Input:
To evaluate the safety and tolerability of sotorasib administered in investigational regimens
 in adult participants with KRAS p.G12C mutant advanced solid tumors.
 ;NA;
 Inclusion Criteria:
 - Men or women greater than or equal to 18 years old.
 - Pathologically documented, locally-advanced or metastatic malignancy with, KRAS p.G12C
 mutation identified through molecular testing performed according to in-country
 requirements. In the United States, this test must be performed in a Clinical
 Laboratory Improvement Amendments (CLIA)-certified laboratory.
 Exclusion Criteria:
 - Primary brain tumor.
 - Spinal cord compression, or untreated, or symptomatic, or active brain metastases, or
 leptomeningeal disease from non-brain tumors.
 - Myocardial infarction within 6 months of study day 1.
 - Gastrointestinal (GI) tract disease causing the inability to take oral medication.


Input:
This is a Phase 1/2, first-in-human, open label, multicenter study to assess safety and
 tolerability, antitumor activity, and immunogenic and pharmacodynamic effects of SQZ-eAPC-HPV
 as monotherapy and in combination with pembrolizumab in patients with recurrent, locally
 advanced, or metastatic HPV16+ solid tumors. The study includes patients with head and neck,
 cervical, anal, vulvar, or penile cancer.
 ;NA;
 Inclusion Criteria - All Patients:
 - Male or female patients ≥18 years of age
 - Histologically confirmed incurable or metastatic solid tumors that are HPV16+
 (performed during screening locally or centrally, or based on documented historic test
 results)
 - Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1
 - At least 1 measurable lesion according to RECIST 1.1
 - Must have a lesion that can be biopsied with acceptable clinical risk and agree to
 have a fresh biopsy at Screening and on Cycle 2 Day 8 (+/- 2 days)
 - Patients must agree to venous access for leukapheresis and be willing to have a
 central line inserted if venous access is an issue
 - Adequate organ function and bone marrow reserve performed within 14 days prior to
 leukapheresis
 Inclusion Criteria - Part 2:
 • Patients must not have been treated with immune check-point inhibitors
 Exclusion Criteria - All Patients:
 - Treatment with anticancer therapy, including investigational therapy, within 2 weeks
 prior to leukapheresis.
 - Systemic treatment with either corticosteroids (>10 mg of prednisone or the equivalent
 per day) or other immunosuppressive medications within 14 days prior to leukapheresis
 - Patients treated with non-corticosteroid based immunosuppressive agents within the
 last 6 months prior to leukapheresis
 - Patients with active, known, or suspected autoimmune disease may not be eligible and
 should be discussed with the Sponsor
 - Patients with >Grade 1 AEs related to previous treatment with anticancer or
 investigational therapy that do not resolve at least 2 weeks prior to leukapheresis,
 except Grade 2 neuropathy, ototoxicity, mucositis, fatigue, alopecia, or endocrine
 disorders managed with hormone replacement
 - Known HIV infection, active hepatitis B or hepatitis C, or active mycobacterium
 tuberculosis infection
 - Has known active central nervous system metastases
 - Have active interstitial lung disease and any history of myocarditis
 - Major surgery within 2 weeks of leukapheresis
 Exclusion Criteria - Part 1B:
 - Known hypersensitivity to pembrolizumab
 - History of any Grade 3 immune-related AE (irAE) from prior immunotherapy
 Exclusion Criteria - Part 2:
 • Prior treatment with an immune check-point inhibitor


Input:
This phase I trial studies the biological effects of DS-8201a on patients with HER2 positive
 cancer that has spread to other places in the body (advanced). DS-8201a works by binding to a
 protein called HER2 that is present on the surface of tumor cells. This allows DS-8201a to
 kill the tumor cells by damaging their deoxyribonucleic acid (DNA), resulting in tumor cell
 death. This study looks at how DS-8201a may affect the levels of certain proteins and immune
 cells in tumors and how well the drug works against tumor cells by examining cells from a
 small piece tumor taken before and after DS-8201a is given.
 ;
 ;
 Inclusion Criteria:
 - Patients must have histologically confirmed malignancy that is metastatic or
 unresectable and for which standard curative or palliative measures do not exist or
 are no longer effective
 - Patients must have measurable or evaluable disease
 - Age >= 18 years of age
 - Patients must have HER2-positive or HER2-expressing tumors as defined by Clinical
 Laboratory Improvement Act (CLIA)-certified labs. Patients must have either:
 - A tumor HER2 immunohistochemistry (IHC) score of 1+ or greater (as determined by
 a CLIA-certified IHC test, per criteria specified) or
 - A tumor with HER2 amplification (as determined by CLIA-certified in situ
 hybridization (ISH) or a CLIA-certified next-generation sequencing assay)
 - Patients with HER2 mutations are eligible, as are patients with HER2-positive breast
 cancer
 - Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =< 1
 (Karnofsky >= 70%)
 - Absolute neutrophil count >= 1,500/mcL (within 8 days of enrollment)
 - Platelets >= 100,000/mcL (within 8 days of enrollment)
 - Leukocytes >= 3,000/mcL (within 8 days of enrollment)
 - Hemoglobin >= 9 g/dL (>= 8.0 g/dL for gastric cancer [GC] only) (within 8 days of
 enrollment)
 - Serum albumin >= 2.5 g/dL (GC only) (within 8 days of enrollment)
 - Total bilirubin =< 1.5 x institutional upper limit of normal (=< 3 x upper limit of
 normal in the presence of documented Gilbert's syndrome or liver metastases at
 baseline) (within 8 days of enrollment)
 - Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
 [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
 =< 3 x institutional upper limit of normal OR =< 5 x institutional upper limit of
 normal for patients with liver metastases at baseline (within 8 days of enrollment)
 - Creatinine =< 1.5 x institutional upper limit of normal OR creatinine clearance >= 60
 mL/min/1.73 m^2 for patients with creatinine levels above 1.5 x institutional normal
 (within 8 days of enrollment)
 - No transfusions with red blood cells or platelets are allowed within 1 week prior to
 screening assessment
 - No administration of granulocyte colony-stimulating factor (G-CSF) is allowed within 1
 week prior to screening assessment
 - International normalized ratio (INR)/prothrombin time (PT) and either partial
 thromboplastin or activated partial thromboplastin time (aPTT) =< 1.5 x upper limit of
 normal (ULN)
 - Ability to understand and the willingness to sign a written informed consent document
 - Willingness to provide blood samples for research purposes
 - Patients must have a lesion or lesions amenable to biopsy and must be willing to
 undergo 3 core needle biopsy procedures for research purposes
 - Patients must have left ventricular ejection fraction (LVEF) >= 50% by either an
 echocardiogram (ECHO), multigated acquisition (MUGA), or cardiac MRI scan within 28
 days prior to enrollment
 - Patients who are human immunodeficiency virus (HIV) positive may participate IF they
 meet the following eligibility requirements:
 - They must be stable on their anti-retroviral regimen, and they must be healthy
 from an HIV perspective
 - They must have a CD4 count of greater than 250 cells/mcL over the past 6 months
 on this same anti-retroviral regimen and must not have had a CD4 count < 200
 cells/uL over the past 2 years, unless it was deemed related to the cancer and/or
 immunotherapy-induced bone marrow suppression
 - For patients who have received chemotherapy in the past 6 months, a CD4
 count < 250 cells/ul during chemotherapy is permitted as long as viral loads
 were undetectable during this same chemotherapy
 - They must have an undetectable viral load and a CD4 count >= 250 cells/uL within
 8 days of enrollment
 - They must not be currently receiving prophylactic therapy for an opportunistic
 infection and must not have had an opportunistic infection within the past 6
 months HIV-infected patients should be monitored every 12 weeks for viral load
 and CD4 counts
 - For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
 load must be undetectable on suppressive therapy, if indicated
 - Patients with a history of hepatitis C virus (HCV) infection must have been treated
 and cured. For patients with HCV infection who are currently on treatment, they are
 eligible if they have an undetectable HCV viral load
 - Patients with treated brain metastases are eligible if follow-up brain imaging after
 central nervous system (CNS)-directed therapy shows no evidence of progression for >=
 1 month after treatment of the brain metastases
 - Patients with a prior or concurrent malignancy whose natural history or treatment does
 not have the potential to interfere with the safety or efficacy assessment of the
 investigational regimen are eligible for this trial
 - The effects of DS-8201a on the developing human fetus are unknown. For this reason and
 because HER2 antibodies conjugated to topoisomerase 1 inhibitor agents are known to be
 teratogenic, women of child-bearing potential and men must agree to use adequate
 contraception (hormonal or barrier method of birth control or abstinence) prior to
 study entry and for the duration of study participation and for at least 7 months
 after the last dose of study drug. Should a woman become pregnant or suspect she is
 pregnant while she or her partner is participating in this study, she should inform
 her treating physician immediately. Men treated or enrolled on this protocol must also
 agree to use adequate contraception prior to the study, for the duration of study
 participation, and 4 months after completion of DS-8201a administration
 - Women of non-child-bearing potential defined as pre-menopausal females with a
 documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of
 spontaneous amenorrhea (in questionable cases, a blood sample with simultaneous
 follicle-stimulating hormone [FSH] > 40 mIU/mL and estradiol < 40 pg/mL [< 147 pmol/L]
 is confirmatory) are eligible. Females on hormone replacement therapy (HRT) and whose
 menopausal status is in doubt will be required to use one of the contraception methods
 outlined for women of child-bearing potential if they wish to continue their HRT
 during the study. Otherwise, they must discontinue HRT to allow confirmation of
 post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4
 weeks will elapse between the cessation of therapy and the blood draw; this interval
 depends on the type and dosage of HRT. Following confirmation of their post-menopausal
 status, they can resume use of HRT during the study without use of a contraceptive
 method
 - Subjects must not freeze, donate, or retrieve for their own use ova or sperm starting
 at screening, throughout the study period, and for at least 4.5 months after the final
 study drug administration. Preservation of sperm or ova should be considered prior to
 enrollment in this study
 - Because there is an unknown but potential risk for adverse events in nursing infants
 secondary to treatment of the mother with DS-8201a, breastfeeding should be
 discontinued if the mother is treated with DS-8201a
 Exclusion Criteria:
 - Patients who have had:
 - Chemotherapy (including antibody drug therapy, retinoid therapy, hormonal therapy
 for cancer) within:
 - 4 weeks or five half-lives, whichever is shorter, for small-molecule
 targeted agents such as 5-fluorouracil-based agents, folinate agents, weekly
 paclitaxel or
 - 6 weeks for nitrosoureas or mitomycin C or
 - Immunotherapy, including monoclonal antibody therapy, within 4 weeks
 - Patients with any of the following pulmonary-related illnesses:
 - A history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that
 required steroids, current ILD/pneumonitis, or for whom suspected ILD/pneumonitis
 cannot be ruled out by imaging at screening
 - Clinically severe pulmonary compromise resulting from intercurrent pulmonary
 illnesses including, but not limited to, any underlying pulmonary disorder (i.e.,
 pulmonary emboli within three months of the study enrollment, severe asthma,
 severe chronic obstructive pulmonary disease [COPD] grade 3-4 per Global
 Initiative for Obstructive Lung Disease [GOLD] criteria, restrictive lung
 disease, pleural effusion, etc.), and any autoimmune, connective tissue, or
 inflammatory disorders with potential pulmonary involvement (i.e., Rheumatoid
 arthritis, Sjogren's, sarcoidosis, etc.), or prior pneumonectomy.
 - Patients who have had radiation therapy within 4 weeks (or palliative stereotactic
 radiation therapy within 2 weeks)
 - Patients who have had a major surgery within 4 weeks
 - Patients who are receiving any other investigational agents
 - Patients with a medical history of myocardial infarction within 6 months before
 enrollment, symptomatic congestive heart failure (CHF) (New York Heart Association
 class II to IV), or with troponin levels consistent with myocardial infarction (as
 defined according to the assay manufacturer) 28 days prior to enrollment
 - History of allergic reactions attributed to compounds of similar chemical or biologic
 composition to DS-8201a (e.g., other topoisomerase I inhibitors) or the inactive
 ingredients in the drug product
 - Patients who have a history of severe hypersensitivity reactions to other monoclonal
 antibodies
 - Patients with a Fridericia's formula-corrected QT interval (QTcF) prolongation to >
 470 ms (females) or > 450 ms (males) based on average of the screening triplicate
 12-lead electrocardiogram (ECG)
 - Patients with spinal cord compression or clinically active central nervous system
 metastases, defined as untreated and symptomatic, or requiring therapy with
 corticosteroids or anticonvulsants to control associated symptoms
 - Patients with an uncontrolled infection requiring IV antibiotics, antivirals, or
 antifungals
 - Patients with unresolved toxicities from previous anticancer therapy, defined as
 toxicities (other than alopecia) not yet resolved to grade =< 1 or baseline. Subjects
 with chronic grade 2 toxicities (e.g., grade 2 chemotherapy-induced neuropathy) may be
 eligible per the discretion of the investigator after consultation with the sponsor
 medical monitor or designee. Subjects should no longer be symptomatic nor require
 treatment with corticosteroids or anticonvulsants and must have recovered from the
 acute toxic effect of radiotherapy
 - Patients with substance abuse or any other medical conditions that would increase the
 safety risk to the subject or interfere with participation of the subject or
 evaluation of the clinical study in the opinion of the investigator
 - Patients with uncontrolled intercurrent illness
 - Patients with psychiatric illness/social situations that would limit compliance with
 study requirements
 - Pregnant women are excluded from this study because DS-8201a is a HER2 antibody
 conjugated to a topoisomerase 1 inhibitor agent with the potential for teratogenic or
 abortifacient effects. Because there is an unknown but potential risk for adverse
 events in nursing infants secondary to treatment of the mother with DS-8201a,
 breastfeeding should be discontinued if the mother is treated with DS-8201a
 - Patients are not allowed to receive chloroquine/hydroxychloroquine. Patients receiving
 chloroquine/hydroxychloroquine require a washout of > 14 days


Input:
Nivolumab (BMS-936558) is a fully human, IgG4 (kappa) isotype mAb that binds PD-1 on
 activated immune cells and disrupts engagement of the receptor with its ligands PD-L1 (B7
 H1/CD274) and PD-L2 (B7-DC/CD273), thereby abrogating inhibitory signals and augmenting the
 host antitumor response. In early clinical trials, nivolumab has demonstrated activity in
 several tumor types, including melanoma, renal cell carcinoma (RCC), and non-small cell lung
 cancer (NSCLC).
 Nivolumab is in clinical development for the treatment of patients with NSCLC, RCC, melanoma,
 squamous cell carcinoma of the head and neck (SCCHN) and other tumors (eg, glioblastoma
 multiforme, mesothelioma, small cell lung cancer, gastric).
 Nivolumab is approved in the United States (US), European Union, and other countries for the
 treatment of patients with unresectable or metastatic melanoma, advanced NSCLC with
 progression on or after platinum-based chemotherapy, advanced RCC whose disease progressed on
 an antiangiogenic therapy, classical Hodgkin lymphoma that has relapsed or progressed after
 autologous hematopoietic stem cell transplantation and post-transplantation brentuximab
 vedotin treatment, and recurrent or metastatic squamous cell carcinoma of the head and neck
 with disease progression on or after a platinum-based therapy.
 The proposed study will evaluate the efficacy and safety of preoperative administration of
 Nivolumab or Nivolumab combined with nab-paclitaxel and carboplatin in neoadjuvant setting
 and administration of Nivolumab in adjuvant setting in patients with high-risk resectable
 NSCLC, and will facilitate a comprehensive exploratory characterization of the tumor immune
 microenvironment and circulating immune cells in these patients. Data obtained in this study
 will provide valuable information for planning further prospective clinical trials of
 anti-PD-1 and other immunotherapies in NSCLC, both in the peri-operative and advanced disease
 setting. Ultimately, it is highly desirable to discover prospective biomarkers of response
 and toxicity to allow patients with NSCLC who are most likely to derive benefit to receive
 anti-PD-1 treatment, and conversely to minimize the risk of toxicity and ineffective
 treatment for patients who are unlikely to benefit.
 ;NA;
 Inclusion Criteria:
 - Early stage IB-IIIA, operable non-small cell lung cancer, confirmed in tissue
 - Lung function capacity capable of tolerating the proposed lung surgery
 - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
 - Available tissue of primary lung tumor
 Exclusion Criteria:
 - Presence of locally advanced, inoperable or metastatic disease
 - Participants with active, known or suspected autoimmune disease
 - Prior treatment with any drug that targets T cell co-stimulations pathways (such as
 checkpoint inhibitors)
 Other protocol defined inclusion/exclusion criteria could apply


Input:
Researchers are looking for a better way to treat people who have advanced non-small cell
 lung cancer (NSCLC), a group of lung cancers that have spread to nearby tissues or to other
 parts of the body.
 Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2)
 are proteins that help cells to grow and divide. A damage (also called mutation) to the
 building plans (genes) for these proteins in cancer cells leads to a production of abnormal
 EGFR and/or HER2. These abnormal proteins drive the growth and the spread of the cancer.
 Several EGFR and/or HER2 mutations exist in the cancer cells. Two mutations observed in NSCLC
 are called EGFR- or HER2exon20ins and EGFR C797X. The study treatment, BAY2927088, works by
 blocking the mutated EGFR protein and also its ex20ins version which are present in NSCLC. It
 is also believed to work against HER2 and HER2ex20ins mutations. Researchers think this may
 help stop the further spread of NSCLC cancer.
 This is the first time that researchers will study BAY2927088 in humans. In this study, the
 researchers want to learn more about using BAY2927088 in participants who have NSCLC with
 EGFR and/or HER2 mutations including EGFRex20ins and/or HER2ex20ins mutations.
 The main aims of this study are to find for BAY2927088
 - how safe BAY2927088 is
 - how it affects the body (also referred to as tolerability)
 - how BAY2927088 moves into, through and out of the body
 - the maximum amount of BAY2927088 that the participants can take without too many side
 effects.
 The researchers will also study the action of BAY2927088 against the cancer. The study will
 have three parts: Dose Escalation, Backfill, and Dose Expansion. Each participant of the
 first, so called dose escalation part, will be assigned to one of specific sequential dose
 groups for BAY2927088. The amount of BAY2927088 that is given increases stepwise from one
 group to the next.
 The second may be initiated at any dose that has already been tested during the first part
 and found to be safe and to have either reached a predicted efficacious exposure range or to
 have induced an objective response. The first part and second part will run concurrently.
 The participants of the third, so called dose expansion part, will receive the most
 appropriate dose of BAY2927088 found in the first and second parts. The third part may be
 initiated in parallel with the first and second part based on emerging data.
 During the study, the participants will take the study treatment in 3 week periods called
 "cycles". They will in general take BAY2927088 once daily until their cancer gets worse,
 until they have medical problems, until they leave the study or until the study is
 terminated. Participants will have around 5 visits in each cycle.
 During the study, the study team will:
 - take blood and urine samples
 - take regular CT or MRI scans to check if the participants' cancer has gotten better or
 worse
 - check the participants' overall health and heart health
 - ask the participants questions about how they are feeling and what adverse events they
 are having.
 An adverse event is any medical problem that a participant has during a study. Doctors keep
 track of all adverse events that happen in studies, even if they do not think the adverse
 events might be related to the study treatments.
 ;NA;
 Inclusion Criteria:
 - Documented histologically or cytologically confirmed locally advanced NSCLC, not
 suitable for definitive therapy or recurrent or metastatic NSCLC at screening (small
 cell or mixed histologies are excluded).
 - Documented disease progression after treatment with at least one prior systemic
 therapy for advanced disease. Participants who do not have standard of care access due
 to any reason, are intolerant to, or are not eligible for standard treatments, may
 also be eligible.
 - Adequate archival tumor tissue (ideally taken after last targeted treatment and not
 older than 6 months) has to be available, either from primary or metastatic sites. If
 archival material is not available, a fresh tumor biopsy should be performed if
 feasible and if the procedure poses no significant risk for the participant.
 - Measurable disease by RECIST v1.1 with at least one lesion not chosen for biopsy
 during the screening period (if a biopsy is taken during screening) that can be
 accurately measured at baseline with computed tomography (CT) or magnetic resonance
 imaging (MRI) and that is suitable for accurate repeated measurements. A biopsied
 lesion should not be used as a target lesion for RECIST 1.1 tumor assessments.
 Previously irradiated lesions must have shown progression to be considered measurable.
 - Documented activating EGFR and/or HER2 mutation assessed by a Clinical Laboratory
 Improvement Amendments (CLIA)-certified (United States [US] sites) or an equally
 accredited (outside of the US) local laboratory
 - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
 - Minimum life expectancy of 12 weeks.
 - Adequate bone marrow function as assessed by the following laboratory tests to be
 conducted within 7 days before the first dose of study treatment:
 1. Hemoglobin ≥ 9.0 g/dL. Criteria must be met without erythropoietin dependency and
 without packed red blood cell (pRBC) transfusion within 2 weeks prior to testing.
 2. Platelets ≥ 100 × 10^9 cells/L.
 3. Absolute neutrophil count ≥ 1.5 ×10^9 cells/L. Criteria must be met without the
 use of hematopoietic growth factors (e.g., G-CSF) within 2 weeks prior to
 testing.
 - Adequate kidney function as assessed by following laboratory test to be conducted
 within 7 days before the first dose of study treatment:
 a. Estimated glomerular filtration rate (eGFR) > 60 mL/min per 1.73 m^2 according to
 the Modification of Diet in renal Disease Study Group (MDRD) formula.
 - Adequate liver function as assessed by following laboratory tests to be conducted
 within 7 days before the first dose of study treatment:
 1. Total bilirubin ≤ 1.5 × ULN (or ≤ 3 X ULN for participants with documented
 Gilbert-Meulengracht Syndrome, or for participants with hyperbilirubinemia
 considered due to liver metastasis).
 2. Aspartate transaminase and alanine transaminase ≤ 2.5 × ULN (or ≤ 5 × ULN if due
 to liver involvement by tumor).
 Exclusion Criteria:
 - Treatment with an EGFR tyrosine kinase inhibitor (TKI) ≤ 8 days or 5x the terminal
 phase, elimination half-lives, whichever is shorter, prior to the first dose of study
 drug.
 - Treatment with a systemic anti-cancer treatment (excluding EGFR TKIs as described
 above) ≤ 14 days prior to the first dose of study drug.
 - Radiation therapy, stereotactic radiosurgery (SRS) and palliative radiation ≤ 14 days
 prior to the first dose of study drug.
 - Treatment with immunotherapy ≤ 28 days prior to the first dose of study drug.
 - Have any unresolved toxicity of Grade ≥ 2 from previous anti-cancer treatment, except
 for alopecia and skin pigmentation. Participants with chronic, but stable Grade 2
 toxicities may be allowed to enroll after agreement between the Investigator and
 Sponsor.
 - Any history of primary brain or leptomeningeal disease (symptomatic or asymptomatic),
 presence of symptomatic central nervous system (CNS) metastases, or CNS metastases
 that require local treatment (such as radiotherapy or surgery).
 - History of spinal cord compression or brain metastases with the following exceptions:
 1. Participants with treated brain metastases that are asymptomatic at screening and
 who are off or receiving low-dose of corticosteroids (≤10 mg prednisone or
 equivalent) for at least 7 days prior to first dose of BAY 2927088 are eligible
 to enroll in Dose Escalation and Backfill.
 2. Participants with treated brain metastases that are asymptomatic at screening are
 eligible in Dose Expansion if all of the following criteria are met:
 - there is no evidence of progression (new or enlarging brain metastases) for
 at least 4 weeks after CNS-directed treatment, as ascertained by clinical
 examination and brain imaging (MRI or CT) during the screening period.
 - Participants must be off or receiving low-dose of corticosteroids (≤10 mg
 prednisone or equivalent) for 7 days prior to first dose of BAY2927088.
 3. Participants with history of spinal cord compression >3 months from definitive
 therapy and stable by imaging (MRI or CT) during the screening period and
 clinically asymptomatic.
 - History of congestive heart failure (CHF) Class >II according to the New York Heart
 Association (NYHA) Functional Classification or serious cardiac arrhythmias requiring
 treatment (e.g. ventricular arrhythmias, atrial fibrillation) or any clinically
 important abnormalities in rhythm, conduction or morphology or resting ECG (e.g.,
 complete left bundle branch block, third degree heart block, second degree heart
 block, PR interval >250 msec)
 - Participants with:
 1. Known human immunodeficiency virus (HIV), except as noted below: Participants
 with history of HIV infection are eligible at the Investigator's discretion
 provided that: • CD4+ T-cell (CD4+) counts are ≥ 350 cells/uL • The participant
 has been on established antiretroviral therapy (ART) for at least 4 weeks prior
 to the start of study drug and has an HIV viral load less than 400 copies/mL
 prior to start of the study treatment • The ART being used does not contain
 strong inducers or inhibitors of CYP3A4, and is not anticipated to cause
 overlapping toxicities with study drug • The participant has not had an
 opportunistic infection within the past 12 months
 2. Active Hepatitis B infection (positive for Hepatitis B surface antigen [HbsAg])
 and Hepatitis B virus [HBV] DNA).
 3. Active Hepatitis C infection (positive anti-HCV Antibody and quantitative HCV RNA
 results greater than the lower limits of detection of the assay).
 NOTE: Participants with history of chronic HBV or HCV infection are eligible at
 the Investigator's discretion provided that the disease is stable and
 sufficiently controlled under treatment.
 - Use of strong CYP3A4 inhibitors and inducers from 14 days prior to first
 administration of study drug. Strong CYP3A4 inhibitors and inducers are prohibited
 during the study and until Safety FU (follow up) visit.


Input:
This is a Phase 1/2, open-label, first-in-human (FIH) study designed to evaluate the safety,
 tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and anticancer activity of
 BLU-222, a selective inhibitor of CDK2.
 ;
 ;
 Inclusion Criteria:
 1. Advanced solid tumors that has progressed beyond standard of care OR
 2. ER+ HER2- BC that has progressed following treatment with a CDK4/6 inhibitor OR
 3. Endometrial and gastric cancer that has progressed after at least 2 prior therapies
 (including one prior platinum therapy) OR
 4. Platinum refractory or platinum resistant ovarian cancer CCNE1 amplified tumors that
 have progressed beyond standard of care
 Exclusion Criteria:
 1. Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis.
 2. Have received the following anticancer therapy:
 a. Previous therapy with CDK2i, PKMYT1i, or WEE1i, except in Part 1A where up to 10
 patients who previously received PKMYT1i, or WEE1 inhibitor will be permitted.
 3. Have central nervous system (CNS) metastases or spinal cord compression that is
 associated with progressive neurological symptoms or requires increasing doses of
 corticosteroids to control the CNS disease.
 4. Have known intracranial hemorrhage and/or bleeding diatheses.
 5. Have clinically active ongoing ILD of any etiology, including drug-induced ILD, and
 radiation pneumonitis within 28 days prior to initiation of study treatment.
 6. Have any unresolved toxicities from prior therapy greater than CTCAE Grade 1 or that
 have not resolved to baseline at the time of starting the study.
 7. Have mean resting QTcF > 450 msec, a history of prolonged QT syndrome or Torsades de
 pointes, or a familial history of prolonged QT syndrome.
 8. Have clinically significant, uncontrolled, cardiovascular disease including congestive
 heart failure Grade III or IV according to the New York Heart Association
 classification; myocardial infarction or unstable angina within the previous 6 months,
 uncontrolled hypertension, or clinically significant, uncontrolled arrhythmias,
 including bradyarrhythmia that may cause QT prolongation (eg, Type II second degree
 heart block or third-degree heart block).
 9. Have a history of another primary malignancy other than completely resected carcinomas
 in situ) that has been diagnosed or required therapy within 2 years prior to
 initiation of study treatment.
 10. Have active, uncontrolled infection (viral, bacterial, or fungal), including
 tuberculosis, hepatitis B virus (HBV), hepatitis C virus, AIDS-related illness, or
 COVID-19 infection (symptoms and a positive test result).
 11. Requires treatment with a prohibited medication or herbal remedy that cannot be
 discontinued at least 2 weeks before the start of study drug administration.
 12. Have planned major surgical procedure within 14 days of the first dose of study drug
 (procedures such as central venous catheter placement, tumor needle biopsy, and
 feeding tube placement are not considered major surgical procedures).
 13. Unwilling or unable to comply with scheduled visits, study drug administration plan,
 laboratory tests, or other study procedures and study restrictions.
 14. Patient is a woman who is not postmenopausal or surgically sterile, and is unwilling
 to abstain from sexual intercourse or employ highly effective contraception OR is a
 man who is not surgically sterile, and is unwilling to abstain from sexual intercourse
 or employ highly effective contraception
 15. Patient is a pregnant female


Input:
This phase II trial studies how well pembrolizumab works before surgery in treating patients
 with mismatch repair deficient solid cancers that have spread to nearby tissue or lymph nodes
 (locally advanced). Cancer is caused by changes (mutations) to genes (DNA) that control the
 way cells function, and some of these mutations can cause tumor cells to grow quickly and out
 of control. Microsatellite instability-high (MSI-H) tumors are made up of cancer cells that
 have a greater than normal number of genetic markers called microsatellites. These cancers
 may have defects in the ability to correct mutations that occur when DNA is copied in the
 cell. Similarly, mismatch repair deficient tumors (dMMR) may have difficulty repairing some
 type of genetic mutation during cellular replication that may affect tumor's response to
 cancer therapy. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the
 body's immune system attack the cancer, and may interfere with the ability of tumor cells to
 grow and spread.
 ;
 ;
 Inclusion Criteria:
 - Male/female participants who are at least 18 years of age on the day of signing
 informed consent with histologically confirmed diagnosis of solid cancer
 - Solid cancer that is deficient in mismatch repair (dMMR) or microsatellite instability
 high (MSI-H) as determined by one of three methods:
 - Immunohistochemistry determined dMMR by complete loss of MLH1, PMS2, MSH2 or MSH6
 - Polymerase chain reaction (PCR) determined microsatellite instability at > 30% of
 tested microsatellites
 - Next-generation sequencing determined MSI-H based upon instability at multiple
 microsatellites as determined by the specific next generation sequencing panel
 - Locally advanced cancer defined as either an unresectable primary cancer or a
 resectable primary cancer with a high chance of recurrence (defined as an estimated
 greater or equal to 20% chance of recurrence by the treating physician). A resectable
 primary may include locoregional disease, as long as all disease is felt by the
 treating physician to be in a resectable distribution
 - The participant (or legally acceptable representative if applicable) provides written
 informed consent for the trial
 - Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST)
 version (v)1.1 (unless discussed and approved by study principal investigator [PI])
 - Have available archival tumor tissue. Availability will be met as long as a request to
 obtain formalin-fixed, paraffin embedded (FFPE) tissue blocks (preferred) or slides
 has been made (unless discussed and approved by study PI)
 - Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
 Evaluation of ECOG is to be performed within 7 days prior to the date of signing study
 consent
 - A female participant is eligible to participate if she is not pregnant, not
 breastfeeding, and at least one of the following conditions applies:
 - Not a woman of childbearing potential (WOCBP) OR
 - A WOCBP who agrees to follow the contraceptive guidance during the treatment
 period and for at least (120 days [corresponding to time needed to eliminate any
 study treatment(s) plus 30 days (a menstruation cycle) for risk of genotoxicity])
 after the last dose of study treatment
 - Absolute neutrophil count (ANC) >= 1500/uL (within 14 days prior to the start of study
 treatment)
 - Platelets >= 100 000/uL (within 14 days prior to the start of study treatment)
 - Hemoglobin >= 8.0 g/dL or >= 5.6 mmol/L (within 14 days prior to the start of study
 treatment)
 - Criteria must be met without erythropoietin dependency and without packed red
 blood cell (pRBC) transfusion within last 2 weeks
 - Creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine
 clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or
 creatinine clearance [CrCl]) >= 30 mL/min for participant with creatinine levels > 1.5
 x institutional ULN (within 14 days prior to the start of study treatment)
 - Creatinine clearance (CrCl) should be calculated per institutional standard
 - Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for participants with total
 bilirubin levels > 1.5 x ULN (within 14 days prior to the start of study treatment)
 - Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and
 alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x
 ULN (=< 5 x ULN for participants with liver metastases) (within 14 days prior to the
 start of study treatment)
 - International normalized ratio (INR) OR prothrombin time (PT) activated partial
 thromboplastin time (aPTT) =< 1.5 x ULN unless participant is receiving anticoagulant
 therapy as long as PT or aPTT is within therapeutic range of intended use of
 anticoagulants (within 14 days prior to the start of study treatment)
 Exclusion Criteria:
 - A woman of childbearing potential (WOCBP) who has a positive urine pregnancy test
 within 72 hours prior to enrollment. If the urine test is positive or cannot be
 confirmed as negative, a serum pregnancy test will be required. Note: in the event
 that 72 hours have elapsed between the screening pregnancy test and the first dose of
 study treatment, another pregnancy test (urine or serum) must be performed and must be
 negative in order for subject to start receiving study medication
 - Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with
 an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g.,
 CTLA-4, OX 40, CD137)
 - Has received prior systemic anti-cancer therapy including investigational agents
 within 2 weeks of study treatment. Note: Participants must have recovered from all
 adverse events (AEs) due to previous therapies to =< grade 1 or baseline. Participants
 with =< grade 2 neuropathy may be eligible
 - If participant received major surgery, they must have recovered adequately from the
 toxicity and/or complications from the intervention prior to starting study treatment
 - Has received prior radiotherapy within 2 weeks of start of study treatment.
 Participants must have recovered from all radiation-related toxicities, not require
 corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
 for palliative radiation (=< 2 weeks of radiotherapy) to non-central nervous system
 (CNS) disease
 - Has received a live vaccine within 30 days prior to the first dose of study drug.
 Examples of live vaccines include, but are not limited to, the following: measles,
 mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
 Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection
 are generally killed virus vaccines and are allowed; however, intranasal influenza
 vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed
 - Is currently participating in or has participated in a study of an investigational
 agent or has used an investigational device within 4 weeks prior to the first dose of
 study treatment. Note: Participants who have entered the follow-up phase of an
 investigational study may participate as long as it has been 4 weeks after the last
 dose of the previous investigational agent
 - Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
 (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
 immunosuppressive therapy within 7 days prior to the first dose of study drug
 - Has a known additional malignancy that is progressing or has required active treatment
 within the past 1 year. Note: Participants with basal cell carcinoma of the skin,
 squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma,
 cervical cancer in situ) or other similar good prognosis cancer with recurrence rates
 expected to be < 10% that have undergone potentially curative therapy are not excluded
 - Known metastatic sites of disease. Note: locoregional lymph nodes or tumor deposits
 are not considered metastatic disease
 - Has severe hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients
 - Has active autoimmune disease that has required systemic treatment in the past 2 years
 (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
 drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
 replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
 form of systemic treatment
 - Has a history of (non-infectious) pneumonitis that required steroids or has current
 pneumonitis
 - Has an active infection requiring systemic therapy
 - Has a known history of human immunodeficiency virus (HIV)
 - Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg]
 reactive) or known active hepatitis C virus (defined as HCV ribonucleic acid [RNA]
 [qualitative] is detected) infection. Note: no testing for hepatitis B and hepatitis C
 is required unless mandated by local health authority
 - Has a history or current evidence of any condition, therapy, or laboratory abnormality
 that might confound the results of the study, interfere with the subject's
 participation for the full duration of the study, or is not in the best interest of
 the subject to participate, in the opinion of the treating investigator
 - Has known psychiatric or substance abuse disorders that would interfere with
 cooperation with the requirements of the trial
 - Is pregnant or breastfeeding, or expecting to conceive or father children within the
 projected duration of the study, starting with the screening visit through 120 days
 after the last dose of trial treatment


Input:
To study the radioactive uptake of [68Ga]P137 in the lesion sites of PCa patients and
 evaluate the ability of [68Ga]P137 to detect PSMA overexpression in PCa patients (especially
 those with recurrent or advanced PCa).
 ;
 ;
 Inclusion Criteria:
 - Men over 18 years of age need to undergo [68Ga]P137 PET/CT examination for suspected
 prostate cancer.
 - The patients can fully understand and voluntarily participate in this experiment, and
 sign the informed consent.
 Exclusion Criteria:
 - Significant hepatic or renal dysfunction;
 - Patients with malignant tumors other than prostate cancer within 2 years;
 - Ready to pregnant;
 - The patient can not tolerate all clinical tests.


Input:
This phase II clinical trial tests a chemotherapy regimen (dose-adjusted etoposide,
 prednisone, vincristine, cyclophosphamide and doxorubicin with or without rituximab
 [DA-EPOCH+/-R]) with the addition of targeted therapy (tafasitamab) for the treatment of
 patients with newly diagnosed Philadelphia chromosome negative (Ph-) B acute lymphoblastic
 leukemia (B-ALL). Chemotherapy drugs, such as those in EPOCH+/-R, work in different ways to
 stop the growth of cancer cells, either by killing the cells, by stopping them from dividing,
 or by stopping them from spreading. Tafasitamab is in a class of medications called
 monoclonal antibodies. It works by helping the body to slow or stop the growth of cancer
 cells. Adding tafasitamab to the DA-EPOCH+/-R regimen may work better than DA-EPOCH+/-R alone
 in treating newly diagnosed Ph- B-ALL.
 ;
 ;
 Inclusion Criteria:
 - Adults (age 18 years and older) with newly-diagnosed CD19+ Ph- B-ALL
 - In the opinion of the treating investigator, patients must be an unsuitable candidate
 for a pediatric-inspired regimen, reasons for which may include (but not be limited
 to) older age (e.g., >= 40 years), practical/logistical barriers to or toxicity
 concerns from administration of a pediatric-inspired regimen
 - Marrow or blood involvement detectable by MFC
 - Total bilirubin =< 2.0 x upper limit of normal (ULN) (unless attributed to Gilbert's
 disease or other causes of inherited indirect hyperbilirubinemia, at which point total
 bilirubin must be =< 4.0 x ULN)
 - Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
 [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
 =< 5.0 x institutional ULN. (Note: Patients with liver test abnormalities attributable
 to hepatic involvement by ALL will be permitted if the total bilirubin is =< 5.0 x ULN
 and ALT/AST are =< 8.0 x ULN)
 - Calculated creatinine clearance of > 30 ml/min, as measured by the Modification of
 Diet in Renal Disease (MDRD) equation, will be eligible
 - As patients with ALL frequently have cytopenias, no hematologic parameters will be
 required for enrollment or to receive the first cycle of treatment. However, adequate
 recovery of blood counts will be required to receive subsequent cycles
 - Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2. (Performance
 status of 3 will be allowed if poor performance status is thought to be directly
 secondary to ALL)
 - Ability to give informed consent and comply with the protocol
 - Anticipated survival of at least 3 months, independent of ALL
 Exclusion Criteria:
 - Burkitt lymphoma/leukemia
 - No prior systemic therapy for ALL except to control acute symptoms and/or
 hyperleukocytosis (e.g., corticosteroids, cytarabine, etc.)
 - No isolated extramedullary or known parenchymal central nervous system (CNS) disease
 - Known hypersensitivity or intolerance to any of the agents under investigation
 - Other medical or psychiatric conditions that in the opinion of the investigator would
 preclude safe participation in the protocol
 - May not be pregnant or nursing
 - Pregnancy test is only required in women, unless they are highly unlikely to
 conceive (defined as [1] surgically sterilized, or [2] postmenopausal [i.e., a
 woman who is > 50 years old or who has not had menses for >=1 year], or [3] not
 heterosexually active)

CD19 positive
Philadelphia chromosome negative


Input:
This study aims to describe the treatment patterns in clinical practice in adult patients
 with mNSCLC with a BRAF V600E mutation. This study will also describe Real-World
 Progression-Free Survival (rwPFS) and Overall Survival (OS) for treatments prescribed in
 routine practice for mNSCLC with BRAF V600E mutation. Adverse events (AEs) related to
 treatment management will also be described.
 ;NA;
 Inclusion Criteria:
 - Age ≥ 18 years at the time of first-line treatment initiation for mNSCLC,
 - Patients who initiated a first systemic treatment for mNSCLC in the metastatic setting
 from 01 December 2017 and before their study entry date (retrospectively enrolled
 patients), or Patients who initiated a first systemic treatment for mNSCLC (metastatic
 setting) at or after their study entry date (prospectively enrolled patients),
 - Confirmed diagnosis of Stage IV mNSCLCat any time before study inclusion Stage IV M1a,
 M1borM1c, as per the American Joint Committee on Cancer (AJCC cancer) staging manual,
 - Confirmed presence of BRAF V600E mutation - via tumor biopsy, metastasectomy, or
 liquid biopsy - at anytime before study inclusion,
 - Signed ICF or non-opposition to study participation,according to local regulations.
 Patients eligible for prospective QoL data collection must, in addition to the above
 mentioned criteria, meet ALL of the following criteria to be eligible for the study:
 - Patients who initiate a first or second systemic treatment line for mNSCLC (metastatic
 setting) with a BRAF V600E mutation at or after their study entry date
 Exclusion Criteria:
 - Concurrent or another previous malignancy within 2 years of study entry, except
 curatively treated basal or squamous cell skin cancer, prostate intraepithelial
 neoplasm, in-situcarcinoma of the cervix, Bowen's disease or Gleason ≤ 6 prostate
 cancer,
 - Previous, ongoing, or planned participation in a clinical trial involving an
 interventional drug as a first-or second-line systemic treatment for mNSCLC.


Input:
This is a Phase I/Ib study in which the safety of the combination therapy of RMC-4630 and
 LY3214996 in the treatment of KRAS mutant cancers will be studied.
 ;
 ;
 Inclusion Criteria:
 1. Part A: Histological or cytological proof of advanced KRASm NSCLC, CRC or PDAC; PART
 B: Histological or cytological proof of advanced KRASm PDAC.
 2. Age => 18 years;
 3. Able and willing to give written informed consent;
 4. WHO performance status of 0 or 1
 5. Able and willing to undergo blood sampling for PK and PD analysis;
 6. Able and willing to undergo tumor biopsies prior to start (or have undergone a biopsy
 within 2 months of inclusion), while on study treatment and upon progression of
 disease;
 7. Life expectancy => 3 months and no deterioration or hospitalizations within 2 weeks
 leading to C1D1, allowing adequate follow up of toxicity evaluation and antitumor
 activity;
 8. Evaluable disease according to RECIST 1.1 criteria; (PART A and PART B);
 9. Women of childbearing potential must have a negative serum pregnancy test within 14
 days prior to registration and agree to use effective contraceptive methods, as
 defined in section 5.9.3, through-out the treatment period, and for 4 months after the
 study treatment
 10. Adequate organ system function.
 Exclusion Criteria:
 1. Part A: No excluded genotypes
 Part B: Excluded genotypes (including co occurring mutations):
 - NRAS (except G12A/C)
 - RASQ61
 - KRASG13
 - BRAF Class 1, 2, or unclassified
 - PIK3CA
 - STK11
 - KEAP1
 2. Any treatment with investigational drugs within 30 days prior to receiving the first
 dose of investigational treatment;
 3. Patients currently using concomitant medication that are strong inhibitors or inducers
 of CYP3A4;
 4. History of another malignancy Exception PART A: Patients who have been disease-free
 for at least 3 years, or patients with a history of completely resected non-melanoma
 skin cancer and/or patients with indolent completely resected second malignancies are
 eligible. Exception PART B: Adequately treated carcinoma in situ of the cervix and
 adequately treated basal cell carcinoma of the skin.
 5. Symptomatic or untreated leptomeningeal disease
 6. Symptomatic brain metastasis. Patients previously treated or untreated for these
 conditions that are asymptomatic in the absence of corticosteroid and anticonvulsant
 therapy (for at least 4 weeks) are allowed to enroll. Radiotherapy for brain
 metastasis must have been completed at least 6 weeks prior to start of study
 treatment. Brain metastasis must be stable with verification by imaging (e.g.
 brain MRI or CT completed at screening demonstrating no current evidence of
 progressive brain metastases). Patients are not permitted to receive antiepileptic
 drugs or corticosteroids.
 7. Patients who have had previous treatment with any targeted drug combination known to
 interfere RAS/MEK/MAPK pathway components.
 8. Toxicities related to prior treatments > grade 1 (excluding alopecia)
 9. History of interstitial lung disease or pneumonitis
 10. Woman who are breast feeding;
 11. Patients who have undergone any major surgery within the last 4 weeks prior to
 starting study drug or who would not have fully recovered from previous surgery.
 12. Radio- or chemotherapy within the last 4 weeks prior to receiving the first dose of
 investigational treatment; except a palliative dose of radiation of 8 Gy, which is
 allowed up to one week before study start and should not be applied to the target
 lesion.
 13. Uncontrolled infectious disease or known Human Immunodeficiency Virus HIV-1 or HIV-2
 type patients;
 14. Patients with a known history of or uncontrolled hepatitis B (HBV) or C (HCV);
 15. Patients with known alcoholism, drug addiction and/or psychiatric of physiological
 condition which in the opinion of the investigator would impair study compliance;
 16. Patients with cardiac comorbidities (myocardial infarct within 6 months of study
 start, NYHA class ≥ III, congestive heart failure or instable angina pectoris),
 uncontrolled hypertension (systolic blood pressure > 160 mm Hg and/or diastolic
 pressure > 90 mm Hg), prolonged QT interval(> 440 ms for men, > 460 ms for women) or
 patients who have had a stroke within 6 months prior to start study.
 17. Other severe, acute, or chronic medical or psychiatric condition, laboratory
 abnormality active infections that may increase the risk associated with study
 participation or study drug administration or that may interfere with the
 interpretation of study results and, in the judgment of the investigator, would make
 the patient inappropriate for the study.
 18. Patients with pulmonary embolisms or deep venous thrombosis (DVT) within 3 months
 prior to start
 19. Known hypersensitivity to one of the study drugs or excipients.
 20. Baseline diarrhea and/or any condition that would impair absorption of oral agents
 21. Patient with a history or findings of central or branch retinal artery or venous
 occlusion with significant vision loss or other retinal diseases that cause current
 visual impairment or would likely cause visual impairment over the time period of the
 study, as assessed by an ophthalmologist.


Input:
This is a surgical biospecimen collection study. The purpose of this study is to understand
 how much of two drugs (dabrafenib and trametinib) are able to penetrate brain tumors and turn
 off the RAF signaling pathway. This is important because these drugs are currently FDA
 approved for other tumors and may have efficacy in brain tumors with the BRAF V600E mutation.
 ;
 ;
 Inclusion Criteria:
 - Subjects must have a history of primary brain tumor (including but not limited to
 glioblastoma (GBM), anaplastic astrocytoma (AA), anaplastic ganglioglioma (AG), and
 anaplastic pleomorphic xanthoastrocytoma (PXA)).
 - Subjects must have a BRAF-V600 mutation identified in previous tissue analysis (may be
 IHC or PCR based). Allowable mutations include V600E, V600K, V600R, and V600D.
 - Subjects must be taking dabrafenib at a dose of at least 50mg twice daily (adults
 only) and / or trametinib at a dose of at least 1mg daily (adults only) for at least 7
 days prior to surgery as prescribed by their treating physician. Note: Pediatric
 patients may be taking any dose of dabrafenib and / or trametinib as prescribed by
 their treating physician for at least 7 days prior to surgery.
 - Subjects must be undergoing surgery for clinical purposes.
 - Written informed consent - a signed informed consent and/or assent (as age
 appropriate) for study participation will be obtained according to institutional
 guidelines.
 Exclusion Criteria:
 - Subjects who are receiving any other investigational agents or chemotherapeutic
 agents.
 - Subjects for whom collection of blood, spinal fluid, or tissue samples is unsafe or
 clinically inadvisable.


Input:
transoral Robotic surgery for rECurrent tumours of the Upper aerodigestive Tract
 ;
 ;
 Inclusion Criteria:
 - Aged over 18
 - Previous HNC treated with radiotherapy
 - Undergoing TORS as part of their management for recurrent disease
 - Surgery performed on or before July 31st 2018.
 Exclusion Criteria:
 - TORS used in a diagnostic setting only
 - Nasopharyngeal and thyroid cancers


Input:
This is a single-arm, multicenter, exploratory clinical study to evaluate the safety and
 efficacy of the combination of etoposide, cytarabine and PEG-rhG-CSF (EAP regimen) on
 hematopoietic stem cell mobilization in poor mobilization patients with hematological
 malignancies. All eligible patients will receive EAP regimen treatment, then the number of
 CD34+ cells and white blood cells will be monitoring. When the collection standard is met,
 hematopoietic stem cell collection will be started.
 ;NA;
 Inclusion Criteria:
 1. According to the diagnostic criteria of the Italian transplantation working group,
 patients with hematological malignancies diagnosed as "confirmed poor mobilization" or
 "predicted poor mobilization".
 2. Patients with auto-HSCT indication.
 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0~2.
 4. Patients should be within age range of ≥18 and ≤75 years old.
 5. Life expectancy ≥ 3 months.
 6. Patients must be able to sign informed consent.
 Exclusion Criteria:
 1. Patients with severe cardiac, hepatic or renal insufficiency, such as:
 - Cardiac function class II or higher or severe arrhythmia;
 - Serum direct bilirubin (DBIL)>2× upper limit of normal (ULN);
 - Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2× ULN;
 - Serum creatinine clearance rate≤50%.
 2. Patients with active infection.
 3. History of allergy to Etoposide (VP-16), Cytarabine (Ara-C), or PEG-rhG-CSF.
 4. Women who are pregnant or breastfeeding.
 5. Have received live vaccine and attenuated live vaccine within 4 weeks before
 enrollment.
 6. For any other reasons, the patients are believed not suitable for participation in
 this study by investigators


Input:
AL2846 is a multi-target receptor tyrosine kinase inhibitor. The purpose of this study is to
 evaluate the safety and efficacy of AL2846 capsules in Chinese patients with type I
 neurofibromatosis (NF1) (neurofibromas and malignant peripheral nerve sheath tumors).
 ;NA;
 Inclusion Criteria:
 - Patients who voluntarily join the study and sign the informed consent form;
 - Aged 18 to 75 years (when signing informed consent); Eastern cooperative oncology
 group（ ECOG） score: ≤2 ; patients with malignant peripheral nerve sheath tumors
 （MPNST）who are expected to survive ≥12 weeks;
 - NF1 patients (including patients with MPNST) who are judged by the investigator as
 incomplete surgical resection, require systemic treatment, and have measurable
 lesions;
 Note: NF1 diagnostic criteria meets at least one of the following:
 1. Genetic examination confirmation: test positive for NF1 germline mutation in a
 Clinical Laboratory Improvement Amendments （CLIA）-certified laboratory (positive NF1
 germline mutation must be confirmed by the central laboratory of this project, or an
 NF1 mutation test report issued by a CLIA-certified laboratory;
 2. Clinical and imaging examination confirmation: According to the clinical National
 Institute of Health (NIH) consensus criteria, at least two of the following NF1
 diagnostic criteria are met:
 1. Six or more café-au-lait macules (≥0.5cm in prepubertal patients or ≥1.5 cm in
 post pubertal patients)
 2. Freckling in axilla or groin
 3. ≥2 neurofibromas of any type, or ≥1 plexiform neurofibromas
 4. Optic glioma
 5. Two or more Lisch nodules
 6. A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or
 thinning of long bone cortex)
 7. A first-degree relative with NF1
 - Patients who are confirmed by direct measurement or according to the Response
 Evaluation Criteria in Solid Tumors（RECIST） 1.1 standard that there is at least
 one evaluable lesion, and the diameter of the lesion is greater than 3 cm, and
 the lesion can be seen in three consecutive sections;
 - The main organs function well and meet the following standards:
 1. Blood routine examination standard (no blood transfusion and no hematopoietic
 stimulating factor drugs used for correction within 7 days before the examination):
 a. White blood cell count (WBC) ≥3.5×109/L b. Hemoglobin (HGB) ≥90 g/L; c. The
 absolute value of neutrophils (NEUT) ≥ 1.5×109/L; d. Platelet count (PLT) ≥ 100×109/L.
 2. The biochemical inspection shall meet the following standards:
 a. Albumin (ALB) ≥35g/L; b. Total bilirubin (TBIL) ≤ 1.5× the upper limit of normal
 (ULN), and patients with Gilbert syndrome are ≤ 2.5× ULN; c. Alanine-based transferase
 (ALT) and aspartate-based transferase (AST) ≤2.5×ULN; d. Serum creatinine (CR)
 ≤1.5×ULN or creatinine clearance (CCR) ≥50ml/min (application of standard
 Cockcroft-Gault formula);
 3. The coagulation function test shall meet the following standards:
 International normalized ratio (INR)≤1.5×ULN (have not received anticoagulant
 therapy);
 4. Thyroid function examination must meet the following standards:
 Thyroid-stimulating hormone (TSH)≤ULN; if abnormal, Triiodothyronine （T3） and
 thyroxine（T4）levels should be examined, and T3 and T4 levels are normal.
 5. Heart color Doppler ultrasound assessment: Left ventricular ejection fraction (LVEF)
 ≥50%.
 - Female patients of childbearing age should agree to use contraceptive measures (such as
 intrauterine devices, contraceptives or condoms) during the study period and within 6
 months after the end of the study; serum pregnancy test within 7 days before study entry
 Negative, and must be a non-lactating subject; male patients should agree to adopt
 avoidance measures during the study period and within 6 months after the end of the study
 period;
 - Patients enrolled in the second stage need to be pathologically confirmed to be enrolled
 in cohort 1, cohort 2 or cohort 3.
 Exclusion Criteria:
 - Combined diseases and medical history:
 1. Patients who have other malignant tumors within 3 years before the first medication
 or are currently suffering from other malignancies. The following two situations can
 be enrolled: other malignant tumors treated by a single operation; achieving 5
 consecutive years of disease-free survival (DFS);
 2. With factors that affect oral medications (such as dysphagia, chronic diarrhea and
 intestinal obstruction, etc.)
 3. Unreliable toxic reactions higher than Common Terminology Criteria for Adverse
 Events(CTCAE) v5.0 level 1 caused by any previous treatment, excluding hair loss;
 4. Received major surgical treatment or obvious traumatic injury within 28 days before
 the first medication;
 5. Long-term unhealed wounds or fractures caused by surgery or trauma;
 6. Arterial/venous thrombosis occurred within 6 months before the first medication,
 such as cerebrovascular accident (including temporary ischemic attack, cerebral
 hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism;
 7. With a history of psychotropic drug abuse and cannot be quit or have mental
 disorders;
 8. There are risk factors for prolonging the corrected QT interval（QTc）interval, such
 as uncorrectable hypokalemia, hereditary long QT syndrome, or taking drugs that
 prolong the QTc interval (mainly class Ia, Ic, and III antiarrhythmic drugs) ；
 9. Past or current retinal vein stenosis, retinal detachment, central retinal vein
 occlusion, glaucoma, grade 1 cataract, related symptoms caused by the disease are not
 considered as exclusion criteria;
 10. Interstitial pneumonia, including clinically significant radiation pneumonia;
 11. Patients with any severe and/or uncontrollable disease, including:
 1. Unsatisfactory blood pressure control (systolic blood pressure ≥150 mmHg or
 diastolic blood pressure ≥100 mmHg);
 2. Suffering from grade ≥2 myocardial ischemia or myocardial infarction, arrhythmia
 (including male QTc ≥450 ms (male), QTc ≥470 ms (female)) and grade ≥2 congestive
 heart failure (New York Heart Association ( NYHA) classification, appendix 2);
 3. Active or uncontrolled serious infection (≥CTCAE v5.0 Grade 2 infection);
 4. Active hepatitis: hepatitis B reference: HBsAg is positive, and the HBV DNA test
 value exceeds the upper limit of normal; hepatitis C reference: HCV antibody is
 positive, and the HCV virus titer test value exceeds the upper limit of normal;
 Note: Those who meet the criteria for entry, hepatitis B surface antigen-positive
 or core antibody-positive patients, and hepatitis C patients need to continue
 antiviral therapy to prevent virus activation;
 5. Renal failure requiring hemodialysis or peritoneal dialysis;
 6. A history of immunodeficiency, including HIV positive or other acquired or
 congenital immunodeficiency diseases, or a history of organ transplantation;
 7. Poor diabetes control (fasting blood glucose (FBG)> 10 mmol/L);
 8. Urine routines suggest that urine protein is ≥++, and the 24-hour urine protein
 quantification is confirmed to be >1.0 g;
 9. Those who suffer from epilepsy and need treatment;
 - Tumor-related symptoms and treatment:
 1. Have received surgery, chemotherapy, radiotherapy or other anti-cancer therapies
 within 4 weeks before the first medication (the washout period will be calculated from
 the end of the last treatment); Note: Those who have received local radiotherapy in
 the past can be included in the group if the following conditions are met: the end of
 radiotherapy is more than 4 weeks from the beginning of the study treatment (brain
 radiotherapy is more than 2 weeks); and the target lesion selected for this study is
 not in the radiotherapy area; Or the target lesion is located in the radiotherapy
 area, but the progress has been confirmed.
 2. Have received National Medical Products Administration(NMPA) approved Chinese
 patent medicines with anti-tumor indications (including compound cantharidin capsules,
 Kangai injections, Kanglaite capsules/injections, Aidi injections, Brucea javanica oil
 injections). /Capsules, Xiaoaiping Tablets/Injections, Huachansu Capsules, etc.)
 treatment;
 - Research and treatment related:
 1. Patients who have previously received one of the following treatments:
 a. Patients who have received NF1 drug treatment within 3 months before
 enrollment, and the related side effects have not yet recovered to below grade 1
 (except for hair loss). Note: Patients who are receiving NF1 drug treatment must
 recover from the acute toxicity of the current NF1 treatment to less than or
 equal to Grade 1 (refer to CTCAE v5.0) before entering this study; b. Patients
 Received tipifarnib, pirfenidone, peg-interferon, sorafenib or other VEGFR
 inhibitor or biological treatments within 14 days before receiving study drug
 treatment ; c. Receiving strong Cytochrome P450 3A4 enzyme（CYP3A4） inhibitors
 (amprenavir, atazanavir, boceprevir, clarithromycin, cornivatan, delavirdine,
 diltiazem, erythromycin) within 14 days before receiving study drug treatment ,
 Fursanavir, Indinavir, Itraconazole, Ketoconazole, Lopinavir, Mibefradil,
 Miconazole, Nefazodone, Nefinavir, Posaconazole, Ritonavir, saquinavir,
 tilarrevir, telithromycin, verapamil, voriconazole, etc.) or strong inducers
 (carbamazepine, felbamate, nevirapine, phenobarbital, phenytoin, Patients with
 primidone, rifabutin, rifampicin, rifapentin, etc.), except for external use on
 the skin;
 2. Unable to perform Magnetic Resonance Imaging(MRI) examination and/or there are
 contraindications for MRI examination, such as prosthesis, orthotics or
 orthodontics, which will interfere with the volume analysis of the target
 Plexiform neurofibroma( PN) on MRI;
 - Patients who need to take more than the recommended dose of vitamin E daily;
 - Patients who have participated within 4 weeks before the first medication and used
 other anti-tumor clinical trial drugs or wihtin 5 half-lives;
 - According to the judgment of the investigator, there are situations that seriously
 endanger the safety of the patients or affect the completion of the study.


Input:
This is a first-in-human, Phase I, open-label, dose-escalation and expansion study designed
 to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary
 efficacy of PT199 (an Anti-CD73 mAb) alone and in combination with a PD-1 inhibitor, in
 patients with locally advanced or metastatic solid tumors that have progressed after all
 available standard therapy or for which standard therapy has proven to be ineffective,
 intolerable, or is considered inappropriate.
 ;
 ;
 Inclusion Criteria:
 1. 18 years or older and able to sign informed consent and comply with the protocol
 2. At least one measurable lesion as defined by RECIST V1.1 criteria for solid tumors
 3. Histologically or cytologically confirmed unresectable advanced or metastatic solid
 tumors previously treated with all available systemic standard therapy or for which
 treatment is not available or not tolerated, or for subjects enrolling in parts B and
 C (combination therapy groups) only anti PD-1 therapy is indicated as standard of care
 therapy.
 4. Able to provide a formalin fixed, paraffin embedded (FFPE) tumor tissue sample
 (archival tissue or fresh biopsy). To be assessed for CD73 and other biomarkers
 (PD-L1) expression.
 - Biopsy must be excisional, incisional, or core. Needle aspiration is
 insufficient.
 - Archival tissue is acceptable if biopsy was completed within 6 months.
 - Biopsy is optional in part A (monotherapy dose escalation).
 5. ECOG performance status of 0 or 1
 6. Adequate organ function confirmed at screening and within 7 days of initiating
 treatment, as evidenced by:
 - Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
 - Hemoglobin (Hgb) ≥ 9 g/dl (RBC and Platelets transfusion are not allowed within 2
 weeks of C1D1).
 - Platelets (plt) ≥ 75 × 109/L
 - AST/SGOT and ALT/SGPT ≤ 2.5 × Upper Limit of Normal (ULN) or ≤ 5.0 × ULN if liver
 metastases are present
 - Total bilirubin ≤ 1.5 × ULN
 - Calculated creatinine clearance ≥ 50 mL/min (Cockcroft Gault formula)
 7. Resolution of all acute adverse events resulting from prior cancer therapies to
 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE
 V5.0) Grade ≤ 1 or baseline (except alopecia or neuropathy)
 8. Negative serum pregnancy test within 72 hours before starting study treatment in all
 pre-menopausal women and women < 24 months after the onset of menopause (had a
 menstrual period in past 24 months) and are of childbearing potential (women who
 underwent hysterectomy or bilateral oophorectomy do not need a pregnancy test)
 9. Must agree to use effective contraceptive methods to avoid pregnancy (including male
 and female participants and partners of study subjects) during the study and until at
 least 6 months after ceasing study treatment. Examples of contraceptive methods with a
 failure rate of < 1% per year include bilateral tubal ligation, male sterilization,
 established, proper use of hormonal contraceptives that inhibit ovulation,
 hormone-releasing intrauterine devices, and copper intrauterine devices. The
 reliability of sexual abstinence should be evaluated in relation to the duration of
 the clinical trial and the preferred and usual lifestyle of the patient. Periodic
 abstinence (e.g., calendar, ovulation, sympto-thermal, or post-ovulation methods) and
 withdrawal are not acceptable methods of contraception
 Exclusion Criteria:
 1. Women who are pregnant or lactating
 2. Women of child-bearing potential (WOCBP) who do not use adequate birth control
 3. Autoimmune disease requiring systemic treatment within the past twelve months
 4. Condition requiring systemic treatment with either corticosteroids or other
 immunosuppressive medications within 14 days prior to study treatment. Corticosteroids
 doses equivalent to Prednisone 10mg per day or less are allowed.
 5. Patients with a history of (non-infectious) pneumonitis that required steroids,
 current pneumonitis, or has a history of interstitial lung disease.
 6. Patients with untreated brain or central nervous system (CNS) metastases or brain/CNS
 metastases that have progressed (e.g., evidence of new or enlarging brain metastasis
 or new neurological symptoms attributable to brain/CNS metastases) Note: Patients with
 treated brain metastases that are off corticosteroids and have been clinically stable
 for 28 days are eligible for enrollment.
 7. Patients with a known concurrent malignancy that is progressing or requires active
 treatment. Exceptions include basal cell carcinoma of the skin, carcinoma in situ of
 the cervix or other noninvasive or indolent malignancy that has previously undergone
 potentially curative therapy.
 8. Patients who have received an investigational product, < 5 half-lives duration.
 9. Patients who have previously received immune checkpoint inhibitor therapy and
 discontinued treatment because of immune-related adverse events
 10. Patients who have allergies or hypersensitivity reactions to immune checkpoint
 inhibitor therapy or any of the inactive ingredients
 11. Prior T-cell, NK cell, or CD73 inhibitor therapy (Prior Checkpoint inhibitor anti PD-1
 and anti PD-L1 therapies are allowed)
 12. Patients that have received a live-virus vaccination within 30 days of planned
 treatment start (exception Janssen JNJ-78436735 COVID-19 vaccine).
 13. Impaired cardiac function or significant diseases, including but not limited to any of
 the following:
 - LVEF < 45% as determined by MUGA scan or ECHO
 - Congenital long QT syndrome
 - QTcF ≥ 480 msec on screening ECG
 - Unstable angina pectoris ≤ 3 months prior to starting study drug
 - Acute myocardial infarction ≤ 3 months prior to starting study drug
 14. Patients with uncontrolled hypertension or blood pressure of ≥ 150 mmHg systolic
 and/or ≥ 90 mmHg diastolic at Screening.
 15. Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g.,
 uncontrolled hypertriglyceridemia [triglycerides > 500 mg/dL], or active or
 uncontrolled infection) that could cause unacceptable safety risks or compromise
 compliance with the protocol
 16. Patients who have received chemotherapy, ≤ 5 half-lives or 3 weeks, whichever is
 shorter (6 weeks for nitrosourea or mitomycin-C), targeted therapy, or immunotherapy
 within 4 weeks prior to starting study drug
 17. Patients who have ≥ Grade 3 neuropathy
 18. Patients who have received wide field radiotherapy ≤ 4 weeks or limited field
 radiation for palliation ≤ 2 weeks prior to starting study drug or who have not
 recovered from adverse events of prior therapy
 19. Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or
 who have not recovered from adverse events of prior therapy
 20. Patients who are currently receiving treatment with therapeutic doses of warfarin
 sodium (Coumadin®) or any other coumarin-derivative anticoagulants (Other
 anticoagulants such as anti-thrombin or factor X are allowed).
 21. Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not
 mandatory; patients with well controlled HIV might be enrolled per investigator's
 discretion and Sponsor approval
 22. Evidence of active infection with Hepatitis B or Hepatitis C that is not adequately
 controlled. (For patients with known prior history of Hepatitis B or Hepatitis C,
 enrollment may be allowed per investigator's discretion and Sponsor approval.)
 23. Has a history or current evidence of any medical or psychiatric condition, therapy, or
 laboratory abnormality that, in the opinion of the investigator, might confound the
 results of the trial, interfere with the patient's safe participation and compliance
 in the trial. For example, conditions that depend on the establishment of collateral
 circulation, such as peripheral arterial vascular disease, myocardial infraction
 recovery period, etc


Input:
The purpose of this study is to assess the safety and tolerability and determine the
 recommended Phase 2 dose of AIC100 Chimeric Antigen Receptor (CAR) T cells in patients with
 relapsed/refractory poorly differentiated thyroid cancer and anaplastic thyroid cancer.
 ;
 ;
 Inclusion Criteria:
 1. Willing and able to participate in the study and provide written informed consent
 2. Be ≥ 18 years of age on the day of signing the ICF
 3. Patients must have thyroid cancer that expresses ICAM-1 and that meets one of the
 following diagnoses:
 1. ATC BRAF wild-type at any stage, including newly diagnosed
 2. ATC BRAF mutant after failure of or inability to tolerate BRAF-specific therapy
 3. PDTC that has failed any of the following treatments: surgery RAI, chemotherapy,
 radiation therapy, and/or targeted therapies
 4. Measurable disease by CT or PET/CT per RECIST v1.1
 5. ECOG performance status 0 to 2 (see Appendix 2; Section 14.2)
 6. Life expectancy greater than 8 weeks
 7. Adequate hepatic, renal, bone marrow, cardiac, and coagulation function, defined as
 the following:
 1. Estimated creatinine clearance ≥ 50 mL/minute
 2. ALT and AST ≤ 2.5 × upper limit of normal (ULN); patients with hepatic
 metastases, ALT and AST ≤ 5 × ULN
 3. Serum total bilirubin < 1.5 mg/dL unless the patient has known Gilbert's
 Syndrome, then total bilirubin ≤ 3 mg/dL
 4. Serum albumin ≥ 2.5 g/dL
 5. Hemodynamically stable and left ventricular ejection fraction ≥ 45%
 6. Hematological parameters
 i. Absolute neutrophil count > 1000/µL without myeloid growth factor support for ≥ 1
 week ii. Absolute lymphocyte count ≥ 100/µL iii. Platelet count ≥ 50 × 10e3/µL without
 platelet transfusion for ≥ 1 week iv. Hemoglobin concentration > 8 g/dL without red
 blood cell transfusion for ≥ 2 weeks
 8. Has met the minimum washout time for previous cancer treatments (Section 5.5.3) before
 undergoing apheresis or LDC, and in the Investigator's judgement, the patient is able
 to safely undergo the procedure
 9. Absolute lymphocyte count ≥100/mm3 prior to apheresis (incorporated into inclusion
 criterion #7)
 10. Females of reproductive potential (defines as all females physiologically capable of
 becoming pregnant) must agree to use 1 highly effective method of contraception and 1
 additional effective method (as defined in Section 6.3 ) from at least 28 days before
 enrollment/apheresis and for at least 1 year after the infusion of AIC100 CAR T Cells.
 11. Females of reproductive potential must have a negative serum beta-human chorionic
 gonadotropin (β-hCG) pregnancy test result at Screening
 12. Detectable ICAM-1 expression by IHC (incorporated into inclusion criterion #3)
 Exclusion Criteria:
 1. Women who are pregnant or breastfeeding
 2. Clinically significant, active, uncontrolled, systemic infection; the following are
 not exclusionary:
 1. Patients with HIV must have been on effective antiretroviral therapy for ≥ 4
 weeks prior to enrollment; must have an HIV viral load < 400 copies/µL; no
 acquired immunodeficiency syndrome related opportunistic infections in the
 previous 12 months; and a CD4+ cell count ≥ 350 cells/µL
 2. Patients with chronic HBV infection must on antiviral therapy and have an HBV
 viral load below the limits of detection
 3. Patients with chronic HCV infection must have completed therapy and have an HCV
 viral load below the limits of detection
 3. Prior treatment with investigational gene therapy or CAR T cell therapy
 4. Presence of active and clinically relevant central nervous system disorder such as
 epilepsy, stroke, or symptomatic or uncontrolled brain metastases
 5. Evidence of another malignancy within 2 years prior to Screening (except in-situ non
 melanoma skin cancers, localized controlled prostate cancer, adequately treated Stage
 1 uterine cancer that has a low risk of recurrence, or any other malignancies with
 similar outcome)
 6. Patients who are seropositive for HIV or who have an uncontrolled HBV or HCV infection
 (incorporated into exclusion criterion #2)
 7. Active autoimmune disease (including but not limited to systemic lupus erythematosus,
 Sjögren's Syndrome, RA, psoriasis, multiple sclerosis, inflammatory bowel disease)
 requiring immunosuppressive therapy within 4 weeks prior to eligibility confirmation,
 with the exception of conditions requiring thyroid replacement therapy
 8. Patients with severe chronic diseases of the kidney, liver, heart, lung; or any other
 serious illness that, in the opinion of the Investigator, may affect the patient's
 treatment, follow up, or assessments, including but not limited to uncontrolled
 clinically significant neurological or psychiatric disorders or metabolic diseases
 9. Patients who need long-term use of systemic corticosteroids > 10 mg/day prednisone or
 equivalent
 10. Allergy to any of the chemotherapy drugs given during lymphodepletion or known
 hypersensitivity to any component of AIC100 CAR T Cells, including excipients (Section
 7.1)
 11. Receipt of a COVID-19 vaccine within 4 weeks before Screening


Input:
This open-label phase II trial studies how well niraparib works in treating patients with
 advanced, metastatic melanoma with the homologous recombination (HR) pathway gene mutation /
 alteration. Niraparib may stop the growth of tumor cells by blocking some of the enzymes
 needed for cell growth. The trial is designed to assess the efficacy and safety of niraparib
 in patients with HR mutation/ alteration whose disease progressed on prior immunotherapy
 and/or BRAF-targeting therapy.
 ;
 ;
 Inclusion Criteria:
 - Have genetic homologous recombination (HR) mutation/ alteration including ARID1A/B,
 ARID2, ATM, ATR, ATRX, BARD1, BRCA1/2, BAP1, BRIP1, CHEK2, FANCD2, MRN11A, PALB2,
 RAD50, RAD51, RAD54B
 - Disease must have progressed on the standard systemic therapies or they could not have
 tolerated the standard therapies.
 - ECOG PS >/=1
 - Have measurable metastatic disease according to RECIST 1.1
 - Prior systemic cytotoxic therapy up to 1 regimens is allowed; There is no limit on the
 number of prior immunotherapy or targeted therapy regimens.
 - All adverse events associated with prior treatment must have resolved to ≤ Grade 1
 prior to day 1 of the study drug administration.
 Exclusion Criteria:
 - Previously treated with a PARP inhibitor
 - Symptomatic brain metastasis or active brain lesions ≥6 mm size or those
 - Require steroid treatment for brain lesions or leptomeningeal disease
 - Systemic cancer therapy within 14 days prior to day 1 of the study drug administration
 - Any major surgery ≤ 3 weeks of starting the study and patient must have recovered from
 any effects of any major surgery
 - Investigational therapy administered ≤ 4 weeks, or within a time interval less than at
 least 5 half-lives of the investigational
 - Prior radiotherapy encompassing > 20% of the bone marrow within 2 weeks; or any
 radiation therapy within 1 week prior to Day 1 of protocol therapy
 - Medical history of immunocompromised condition
 - Systemic treatment of another type of cancer ≤ 2 years prior to registration
 - Known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)


Input:
Quizartinib is an experimental drug. It is not approved for regular use. It can only be used
 in medical research.
 Children or young adults with a certain kind of blood cancer (FLT3-ITD AML) might be able to
 join this study if it has come back after remission or is not responding to treatment.
 ;
 ;
 Inclusion Criteria:
 - Has diagnosis of AML according to the World Health Organization (WHO) 2008
 classification with ≥5% blasts in bone marrow, with or without extramedullary disease
 - Is in first relapse or refractory to first-line high-dose chemotherapy with no more
 than 1 attempt (1 to 2 cycles of induction chemotherapy) at remission induction -
 prior HSCT is permitted
 - Has presence of the FLT3-ITD activating mutation in bone marrow or peripheral blood as
 defined in the protocol
 - Is between 1 month and 21 years of age at the time the Informed Consent/Assent form is
 signed
 - Has protocol-defined adequate performance status score
 - Has fully recovered from the acute clinically significant toxicity effects of all
 prior chemotherapy, immunotherapy, or radiotherapy, per protocol guidelines
 - Has protocol-defined adequate renal, hepatic and cardiac functions
 - If of reproductive potential, is permanently sterile or agrees to use highly effective
 birth control upon enrollment, during the period of therapy, and for 6 months
 following the last dose of study drug or cytarabine, whichever is later
 - If female of child-bearing potential, tests negative for pregnancy and agrees not to
 breast feed
 - Participant/legal representative is capable of understanding the investigational
 nature of the study, potential risks, and benefits, and the patient (and/or legal
 representative) signs a written assent/informed consent
 - Meets protocol-specified guidelines before inclusion in the continuation therapy phase
 Exclusion Criteria:
 - Has been diagnosed with isolated central nervous system relapse, certain kinds of
 leukemia, or with myeloid proliferations related to Down syndrome
 - Has uncontrolled or pre-defined significant cardiovascular disease as detailed in the
 protocol
 - Has systemic fungal, bacterial, viral or other infection that is exhibiting ongoing
 signs/symptoms related to the infection without improvement despite appropriate
 antibiotics or other treatment. The patient must be off vasopressors and have negative
 blood cultures for at least 48 hours prior to the start of systematic protocol
 therapy.
 - Has known active clinically relevant liver disease (e.g., active hepatitis B or active
 hepatitis C)
 - Has known history of human immunodeficiency virus (HIV)
 - Has history of hypersensitivity to any of the study medications or their excipients
 - Is receiving or is anticipated to receive concomitant chemotherapy, radiation, or
 immunotherapy other than as specified in the protocol
 - Has any significant concurrent disease, illness, psychiatric disorder or social issue
 that would compromise subject safety or compliance, interfere with consent/assent,
 study participation, follow up, or interpretation of study results
 - Is currently participating in another investigative interventional procedure
 (observational or long-term interventional follow-up is allowed)
 - Is otherwise considered inappropriate for the study by the Investigator


Input:
Multicenter, retrospective and prospective, cohort, observational study evaluating the
 clinical efficacy and tolerability of Eribulin as second-line treatment in accordance with
 the indications authorized by AIFA in patients with triple negative advanced breast cancer in
 a real world setting.
 ;
 ;
 Inclusion Criteria:
 - Performance status according to ECOG equal to 0-2
 - Locally advanced or triple negative metastatic breast cancer (HR- and HER2-) confirmed
 histologically
 - Progressing after first-line chemotherapy for advanced disease
 - Previous anthracyclines and taxanes therapy (in an adjuvant, neoadjuvant or
 metastatic), unless the patient is ineligible to receive such treatments
 - Treatment with Eribulin mesylate since 2017, in accordance with AIFA indications
 - Adequate haematological, renal and hepatic function, as per clinical practice
 - Written informed consent
 Exclusion Criteria:
 - Breast cancer HER2 + or HR +
 - Treatment with Eribulin in the context of clinical studies
 - Patients unsuitable for treatment with Eribulin
 - Diagnosis of other malignancies in the two years prior to enrollment, with one
 exception of adequately treated localized basal cell or squamous cell carcinomas of
 the skin o cervical carcinomas undergoing curative treatment


Input:
Diffuse intrinsic pontine gliomas (DIPGs), which diffusely occupy the pons of brainstem, are
 the deadliest primary brain cancer in children. Biopsy for pathology plus radiotherapy
 remains the current standard-of-care treatment that is minimal effective. Thus, the median
 overall survival after diagnosis is just 10 months. Recent studies have identified a lysine
 27-to-methionine (K27M) somatic mutation at histone H3 variant (H3.3), as a feature mutation
 in DIPGs. Several preclinical studies have already demonstrated H3.3-K27M as a promising
 target for immunotherapy. The researched vaccine is a cancer-treatment vaccine containing an
 H3.3-K27M targeted neoantigen peptide, that can be taken up by antigen-presenting cells
 (APCs). APCs can present the peptide with the major histocompatibility complex (MHC)
 molecules on cell surface, thereby activating neoantigen-specific T cells and triggering
 corresponding cytotoxic T cell immune responses to eliminate H3.3-K27M-expressing DIPG cells.
 The main goal of this study is investigating the safety and preliminary efficacy of the
 vaccine in treating newly-diagnosed DIPGs when the vaccine is administered in combination
 with the standard-of-care treatment.
 ;NA;
 Inclusion Criteria:
 A. First entry criteria
 1. Age ≥ 5 years old;
 2. Newly-diagnosed patients with DIPG appearance on MRI image;
 3. HLA-A2 subtype;
 4. The expected survival time exceeds 24 weeks;
 5. The KPS score is greater than 50; B. Second entry criteria
 1. The KPS score is greater than 50; 2. DIPG is diagnosed histologically on tumor tissue
 obtained by biopsy or surgical resection; 3. H3.3K27M mutation is detected on tumor tissue
 obtained by biopsy or surgical resection ; 4. Adequate organ functions that meet the
 following criteria: The absolute number of neutrophils: ≥1500/mm3 Platelet count: ≥75000/uL
 Hemoglobin: ≥80 g/L Creatinine≤1.5×ULN Bilirubin≤1.5×ULN ALT≤3×ULN AST≤3×ULN 5. Ability to
 comprehend and sign an informed consent form.
 Exclusion Criteria:
 1. With past medical history of malignant tumors (except being asymptomatic for more than
 3 years);
 2. History of allergy to chemotherapeutics or radiosensitizers for the treatment of
 cancer in central nervous system and head/neck;
 3. History of allergy to the vaccine and its ingredients;
 4. Comorbidity with HIV infection and/or acute phase of hepatitis B/C;
 5. Any progressive diseases that hinder participation in the trial;
 6. With unstable cardiovascular diseases such as coronary heart disease, angina pectoris,
 myocardial infarction, arrhythmia et.al.;
 7. History of uncontrolled mental illnesses;
 8. Inability to comprehend or sign informed consent form or abide by the research
 procedures;
 9. Other conditions believed to hinder participation in this trial at investigator'
 discretion.


Input:
The ATR (ataxia-telangiectasia and Rad3 related protein) inhibitor BAY1895344 is developed
 for the treatment of patients with advanced solid tumors and lymphomas. The purpose of the
 proposed trial is to evaluate the safety and tolerability of BAY1895344, and to identify the
 maximum tolerated dose of BAY1895344 that could be safely given to cancer patients. Further,
 the response of the cancer to the treatment will be determined.
 ;NA;
 Inclusion Criteria:
 Part A - single-agent dose-escalation:
 - Patients with histologically confirmed solid tumors or NHL. Patients with tumors known to
 be positive for deoxyribonucleic acid damage repair (DDR) defects (such as
 ataxia-telangiectasia mutated [ATM] deleterious mutation or low ATM expression) can be
 included.
 J-arm of Part A - single-agent dose-escalation in Japanese:
 - Japanese patients with histologically confirmed solid tumors. Patients with tumors known
 to be positive for DDR defects (such as ATM deleterious mutation or low ATM expression) can
 be included.
 Part A.1 - single-agent dose-escalation with alternative dosing schedule:
 - Patients with histologically confirmed solid tumors or NHL known to be positive for ATM
 loss and/or ATM deleterious mutations will be included. The biomarker status of patients in
 Part A.1 will be evaluated before general screening and only patients with the presence of
 the putative biomarkers of DDR deficiency will be recruited into general screening.
 Part B - single-agent expansion:
 - Patients with DDR deficiency biomarker-positive advanced solid tumors of the following
 histologies: i) CRPC; ii) HER2-negative BC that is hormone-receptor positive
 (estrogen-receptor positive, progesterone-receptor positive, or both) or TNBC; iii)
 CRC, and iv) gynecological tumors (ovarian, primary peritoneal, and fallopian tube
 cancers, endometrial cancer, or cervical cancer).
 - Patients with histologically confirmed advanced solid cancer, regardless of the cancer
 type, or NHL and loss of ATM protein by IHC.
 - The biomarker status of patients in Part B will be evaluated before general screening
 and only patients with the presence of the putative biomarkers of DDR deficiency will
 be recruited into general screening.
 Part A.1 And Part B:
 - Patients must be able to provide either samples of archival tumor tissue not older than 6
 months or a fresh tumor biopsy during general screening.
 Part B.1 - single-agent expansion with alternative dosing schedule:
 - Patients with histologically confirmed R/R MCL. These patients do not undergo biomarker
 testing to determine eligibility. The provision of baseline tumor tissue (archival or
 fresh) is strongly encouraged. If archival tissue ≤ 6 months old is unavailable, a fresh
 baseline biopsy may be obtained if safe and feasible.
 The following inclusion criteria apply to ALL (dose-escalation and expansion) patients:
 - Patients with tumors resistant or refractory to standard treatment and in which, in
 the opinion of the investigator, experimental treatment with BAY1895344 may be of
 benefit. Furthermore, no standard therapy would confer clinical benefit to the
 patient. Patients in the MCL cohort of Part B.1 are to be relapsed or refractory to
 standard treatments.
 - Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. For MCL
 patients: ECOG of 0 to 2.
 - Patients must have adequate bone marrow function as assessed by the following
 laboratory tests to be conducted within 7 (+2) days before the first dose of study
 drug. Note that the below values are to be independent of red blood cell transfusions
 or granulocytes colony-stimulating factor (G-CSF) (i.e., no red blood cell or
 platelets transfusion within 28 days prior to the screening complete blood count [CBC]
 result, or administration of G-CSF is to occur within 14 days prior to the CBC
 result). Requirements for MCL patients are indicated below.
 - a. Hemoglobin ≥ 9 g/dL. Patients with chronic erythropoietin treatment consistent
 with institutional guidelines can be included. For MCL patients: ≥ 8 g/dL; red
 blood cell transfusions during the screening period are allowed, and patients
 with chronic erythropoietin treatment consistent with institutional guidelines
 can be included
 - b. Absolute neutrophil count (ANC) ≥ 1.5 X 10^9/L (≥ 1500/mm^3). For MCL
 patients: ANC ≥ 1.0 X 10^9/L. Patients with ANC ≤ 1.0 X 10^9/L due to marrow
 infiltration may receive G-CSF during screening to bring pretreatment ANC levels
 to ≥ 1.0 X 10^9/L
 - c. Platelet count ≥ 100 X 10^9/L (≥100,000/mm^3). For MCL patients: ≥ 75 X 10^9/L
 Exclusion Criteria:
 - Known hypersensitivity to the study drugs or excipients of the preparations or any
 agent given in association with this study
 - History of cardiac disease: congestive heart failure New York Heart Association (NYHA)
 class >II, unstable angina (angina symptoms at rest), new-onset angina (within the
 past 6 months before study entry), myocardial infarction within the past 6 months
 before study entry, or cardiac arrhythmias requiring anti-arrhythmic therapy (beta
 blockers, calcium channel blockers, and digoxin are permitted)
 - Moderate or severe hepatic impairment, i.e. Child-Pugh class B or C
 - Known human immunodeficiency virus (HIV)-infected persons are not eligible if any of
 the following criteria apply：
 - CD4+ T-cell count less than 350 cells/μL
 - History of AIDS-defining opportunistic infection within the past 12 months
 - On established antiretroviral therapy (ART) for less than 4 weeks or presenting
 with a viral load of more than 400 copies/mL prior to enrollment
 - On ART or prophylactic antimicrobials that are expected to cause significant
 drug-drug interactions or overlapping toxicities with study intervention
 - Patients who have an active hepatitis B virus (HBV) or hepatitis C virus (HCV)
 infection requiring treatment. Patients with chronic HBV or HCV infection are eligible
 at the investigator's discretion provided that the disease is stable and sufficiently
 controlled under treatment.
 - Infections of Common Terminology Criteria for Adverse Events Version (CTCAE) Grade 2
 not responding to therapy or active clinically serious infections of CTCAE Grade > 2
 - Metastatic solid brain, spinal, or meningeal tumors or central nervous system (CNS)
 lymphoma manifestations (including meningeosis lymphomatosa and parenchymal lymphoma
 lesions) unless the patient is > 3 months from definitive therapy, has a stable
 imaging study within 4 weeks prior to the first dose of study drug and is clinically
 stable with respect to the tumor at the time of study entry. Patients with
 asymptomatic brain metastases must not be on steroid therapy. Patients with
 neurological symptoms should undergo a CT / MRI scan of the brain or spinal column to
 exclude new or progressive brain, meningeal, or spinal metastases or CNS lymphoma
 manifestations.
 - History of organ allograft transplantation. For MCL patients: Those who received an
 allogeneic stem cell transplant may participate provided that engraftment has
 occurred, there is no evidence of GVHD, and the patient is not taking immune
 suppressants. MCL patients who received an autologous stem cell transplant may
 participate once they have recovered from the procedure.
 - Treatment with anticancer chemotherapy or immunotherapy during the study or within 3
 weeks before the first dose of study drug. For small-molecule drugs, a period of at
 least 3 half-lives before the first dose of study drug is acceptable. Mitomycin C or
 nitrosoureas should not be given within 6 weeks before the first dose of study drug.
 - Treatment with systemic steroids (methylprednisolone dose ≥10 mg/day or equivalent
 dose). For MCL patients: Treatment with systemic corticosteroids > 20 mg/day
 prednisone equivalent (unless patient has been taking a stable dose for >3 weeks and
 has shown tumor progression).

DDR deficiency
estrogen-receptor positive

DDR deficiency
progesterone-receptor positive

DDR deficiency
estrogen-receptor positive
progesterone-receptor positive


Input:
The purpose of this single arm,phase Ⅱ clinical trail is to determine the safety and efficacy
 of docetaxel and cisplatin combined with Nimotuzumab in the treatment of recurrent and
 metastatic nasopharyngeal carcinoma
 ;NA;
 Inclusion Criteria:
 - biopsy proved nasopharyngeal carcinoma;
 - stage IVc according to Union for International Cancer Control (UICC) edition VIII,or
 recurrent disease after chemotherapy and/or radiotherapy;
 - 18 years or older; without other malignancy;
 - proper functioning of the major organs.
 Exclusion Criteria:
 - allergic to docetaxel or cisplatin or Nimotuzumab ;
 - female within gestation period or lactation;
 - patients received drug of other clinical trail within 3 months