Input:
This is a Phase I/II, multicenter, open-label study to evaluate the safety, efficacy,
 tolerability, and pharmacokinetics of a novel BTK inhibitor, Orelabrutinib (ICP-022) in
 Patients with B-cell malignancies. The study contains two parts, Part 1 (dose escalation) and
 Part 2 (dose expansion).
 ;NA;
 Inclusion Criteria:
 1. Signed Informed Consent.
 2. Age ≥ 18 years.
 3. Part 1: Patients with histologically confirmed relapsed or refractory B-cell
 malignancies, including Grades 1-3a FL, MZL, MCL, and CLL/SLL.
 Part 2: Patients with histologically confirmed B-cell malignancies including r/r FL,
 r/r MZL and CLL/SLL with/without prior treatment.
 4. Life expectancy (in the opinion of the investigator) of ≥ 4 months.
 5. ECOG performance status of 0 ~1.
 6. Must have adequate organ function.
 7. Negative test results for HBV ([HBsAg (-)] and non-active HBV or HCV infection
 Exclusion Criteria:
 1. Pregnant or breast-feeding or intending to become pregnant during the study.
 2. Prior treatment with systemic immunotherapeutic agents.
 3. Known allergies to Orelabrutinib (ICP-022) or its excipients or infection with HIV.
 4. Treatment with any chemotherapeutic agent, or any other investigational therapies
 within 4 weeks prior to first dose of the study drug.
 5. History of allogeneic stem-cell (or other organ) transplantation or confirmed
 progressive PML.
 6. Any external beam radiation therapy within 6 weeks prior to the first dose of the
 study drug.
 7. Concurrent use of warfarin or other vitamin K antagonists or anticoagulation therapies
 or strong CYP3A inhibitor.
 8. Active uncontrolled infections.
 9. Recent infection requiring IV anti-infective treatment that was completed ≤ 14 days
 before the first dose of study drug.
 10. Unresolved toxicities from prior anti-cancer therapy.
 11. Medically apparent CNS lymphoma or leptomeningeal disease.
 12. Current or previous history of CNS disease.
 13. Major surgery or significant traumatic injury < 28 days prior to the first dose of the
 study drug.
 14. Patients with another invasive malignancy in the last 2 years.
 15. Significant cardiovascular disease or active pulmonary disease.
 16. Received systemic immunosuppressive medications.


Input:
The purpose of this study is to determine the recommended Phase 2 dose (RP2D) candidate(s) of
 JNJ-75276617 in combination with AML directed therapies (dose selection) and further to
 evaluate safety and tolerability of JNJ-75276617 in combination with AML directed therapies
 at the RP2D(s) (dose expansion).
 ;
 ;
 Inclusion Criteria:
 - Diagnosis of AML according to World Health Organization (WHO) 2016 criteria a) De novo
 or secondary AML; b) relapsed /refractory (Arm A); c) harboring NPM1 / KMT2A
 alterations
 - Pretreatment clinical laboratory values meeting the following criteria -listed below:
 White blood cell (WBC) count: less than or equal to <=25 x 10^9 per liter (/L),
 adequate liver and renal function
 - ECOG performance status grade of 0, 1 or 2
 - A woman of childbearing potential must have a negative highly sensitive serum
 beta-human chorionic gonadotropin at screening and within 48 hours prior to the first
 dose of study treatment
 - Must sign an informed consent form (ICF) indicating participant understands the
 purpose of the study and procedures required for the study and is willing to
 participate in the study.
 - Willing and able to adhere to the prohibitions and restrictions specified in this
 protocol
 Exclusion Criteria:
 - Acute promyelocytic leukemia according to WHO 2016 criteria
 - Leukemic involvement of the central nervous system
 - Recipient of solid organ transplant
 - Cardiovascular disease that is uncontrolled, increases risk for Torsades de Pointes or
 that was diagnosed within 6 months prior to the first dose of study treatment
 including, but not limited to:(a) Myocardial infarction; (b) Severe or unstable
 angina; (c) Clinically significant cardiac arrhythmias, including bradycardia (less
 than [<] 50 beats per minute); (d) Uncontrolled (persistent) hypertension: (example,
 blood pressure greater than [>] 140/90 millimeters of mercury [mm Hg]; (e) Acute
 neurologic events such as stroke or transient ischemic attack, intracranial or
 subarachnoid hemorrhage, intracranial trauma; (f) Venous thromboembolic events
 (example, pulmonary embolism) within 1 month prior to the first dose of study
 treatment (uncomplicated Grade less than or equal to [≤]2 deep vein thrombosis is not
 considered exclusionary);(g)Congestive heart failure (NYHA class III to IV); (h)
 Pericarditis or clinically significant pericardial effusion; (i) Myocarditis; (j)
 Endocarditis (k) Clinically significant hypokalemia, hypomagnesemia, hypocalcemia
 (corrected for hypoalbuminemia)
 - Any toxicity (except for alopecia, stable peripheral neuropathy, thrombocytopenia,
 neutropenia, anemia) from previous anticancer therapy that has not resolved to
 baseline or to grade 1 or less
 - Pulmonary compromise that requires the need for supplemental oxygen use to maintain
 adequate oxygenation


Input:
Circulating tumor DNA can be used to monitor the treatment effect and identify developing
 resistance mutations during ALK directed TKI treatment.
 ;
 ;
 Inclusion Criteria:
 1. Patients with ALK translocated metastatic NSCLC, treated with alectinib as 1st line
 therapy in routine clinical practice
 2. Written (personally dated and signed) informed consent
 Exclusion Criteria:


Input:
Decitabine is a cytosine analogue and is a specific DNA methyltransferase (DNMT) inhibitor.
 It directly inhibits DNMT by phosphorylating DNA and inhibits DNMT, thereby reversing DNA
 methylation and inducing tumor cells to Normal cell differentiation or induction of tumor
 cell apoptosis.Diffuse large B-cell lymphoma (DLBCL) is the most common pathological type in
 non-Hodgkin's lymphoma. The first-line chemotherapy regimen using
 Rituximab+Cyclophosphamide+Doxorubicin +Vincristine+Bonisone（R-CHOP）significantly increases
 the remission rate and disease-free survival of patients with DLBCL, but it is difficult to
 partially relapse. Long-term remission and survival rates in treating patients are not
 satisfactory.Due to the greater cardiac toxicity of adriamycin, more patients can not be
 uncomfortable, so the COP program is also widely used in patients with DLBCL, and achieved a
 good response rate.In 2008, the FDA had approved decitabine for the demethylation treatment
 of Myelodysplastic syndrome（MDS）. Over the years, good initial remission rates and better
 long-term survival rates have been achieved in patients with MDS.There are also a variety of
 clinical trials of decitabine for patients with solid tumors that have achieved significant
 clinical efficacy.Due to the high side effects of high-dose decitabine, patient tolerance is
 poor. Therefore, the purpose of this study was to evaluate the efficacy and safety of
 low-dose decitabine combined with Cyclophosphamide+Vindesine+Bonisone(COP) regimen (D-COP)
 4-6 course of treatment for relapsed and refractory diffuse large B-cell lymphoma.
 ;
 ;
 Inclusion Criteria:
 1. Histopathology confirmed as DLBCL.
 2. Relapsed and refractory patients.
 3. Age ≥ 18 years old.
 4. ECOG ≥ 3.
 5. Women are not lactating, not pregnant, and agree not to become pregnant during the
 study period and within the next 12 months. Male patients agree that their spouse is
 not pregnant during the study period and within the next 12 months。
 6. There is an assessable lesion (lymph node diameter ≥ 1.0cm; or a dermatologic lesion
 that can be assessed by a physical examination)Signed informed consent
 Exclusion Criteria:
 1. Bone marrow involvement and lymphoma cells ≥ 25%.
 2. Severe abnormal liver and kidney function (alanine aminotransferase, bilirubin,
 creatinine> 3 times the upper limit of normal).
 3. Uncontrolled active infections.
 4. Organic heart disease and clinical symptoms or abnormal heart function (NYHA ≥ 2).
 5. Simultaneous presence of other tumors.
 6. Other psychological conditions that prevent patients from participating in the study
 or signing informed consent


Input:
The primary objective of this study is to assess the safety and tolerability, feasibility of
 the NeoPep Vaccine in newly diagnosed glioblastoma (GB) patients.
 ;
 ;
 Inclusion Criteria:
 1. Ability of subject to understand and the willingness to sign written informed consent
 for study participation;
 2. Patients with newly diagnosed high-grade glioma confirmed by histopathological and
 imaging evaluation;
 3. Gross total resection (as defined by less than 1 cm2 residual tumor mass on the
 largest perpendicular axes in post-operative scan taken within 48 h post-surgery;
 standard MRI conformable to the present national and international guidelines is
 sufficient)；
 4. At least 0.5 g tumor tissue freshly cryopreserved during surgery，and could provide
 adequate amounts of PBMC；
 5. Patient is a candidate for and willing to receive standard CRT with TMZ followed by
 maintenance TMZ cycles;
 6. Age 18-70;
 7. Life expectancy > 9 months;
 8. KPS≥70;
 9. Sufficient tumor tissue samples and peripheral blood samples can be obtained for
 sequencing analysis, or whole exome sequencing and RNA sequencing of tumor tissue
 samples and peripheral blood samples have been obtained, and the sequencing data meet
 the prediction requirements;
 10. Consent of women and men of reproductive age to use adequate and effective
 contraception during clinical trials;
 11. Normal laboratory values for hematology, liver and renal function (serum
 creatinine).In detail the following values apply as inclusion criteria:
 1. White blood cell count (WBC) ≥3.0×109/L；
 2. Absolutely neutrophil count≥1.0×109/L；
 3. Platelet count≥80×109/L；
 4. Hemoglobin content≥90g/L；
 5. Serum creatinine≤1.5 ULN or Creatinine clearance rate≥40 mL/min;
 6. TBil(total bilirubin)≤1.5 x ULN;
 7. Aspartic transaminase(AST)≤2.5x ULN or Alanine aminotransferase（ALT）≤2.5x
 ULN；Patients with liver metastases must have ≤5x ULN;
 8. Blood coagulation function :INR≤1.5x ULN；pT and APTT≤1.5x ULN;
 9. Urine protein< 2 +;if Urine protein≥2+,24-hour urinary protein must be less than
 1g.
 Exclusion Criteria:
 1. Patients treated with immunosuppressive agents (e.g., cyclosporin CsA, tacrolimus,
 rapamycin, azathioprine, etc.) within the previous month; Other immunotherapy within 3
 months;
 2. History of other malignancies (except for adequately treated basal or squamous cell
 carcinoma or carcinoma in situ) within the last 5 years unless the patient has been
 disease-free for 5 years;
 3. Participated in other clinical trials within 30 days prior to screening;
 4. Have a history of severe allergy or allergic constitution;
 5. Patients who have undergone splenectomy;
 6. Persons with primary or secondary immunodeficiency diseases (e.g. AIDS);Patients with
 autoimmune diseases;
 7. Patients who received multiple oral, intramuscular, or intravenous corticosteroids
 within 30 days before the first dose; However, patients who received a single oral,
 intramuscular, or intravenous dose of dexamethasone of 5mg or less (or another hormone
 of equivalent potency) 14 days before the first dose were allowed; Allow inhaled
 corticosteroids to treat respiratory insufficiency (e.g., chronic obstructive
 pulmonary disease), or topical steroids;
 8. Patients with uncontrollable seizures, central nervous system disorders, or psychotic
 loss of cognition;
 9. Uncontrolled central nervous system metastases;
 10. Patients had a history of chronic alcohol or drug abuse in the 6 months before
 screening;
 11. With unstable systemic disease, such as active infection, liver cirrhosis, chronic
 renal failure, severe chronic pulmonary disease, unstable hypertension, unstable
 angina pectoris, congestive heart failure, myocardial infarction within one year, etc.
 ;
 12. According to this procedure, the number of candidate neoantigens that can be used to
 make personalized vaccines is less than 20;
 13. The investigator did not consider it appropriate to participate in this study.


Input:
Study to investigate the safety and activity of NEO-PTC-01 in patients with unresectable or
 metastatic melanoma. NEO-PTC-01 is an autologous personalized T cell (PTC) product for
 adoptive cell therapy that is manufactured ex vivo and targets neoantigens displayed on the
 patient's tumor and the tumor microenvironment.
 The study will be conducted in two parts, Part 1 (Dose Finding) and Part 2 (Dose Expansion).
 The dose-finding part of the study will test two doses of NEO-PTC-01 and will be structured
 according to a 3+3 dose escalation design. After the highest tolerated NEO-PTC-01 dose is
 identified, 2 additional evaluations in Part 1 are planned, a cohort to investigate
 NEO-PTC-01 in combination with interleukin (IL)-2 and another cohort introducing α programmed
 cell death protein 1 (αPD-1) therapy. The dose expansion part of the study will test the dose
 deemed to be safe in the dose-finding part of the study in an expanded cohort of patients to
 further define the safety of NEO-PTC-01.
 ;NA;
 Inclusion Criteria:
 - Adult (age 18 to 75) men and women willing and able to give written informed consent.
 - Histologically confirmed unresectable or metastatic melanoma.
 - Part 1:
 - Have previously received a PD-1/PD-L1 inhibitor (either as single agent or in
 combination) and a CTLA-4 inhibitor-containing regimen (single agent or
 combination) prior to NEO-PTC-01, with disease progression following these
 therapies or otherwise lack of clinical benefit as determined by the study
 investigator.
 - Part 2:
 - Have received/are currently receiving a PD-1/PD-L1 inhibitor (as a single agent
 or in combination with CTLA-4) for at least 3 months.
 - Have documented SD by RECIST v1.1 or clinically asymptomatic progressive disease
 on the most recent imaging assessment, which must have occurred within 3 months
 of enrollment.
 - In the opinion of the investigator, are medically eligible and able to continue
 with PD-1/PD-L1 inhibitor therapy.
 - In the opinion of the investigator, would benefit from the addition of a T-cell
 based therapy.
 - For known BRAF mutant patients: patients must have also received targeted therapy
 (B-raf inhibitor or B-raf/MEK combination therapy) prior to NEO-PTC-01, unless deemed
 not appropriate to receive these treatments by the investigator.
 - Have at least one site of measurable disease by RECIST v1.1.
 - At least one site of disease must be accessible to biopsy for tumor tissue for
 sequence and immunological analysis. The biopsy site may be the same as the measurable
 site so long as it remains measurable. Surgical resection of the measurable site may
 not be performed if that site is the only measurable lesion. An archival biopsy may be
 used in place if the biopsy was taken within 6 months of informed consent.
 - Have Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
 - Recovered from all toxicities associated with prior treatment to acceptable baseline
 status (for laboratory toxicities see below limits for inclusion) or an National
 Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version
 5.0, Grade of 0 or 1, except for toxicities not considered by the treating physician
 to be a safety risk (e.g., alopecia).
 - Screening laboratory values must meet the following criteria and should be obtained
 prior to any production phase assessments:
 1. White blood cell (WBC) count ≥ 3 × 10^3/μL.
 2. Absolute neutrophil count (ANC) ≥ 1.5 × 10^3/μL.
 3. Platelet count ≥ 100 × 10^3/μL.
 4. Hemoglobin > 9 g/dL or 6 mmol/L.
 5. Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance
 (CrCl) ≥ 50 mL/min by Cockcroft-Gault.
 6. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN.
 7. Total bilirubin ≤ 1.5 × ULN (except in patients with Gilbert Syndrome, who can
 have total bilirubin < 3.0 mg/dL).
 8. International Normalized Ratio (INR), Prothrombin Time (PT), or Activated Partial
 Thromboplastin Time (aPTT) ≤ 1.5 × ULN unless the patient is receiving
 anticoagulant therapy, as long as PT or aPTT is within therapeutic range of
 intended use of anticoagulants.
 Exclusion Criteria:
 - Age greater than 75 years or less than 18 years.
 - Received more than three prior lines of therapy for metastatic disease.
 - Have an active or history of autoimmune disease (known or suspected). Exceptions are
 permitted for vitiligo, type I diabetes mellitus, residual hypothyroidism due to
 autoimmune condition requiring only hormone replacement, psoriasis not requiring
 systemic treatment, or conditions not expected to recur in the absence of an external
 trigger.
 - Have known active central nervous system (CNS) metastases and/or carcinomatous
 meningitis. Patients with previously treated brain metastases may participate provided
 they are stable (without evidence of progression by imaging [using the identical
 imaging modality for each assessment, either MRI or CT scan] for at least 4 weeks
 prior to enrollment and any neurologic symptoms have returned to baseline), have no
 evidence of new or enlarging brain metastases, and are not using steroids for at least
 7 days prior to enrollment. This exception does not include carcinomatous meningitis,
 which is excluded regardless of clinical and/or radiographic stability.
 - Active systemic infections requiring intravenous antimicrobial therapy, coagulation
 disorders or other active major medical illnesses of the cardiovascular, respiratory
 or immune system, as evidenced by a positive stress thallium or comparable test,
 myocardial infarction, clinically significant cardiac arrhythmias such as uncontrolled
 atrial fibrillation, ventricular tachycardia, or second- or third-degree heart block,
 and obstructive or restrictive pulmonary disease.
 - Active major medical illnesses of the immune system including conditions requiring
 systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents)
 or other immunosuppressive medications within 14 days prior to NEO-PTC-01 infusion.
 Inhaled or topical steroids and adrenal replacement doses (≤ 10 mg daily prednisone
 equivalents) are permitted in the absence of active autoimmune disease.
 - Known human immunodeficiency virus (HIV) infection, active chronic hepatitis B or C,
 and/or life-threatening illnesses unrelated to cancer that could, in the
 investigator's opinion, interfere with participation in this study.
 - Have any underlying medical condition, psychiatric condition, or social situation
 that, in the investigator's opinion, would interfere with participation in the study.
 - Have a planned major surgery that is expected to interfere with study participation or
 confound the ability to analyze study data.
 - Are 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 end of the trial (EOT) visit. Nursing women are excluded from this study
 because there is an unknown but potential risk of AEs in nursing infants secondary to
 treatment of the mother with treatments to be administered in this study.
 - Have a history of another invasive malignancy aside from melanoma, except for the
 following circumstances:
 1. Patient has been disease-free for at least 2 years and is deemed by the
 investigator to be at low risk for recurrence of that malignancy.
 2. Patient was not treated with systemic chemotherapy for carcinoma in situ of the
 breast, oral cavity, or cervix, basal cell, or squamous cell carcinoma of the
 skin.


Input:
Participants with CD30-positive lympoma will be treated with brentuximab vedotin according to
 their clinic's standard practice.
 The main aim of this study is to collect information on any side effects from treatment with
 brentuximab vedotin. Other aims are to collect information on how brentuximab vedotin is used
 to treat these participants and the outcomes of these participants.
 ;
 ;
 Inclusion Criteria:
 1. Undergoing treatment with brentuximab vedotin (of less than 3 months from initial
 treatment with brentuximab vedotin) or to be received with brentuximab vedotin.
 2. CD30-positive lymphoma by INV (any CD30 expression)
 Exclusion Criteria:
 1. Who currently participates in or with plan to participate in any interventional clinical
 trial.


Input:
The purpose of the study is to evaluate whether receiving the pneumococcal 13-valent
 conjugate vaccine (PCV13) before and after CD19-targeted CAR T cell therapy will optimize
 cellular and humoral immunity to pneumococcus.
 ;
 ;
 Inclusion Criteria:
 - In good health as evidenced by medical history or diagnosed with relapsed or
 chemotherapy-refractory diffuse large B cell lymphoma (DLBCL), primary mediastinal B
 cell lymphoma (PMLBCL), transformed follicular lymphoma (TFL) high-grade B cell
 lymphoma (HGBCL) or Follicular Lymphoma. Patients must be under consideration for
 treatment with any CD19-targeted CAR T cell therapy, per institutional standards.
 Patients undergoing active vital organ testing with a planned apheresis date for CAR T
 cell therapy may be considered eligible.
 - Signed informed consent form in accordance with institutional and federal law policies
 - Stated willingness to comply with all study procedures and availability for the
 duration of the study
 - Male or female, age over 18
 - For females of reproductive potential: use of highly effective contraception for at
 least 1 month prior to screening and agreement to use such a method during study
 participation
 Exclusion Criteria:
 - Pregnant or lactating woman, as evaluated by serum testing within 2 weeks of
 administration of the first vaccine. Only women of childbearing potential will undergo
 serum/urine pregnancy testing. A woman will be considered of childbearing potential
 unless she is status-post hysterectomy or tubal ligation or without menstrual periods
 in the preceding 12 months.
 - Common variable immunodeficiency or other inherited systemic immunodeficiency syndrome
 - History of severe allergy (e.g., anaphylaxis) to any component of pneumococcal
 conjugate vaccine 7 valent (PCV7), PCV13, or any diphtheria-toxoid containing vaccine.
 - Inclusion on a separate trial in which patients may be randomized or otherwise started
 on maintenance chemotherapies within the first 3 months of CD19-targeted CAR T cell
 therapy
 - Patients with significant psychiatric illness likely to affect compliance, as
 determined by the treating physician
 - Active or uncontrolled infections
 - Platelet count <10,000 cells/microliter
 - Lymphocyte count <200 cells/microliter
 - Intervenous immunoglobulin (IVIG) administration within one month of planned apheresis
 for collection for CD19-targeted CAR T cell manufacture
 - History of PCV13 administration within one month of planned apheresis for collection
 for CD19-targeted CAR T cell manufacture


Input:
The overall objective of this research study is to evaluate outcomes associated with
 flex-dosing in Y90 SIR-Sphere administration in a prospective cohort of unresectable HCC
 patients eligible for segmental/super selective treatment at Methodist Dallas Medical Center
 (MDMC).
 ;
 ;
 Inclusion Criteria:
 - Age 18 years or older
 - All patients diagnosed with unresectable HCC in two of fewer hepatic segments at MDMC
 who undergo at least one SIRT procedure with Y-90 resin microspheres (SIR-Spheres®,
 Sirtex Medical Limited, Sydney, Australia) will be included in data capture. HCC is
 considered unresectable if it is multifocal or bilobar, or if the patient has
 malignant portal vein thrombosis, portal hypertension, or decompensated liver disease
 (Child-Pugh B or C).
 - Eligible cases for inclusion are those that would have undergone Y-90 resin SIRT and
 had an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2;
 platelets >60,000; creatinine <2 mg/dL; bilirubin <2 mg/dL; and international
 normalized ratio (INR) <1.2.
 Exclusion Criteria:
 - Subjects that do not meet the inclusion criteria
 - Patients are not eligible for SIRT if they had any extrahepatic disease;
 contraindication to hepatic artery catheterization such as vascular abnormalities,
 bleeding diathesis, allergy to contrast dye, concurrent malignancy, refractory
 ascites, previous external beam radiation, or evidence of any uncorrectable flow to
 the gastrointestinal tract; or greater than 30 Gy of radiation estimated to be
 delivered to the lung based on angiography or Tc-99 microaggregated albumin scan
 (shunt fraction of 20% or greater).


Input:
HS-10352 is a highly potent and selective small molecule inhibitor of phosphoinositide
 3-kinase (p110α). The purpose of this study is to assess the safety, tolerability,
 pharmacokinetics (PK), and efficacy of HS-10352 plus fulvestrant in patients with hormone
 receptor (HR) positive, human epidermal growth factor 2 (HER2)-negative, advanced breast
 cancer (ABC) harboring PIK3CA mutations.
 ;
 ;
 Inclusion Criteria:
 1. Men or women aged more than or equal to (≥) 18 years
 2. HR+ HER2- breast cancer confirmed by histology or cytology.
 3. Locally advanced disease not amenable to curative treatment by surgery or metastatic
 disease.
 4. Have adequate tumor tissue for the analysis of PIK3CA mutational status. At dose
 expansion stage, participants should be identified as PIK3CA-mutation positive before
 enrollment.
 5. Females should have postmenopausal status due to either surgical/natural menopause or
 ovarian suppression with a luteinizing hormone releasing hormone (LHRH) agonist before
 enrollment. Males should be pre-treated with a LHRH agonist.
 6. Have either measurable disease per RECIST v1.1 criteria or at least one predominantly
 lytic bone lesion must be present.
 7. ECOG performance status was 0-1 and did not deteriorate in the previous 2 weeks.
 8. Estimated life expectancy for at least three months
 9. Females should be using adequate contraceptive measures and should not be
 breastfeeding at the time of screening, during the study and until 6 months after
 completion of the study; and have negative results of blood pregnancy test prior to
 C1D1.
 Males should be using adequate contraceptive measures at the time of screening, during
 the study and until 6 months after completion of the study.
 10. Have signed Informed Consent Form
 11. Dose escalation stage-Cohort 1: subjects resistant to endocrine therapy Dose expansion
 stage-Cohort 2: subjects resistant to endocrine therapy Dose expansion stage-Cohort 3:
 endocrine therapy-sensitive or endocrine-naive subjects
 Exclusion Criteria:
 1. Participant with symptomatic visceral disease or any disease burden that makes the
 participant ineligible for endocrine therapy per the investigator's best judgment
 2. Treatment with any of the following:
 1. Previous or current treatment with PI3K, AKT or mTOR inhibitors
 2. For expansion stage, prior treatment with fulvestrant
 3. Any cytotoxic chemotherapy, investigational agents within 21 days of the first
 dose of study drug; anticancer drugs which have been received within 14 days
 before the first administration.
 4. Radiotherapy with a limited field of radiation for palliation within 2 weeks of
 the first dose of study drug, or patients received more than 30% of the bone
 marrow irradiation, or large-scale radiotherapy within 4 weeks of the first dose.
 5. Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4
 weeks of the first dose of study drug.
 3. With inflammatory breast cancer at screening.
 4. Inadequate bone marrow reserve or organ function.
 5. Uncontrolled pleural effusion or ascites or pericardial effusion.
 6. Known and untreated, or active central nervous system metastases.
 7. History of primary or secondary diabetes.
 8. History of acute or chronic pancreatitis
 9. Refractory nausea, vomiting, or chronic gastrointestinal diseases, or inability to
 swallow the study drug that would preclude adequate absorption of HS-10352 or
 fulvestrant.
 10. History of hypersensitivity to any active or inactive ingredient of HS-10352/
 fulvestrant or to drugs with a similar chemical structure or class to HS-10352.
 11. Judgment by the investigator that the patient should not participate in the study if
 the patient is unlikely to comply with study procedures, restrictions, and
 requirements.
 12. Any disease or condition that, in the opinion of the investigator, would compromise
 the safety of the patient or interfere with study assessments.

HR positive
HER2 negative
PIK3CA mutation


Input:
This is a first-in-human, open-label, multicenter, Phase I multiple-ascending dose (MAD)
 study of RO7247669, an anti PD-1 (programmed death-1) and LAG-3 (Lymphocyte-activation gene
 3) bispecific antibody, for participants with advanced and/or metastatic solid tumors. This
 study aims to establish the maximum tolerated dose (MTD) and/or define the recommended phase
 2 dose (RP2D) based on the safety, tolerability, pharmacokinetic (PK) and/or pharmacodynamic
 (PD) profile of RO7247669, and to evaluate preliminary anti-tumor activity in participants
 with solid tumors. An expansion part of the study is planned to enroll tumor-specific cohorts
 to evaluate anti-tumor activity of the MTD and/or RP2D of RO7247669 and to confirm safety and
 tolerability in participants with selected tumor types.
 ;NA;
 Inclusion criteria
 - Patient must have histologically or cytologically confirmed advanced and/or metastatic
 solid tumor malignancies for which standard curative or palliative measures do not
 exist, are no longer effective, or are not acceptable to the patient
 - Eastern Cooperative Oncology Group Performance Status 0-1
 - Fresh biopsies may be required
 - Women of childbearing potential and male participants must agree to remain abstinent
 or use contraceptive methods as defined by the protocol
 Additional Specific Inclusion Criteria for Participants with Melanoma
 - Histologically confirmed, unresectable stage III or stage IV melanoma
 - Not more than 2 prior lines of treatment for metastatic disease are allowed prior to
 enrolling in the study
 - Prior treatment with an approved anti-PD-1 or anti-PD-L1 agent
 Additional Specific Inclusion Criteria for Participants with Non-Small Cell Lung Cancer who
 Previously Received Treatment for Metastatic Disease
 - Participants with histologically confirmed advanced non-small cell lung cancer
 - Not more than 2 prior lines of treatment for metastatic disease are allowed prior to
 enrolling in the study
 - Previously treated with approved PD-L1/PD-1 inhibitors
 - Tumor PD-L1 expression as determined by immunohistochemistry assay of archival tumor
 tissue or tissue obtained at screening
 Additional Specific Inclusion Criteria for Participants with Esophageal Squamous Cell
 Carcinoma
 - Participants whose major lesion was histologically confirmed as squamous cell
 carcinoma or adenosquamous cell carcinoma of the esophagus
 - Participants who have previously received not more than 1 prior line of treatment for
 metastatic disease prior to enrolling in the study
 Additional Specific Inclusion Criteria for Participants with Non-Small Cell Lung Cancer who
 Previously did not Receive Treatment for Metastatic Disease
 - Participants with histologically confirmed advanced non-small cell lung cancer
 - Tumor PD-L1 expression as determined by immunohistochemistry assay of archival tumor
 tissue or tissue obtained at screening
 Exclusion criteria
 - Pregnancy, lactation, or breastfeeding
 - Known hypersensitivity to any of the components of RO7247669
 - Active or untreated central nervous system (CNS) metastases
 - An active second malignancy
 - Evidence of concomitant diseases, metabolic dysfunction, physical examination finding,
 or clinical laboratory finding giving reasonable suspicion of a disease or condition
 that contraindicates the use of an investigational drug or that may affect the
 interpretation of the results or render the participant at high risk from treatment
 complications
 - Positive HIV, hepatitis B, or hepatitis C test result
 - Known active or uncontrolled bacterial, viral, fungal, mycobacterial, parasitic, or
 other infection
 - Vaccination with live vaccines within 28 days prior to Cycle 1 Day 1
 - Treatment with oral or IV antibiotics within 2 weeks prior to Cycle 1 Day 1
 - Active or history of autoimmune disease or immune deficiency
 - Prior treatment with adoptive cell therapies, such as CAR-T therapies
 - Concurrent therapy with any other investigational drug < 28 days or 5 half-lives of
 the drug, whichever is shorter, prior to the first RO7247669 administration
 - Regular immunosuppressive therapy
 - Radiotherapy within the last 4 weeks before start of study drug treatment, with the
 exception of limited palliative radiotherapy
 - Prior treatment with a lymphocyte activation gene-3 (LAG-3) inhibitor
 Additional Specific Exclusion Criteria for Participants with Non-Small Cell Lung Cancer who
 Previously Received Treatment for Metastatic Disease
 - Participants with the following muations, rearrangements, translocations are not
 eligible: EGFR, ALK, ROS1, BRAFV600E, and NTRK
 Additional Specific Exclusion Criteria for Participants with Esophageal Squamous Cell
 Carcinoma
 - Prior therapy with any immunomodulatory agents
 Additional Specific Exclusion Criteria for Participants with Non-Small Cell Lung Cancer who
 Previously did not Receive Treatment for Metastatic Disease
 - Prior therapy for metastatic disease is not permitted
 - Neo-adjuvant anti-PD-1 or anti-PD-L1 therapy is not allowed


Input:
A transcriptomic analysis of bone marrow from B-ALL patients was performed by our research
 group for identifying novel protein/factor with a putative role of disease biomarker. Along
 with some already known B-ALL biomarkers, our analysis highlighted deregulation of some
 members of an emerging protein class denoted as KCTD (Potassium ChannelTetramerization
 Domain-containing proteins). Starting from our preliminary observations, and considering that
 KCTDs havenever been studied in ALL, we decided to study these proteins in B- and T-ALL
 affected pediatric patients, enrolled by our research group in collaboration with AORN
 Santobono-Pausilipon pediatric oncological hospital.Indeed, the present research program aims
 at opening a new scenario for the study of KCTD proteins in childhood leukemias. The final
 goal of the project will be to evaluate the translational relevance of selected deregulated
 KCTDs as novel biomarkers useful for B-ALL and T-ALL diagnostics, and patient management.
 ;NA;
 Inclusion Criteria:
 - Patients aged 1-18 years of both sexes diagnosed with B- ALL and T-ALL;
 - Patients who will have signed the informed consent
 Exclusion Criteria:
 - Patients who refuse to participate in the study;
 - Patients who do not fall within the age range mentioned above


Input:
This is a Phase 1, nonrandomized, open-label, single-dose, dose-escalation, and
 dose-expansion study to evaluate the safety and clinical activity of PBCAR19B in adult study
 participants with CD-19 expressing malignancies.
 ;NA;
 Inclusion Criteria:
 - Relapsed or refractory CD19+ expressing malignancies
 - At least 2 prior regimens per Standard of Care
 Exclusion Criteria:
 - No history of active CNS involvement


Input:
This study will test the safety of the study drug, GDC-0084, in combination with radiation
 therapy in people who have solid tumor brain metastases or leptomeningeal metastases. All
 participants will have cancer with a PIK3CA mutation. The researchers will test increasing
 doses of GDC-0084 to find the highest dose that causes few or mild side effects in
 participants. The study will also try to find out if the combination of the study drug with
 radiation is effective against participants' cancer.
 ;NA;
 Inclusion Criteria:
 - Histologically confirmed solid tumor malignancies harboring PIK3CA mutations which
 include mutations in any of the following genes: PIK3CA, PIK3CB, PIK3CD, PIK3CG,
 PIK3R1, PIK3R2, PIK3R3, PIK3C2G, PIK3C3, INPP4A, INPP4B, INPPL1, INPP5D, PTEN, AKT1,
 AKT2, AKT3, and MTOR.
 - Brain metastases and/or leptomeningeal metastases involving the brain demonstrated by
 MR imaging of the brain. For patients with brain metastases, measurable lesion by
 RANO-BM is required28. Patients with spine leptomeningeal metastases are eligible for
 the study if they have leptomeningeal metastases of the brain demonstrated by MRI
 imaging of the brain.
 - KPS ≥ 70
 - Age ≥ 18 years
 - Able to provide informed consent.
 - If a patient is on corticosteroid, he/she must be on a stable daily dose of < 4mg
 dexamethasone or equivalent. Patient does not need to be given corticosteroid as
 prophylaxis if not clinically indicated.
 - No limit to prior therapies with the last systemic therapy ≥ 1 week from initiation of
 protocol therapy. Systemic therapy can resume after completion of protocol DLT
 assessment period.
 - Patients with prior SRS are eligible, provided that there are new, non-irradiated
 brain lesions or leptomeningeal metastases. Patients must be ≥ 3 months post prior
 cranial radiation therapy.
 - Patients with seizure history related to brain metastases or leptomeningeal metastases
 controlled on antiepileptic medications are eligible.
 - Patient at reproductive potential must agree to practice an effective contraceptive
 method
 - Patient must be able to swallow and retain oral medication
 - Adequate organ function as assessed by laboratory tests.
 - Adequate bone marrow function
 - Hemoglobin ≥ 8g/dL
 - Absolute neutrophil count ≥1,000/mm^3
 - Platelet count ≥ 100,000/mm^3
 - Adequate liver function
 - Bilirubin ≤1.5 times upper limit normal (ULN)
 - AST and ALT ≤ 2.5 times ULN
 - Alkaline phosphatase ≤ 2 times ULN
 - Adequate renal function ° BUN and Creatinine ≤ 1.5 times ULN
 Exclusion Criteria:
 - Previous radiotherapy to the intended treatment site that precludes developing a
 treatment plan that respects tissue tolerances
 - Patients with brain metastases eligible for single fraction stereotactic radiation
 therapy
 - Serious medical co-morbidities precluding radiotherapy
 - Insulin-treated diabetes; subjects with diabetes or impaired glucose tolerance that is
 not treated with insulin may be enrolled
 - QT interval ≥ 450 msec on EKG
 - Cardiac dysfunction defined as: myocardial infarction within 6 months of study entry,
 NYHA Class II/III/IV heart failure, unstable angina or unstable cardiac arrhythmias
 - Known hypersensitivity or intolerance to GDC-0084 or to any other inhibitor of the
 PI3K/ Akt/ mTOR pathway
 - Past medical history of interstitial lung disease, drug-induced ILD, radiation
 pneumonitis that required steroid treatment, or any evidence of clinically active
 interstitial lung disease
 - Subject receiving any medications or substances that are moderate and/or potent enzyme
 inducers or inhibitors which may have an effect on the metabolism of GDC-0084.
 - Pregnant or lactating women.


Input:
HS-10365 is a small molecular, oral potent, selective RET inhibitor. The purpose of this
 study is to investigate the safety/tolerability and the pharmacokinetic profile of HS-10365
 in Chinese advanced solid tumor patients. Anti-tumor activity will be also investigated in
 this study.
 ;
 ;
 Inclusion Criteria:
 Subjects must meet all of the following inclusion criteria to be eligible for participation
 in this study:
 1. Men or women aged more than or equal to (≥) 18 years.
 2. Locally advanced or metastatic cancer patients confirmed by histology or cytology for
 who that standard treatment is invalid, unavailable or intolerable
 3. Enrollment will be restricted to participants with evidence of a RET gene alteration
 in tumor as determined by local or central testing. And tumor tissue samples should be
 provided before the first administration for retrospective detection of RET gene
 status; blood samples are also allowed.
 4. At least one extra-cranial measurable lesion according to Response Evaluation Criteria
 in Solid Tumors (RECIST) criteria version 1.1.
 5. Eastern Cooperative Oncology Group (ECOG) performance status: 0~1.
 6. Estimated life expectancy greater than (>) 12 weeks.
 7. Men or women should be using adequate contraceptive measures throughout the study;
 Females should not be breastfeeding at the time of screening, during the study and
 until 6 months after completion of the study\
 8. Females must have evidence of non-childbearing potential.
 9. Signed and dated Informed Consent Form.
 Exclusion Criteria:
 1. Treatment with any of the following:
 Previous or current treatment with selective RET inhibitors. Any cytotoxic
 chemotherapy, investigational agents and anticancer drugs within 14 days of the first
 dose of study drug.
 Radiotherapy with a limited field of radiation for palliation within 2 weeks of the
 first dose of study drug, or patients received more than 30% of the bone marrow
 irradiation, or large-scale radiotherapy within 4 weeks of the first dose.
 Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks
 of the first dose of study drug.
 2. Inadequate bone marrow reserve or organ function.
 3. Uncontrolled pleural effusion or ascites or pericardial effusion.
 4. Known and untreated, or active central nervous system metastases.
 5. Refractory nausea, vomiting, or chronic gastrointestinal diseases, or inability to
 swallow the study drug that would preclude adequate absorption of HS-10365.
 6. History of hypersensitivity to any active or inactive ingredient of HS-10365 or to
 drugs with a similar chemical structure or class to HS-10365.
 7. Judgment by the investigator that the patient should not participate in the study if
 the patient is unlikely to comply with study procedures, restrictions, and
 requirements.
 8. Any disease or condition that, in the opinion of the investigator, would compromise
 the safety of the patient or interfere with study assessments. Pregnant women, women
 who are breastfeeding or who believe they may wish to become pregnant during the
 course of the study.
 9. History of neuropathy or mental disorders, including epilepsy and dementia
 10. Determined by the physician, any coexisting disease might lead to life threatening
 complications or avoid the patients from accomplishing the treatment.


Input:
This is a Phase 1/2, open-label, multicenter, study of the safety, tolerability, PK, PD, and
 anti-tumor activity of MRTX1719 patients with advanced, unresectable or metastatic solid
 tumor malignancy with homozygous deletion of the MTAP gene.
 ;
 ;
 Inclusion Criteria:
 - Histologically confirmed diagnosis of a solid tumor malignancy with homozygous
 deletion of the MTAP gene detected in tumor tissue or ctDNA
 - Unresectable or metastatic disease.
 - Patients must have received standard therapies appropriate for their tumor type and
 stage with disease progression on or after the most recent treatment.
 1. Phase 1 dose escalation, RECIST 1.1 measurable or evaluable disease
 2. Phase 1b and Phase 2 cohorts, RECIST 1.1 measurable disease.
 - Presence of a tumor lesion amenable to mandatory biopsy for pharmacodynamic evaluation
 at baseline and on-study unless Sponsor-confirmed as medically unsafe or infeasible.
 - Age ≥ 18 years.
 - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
 - Adequate organ function
 Exclusion Criteria:
 - Prior treatment with a PRMT5 or MAT2A inhibitor therapy (Phase 2 only).
 - Active brain metastases or carcinomatous meningitis.
 - History of significant hemoptysis or hemorrhage within 4 weeks of the first dose of
 study treatment.
 - Major surgery within 4 weeks of first dose of study treatment.
 - History of intestinal disease, inflammatory bowel disease, major gastric surgery, or
 other gastrointestinal conditions (eg, uncontrolled nausea, vomiting, malabsorption
 syndrome) likely to alter absorption of study treatment or result in inability to
 swallow oral medications
 - Cardiac abnormalities


Input:
This is a single-arm, open-label, multicenter, investigator-initiated Phase 2 trial to
 evaluate the efficacy and safety of E7090 in patients with advanced or recurrent solid tumors
 harboring FGFR genetic alterations (including fusion, mutation, amplification).
 ;NA;
 Inclusion Criteria:
 1. Participants with histologically or cytologically confirmed metastatic, unresectable,
 or recurrent solid tumor who agree to provide an archival tumor sample, a residual
 biopsy sample, or a fresh tumor biopsy sample
 2. Ineffective to or intolerant to initial treatment, or for which standard treatment is
 no longer available
 3. Participants with an FGFR gene alteration detected by NGS panel, who fall under one of
 the categories of groups A to C defined as below
 Group A: FGFR1-3 fusion
 Group B: FGFR1-3 specific activating mutations as below;
 FGFR1: P150S, T340M, R445W, N546K, K656E
 FGFR2: C62Y, A67V, N82K, D101Y, E160K, E163K, M186T, R203H, R210Q, Q212K, R251Q,
 S252W, P253R, P253L, A264T, W290C, K310R, Y328N, G364E, Y375C, C382R, A389T, V392A,
 R399Q, H416R, I422V, H544Q, N549H, N549K, N549D, N549S, L560F, K659E, K659N, R664W,
 E718K, S791T
 FGFR3: G380E, G380R, A391E, K650T, K650E, K650Q, K650N
 Group C: FGFR1-3 activating mutation not applicable to group B, or FGFR1, 2 gene
 amplification
 4. For Group D, participants with cholangiocarcinoma who have previously received a
 selective FGFR inhibitor other than E7090 and have demonstrated progressive disease or
 resistance
 5. Karnofsky Performance Status (KPS) >= 70 for patients with primary CNS tumors.
 Performance Status (ECOG) 0-1 for patients with non-primary CNS tumors
 6. For patients with non-primary CNS tumors, they have at least 1 lesion of >= 10
 millimeter (mm) in the longest diameter for a non-lymph node or >= 15 mm in the
 short-axis diameter for a lymph node that is considered as serially measurable
 according to RECIST v1.1 using computerized tomography or magnetic resonance imaging
 (CT or MRI) within 28 days of enrollment. However, lesions that have received local
 treatment such as external-beam radiation therapy (EBRT) or radiofrequency ablation
 (RFA) must have progressed after these local treatment to count as measurable lesion
 7. Participants with primary CNS tumors must meet all of the following criteria:
 1. Have received prior treatment including radiation and/or chemotherapy, as
 recommended or appropriate for the CNS tumor type
 2. Have >= 1 site of bi-dimensionally measurable disease (confirmed by magnetic
 resonance imaging (MRI) and evaluable by RANO criteria), with the size of at
 least one of the measurable lesions >= 1 cm in each dimension and noted on more
 than one imaging slice. Imaging study performed within 28 days before enrollment
 3. Must be neurologically stable based on neurologic exam at least for the last 7
 days prior to enrollment. (based on medical examination/interview)
 8. Corrected calcium <= 10.1 mg/dL
 9. Phosphate <= 4.6 mg/dL
 10. Required treatment washout period, from the last day of prior treatment until
 enrollment of this trial, is as follows:
 1. Antibody and other investigational drugs: >= 28 days
 2. Prior chemotherapy (excluding small-molecule targeted therapy), surgical therapy,
 radiation therapy: >= 21 days (>= 90 days from the date of the last radiation
 therapy for primary CNS tumors)
 3. Endocrine therapy, immunotherapy, small-molecule targeted therapy: >=14 days
 Exclusion Criteria:
 1. Participants with brain, subdural or leptomeningeal metastases
 2. Participants with primary CNS tumor located in either cerebellum, brainstem, spinal
 cord, pituitary gland, optic nerve or olfactory nerve
 3. Positive for either human immunodeficiency virus (HIV) antibody, HBs antigen, or HCV
 antibody (patients with positive HCV antibody but no detectable HCV-RNA are not
 excluded)
 4. Negative for HBs antigen, but positive for HBs antibody or HBc antibody, and also
 positive for HBV-DNA quantification (not excluded if HBV-DNA is below detection
 sensitivity)
 5. Child-Pugh score B or C
 6. Participants with pericardial effusion, pleural effusion, or ascites requiring
 treatment
 7. Have any of the following ocular diseases
 1. Grade 2 or higher corneal disorders
 2. Active retinopathy (e.g., age-related macular degeneration, central serous
 chorioretinal disease, retinal tear)
 8. Participants whose toxicity of previous treatment has not recovered to Grade 1 or
 lower per Common Terminology Criteria for Adverse Events (CTCAE v5.0), except for
 alopecia, infertility, and the laboratory test results listed in the inclusion
 criteria
 9. Participants who received a prior selective FGFR inhibitor in the recurrent/metastatic
 disease setting; except for patients with cholangiocarcinoma harboring FGFR2 fusion
 (Group D). Note that prior use of a multi-kinase inhibitor which includes anti-FGFR
 activity is acceptable after review by the lead investigator
 10. Participants who need the use of drugs that strongly inhibits or induces the
 metabolizing enzyme cytochrome P450 (CYP) 3A
 11. The presence of FGFR gatekeeper mutations as follows: FGFR1 V561, FGFR2 V564/565,
 FGFR3 V555/557, FGFR4 V550
 12. The presence of any of the following coexisting driver gene abnormalities:
 1. Genetic mutations (excluding VUS): KRAS, NRAS, EGFR, or BRAF V600
 2. Gene translocations: ALK, ROS1, or NTRK


Input:
This is a phase I clinical trial to determine the maximum tolerated dose (MTD) of KK-LC-1
 TCR-T cells for the treatment of metastatic cancers that express KK-LC-1. Participants will
 receive a conditioning regimen, KK-LC-1 TCR-T cells, and aldesleukin. The safety profile and
 clinical response to treatment will be determined.
 ;
 ;
 1. Signed, written informed consent obtained prior to any study procedures.
 2. Age > 18 years at the time of informed consent.
 3. Metastatic solid tumor with ≥ 25% of tumor cells positive for KK-LC-1 by IHC assay.
 Due to the low frequency of KK-LC-1 expression in most cancers, screening will focus
 on gastric, NSCLC, TNBC, and cervix cancers. The IHC test will be performed by the
 Rutgers Cancer Institute of New Jersey, Department of Biorepository Services.
 4. HLA-A*01:01 allele by HLA haplotype test.
 5. Measureable disease per RECIST Criteria Version 1.1 at time of enrollment.
 6. Prior treatment with cancer type-specific stand of care systemic cancer therapy is
 required. Standard treatment options must be considered and declined. Documentation of
 rationale is required if a subject is deemed unsuitable for standard therapy.
 7. Subjects with < 3 brain metastases that have been treated with surgery or stereotactic
 radiosurgery are eligible. Lesions that have been treated with stereotactic
 radiosurgery must be clinically stable for one month before protocol treatment.
 Patients with surgically resected brain metastases are eligible.
 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening.
 9. Negative pregnancy test for women under 55 and all women who have had a menstrual
 period in the last 12 months. A pregnancy tests is not required for women who have had
 a bilateral oophorectomy or hysterectomy.
 10. Women of child-bearing potential must agree to use adequate contraception (i.e.,
 intrauterine device, hormonal barrier method of birth control; abstinence; tubal
 ligation or vasectomy) prior to study entry and for four months after treatment.
 Should a women become pregnant or suspect she is pregnant while she is participating
 in this study, she should inform her treating physician immediately.
 11. Participants must have organ and marrow function as defined below:
 1. Leukocytes > 3,000/mcL
 2. Absolute neutrophil count > 1,500/mcL
 3. Platelets > 100,000/mcL
 4. Hemoglobin > 9.0 g/dL
 5. Total bilirubin within normal institutional limits except in participants with
 Gilbert's Syndrome who must have a total bilirubin < 3.0 mg/dL.
 6. Serum AST (SGOT)/ALT (SGPT) < 2.5 x ULN
 7. Calculated creatinine clearance (CrCl) >50 mL/min/1.73 m2for participants with
 creatinine levels above institutional normal (by the Chronic Kidney Disease
 Epidemiology Collaboration (CKD-EPI) equation).
 8. INR or a PTT ≤1.5 X ULN unless the subject is receiving anticoagulant therapy.
 Subjects on anticoagulant therapy must have a PT or PTT within therapeutic range
 and no history of severe hemorrhage.
 12. Serology:
 - HIV antibody negative
 - Hepatitis B antigen negative
 - Hepatitis C antibody negative or HCV RNC negative (i.e., no current HCV
 infection)
 13. More than four weeks must have elapsed since any prior systemic therapy or
 radiotherapy at the time the patient receives the KK-LC-1 TCR T cells. Adverse events
 from prior therapy must have resolved to≤ grade 1 according to CTCAE Version 5 or have
 demonstrated clinical stability and meet the eligibility criteria for the protocol.
 14. Oxygen saturation ≥ 92% on room air.
 15. Left ventricular ejection fraction ≥45% by echocardiogram or MUGA for patients 50
 years of age or older.


Input:
Chemotherapy is an important means to prolong the survival time of advanced breast cancer. As
 a new type of microtubule inhibitor, eribulin has a unique mechanism of action. Compared with
 single drug chemotherapy, it can improve the overall survival time of 2.5 months, increase
 the clinical benefit rate by 5 times, and the tolerance of eribulin is good. Therefore, the
 guidelines at home and abroad recommend eribulin for the rescue of advanced breast cancer.
 However, up to now, there is no large sample data on the efficacy of eribulin combined with
 anti HER2 targeted therapy in HER2 + metastatic breast cancer, and the efficacy of combined
 immunotherapy in triple negative metastatic breast cancer. Moreover, as a newly marketed
 chemotherapy drug in China, the efficacy and safety data of eribulin in Chinese population
 are relatively lacking. Therefore, we plan to include different types and line numbers of
 advanced breast cancer patients based on the Chinese population through real-world research,
 and receive the treatment regimen containing eribulin respectively. In HR + / her2-mbc, we
 use eribulin monotherapy; in HER2 + MBC, we use eribulin + anti HER2 targeted therapy; in
 TNBC, we use eribulin + immunotherapy / chemotherapy, The efficacy and safety of eribulin
 were evaluated.
 ;NA;
 Inclusion Criteria:
 1. Adult female patients (aged 18-80 years, including 18 and 80 years) with metastatic
 breast cancer confirmed by pathology or imaging are not suitable for surgical
 resection or radiotherapy for the purpose of cure;
 2. The starting time of eribulin treatment was between January 2021 and December 2021;
 3. They received no more than 2-line chemotherapy in the past;
 4. In HR + / her2-mbc, patients were treated with eribulin monotherapy; in HER2 + MBC,
 patients were treated with eribulin + anti HER2 targeted therapy; in TNBC, patients
 were treated with eribulin + immunotherapy / chemotherapy; in patients with HER2 +
 MBC, patients were treated with eribulin + immunotherapy /chemotherapy;
 Exclusion Criteria:
 1. Patients without pathological diagnosis;
 2. Patients with central nervous system metastasis;
 3. She has received more than two chemotherapy regimens for metastatic breast cancer;
 4. Participating in any intervention drug clinical trials.
 5. Those who have been known to have allergic history to the components of this regimen;
 6. The patient, the patient, or the person with serious harm to the safety of the study.
 7. Any other situation in which the researcher considers that the patient is not suitable
 for the study may interfere with the concomitant diseases or conditions involved in
 the study, or there are any serious medical barriers that may affect the safety of the
 subjects (e.g., uncontrollable heart disease, hypertension, active or uncontrollable
 infection, active hepatitis B virus infection)


Input:
The purpose of this study is to further evaluate the efficacy and safety of niraparib in
 patients with locally advanced or metastatic solid tumors and a pathogenic or likely
 pathogenic tumor PALB2 (tPALB2) mutation.
 ;NA;
 Inclusion Criteria:
 - Participants must be at least 18 years of age or older.
 - Participants must have a histologically or cytologically confirmed diagnosis of
 locally advanced or metastatic solid tumor(s).
 - Participants must have tested positive for a pathogenic or likely pathogenic tPALB2
 gene mutation using a CLIA-certified laboratory as described in the Next-Generation
 Sequencing (NGS) Laboratory Manual.
 - Participants who have stable and asymptomatic Central Nervous System (CNS) disease
 must be receiving a stable (for at least 7 days) or decreasing corticosteroid dose at
 the time of study entry.
 - Participants must submit fresh or archived (collected within 24 months of enrollment)
 Formalin-Fixed Paraffin-Embedded (FFPE) tumor sample to the central laboratory for
 post-enrollment confirmation of tPALB2 status.
 - Participants must have received all standard therapies appropriate for their tumor
 type and stage of disease or, in the opinion of the Investigator, the patient would be
 unlikely to tolerate or derive clinically meaningful benefit from appropriate standard
 of care therapy, or the participant has no satisfactory alternative treatments.
 Exclusion Criteria:
 - Participants have other active concomitant malignancy that warrants systemic,
 biologic, or hormonal therapy.
 - Participants who have ovarian or prostate cancer.
 - Participants who have variants of undetermined significance (VUS), but not pathogenic
 variants of PALB2, at the time of screening.
 - Participants who relapsed while receiving platinum based therapy in the
 adjuvant/curative setting.
 - Participants progressing within 14-18 weeks while receiving platinum based therapy in
 the metastatic setting.
 - Participants who have received Poly (ADP-ribose) polymerase (PARP) inhibitor(s) in
 prior lines of treatment.
 - Participants with leptomeningeal disease, carcinomatous meningitis, symptomatic brain
 metastases, or radiologic signs of CNS hemorrhage.
 - Participants with germline or somatic BRCA1 or BRCA2 mutations.
 - Participant has systolic blood pressure (BP) over 140 mmHg or diastolic BP over 90
 mmHg, despite optimal medical therapy.
 - Participants have previously or are currently participating in a treatment study of an
 investigational agent within 3 weeks of the first dose of therapy preceding the study.
 - Participants have received prior systemic cytotoxic chemotherapy, biological therapy,
 or hormonal therapy for cancer, or received radiation therapy within 3 weeks of the
 first dose therapy preceding the study.

PALB2 variants of undetermined significance


Input:
This is a Phase 1/2a, first-in-human, open-label study of JAB-8263, this study has two parts:
 solid tumor dose escalation and expansion study and hematology tumor dose escalation and
 expansion study.
 These two parts will determine the maximum tolerated dose (MTD), recommended Phase 2 dose
 (RP2D) and assess the DLT of JAB-8263 in treatment with patients with advanced solid tumors
 and hematology tumors separately. 30 subjects each will be enrolled.
 ;
 ;
 Inclusion Criteria:
 - Subjects must meet all the following criteria in order to be included in the research
 study:
 1. Subject must be ≥18 years-of-age at the time of signature of the informed consent
 form (ICF).
 2. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
 3. Subjects with histologically or cytologically confirmed advanced solid tumors
 which have progressed despite standard therapy(ies), or are intolerant to
 standard therapy(ies), or have a tumor for which no standard therapy(ies) exists.
 4. Subjects with recurrent/refractory AML according to WHO 2016
 5. Subjects with life expectancy ≥3 months.
 6. Patients with solid tumor must have at least one measurable lesion as defined by
 RECIST v1.1.
 7. Patients who have sufficient baseline organ function.
 Exclusion Criteria:
 1. History (≤3 years) of cancer that is histologically distinct from the cancer under
 study.
 2. Known serious allergy to investigational drug or excipients
 3. Active brain or spinal metastases
 4. History of pericarditis or Grade ≥2 pericardial effusion
 5. History of interstitial lung disease.
 6. History of Grade ≥2 active infections within 2 weeks
 7. Known human immunodeficiency virus (HIV) infection
 8. Seropositive for hepatitis B virus (HBV)
 9. Seropositive for hepatitis C virus (HCV), or HCV-RNA viral levels are not detectable.
 10. Any severe and/or uncontrolled medical conditions
 11. History of myocardial infarction, unstable angina pectoris, coronary artery bypass
 graft, or cerebrovascular accident
 12. Impaired cardiac function or clinically significant cardiac diseases
 13. QTcF >470 msec at screening
 14. History of medically significant thromboembolic events or bleeding diathesis
 15. Unresolved Grade >1 toxicity
 16. History of malignant biliary obstruction
 17. Pregnant or breast-feeding


Input:
This is a single center, Phase I dose finding study of HCW9218 for the treatment of
 advanced/metastatic solid tumor cancer (except pancreatic and primary brain cancers). HCW9218
 is a novel bi-functional fusion protein complex administered by subcutaneous (SC) injection.
 It is comprised of a soluble fusion of two human TGFβRII domains, human tissue factor, and
 human IL-15, and a second soluble fusion of two human TGFβRII domains and a sushi domain of
 human IL-15Rα. HCW9218 activates IL-15R signaling on effector immune cells and the dimeric
 TGFβRII functions as a "trap" for all three human TGF-β isoforms.
 ;NA;
 Inclusion Criteria:
 - Histologically or cytologically confirmed advanced/metastatic solid tumor cancer
 (except pancreatic and primary brain cancers), has failed at least 2 prior lines of
 therapy given either in the recurrent or metastatic setting and must be refractory to
 or intolerant of existing therapy(ies) known to provide clinical benefit for their
 condition.
 - Measurable disease per RECIST v 1.1.
 - Acute effects of any prior therapy must have resolved to baseline or Grade ≤1 NCI
 CTCAE v5 except for AEs not constituting a safety risk by enrolling Investigator
 judgment.
 - Age 18 years or older at the time of consent.
 - ECOG Performance Status 0 or 1.
 - Evidence of adequate organ function within 14 days prior to enrollment as defined in
 Section 4.1.6.
 - Adequate pulmonary function with PFTs >50% FEV1 if symptomatic or known impairment.
 - Sexually active persons of child-bearing potential or with partners of childbearing
 potential must agree to use a highly effective form of contraception (refer to Section
 4.1.10 for acceptable methods) for at least 28 days after the last dose of HCW9218.
 - Provides voluntary written consent prior to the performance of any research related
 activity.
 Exclusion Criteria:
 - Pregnant or breastfeeding.
 - History of clinically significant vascular disease, including any of the following
 within 6 months prior to start of study treatment: MI or unstable angina, percutaneous
 coronary intervention, bypass grafting, ventricular arrhythmia requiring medication,
 stroke or transient ischemic attack, symptomatic peripheral arterial disease.
 - Marked baseline prolongation of QT/QTc interval (e.g., demonstration of a QTc interval
 greater or equal to 470 milliseconds by Fridericia's correction).
 - Known or suspected untreated CNS metastases.
 - Anti-cancer treatment including surgery, radiotherapy, chemotherapy, other
 immunotherapy, or investigational therapy within 14 days before treatment start.
 - Other prior malignancy except for the following: adequately treated basal cell or
 squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II
 cancer from which the subject is currently in complete remission, or any other cancer
 from which the subject has been disease-free for 3 years after surgical treatment.
 - Known hypersensitivity or history of allergic reactions attributed to compounds of
 similar chemical or biologic composition to the agents used in the study.
 - Prior therapy with TGF-β antagonist, IL-15 or analogs.
 - Concurrent use of St. John's wort and and/or other herbal CYP modulators within 7 days
 of Day 1. Must agree to not use during study treatment through the end of treatment
 visit to be eligible.
 - Known autoimmune disease requiring active treatment. Persons with a condition
 requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone
 equivalent) or other immunosuppressive medications within 14 days of enrollment.
 Inhaled or topical steroids, and adrenal replacement steroid doses ≤ 10 mg daily
 prednisone equivalent, are permitted in the absence of active autoimmune disease.
 - Active systemic infection requiring parenteral antibiotic therapy. All prior
 infections must have resolved following optimal therapy.
 - Prior organ allograft or allogeneic transplantation.
 - Known HIV-positive or AIDS.
 - Psychiatric illness/social situations that would limit compliance with study
 requirements.
 - Other illness or a medical issue that in the opinion of the Investigator would exclude
 the subject from participating in this study


Input:
This research study is studying a targeted therapy as a possible treatment for Non-Small Cell
 Lung Cancer (NSCLC) with an EGFR mutation.
 The names of the study drug involved in this study is:
 - Osimertinib (Tagrisso)
 ;
 ;
 Inclusion Criteria:
 - Participants must have histologically confirmed stage IV NSCLC (per AJCC 7th edition)
 with either the L858R or exon 19 deletion activating EGFR mutation as identified in a
 CLIA-approved laboratory from tumor tissue.
 --Note: recurrent stage IV disease initially diagnosed at an earlier stage is
 considered eligible, provided prior treatment criteria is met.
 - Participants must have measurable disease at baseline, defined as at least one lesion
 that can be accurately measured in at least one dimension (longest diameter to be
 recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with
 conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical
 exam.
 - Participants must be aged ≥ 18 years
 - Participants must have an ECOG performance status of 0-1 (Appendix A)
 - Participants must have normal organ and marrow function as defined below:
 - absolute neutrophil count ≥1,500/mcL
 - platelets ≥100,000/mcL
 - hemoglobin >9.0 g/dL
 - total bilirubin < 1.5 times the ULN if no liver metastases or < 3 times the ULN
 in the presence of documented Gilbert's syndrome (unconjugated
 hyperbilirubinemia) or liver metastases
 - AST(SGOT)/ALT(SGPT) <2.5 × institutional upper limit of normal or <5 times the
 ULN in the presence of liver metastases
 - creatinine ≤ 1.5 x institutional upper limit of normal
 --- OR
 - creatinine clearance ≥50 mL/min as determined by the Cockcroft-Gault formula.
 - Note: For participants entering study after starting commercial osimertinib,
 elevations in hepatic transaminases (AST/ALT) and/or total bilirubin < grade 2 at
 study entry are acceptable (see protocol Table 2).
 - Participants must have biopsy tissue at time of diagnosis available and sufficient for
 targeted next-generation sequencing. The sequencing can be performed at a commercial
 vendor such as Foundation Medicine. The testing does not have to be completed prior to
 study enrollment. If the specimen is insufficient a repeat biopsy will need to be
 performed.
 --Note: Cytology specimen may be acceptable for baseline NGS if tumor cellular content
 is sufficient and following PI approval. If there is no cytology specimen or tissue
 sample available for NGS, plasma-based NGS may be acceptable for enrollment following
 discussion with PI.
 - For participants entering study after starting commercial osimertinib: a tissue sample
 from the time of diagnosis must be available and sufficient for NGS testing.
 Participants who have had commercial tumor NGS testing performed on their
 pre-osimertinib treated specimen do not need NGS repeated as part of this study.
 - Participants must be willing to undergo a repeat tumor biopsy during study treatment
 between cycles 4 and 8 (if considered medically safe) and at the time of disease
 progression.
 - Participants must be ≥2 weeks since any major surgery (excluding vascular access
 placement, mediastinoscopy, or biopsies performed by an interventional service)
 - Male patients should be asked to use barrier contraceptives (i.e., by use of condoms)
 during sex with all partners who are women of child bearing potential, including
 pregnant women, during the trial and for a washout period of 4 months. Male patients
 should avoid procreation for 4 months after completion of trial treatment. Patients
 should refrain from donating sperm from the start of dosing until 4 months after
 discontinuing study treatment.
 - Female patients (women of child-bearing potential): Willing to use adequate
 contraception (barrier or abstinence) at least 2 weeks before receiving any study
 medication, while on treatment with study drug, and for 6 weeks after finishing
 treatment.
 - Female patients: Must not be pregnant or breast-feeding. Women of child-bearing
 potential must have a negative pregnancy test (urine or serum) prior to start of
 dosing or must have evidence of non-child-bearing potential by fulfilling one of the
 following criteria at screening:
 - a) Post-menopausal defined as aged more than 50 years and amenorrheic for at
 least 12 months following cessation of all exogenous hormonal treatments
 - b) Women under 50 years are considered postmenopausal if they have been
 amenorrheic for 12 months or more following cessation of exogenous hormonal
 treatments and with LH and FSH levels in the post-menopausal range for the
 institution.
 - c) Documentation of irreversible surgical sterilization by hysterectomy,
 bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation.
 - Ability to understand and the willingness to sign a written informed consent document.
 - Subjects may enter the study even if they have started their treatment using
 commercial osimertinib. Subjects may enter the study anytime during the first 3 months
 of receiving commercial osimertinib therapy (up to 84 days of commercial osimertinib
 before entering the study). In order to enter the study after starting commercial
 osimertinib, subjects must meet all eligibility criteria listed above, have baseline
 and follow up imaging available for review for response assessment, and must not have
 developed disease progression during the first 3 months of commercial osimertinib
 therapy.
 Exclusion Criteria:
 - Subjects should not enter the study if any of the following exclusion criteria are
 fulfilled:
 - Prior or ongoing treatment with any of the following:
 - EGFR targeted therapy (TKI or antibody) or any other targeted therapies targeting
 the ERBB family except for subjects receiving first line osimertinib during the
 first three months of therapy.
 - Any cytotoxic chemotherapy, investigational agents, immunotherapy or anticancer
 drugs for the treatment of metastatic NSCLC
 - Note: Patients who have completed adjuvant or neo-adjuvant chemotherapy > 6
 months ago are considered treatment naïve
 - Prior radiotherapy, including CNS radiation, within 2 weeks of the first dose of study
 treatment.
 - Uncontrolled central nervous system (CNS) disease, including parenchymal brain
 metastases, leptomeningeal disease, or spinal cord compression. Patients with
 asymptomatic untreated brain metastases are eligible. Patients with treated CNS
 disease will be allowed to enroll provided they have asymptomatic clinically confirmed
 stable disease with ≥2 weeks since definitive CNS therapy (radiation or surgery) and
 ≥2 weeks without systemic steroids. Patients may undergo either whole brain radiation
 or stereotactic radiosurgery prior to study entry.
 - History of allergic reactions attributed to compounds, or any of its excipients, of
 similar chemical or biologic composition to osimertinib.
 - Patients currently receiving and unable to stop using medications or herbal
 supplements known to be potent inhibitors or inducers of CYP3A4. The full list of
 medications that would make a patient ineligible are provided in Appendix B, along
 with indicated washout times.
 - Any unresolved toxicities from prior therapy, including commercial osimertinib,
 greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the
 time of starting study treatment.
 - Malignancies within the past 3 years excluding adequately treated basal or squamous
 cell carcinomas of the skin without local or distant metastases.
 - Refractory nausea and vomiting, chronic gastrointestinal diseases, previous
 significant bowel resection, or any process that compromises the ability to swallow or
 absorb oral medication
 - Significant medical history or unstable medical comorbidities, including:
 - heart disease including congestive heart failure (NYHA Grade II or greater);
 unstable angina; prior myocardial infarction (NSTEMI or STEMI) within 6 months
 prior to study enrollment; hypertension with a systolic blood pressure of >150 mm
 Hg or diastolic blood pressure of >100 mm Hg while on antihypertensive medication
 - any clinically important abnormalities in rhythm, conduction or morphology of
 resting ECG, e.g. complete left bundle branch block, third-degree heart block,
 second-degree heart block, PR interval >250msec, have normal QT interval on ECG
 evaluation QT corrected Fridericia (QTcF) of ≤ 450 ms in males or ≤ 470 ms in
 females
 - any factors that increase the risk of QTc prolongation or risk of arrhythmic
 events such as heart failure, hypokalemia, congenital long QT syndrome, family
 history of long QT syndrome or unexplained sudden death under 40 years of age in
 first degree relatives, or any concomitant medication known to the prolong the QT
 interval and cause Torsades de Pointes and listed in Appendix B that a patient is
 unable to stop
 - past medical history of interstitial lung disease, drug-induced interstitial lung
 disease, radiation pneumonitis which required steroid treatment, or any evidence
 of clinically active interstitial lung disease
 - active bleeding diatheses, which in the investigator's opinion makes it
 undesirable for the patient to participate in the trial or which would jeopardize
 compliance with the protocol
 - known active infection or ongoing antiviral medication for viral infections
 including hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
 Screening for chronic conditions is not required. HIV-positive participants on
 combination antiretroviral therapy are ineligible because of the potential for
 pharmacokinetic interactions with osimertinib.
 - cardiac ejection fraction of < 45%
 - Any evidence of severe or uncontrolled systemic diseases, including active
 bleeding diatheses, which in the investigator's opinion makes it undesirable for
 the patient to participate in the trial or which would jeopardize compliance with
 the protocol
 - Known to be T790M+ (on pre-treatment tumor or plasma) or known germline T790M. Note:
 testing is not required for study entry.
 - Males and females of reproductive potential who are not using an effective method of
 birth control and females who are pregnant or breastfeeding or have a positive (urine
 or serum) pregnancy test prior to study entry. Women of child-bearing potential must
 have a negative pregnancy test prior to start of dosing.
 - Pregnant women are excluded from this study because the effects of osimertinib on the
 development of the fetus are unknown, and there is 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 osimertinib,
 breastfeeding should be discontinued if the mother is treated with osimertinib.


Input:
The aim of this trial is to identify the maximum tolerated dose (MTD)/recommended phase II
 dose (RP2D), to define pharmacokinetic (PK) parameters and the preliminary efficacy of a
 continuous treatment with EGF816 and trametinib in locally advanced or metastatic (stage IIIB
 or IV) lung cancer patients with activating mutations in the epithelial growth factor
 receptor (EGFR).
 ;
 ;
 Inclusion Criteria:
 1. Written informed consent must have been obtained prior to any screening procedures.
 2. Patients (male or female) ≥ 18 years of age.
 3. Histologically documented, locally advanced or recurrent (stage IIIB who are not
 eligible for combined modality treatment) or metastatic (stage IV) non-small cell lung
 cancer.
 4. Presence of at least one measurable lesion according to RECIST v.1.1.
 5. ECOG performance status ≤ 2
 6. Patients must have NSCLC harbouring EGFR p.L858R or EGFR del19 as assessed by local
 testing.
 7. Patients must be EGFR TKI treatment naïve (prior chemotherapy treatment is allowed) or
 must have progressed while on continuous treatment with a first- or second-generation
 EGFR TKI (EGFR p.T790M-negative or -positive) or must have progressed while on
 continuous treatment with osimertinib (EGFR p.T790M-negative or -positive)
 8. In patients who have received no prior EGFR TKI treatment, an archival biopsy sample,
 defined as a sample being obtained prior to any anti-cancer treatment is mandatory. If
 an archival biopsy fulfilling this criterion is not available, patients must be
 suitable and willing to undergo baseline biopsy according to the local institution's
 guidelines (newly obtained biopsy).
 9. In patients who have received prior EGFR TKI treatment, an archival biopsy sample,
 defined as a sample being obtained after or during progression upon the last
 anti-cancer treatment is mandatory. No consecutive line of treatment must have been
 given after collection of the rebiopsy and inclusion into this trial. If an archival
 rebiopsy fulfilling these criteria is not available, patients must be suitable and
 willing to undergo baseline biopsy according to the local institution's guidelines
 (newly obtained biopsy).
 10. In patients who have received prior EGFR TKI treatment, EGFRp.T790M mutation status
 must have been assessed by local testing in the tumour sample fulfilling the
 requirements of inclusion criterion 9.
 11. Patients who have received prior osimertinib treatment, may only be eligible if no
 standard treatment approach outside this trial is available or feasible (e.g.
 chemotherapy)
 12. Patients who have progressed while on continuous treatment with a first- or
 second-generation EGFR inhibitor and whose tumour has been tested EGFR
 p.T790M-negative may only be eligible if no standard treatment approach outside this
 trial is available or feasible (e.g. chemotherapy).
 13. In patients who have received prior EGFR TKI treatment, progression of disease
 according to RECIST v1.1 while on continuous treatment with an EGFR TKI (e.g.
 erlotinib, gefitinib, afatinib or osimertinib) must be documented.
 Exclusion Criteria:
 1. History of allergic reactions or hypersensitivity to one of the study drugs or to any
 component of the study drugs
 2. Prior treatment with any investigational agent known to inhibit EGFR (mutant or
 wild-type)
 3. Prior treatment with any agent known to inhibit MEK/ERK or other mediators of RAS
 pathway.
 4. Patients with high level MET amplification in the archival or newly obtained biopsy
 sample as determined by local testing. High-level MET amplification is defined as: a)
 a MET/CEN7 ratio ≥2.0 and/or b) an average MET gene copy number per cell of ≥6.0
 [modified Schildhaus et al., 2015].
 5. Patients with EGFR mutations other than EGFR del19, p.L858R or p.T790M.
 6. Patients with brain metastases. However, if radiation therapy and/or surgery has been
 completed at least 4 weeks prior to screening for the trial and evaluation by CT (with
 contrast enhancement) or MRI at study baseline demonstrates the disease to be stable
 and if the patient remains asymptomatic and off steroids, then patients with brain
 metastases may be enrolled.
 7. Patients with presence or history of carcinomatous meningitis.
 8. Any acute or chronic medical, mental or psychological condition, which in the opinion
 of the investigator would not permit the patient to participate or complete the study
 or understand the patient information
 9. History of hepatitis B (HBV) or hepatitis C (HCV) or positive result in mandatory
 testing for acute or chronic hepatitis B or hepatitis C
 10. Known HIV infection or history of HIV infection independent from the cellular immune
 status
 11. Patients who receive any continuous, long term immunosuppressive treatment, including
 long term treatment with steroids at immunosuppressive doses at the time of study
 entry
 12. Patients who underwent bone marrow or solid organ transplantation, including patients
 who do not receive any immunosuppressive treatment.
 13. Presence or history of any other primary malignancy other than NSCLC within 5 years
 prior to enrolment into the trial. Except from this: Adequately treated basal or
 squamous cell carcinoma of the skin or any adequately treated in situ carcinoma
 14. Any of the following within 6 months prior to first trial drug administration:
 Myocardial infarction (NSTEMI or STEMI), severe/unstable angina pectoris, symptomatic
 congestive heart failure (> NYHA II), uncontrolled hypertension, coronary/peripheral
 artery bypass graft, cerebrovascular accident or transient ischemic attack, atrial
 fibrillation of CTCAE Grade ≥ 2, ongoing cardiac dysrhythmias of CTCAE Grade ≥ 2,
 including corrected QTcF prolongation of > 480 ms,
 15. Aortic valve stenosis with mean gradient ≥ 25 mmHg and aortic valve area of ≤ 1.5 cm2
 16. Any other cardiac valve abnormality of more than mild degree/stage
 17. Left ventricular ejection fraction (LVEF) of < 50 %
 18. History of congenital long QT-syndrome or Torsades de Pointes
 19. History of retinal vein occlusion (RVO) or retinal pigment epithelial detachment
 (RPED)
 20. Unable or unwilling to swallow tablets or capsules
 21. Patients with impaired gastrointestinal function or gastrointestinal disease that may
 significantly alter the absorption of EGF816 (e.g., ulcerative diseases, uncontrolled
 nausea, vomiting diarrhoea, or malabsorption syndromes
 22. Patients have received anticancer treatment within the following time frames prior to
 the first dose of study treatment:
 1. Conventional cytotoxic chemotherapy: ≤ 4 weeks (≤ 6 weeks for nitrosoureas,
 mitomycin-C and suramin)
 2. Biological therapy (e.g., antibodies, excluding PD-1 or PD-L1 antibodies): ≤ 4
 weeks
 3. PD-1/PD-L1 antibodies (e.g., nivolumab, pembrolizumab): ≤ 5 half-times
 4. Non-cytotoxic anti-cancer therapeutic (e.g., tyrosine kinase inhibitors): ≤ 5
 half-times or ≤ 1 weeks (whichever is longer)
 5. Other investigational agent: ≤ 4 weeks
 6. Radiation therapy (excluding palliative radiation, e.g., of bone metastases): ≤ 4
 weeks
 7. Major surgery (excluding minor surgical interventions, e.g., vascular device
 implantation): ≤ 2 weeks
 23. Laboratory values as listed below, that cannot be corrected to normal limits within
 screening :
 1. Absolute Neutrophil Count (ANC) < 1.5 x 10^9/L
 2. Haemoglobin (Hb) < 9 g/dL
 3. Platelets (PLT) < 100 x 10^9/L
 4. Total bilirubin > 1.5 x upper limit of normal (ULN). For patients with confirmed
 Gilbert's disease total bilirubin > 2.5 x ULN
 5. AST and/or ALT > 3 x ULN
 6. AST and/or ALT > 5 x ULN in patients with liver involvement
 7. Serum creatinine > 1.5 x ULN
 8. Measured or calculated creatinine clearance ≤ 45 mL/min
 9. Serum amylase and/or lipase CTCAE Grade > 2
 10. Potassium, magnesium, phosphorus, total calcium (corrected from serum albumin) >
 ULN
 24. Patients receiving treatment with any medication that are known to be
 1. Strong inhibitors or inducers of CYP3A4/5
 2. Substrates of CYP2D6 with narrow therapeutic index
 3. and that cannot be discontinued at least 7 days prior to the first dose of the
 study drugs.
 4. For further information please refer to Section 11.7 and the Concomitant
 Medication Manual.
 25. Patients with a history of or presence of interstitial lung disease or interstitial
 pneumonitis, including clinically significant radiation pneumonitis
 26. Pregnancy or breastfeeding/nursing women
 27. Women of child-bearing potential (for definition see Section 8.3.3) unless they use
 highly effective methods of contraception during treatment and for four months after
 withdrawal of study treatment (for methods of contraception see Section 8.3.4)
 28. Sexually active males unless they use a condom during intercourse for the time of
 study treatment and for four months after the withdrawal of study treatment.


Input:
This study will evaluates the safety and efficacy of Chimeric antigen receptor T cells
 (CAR-T) in treating central nervous system B-cell acute lymphocytic leukemia.
 ;
 ;
 Inclusion Criteria:
 1. Patients with CD19 positive central nervous system B-cell acute lymphocytic leukemia
 2. ALT/ AST 《 3x normal
 3. Creatinine 《 3x normal
 4. Age:10-60.
 5. Signed informed consent
 Exclusion Criteria:
 1. Active hepatitis B , hepatitis C or HIV infection
 2. Uncontrolled active infection
 3. Pregnancy or breast-feeding women
 4. Survival less than four weeks


Input:
The purpose of this study is to find out what effects, a drug called ado-trastuzumab
 emtansine has on the patient and their cancer which is thought to be controlled by the
 abnormal HER2 gene.
 ;NA;
 Inclusion Criteria:
 - Adults who are ≥18 years old.
 - Pathologically confirmed advanced solid tumor cancers
 - For Cohort 1, documented activating HER2 mutation in lung cancer by CLIA laboratory,
 specifically exon 20 insYVMA (Y772_A775dup), insGSP (G778_P780dup), insTGT
 (G776delinsVC), single base pair substitutions L755A, L755S, V777L, V659E, S310F, or
 another HER2 mutation approved by the Principal Investigator
 - For Cohorts 2, 3, 4, 5, 6 documented HER2 amplification identified through next
 generation sequencing by MSK-IMPACT or at another Clinical Laboratory Improvement
 Amendments (CLIA) laboratory, or documented HER2 amplification by in-situ
 hybridization (ISH) with HER2/CEP17 ratio ≥2.0 at a CLIA laboratory. Patients with
 HER2 amplification identified by another method or criteria must be approved by the
 Principal Investigator and may enroll in the "Other" Cohort 4.
 - Measurable or evaluable indicator lesion(s) as defined by RECIST v1.1. Patients
 without RECIST measurable disease will be eligible for enrollment to "Other" cohort
 provided their disease can be evaluated using another accepted response criteria (e.g.
 Gynecologic Cancer InterGroup (GCIG) CA125 Response Criteria, modified PET Response
 Criteria in Solid Tumors (PERCIST)). Patients with salivary gland cancers (Cohort 5)
 may be eligible on the basis of evaluable disease on modified PET.
 - Karnofsky Performance Status 70% or above.
 - Left ventricular ejection fraction (LVEF) ≥50% measured by echocardiogram (ECHO) or
 multiple gated acquisition scan (MUGA).
 - Negative β-human chorionic gonadotropin (hCG) pregnancy test within 2 weeks before
 enrollment for premenopausal women of reproductive capacity and for women less than 12
 months after menopause. Pregnancy screening will be conducted for women up to the age
 of 50 years per institutional standard.
 - Women of childbearing potential must agree to use of a highly effective method of
 contraception. Effective contraception is required during treatment and for 7 months
 following the last dose for female participants of reproductive potential and during
 treatment and for 4 months following the last dose for male participants with female
 sexual partners of reproductive potential. Male participants should also refrain from
 donating sperm during treatment and for 4 months following the last dose.
 - Absolute neutrophil count ≥ 1,000/µL within 30 days prior to C1D1
 - Platelet count ≥ 100,000/µL within 30 days prior to C1D1
 - Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN), in case of
 Gilbert's syndrome, ≤ 2x ULN within 30 days prior to C1D1
 - Aspartate aminotransferase and/or alanine aminotransferase ≤ 3 x ULN (≤ 5 x ULN if
 liver metastases are present) within 30 days prior to C1D1
 - Provide written, informed consent to participate in the study and follow the study
 procedures
 Exclusion Criteria:
 - Prior therapy resulting in cumulative epirubicin dose ≥ 900mg/m2 or cumulative
 doxorubicin dose ≥ 500mg/m2 or equivalent dose of another anthracycline.
 - Prior therapy with ado-trastuzumab emtansine (patients who had prior trastuzumab or
 other HER2 targeted agents are eligible).
 - Symptomatic congestive heart failure (New York Heart Association Classification
 II-IV).
 - Myocardial infarction or unstable angina within 6 months of enrollment.
 - Unstable ventricular arrhythmia requiring treatment.
 - Grade 3 or worse peripheral neuropathy as defined by CTCAE v4.1.
 - Women who are pregnant or breast-feeding.
 - Known hypersensitivity to any component of ado-trastuzumab emtansine.
 - History of interstitial lung disease or pneumonitis.


Input:
LVGN6051 is a humanized monoclonal antibody that specifically binds to CD137, and acts as an
 agonist against CD137.
 This first in human study of LVGN6051 is designed to establish the maximum tolerated dose
 (MTD) and/or the recommended dose for expansion (RDE) as well as the recommended Phase 2
 dose(s) (RP2D) of LVGN6051, both as a single agent (monotherapy) and in combination with a
 fixed dose of anti-PD-1 antibody (Pembrolizumab/MK-3475) in the treatment of advanced or
 metastatic malignancy.
 ;
 ;
 Inclusion Criteria:
 - Males or females aged ≥ 18 years.
 - Ability to understand and willingness to sign a written informed consent document.
 - Patients must have a histologically or cytologically confirmed metastatic or
 unresectable malignancy.
 - Estimated life expectancy, in the judgment of the Investigator, of at least 90 days.
 - Adequate bone marrow, liver, and renal functions.
 - Men and women of childbearing potential must agree to take highly effective
 contraceptive methods.
 - Patients should recover from all reversible AEs of previous anticancer therapies to
 baseline.
 - Patients infected with the HIV virus will be eligible if the disease is under control
 of effective therapy.
 Exclusion Criteria:
 - Receipt of systemic anticancer therapy including investigational agents or devices
 within 5 half-lives of the first dose of study treatment.
 - Previous radiotherapy within 14 days of the first dose of study treatment.
 - Known active CNS metastasis and/or carcinomatous meningitis.
 - Has received a live-virus vaccine within 30 days.
 - Has had a Grade ≥ 3 allergic reaction to treatment with a monoclonal antibody.
 - Abnormality of QT interval or syndrome.
 - Patients with history of Grade ≥ 3 immune-related AEs (irAEs) or irAE.
 - Patients who are receiving an immunologically-based treatment for any reason.
 - Treatment with systemic immune-stimulatory agents within 4 weeks prior to the first
 dose of study drug.
 - Active or chronic autoimmune disease that has required systemic treatment in the past
 2 years or who are receiving systemic therapy for an autoimmune or inflammatory
 disease.
 - Has a clinically significant cardiac condition, including unstable angina, acute
 myocardial infarction within 6 months.
 - Has an active infection requiring intravenous (i.v.) anti-infectives within 14 days
 before the first dose of study treatment.
 - Current evidence or history of interstitial lung disease or active, noninfectious
 pneumonitis requiring treatment such as oral or intravenous glucocorticoids to assist
 with management.
 - Female patients who are pregnant or breastfeeding.
 - Any evidence of severe or uncontrolled systemic disease.
 - Any other disease or clinically significant abnormality in laboratory parameters.
 - Has previously had a stem cell or bone marrow or solid organ transplant.


Input:
This is a US, multicenter, open-label expanded access program to provide access to
 avapritinib until such time that avapritinib becomes available through other mechanisms or
 the Sponsor chooses to discontinue the program.
 ;NA;
 Inclusion Criteria:
 1. Patient is ≥ 16 years of age.
 2. Diagnosis of unresectable or metastatic GIST
 3. The patient is not eligible for an ongoing study of avapritinib or cannot access an
 ongoing study of avapritinib.
 4. Patient has received 3 or more TKI therapies including imatinib, or the patient has
 GIST that carries a mutation in exon 18 of the PDGFRA gene (such as D842V).
 5. The patient has adequate vital organ function, including heart, lungs, liver, kidneys,
 bone marrow and endocrine, and is expected to tolerate therapy with a TKI.
 6. Patient or legal guardian, if permitted by local regulatory authorities, provides
 informed consent.
 Exclusion Criteria:
 1. Patients who have poor organ function as defined by one or more of the following
 laboratory parameters;
 1. Total bilirubin > 2 × ULN; or > 3 × ULN in the presence of Gilbert's Disease;
 2. Platelet count < 75 × 10^9/L.
 2. Patient requires therapy with a concomitant medication that is a strong inhibitor or
 strong inducer of cytochrome P450 (CYP) 3A4
 3. Patient has had a major surgical procedure (minor surgical procedures such as central
 venous catheter placement, tumor needle biopsy, and feeding tube placement are not
 considered major surgical procedures) within 14 days of the first dose of avapritinib.
 4. Patient has a history of a cerebrovascular accident or transient ischemic attacks
 within 1 year prior to the first dose of program drug.
 5. Patient has a known risk of intracranial bleeding, such as a brain aneurysm or history
 of subdural or subarachnoid bleeding.
 6. Women who are unwilling, if not postmenopausal or surgically sterile, to abstain from
 sexual intercourse or employ highly effective contraception from the time of
 randomization and for at least 30 days after the last dose of avapritinib. Men who are
 unwilling, if not surgically sterile, to abstain from sexual intercourse or employ
 highly effective contraception from the time of first dose and for at least 90 days
 after the last dose of avapritinib.
 7. Women who are pregnant, as documented by a serum beta human chorionic gonadotropin
 (β-hCG) pregnancy test consistent with pregnancy, obtained within 7 days before the
 randomization. Females with β-hCG values that are within the range for pregnancy but
 are not pregnant (false-positives) may be enrolled with written consent of the
 Sponsor, after pregnancy has been ruled out. Females of non- childbearing potential
 (postmenopausal for more than 1 year; bilateral tubal ligation; bilateral
 oophorectomy; hysterectomy) do not require a serum β-hCG test.
 8. Women who are breast feeding.


Input:
This is a Phase 2 open-label, multicenter study to evaluate the clinical activity, safety,
 pharmacokinetics (PK), and biomarker profile of ZN-c3 in subjects with Cyclin E driven
 High-Grade Serous Ovarian, Fallopian Tube, Or Primary Peritoneal Cancer
 ;NA;
 Inclusion Criteria:
 1. Age ≥18 years at the time of informed consent.
 2. Histologically or cytologically confirmed recurrent, high-grade serous ovarian,
 fallopian tube, or primary peritoneal cancer with copy number amplification in the
 CCNE1 gene
 3. Prior therapy:
 1. Documented progressive disease ≤6 months
 2. One to 3 prior lines or regimens are allowed
 3. Prior bevacizumab treatment is required
 4. Subjects must have at least one measurable lesion as defined by RECIST Guideline
 Version 1.1.
 5. Performance Status: Eastern Cooperative Oncology Group (ECOG) score of ≤1.
 6. Adequate hematologic and organ function
 7. Females of childbearing potential and male subjects must agree to use an effective
 method of contraception prior to the first dose and for 6 months after the last dose
 of ZN-c3. Male subjects must agree to use an effective method of contraception prior
 to the first dose and for at least 3 months after the last dose of ZN-c3.
 8. Willingness and ability to comply with scheduled visits, treatment plan, laboratory
 tests, and other study procedures.
 Exclusion Criteria:
 1. 1. Any of the following treatment interventions within the specified time frame prior
 to C1D1:
 1. Major surgery within 28 days (any surgical incision should be fully healed prior
 to study drug administration);
 2. Any chemotherapy or targeted tumor therapy within 14 days or 5 half-lives
 (whichever is shorter);
 3. Radiation therapy within 21 days; however, if the radiation portal covered ≤5% of
 the bone marrow, the subject is eligible irrespective of the end date of
 radiotherapy.
 4. Autologous or allogeneic stem cell transplant within 3 months.
 5. Current use of any other investigational drug therapy <28 days or 5 half-lives
 (whichever is shorter).
 6. Inability to discontinue treatment prescription or non-prescription drugs, or to
 discontinue consumption of food and herbal supplements, that are strong/ and
 moderate CYP3A4 inhibitors and inducers, or P-gp inhibitors at least 14 days
 prior to C1D1.
 2. Prior therapy with ZN-c3 or any other WEE1 inhibitor, ATR inhibitor, or CHK1/2
 inhibitor.
 3. Known hypersensitivity to any inactive ingredients present in ZN-c3.
 4. A serious illness or medical condition(s)
 5. Unresolved toxicity of Grade >1 attributed to any prior therapies (excluding Grade ≤2
 neuropathy, alopecia or skin pigmentation).
 6. Pregnant or lactating females or females of childbearing potential who has a positive
 serum pregnancy test within 14 days prior to C1D1.
 7. Subjects with active (uncontrolled, metastatic) second malignancies or requiring
 therapy.
 8. Individuals who are judged by the Investigator to be unsuitable as study subjects.
 9. 12-lead ECG demonstrating a corrected QT interval using Fridericia's formula (QTcF) of
 >470 ms, except for subjects with atrioventricular pacemakers or other conditions
 (e.g., right bundle branch block) that render the QT measurement invalid.
 10. History or current evidence of congenital or family history of long QT syndrome or
 Torsade de Pointes (TdP).