Non-small-cell lung cancer
Conditions
Interventions
Experimental group-dose escalation:vebreltinib combined with Tislelizumab
Experimental group-dose expansion:vebreltinib combined with Tislelizumab
Sponsors
Cancer Hospital Chinese Academy of Medical Sciences
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Signed an informed consent form.; 2. Patients aged =18; 3. Histologically or cytologically confirmed locally or metastatic NSCLC; 4. Patients must harbor MET-amplification confirmed by tumor tissue; 5.PD-L1 expression postive; 6. Cohort 1 :participants must not have received prior systemic therapy with EGFR-wild type; Cohort 2:participants who previously received prior EGFR-TKI therapy with EGFR sensitive mutation; 7.ECOG PS 0-1.8.The expected survival is more than 3 months. 9.at least one measurable lesion according to RECIST 1.1 criteria. 10. Adequate organ and bone marrow function, defined as: 1) Absolute neutrophil count = 1.5 x10^9/L;2)Hemoglobin = 9.0 g/dL.c) platelet count > 75 x10^9/L; 3) total bilirubin (TBIL) = 1.5 × upper limit of normal (ULN);4) alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) = 3 × ULN; 5) Serum Creatinine(Cr) = 1.5 × ULN ;6)Creatinine Clearance (CCr)= 50 mL /min; 11. For female subjects of reproductive age, a urine or serum pregnancy test should be performed negative within 7 days prior to receiving the first study drug administration .If there is a risk of conception, all subjects (male or female) must agree to use effective contraception from the time they sign an informed consent until 3 months after the final administration of the study drug.
Exclusion criteria
Exclusion criteria: 1.Patients with METex 14 skipping mutation; 2.Previous treatment history meets one of the following criteria: Cohort 2:The last dosing of EGFR-TKI was less than 14 days or 5 half-life period before the initiation of study agents;Received platinum-based adjuvant/neoadjuvant chemotherapy within 6 months before the initiation of study agents;The last administration of other anti-tumor drugs was less than 14 days before the initiation of study agents; Received major surgery within the past 4 weeks, or received resection of brain metastatic lesion within 2 weeks, or the side effects of such surgery have not yet been recovered; Thoracic radiotherapy to lung fields (including whole brain radiotherapy) =4 weeks prior to initiation of study treatment , for all other sites (including thoracic vertebrae or rib radiotherapy) =2 weeks prior to initiation of study treatment, or the patient has not recovered from radiation-induced adverse events to = grade 1 (except permanent radiation-induced damage); Received traditional Chinese medicine with anti-tumor indications within 1 week prior to initiation of treatment; Receive a potent inducer and/or potent inhibitor of CYP3A4 and cannot be discontinued for at least 1 week prior to initiation of study drug and during the study period; 3.Previous anti-tumor therapy toxicity have not been recovered to = Grade 1 (NCI-CTCAE 5.0) or baseline, except for alopecia, skin pigmentation and grade 2 peripheral neurotoxicity; 4. Patients with symptomatic, neurologically unstable central nervous system (CNS) metastases, or CNS diseases that require increased steroid doses to control; 5. Any serious or uncontrolled systemic disease, including, but not limited to, other serious or psychiatric disorders or laboratory abnormalities, in which the investigator determines that the study drug is not suitable for the patient or affects protocol adherence; 6.Cardiac function and disease meet one of the following criterias: QTc > 470 ms; Severe cardiac arrhythmia; Any risk factors that increase the length of the QTc; New York College of Cardiology (NYHA) Heart function grade =3; Poorly controlled hypertension; 7. Presence or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years. Exceptions to this exclusion include: completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type; 8.Active infection, including but not limited to:infected with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) (HIV antibody positive), infected with syphilis, active tuberculosis, the presence of active infections (such as pneumonia) requiring systematic anti-infective therapy within 2 weeks before drug administration in the first study; 9. Patients with poorly controlled pleural effusion, peritoneal effusion, or pericardial effusion were judged by the investigators to be unsuitable for inclusion; 10. A history of thromboembolic or venous thromboembolic events (including myocardial infarction, cerebrovascular event or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or any other severe thromboembolic event) in the 6 months prior to the initial study drug administration, Any life-threatening bleeding event (including treatment requiring blood transfusion, surgery or local treatment, and ongoing medication) was judged to have a bleeding tendency; 11.Have a history of interstitial lung disease, drug-induc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety;Maximum tolerated dose;Recommended dosage for Phase II;objective response rate; | — |
Countries
China
Contacts
Public ContactZhijie Wang
Cancer Hospital Chinese Academy of Medical Sciences
Outcome results
None listed