Non-small cell lung cancer
Conditions
Interventions
Treatment group:Vebreltinib combined with bevacizumab
Sponsors
The First Affiliated Hospital of Zhengzhou University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: The following inclusion criteria: 1. Able to understand and voluntarily sign a written informed consent form; 2. Male or female aged >=18 years; 3. Histologically or cytologically confirmed non-squamous non-small cell lung cancer (NSCLC), clinically diagnosed as locally advanced (stage ?B/?C), metastatic, or recurrent (stage ?) non-squamous NSCLC that is inoperable and cannot receive radical concurrent chemoradiotherapy; 4. Detected with MET exon 14 skipping mutations in blood, tissue, or other samples (methods such as NGS or PCR are acceptable, including but not limited to test results from tissue, blood, pleural effusion, etc.); 5. Patients with a history of only systemic chemotherapy are allowed to enroll; 6. Asymptomatic patients or patients with central nervous system (CNS) metastases who are stable for at least 4 weeks after treatment may enroll; 7. At least 1 measurable lesion according to RECIST 1.1 criteria (lesions previously treated with radiotherapy cannot be considered target lesions unless there is clear progression after radiotherapy); 8. ECOG performance status score of 0–2; 9. Laboratory test parameters meeting the following requirements: 1) Absolute neutrophil count >=1.5×10^9/L (without growth factor use within 7 days before treatment initiation); 2) Hemoglobin >=90 g/L (without blood transfusion or growth factor use within 7 days before treatment initiation); 3) Platelet count >=80×10^9/L (without blood transfusion or growth factor use within 7 days before treatment initiation); 4) Serum total bilirubin =60 mL/min, calculated using the Cockcroft-Gault formula: (140 - age [yr]) × weight (kg) × 1.23 × (0.85 if female) / serum creatinine (µmol/L); 7) International normalized ratio (INR) =3 months as judged by the investigator.
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following criteria will be ineligible for participation in this study: 1. Presence of other driver mutations (EGFR sensitive mutation, ALK fusion-positive, ROS1 fusion-positive, KRAS G12C, BRAF V600E, NTRK fusion, HER2 mutation, RET fusion); 2. Spinal cord compression, meningeal metastases, or symptomatic brain metastases requiring increased steroid dosage for central nervous system (CNS) disease control; however, patients with controlled symptomatic CNS metastases may enroll (neurological function must be stable, no new neurological deficits on clinical examination, and no new findings on CNS imaging. If steroids are used for CNS metastases, the dosage must have been stable for at least 2 weeks prior to study entry); 3. History of hemoptysis defined as >2.5 mL per episode within 3 months prior to randomization; 4. Imaging evidence of tumor invasion into major blood vessels. The investigator or local radiologist must exclude evidence of complete attachment, encirclement, or invasion of major vessels (e.g., pulmonary artery or superior vena cava) by the tumor; 5. Major surgery (including open biopsy) or significant trauma within 28 days prior to randomization, or anticipated need for major surgery during study treatment; 6. Core biopsy or other minor surgery (except vascular access device placement) within 7 days prior to study treatment initiation. Vascular access device placement must be performed at least 2 days before study treatment initiation; 7. Current or recent (within 10 days of first bevacizumab administration) use of aspirin (325 mg/day) or other nonsteroidal anti-inflammatory drugs known to inhibit platelet function; 8. Current or recent (within 10 days of first bevacizumab administration) therapeutic use of full-dose oral or parenteral anticoagulants or thrombolytics. Prophylactic anticoagulation is permitted; 9. Unhealed wounds, active peptic ulcer, or fracture; 10. History of other malignancies (except completely resected in situ carcinoma of any type, basal cell or squamous cell skin cancer, or other tumors/cancers with no evidence of disease for at least 3 years after curative treatment); 11. Prior anticancer treatment history meeting any of the following conditions: 1) Prior receipt of advanced systemic therapy other than chemotherapy (e.g., monoclonal antibodies, tyrosine kinase inhibitors, EGFR inhibitors, VEGF receptor inhibitors, etc.), unless completed >= 6 months prior to randomization. Adjuvant or neoadjuvant therapy for non-metastatic disease is permitted (any MET inhibitor, ADC, or monoclonal antibody targeting MET abnormalities is prohibited for enrollment); 2) Receipt of anticancer or investigational drugs within 2 weeks prior to first study drug administration or within 5 times the drug half-life (whichever is longer); 3) Receipt of traditional Chinese medicine or proprietary Chinese medicine with anticancer indications within 1 week prior to first study drug administration; 4) Radiotherapy to the lung field or whole brain within 4 weeks prior to first study drug administration, or radiotherapy to other sites (excluding lung field and whole brain) within 2 weeks prior to administration. Palliative radiotherapy for bone metastases to relieve pain or prevent bone events is excluded; 12. Failure to recover from any toxicity and/or complications of prior chemotherapy, surgery, radiotherapy, etc., i.e., not reduced to <=Grade 1 (National Cancer Institute Common Terminology Criteria f
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| objective response rate (Investigator);progression-free survival (PFS) by Investigator; | — |
Secondary
| Measure | Time frame |
|---|---|
| duration of response (DoR) by Investigator;disease control rate (DCR) by Investigator;overall survival (OS);safety; | — |
Countries
China
Contacts
Public ContactYan Ningning
The First Affiliated Hospital of Zhengzhou University
Outcome results
None listed