prior to study
 treatment
 - Other active infection requiring IV antibiotic usage within the last week prior to
 study treatment
 - Any other medical intervention or other condition which, in the opinion of the
 Principal Investigator, could compromise adherence to study requirements or confound
 the interpretation of study results
 - Receipt of an investigational product on a clinical trial within 5 elimination
 half-lives or within 28 days, whichever is shorter, prior to C1D1 on this study, or
 currently enrolled in a clinical trial, involving an investigational product or any
 other type of medical research judged not to be scientifically or medically compatible
 with this study
 - Previously completed or withdrawn from this study or any other study investigating an
 ERK1/2 inhibitor.
 - If female, pregnant, breast-feeding, or planning to become pregnant


Input:
The main purpose of this first-in-human study of GEN1056, is to evaluate safety. In addition,
 the study will determine the recommended dose and frequency for subsequent clinical studies
 and will assess the preliminary anti-tumor activity of GEN1056. GEN1056 will be studied in
 patients with advanced or metastatic solid cancer, for whom standard of care (SOC) therapy is
 not an option. All participants will get GEN1056.
 ;
 ;
 Key Inclusion Criteria:
 - Subjects with histologically or cytologically confirmed non-CNS advanced or metastatic
 solid tumors which has progressed despite standard therapy, or subjects who are
 intolerant of standard therapy, or for which no standard therapy exists, and for whom,
 in the opinion of the investigator, experimental therapy with GEN1056 may be
 beneficial
 - Have personally (or in countries where permitted, their legally acceptable
 representative) signed an Informed Consent Form (ICF)
 - Are at least 18 years of age.
 - Have measurable disease according to the RECIST v1.1 criteria.
 - Have an ECOG PS of 0 to 1 at screening and on C1D1 pre-treatment.
 - Have acceptable laboratory test results during the screening period.
 - Must provide an archival (FFPE) tumor tissue sample or newly obtained core or
 excisional biopsy of a tumor lesion not previously irradiated.
 - A female subject with reproductive potential must agree to use adequate contraception
 during the trial, and for 4 months after receiving the last dose of trial drug
 GEN1056.
 Key Exclusion Criteria:
 - Subject is considered a poor medical risk due to a serious, uncontrolled inter-current
 illness
 - Prior therapy with a checkpoint inhibitor agent or with an agent directed to another
 stimulatory or co-inhibitory T-cell receptor.
 - Prior exposure to any of the following prior therapies within the specified
 timeframes:
 1. Systemic cytotoxic chemotherapy or antineoplastic biological therapy within 28
 days or at least 5 elimination half-lives of the drug (whichever is shorter) of
 the first dose of trial treatment
 2. Radiotherapy within 21 days of start of trial treatment. Note: palliative
 radiotherapy be allowed.
 3. Prior treatment with live, attenuated vaccines within 28 days prior to initiation
 of GEN1056
 - Known active CNS metastases and/or carcinomatous meningitis, or spinal cord
 compression.
 - Positive for Human Immunodeficiency Virus (HIV), Hepatitis B (Hepatitis B Surface
 Antigen (HBsAg), HBV DNA), or Hepatitis C infection (Hepatitis C Virus Ribonucleic
 Acid (HCV RNA), HCV antibodies).
 - An active, known, or suspected autoimmune disease, requiring systemic steroid.
 - A condition requiring systemic treatment with either corticosteroids (>10 mg daily
 prednisone equivalent) or other immunosuppressive medications within 14 days of first
 treatment.
 - History of non-infectious pneumonitis/interstitial lung disease that required steroids
 or has current pneumonitis/interstitial lung disease requiring treatment with
 steroids.
 NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.


Input:
The primary objectives of the study are:
 In the Dose Escalation Phase:
 - To assess the safety, tolerability, and pharmacokinetics (PK) of REGN5668 alone and in
 separate combinations with cemiplimab or REGN4018, in order to determine a maximally
 tolerated dose(s) (MTD) or recommended phase 2 dose(s) (RP2D) of these combinations
 In the Dose Expansion Phase:
 - To assess the preliminary efficacy of REGN5668 in combination with cemiplimab or
 REGN4018, (separately by cohort and combination) as determined by the objective response
 rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
 The secondary objectives of the study are:
 In the Dose Escalation Phase:
 - To assess the preliminary efficacy of REGN5668 in combination with cemiplimab or
 REGN4018 (separately by cohort and combination) as determined by ORR by RECIST 1.1
 In the Dose Expansion Phase:
 - To characterize the safety profile in each expansion cohort
 - To characterize the PK of REGN5668 in combination with cemiplimab or REGN4018
 (separately by cohort and combination)
 In both the Dose Escalation and Dose Expansion Phases:
 - To assess preliminary efficacy of REGN5668 in combination with cemiplimab or REGN4018
 (separately by cohort and combination) as measured by ORR based on immune based therapy
 RECIST (iRECIST), best overall response (BOR), duration of response (DOR), disease
 control rate (DCR), and progression-free survival (PFS) based on RECIST 1.1 and iRECIST
 - To assess changes in CA-125 levels from baseline after treatment with REGN5668 in
 combinations with cemiplimab or REGN4018 (separately by cohort and combination)
 - Immunogenicity of REGN5668, alone and in combinations with cemiplimab or REGN4018
 ;NA;
 Key Inclusion Criteria:
 1. Has histologically or cytologically confirmed diagnosis of advanced epithelial ovarian
 cancer (except carcinosarcoma), primary peritoneal, or fallopian tube cancer that has
 received at least 1 line of platinum-based systemic therapy as defined in the protocol
 2. Has a serum CA-125 level ≥2x ULN (in screening)
 3. Has adequate organ and bone marrow function as defined in the protocol
 4. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
 5. Has a life expectancy of at least 3 months
 Key Exclusion Criteria:
 1. Prior anti-cancer immunotherapy as defined in the protocol
 2. Recent treatment with anti-Programmed Cell Death (PD-1)/PDL-1 therapy
 3. Has had another malignancy within the last 5 years that is progressing, requires
 active treatment, or has a high likelihood of recurrence as defined in the protocol
 4. Prior treatment with a MUC16-targeted therapy
 5. Expansion cohorts only: More than 3 prior lines of cytotoxic chemotherapy for
 platinum-experienced and/or intolerant disease
 6. Has any condition that requires ongoing/continuous corticosteroid therapy as defined
 in the protocol within 1 week prior to the first dose of study drug
 7. Has ongoing or recent (within 5 years) evidence of significant autoimmune disease that
 required treatment with systemic immunosuppressive treatments as defined in the
 protocol
 8. Has untreated or active primary brain tumor, CNS metastases, leptomeningeal disease,
 or spinal cord compression as defined in the protocol
 9. Has history of clinically significant cardiovascular disease as defined in the
 protocol
 Note: Other protocol-defined Inclusion/Exclusion criteria apply


Input:
The purpose of this clinical trial is to assess the feasibility, safety and efficacy of
 4SCAR-CD44v6 T-cell therapy targeting multiple cancers. The study also aims to learn more
 about the function of the CD44v6 CAR-T cells and their persistency in the patients.
 ;
 ;
 Inclusion Criteria:
 1. Age older than 6 months.
 2. Confirmed expression of CD44v6 in tumor specimens by immuno-histochemical staining or
 flow cytometry.
 3. Karnofsky performance status (KPS) score is higher than 70 and life expectancy > 3
 months.
 4. Adequate bone marrow, liver and renal function as assessed by the following laboratory
 requirements: cardiac ejection fraction ≥ 50%, oxygen saturation ≥ 90%, creatinine ≤
 2.5 × upper limit of normal, aspartate aminotransferase (AST) and alanine
 aminotransferase (ALT) ≤ 3 × upper limit of normal, total bilirubin ≤ 2.0mg/dL.
 5. Hgb≥80g/L.
 6. No cell separation contraindications.
 7. Abilities to understand and the willingness to provide written informed consent.
 Exclusion Criteria:
 1. Sever illness or medical condition, which would not permit the patient to be managed
 according to the protocol, including active uncontrolled infection.
 2. Active bacterial, fungal or viral infection not controlled by adequate treatment.
 3. Known HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
 4. Pregnant or nursing women may not participate.
 5. Use of glucocorticoid for systemic therapy within one week prior to entering the
 trial.
 6. Receive treatment related to CD44v6 targeted therapy.
 7. Patients, in the opinion of investigators, may not be able to comply with the study.


Input:
The drug that will be investigated in the study is an antibody, GEN3009. Since this is the
 first study of GEN3009 in humans, the main purpose is to evaluate safety. Besides safety, the
 study will determine the recommended GEN3009 dose to be tested in a larger group of patients
 and assess preliminary clinical activity of GEN3009. GEN3009 will be studied in a broad group
 of cancer patients, having different kinds of lymphomas. All patients will get GEN3009 either
 as a single treatment (monotherapy) or in combination with another antibody-candidate for
 treatment of cancer in the blood. The study consists of two parts: Part 1 tests increasing
 doses of GEN3009 ("escalation"), followed by Part 2 which tests the recommended GEN3009 dose
 from Part 1 ("expansion").
 ;
 ;
 Key Inclusion Criteria:
 1. Be at least 18 years of age.
 2. Must sign an informed consent form prior to any screening procedures.
 3. Dose Escalation: Has histologically or cytologically confirmed relapsed and/or
 refractory B-cell NHL with no available standard therapy or is not a candidate for
 available standard therapy, and for whom, in the opinion of the investigator, the
 experimental therapy may be beneficial. All subjects must have received at least two
 prior lines of systemic therapy.
 Dose Expansion: Has histologically or cytologically confirmed relapsed or refractory
 B-cell NHL. All subjects must have received at least 2 prior lines of systemic
 therapy, and,
 1. For FL and DLBCL, at least 1 of the 2 prior lines of treatment must have been a
 CD20 containing systemic regimen;
 2. For CLL, subjects must have received at least one prior line of BTK inhibitor or
 BCL 2 inhibitor.
 4. Has one of the eligible subtypes of B-cell NHL :
 Dose Escalation: (DLBCL, HGBCL, PMBCL, FL, MCL, MZL, SLL, or CLL). Dose Expansion:
 (DLBCL, FL, CLL)
 5. Has measurable disease for B-cell NHL or has active disease for Chronic Lymphocytic
 Leukemia (CLL).
 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
 7. Has adequate hepatic, renal, and bone marrow functions.
 8. Before the first dose of GEN3009, during the trial, and for 12 months after the last
 dose of GEN3009 and/or the combination, a woman must be either not of childbearing
 potential or of childbearing potential and practicing a highly effective method of
 birth control, and must have a negative serum beta-human chorionic gonadotropin
 (beta-hCG) and urine pregnancy test at screening.
 9. A man who is sexually active with a woman of childbearing potential and has not had a
 vasectomy must agree to use a barrier method of birth control.
 10. Subjects must have a life expectancy of at least 3 months.
 Key Exclusion Criteria:
 1. Prior treatment with a CD37-targeting agent.
 2. Prior allogeneic Hematopoietic Stem Cell Transplantation (HSCT).
 3. Prior treatment with a CD3xCD20 bispecific antibody (Combination Expansion cohort
 only).
 4. Autologous HSCT within 3 months before the first dose of GEN3009.
 5. Lymphomas leukemic phase: high absolute lymphocyte count or the presence of abnormal
 cells in the peripheral blood indicating circulating lymphoma cells.
 6. Treatment with an anti-cancer biologic including anti-CD20 therapy, radio-conjugated
 or toxin-conjugated antibody or chimeric antigen receptor (CAR) T-cell therapy within
 4 weeks or 5 half-lives, whichever is shorter, before the first dose of GEN3009.
 Treatment with small molecules such as BTK inhibitors, BCL2 inhibitors, or PI3K
 inhibitors within 5 half-lives prior to the first dose of GEN3009.
 7. Chemotherapy or radiation therapy within 2 weeks of the first dose of GEN3009.
 8. Treatment with an investigational drug or an invasive investigational medical device
 within 4 weeks or 5 half-lives, whichever is shorter, prior to the first dose of
 GEN3009, and at any time during the study treatment period.
 9. Autoimmune disease or other diseases that require permanent or high-dose
 immunosuppressive therapy.
 10. Received a cumulative dose of corticosteroids more than the equivalent of 250 mg of
 prednisone within the 2-week period before the first dose of GEN3009.
 11. Has uncontrolled intercurrent illness.
 12. Seizure disorder requiring therapy (such as steroids or anti-epileptics) (Combination
 Expansion cohort only).
 13. Toxicities from previous anti-cancer therapies have not resolved to baseline levels or
 to Grade 1 or less except for alopecia and peripheral neuropathy.
 14. Primary central nervous system (CNS) lymphoma or known CNS involvement at screening.
 15. Known past or current malignancy other than inclusion diagnosis.
 16. Had allergic reactions to anti-CD20 or anti-CD37 monoclonal antibody treatment or
 intolerant to GEN3009 or to the combination therapy excipients.
 17. Has had major surgery within 4 weeks before screening or will not have fully recovered
 from surgery, or has major surgery planned during the time the subject is expected to
 participate in the trial (or within 4 weeks after the last dose of GEN3009 and/or the
 combination therapy).
 18. Known history/positive serology for hepatitis B.
 19. Known medical history or ongoing hepatitis C infection that has not been cured.
 20. Known history of seropositivity for HIV infection.
 21. Is a woman who is pregnant or breast-feeding, or who is planning to become pregnant
 while enrolled in this trial or within 12 months after the last dose of GEN3009 and/or
 the combination therapy.
 22. Is a man who plans to father a child while enrolled in this trial or within 12 months
 after the last dose of GEN3009 and/or the combination therapy.
 23. Has any condition for which, in the opinion of the investigator, participation would
 not be in the best interest of the subject (eg, compromise the well-being) or that
 could prevent, limit, or confound the protocol-specified assessments. Additionally,
 vulnerable subjects or subjects under guardianship, curatorship, judicial protection
 or deprived of liberty), are excluded from participation in this trial.
 24. Exposed to live/live attenuated vaccine within 4 weeks prior to initiation of GEN3009
 treatment.
 NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.


Input:
This study is designed as a single arm open label Phase I, 3x3, multicenter study of
 CD4-directed chimeric antigen receptor engineered T-cells (CD4CAR) in patients with relapsed
 or refractory T-cell leukemia and lymphoma. Specifically, the study will evaluate the safety
 and tolerability of CD4CAR T-cells. Funding Source - FDA OOPD
 ;
 ;
 Inclusion Criteria
 In order to be eligible to participate in this study, an individual will be enrolled if
 they meet the following criteria:
 1. Patients must voluntarily sign and date informed consent forms that state his or her
 willingness to comply with all study procedures and availability for the duration of
 the study.
 2. Age 18 years old or older
 3. T-cell ≥ 500
 4. Subjects with documented CD4+ hematologic malignancies. Male and female subjects with
 CD4+ T-cell malignancies with either relapsed or refractory disease (including those
 patients who have undergone a prior transplant and patients with an inadequate
 response after 4-6 cycles of standard chemotherapy)
 5. For patients who present with CD4+ Leukemia, either relapsed disease or minimal
 residual disease (MRD); any of the following are eligible:
 1. Peripheral T-cell leukemia, NOS
 2. T-cell prolymphocytic leukemia
 3. Adult T-cell leukemia
 4. T-cell large granular lymphocytic leukemia
 5. T cell acute lymphoblastic leukemia T-ALL
 6. For patients with CD4+ Lymphoma, either relapsed or refractory disease; any of the
 following are eligible:
 1. Peripheral T-cell lymphoma, NOS
 2. Sezary syndrome/cutaneous T-cell lymphoma
 3. Angioimmunoblastic T-cell lymphoma
 4. Adult T-cell lymphoma
 5. Blastic plasmacytoid dendritic cell neoplasm (BPDCN)
 7. Creatinine clearance of > 60 ml/min (or otherwise non clinically-significant, per
 study investigator)
 8. ALT/AST < 3 x ULN
 9. Bilirubin < 2 x ULN
 10. Pulmonary Function Test (PFT) with a DLCO of ≥ 60%.
 11. Adequate echocardiogram with EF of ≥50%
 12. Adequate venous access for apheresis and no other contraindications for leukapheresis
 Exclusion Criteria
 1. Pregnant or lactating women. The safety of this therapy on unborn children is not
 known. Female study participants of reproductive potential (see definition below) must
 have a negative serum or urine pregnancy test prior to initiation of conditioning
 chemotherapy, per research sites' clinical policy.
 2. Uncontrolled active infection.
 3. Active hepatitis B or hepatitis C infection.
 4. Concurrent use of systemic glucocorticoids in greater than replacement doses or
 steroid dependency. Recent or current use of inhaled glucocorticoids is not
 exclusionary.
 • Note: The following doses of glucocorticoids are permitted:
 1. Hydrocortisone 25mg/day or less
 2. Prednisone 10mg/day or less
 3. Dexamethasone 4mg or less
 5. Any previous treatment with any gene therapy products.
 6. Any uncontrolled active medical disorder that would preclude participation as outlined
 in the opinion of the treating investigator and/or study chair
 7. HIV infection.
 8. Patients declining to consent for treatment
 9. Absolute lymphocyte count <500/mm3 (<0.5 x 109 /L) (can be repeated, if indicated and
 possible)
 Screen Failures
 First point screen failure: Apheresis Subject with an absolute lymphocyte count < 500/mm3
 at the time of apheresis will be considered a screenfailure.
 Note: This test may be repeated in 2-3 weeks or often as needed to meet eligibility for
 apheresis, as long as the subject otherwise continues to be eligible.
 Second point screen failure
 Subjects who fail to cytoreduce with conditioning chemotherapy with persistence of high
 disease burden will be considered a screenfail according to the guidelines below:
 1. CD4+ Leukemias ( Liquid Blood and marrow disease):
 1. Subjects at study entry with bone marrow malignant replacement estimated at > 80%
 of total cellularity and accompanied by significant peripheral pancytopenia, ANC
 <500, platelet count < 50,000 will need to have roughly 50% or greater reduction
 on the marrow malignant component to be considered eligible after cytoreductive
 chemotherapy and for CD4CAR infusion. This will be determined and approved by PI,
 treating physician and study team as applicable.
 2. Subjects at study entry with bone marrow malignant replacement estimated at less
 than 80% of total cellularity will need to have stable disease or disease that is
 less than 80% in the marrow as determined and approved by the PI, treating
 physician and study team as applicable.
 Note: Bone marrow sampling is not an accurate reflection of disease burden because
 only a small biopsy is obtained to represent a patchy disease distributed all over the
 marrow. Hence these numbers and in the absence of severe cytopenias that are
 attributed to documented marrow replacement with malignant cells should not be
 formidable as is and borderline cases should be discussed and approved by the PI and
 the study team as applicable before moving forward.
 2. Solid Mass Forming CD4+ lymphomas: (in lymph nodes or extra nodal sites)
 1. Stage IV disease: Subjects with Stage IV disease that is deemed bulky by the
 standard definition of the presence of at least one site with a mass that is >
 7.5 cm in largest diameter who have a 50% estimated reduction of total disease
 burden by imagining as read by radiology after conditioning chemotherapy are
 eligible to continue on study. In borderline cases, where they don't meet this
 criteria but are thought to have bulky disease by the treating investigator,
 clinical judgment will be required to determine eligibility of subjects who
 experience for example mixed responses; improved sites and progressed sites. In
 these cases, the PI, treating physician, and study team as applicable should
 agree and document that total disease burden has been reduced by about 50% when
 taking all sites involved into account as there is no objective method to make
 this estimated reduction if some areas improve and others don't, or even new
 sites arise.
 2. Stage I-III disease: Subjects with stage I-III ( No extra nodal disease) who
 continue to have stable disease or better after conditioning chemotherapy are
 eligible to continue on study.
 3. Skin Disease a. There will be no response or non-response criteria assessed that will
 be specific to skin disease since disease burden is almost never expected to be high
 without skin barrier violation and often involve infections that would make subjects
 ineligible at the time
 Eligibility for CD4CAR infusion:
 Inclusion
 1. Afebrile and not receiving antipyretics, and no evidence of active infection
 2. Specific organ function criteria for cardiac, renal, and liver function must be
 similar to initial inclusion values. Tests such as echocardiogram and PFTs need not be
 repeated if within 6 weeks of initial assessment.
 3. Negative pregnancy testing (if applicable)
 4. If previous history of corticosteroid chemotherapy, subject must be off all but
 adrenal replacement doses
 5. Planned infusion dose was successfully manufactured and met release criteria.


Input:
This is a prospective, open-label, single-center clinical trial. This study will evaluate the
 safety and efficacy of anti-CD7 CAR-T cells in the treatment of relapsed or refractory CD7
 positive T-ALL, T-NHL and AML. The primary endpoints are dose limiting toxicity (DLT) and the
 incidence of treatment emergent adverse event (TEAE).
 ;NA;
 Inclusion Criteria:
 1. Total bilirubin ≤ 51 μmol / L, ALT and AST ≤ 3 times of the upper limit of normal
 value, serum creatinine ≤ 176.8 μmol / L;
 2. Echocardiography shows left ventricular ejection fraction (LVEF) ≥ 50%;
 3. There is no active pulmonary infection, and the oxygen saturation during air
 inhalation is more than 92%;
 4. The estimated survival time is more than 3 months;
 5. ECOG score was 0-2;
 6. The patients or their legal guardians voluntarily participated in the trial and signed
 the informed consent.
 For T-ALL:
 1. Patients is histologically diagnosed with CD7 Positive T-ALL according to the Clinical
 Practice Guidelines for Acute Lymphoblastic Leukemia (ALL) (2020. V1) by National
 Comprehensive Cancer Network (NCCN).
 2. The diagnosis is consistent with r/r CD7 + T-ALL, and includes any of the following
 conditions:
 1. No CR was obtained by standard chemotherapy;
 2. The first induction was CR, but the duration of CR was less than 12 months;
 3. No CR was obtained after the first or multiple remedial treatment;
 4. Relapse twice or more;
 3. The number of blast cells in bone marrow was more than 5% (morphology) and / or > 1%
 (flow cytometry).
 For T-NHL:
 1. Patients is histologically diagnosed with CD7 Positive T-NHL according to The 2016
 revision of the World Health Organization classification of lymphoid neoplasms.
 2. r/r T-NHL, and includes any of the following conditions:
 1. No response or relapse after second or more lines of chemotherapy;
 2. Primary refractory ot chemotherapy;
 3. Relapse after autologous stem cell transplantation;
 3. According to the Lugano 2014 criteria, there is at least one evaluable tumor lesion.
 For AML:
 1. Patients is histologically diagnosed with CD7 Positive AML according to the Clinical
 Practice Guidelines for Acute Myeloid Leukemia (AML) (2020. V3) by National
 Comprehensive Cancer Network (NCCN).
 2. The diagnosis is consistent with r/r CD7 + AML, and includes any of the following
 conditions:
 1. No CR was obtained by standard chemotherapy;
 2. The first induction was CR, but the duration of CR was less than 12 months;
 3. No CR was obtained after the first or multiple remedial treatment;
 4. Relapse twice or more;
 3. The number of blast cells in bone marrow was more than 5% (morphology) and / or > 1%
 (flow cytometry).
 Exclusion Criteria:
 1. Patients with history of epilepsy or other central nervous system diseases;
 2. Patients with prolonged QT or severe heart disease;
 3. Pregnant or lactating women (the safety of this therapy for unborn children is
 unknown);
 4. The patients with uncontrolled active infection;
 5. Active hepatitis B or hepatitis C virus infection;
 6. Previous application of gene therapy;
 7. The proiferation rate is less than 5 times response to CD3/CD28 co-stimulation signal;
 8. Serum creatinine > 2.5mg/dl or ALT / AST > 3 times ULN or bilirubin > 2.0mg/dl;
 9. Those who suffer from other uncontrolled diseases are not suitable to join the study;
 10. HIV infection;
 11. Any situation that the researchers believe may increase the risk of patients or
 interfere with the test results.