A Single-arm, Multicenter, Phase Il clinical Study of Platinum-based Doublet Chemotherapy Sequential Vebreltinib as adjuvant Therapy for Patients With Resectable, stage IB-IIIB(N2) Non-Small Cell Lung Cancer with c-MET Exon 14 skipping mutation with or without other MET Alterations
Phase 4
Recruiting
- Conditions
- Non-small-cell lung cancer
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- Not specified
Inclusion Criteria
- Signed an informed consent form.<br>2. Patients aged =18.<br>3. Histologically or cytologically confirmed NSCLC, the postoperative pathology showed stage IB-IIIB (N2).<br>4. Radical resection was performed, and complete resection (a negative surgical margin, R0) must be confirmed in the pathology report.<br>5. Have not received any anti-tumor systemic treatment before radical resection.<br>6. The expected survival is more than 12 weeks.<br>7. An Eastern Cooperative Oncology Group performance status (ECOG PS ) of 0–1.<br>8. Patients must harbor METex 14 skipping mutation(NGS reports from tissue/blood samples must be approved by organizations with CLIA or CAP certification ), with or without MET amplification/ MET protein overexpression.<br>9. Normal lung function, withstand surgery.<br>10. Adequate organ and bone marrow function, defined as:<br> a) blood routine: Absolute neutrophil count = 1.5 x10^9/L; platelet count > 100 x10^9/L; Hemoglobin = 9.0 g/dL.<br> b) hepatic function: total bilirubin (TBIL) = 1.5 × upper limit of normal (ULN);For patients with HCC, liver metastasis, or a history of Gilbert syndrome/suspected Gilbert syndrome (persistent or recurrent hyperbilirubinemia, primarily unbound high bilirubin, with no evidence of hemolysis or liver disease) , TBIL=3×ULN; For patients without HCC or liver metastasis, alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) = 2.5 × ULN; <br> c) renal function: Serum Creatinine(Cr) = 1.5 × ULN or Creatinine Clearance (CCr)= 50 mL /min; The urine test paper showed that urine protein <2+<br> d) Coagulation function: Activated partial thromboplastin time (APTT) and international standardized ratio (INR) =1.5×ULN.<br> e) Normal thyroid function, defined as thyroid stimulating hormone (TSH) within the normal range. If baseline TSH is outside the normal range, subjects with total T3 (or FT3) and FT4 within the normal range can also be enrolled;<br> f) Myocardial enzyme profiles were within the normal range (laboratory abnormalities not clinically significant were also allowed to be enrolled);<br>11. For female subjects of reproductive age, a urine or serum pregnancy test should be performed negative within 3 days prior to receiving the first study drug administration (day 1 of cycle 1). If the urine pregnancy test results cannot be confirmed as negative, a blood pregnancy test is requested. Women of non-reproductive age were defined as having been postmenopausal for at least 1 year or having undergone surgical sterilization or hysterectomy.<br>12. If there is a risk of conception, all subjects (male or female) are required to use a contraceptive with an annual failure rate of less than 1% for the entire duration of treatment up to 120 days after the last study drug administration.
Exclusion Criteria
- Patients with EGFR/ALK/ROS1 or other mutations besides MET.<br>2. Receive live attenuated vaccine within 4 weeks prior to enrollment or during the study period.<br>3. All participants should undergo brain imaging (MRI brain or CT brain contrast) prior to enrollment to rule out brain metastases.<br>4. Major surgery (such as intrathoracic, abdominal, or pelvic surgery) was performed within 4 weeks prior to the start of the study treatment, or the side effects of such surgery have not yet recovered.<br>5. Malignant diseases diagnosed other than NSCLC (excluding radical basal cell carcinoma of the skin, squamous epithelial carcinoma of the skin, and/or carcinoma in situ after radical resection, including papillary thyroid carcinoma after radical resection) within 5 years prior to study initiation.<br>6. received MET inhibitor treatment.<br>7. An active, known, or suspected autoimmune disease.<br>8. History of primary immunodeficiency.<br>9. History of allogeneic organ transplantation allogeneic hematopoietic stem cell transplantation.<br>10. Allergic to active ingredients or excipients allergic of vebreltinib, pemetrexed, gemcitabine, carboplatin, cisplatin and so on.<br>11. Have not fully recovered from toxicity and/or complications caused by any intervention before starting treatment (i.e., = grade 1 or baseline, excluding weakness or hair loss).<br>12. Untreated active hepatitis B (defined as HBsAg positive combined with a detected HBV-DNA copy number greater than the upper limit of normal in the laboratory of the study center).<br>Note: Hepatitis B subjects who meet the following criteria can also be enrolled:<br>a) HBV viral load <1000 copies /ml (200 IU/ml) prior to initial dosing, subjects should receive anti-HBV therapy to avoid viral reactivation throughout study chemotherapeutic therapy<br>b) For subjects with anti-HBC (+), HBsAg (-), anti-HBS (-), and HBV viral load (-), prophylactic anti-HBV therapy is not required, but close monitoring of viral reactivation is required.<br>13. Active HCV-infected subjects (HCV antibody positive with HCV-RNA levels above the lower limit of detection).<br>14. Uncontrolled comorbidities, including but not limited to:<br>a) The resting electrocardiogram has a significant abnormality in rhythm, conduction or morphology with severe symptoms that are difficult to control, such as complete left bundle branch block, heart block above degree II, ventricular arrhythmia or atrial fibrillation;<br>b) Unstable angina, congestive heart failure, New York Heart Association (NYHA) grade = 2 chronic heart failure;<br>c) any arterial thrombosis, embolism, or ischemia, such as myocardial infarction, unstable angina pectoris, cerebrovascular accident, or transient ischemic attack, occurred within 6 months prior to treatment;<br>d) Poor blood pressure control (systolic > 140 mmHg, diastolic > 90 mmHg);<br>e) A history of non-infectious pneumonia requiring glucocorticoid therapy within 1 year prior to initial administration, or a current clinically active interstitial lung disease;<br>f) active tuberculosis;<br>g) There is an active or uncontrolled infection that requires systemic treatment;<br>h) Clinically active diverticulitis, abdominal abscess, gastrointestinal obstruction;<br>i) liver diseases such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis;<br>j) Poor diabetes control (fasting blood glucose (FBG) > 10mmol/L);<br>k) Urine routine indicated urine protein =++, and confirmed 24-hour urine protein quantity > 1.0 g;<br>l) Patients with mental disorders who are
Study & Design
- Study Type
- Interventional study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1 year disease-free rate;
- Secondary Outcome Measures
Name Time Method Disease-free time;3 year disease-free rate;3 year survival rate;overall survival;Life quality evaluation;1 year disease-free rate of the central nervous system;3 year disease-free rate of the central nervous system;