CABOZANTINIB for Non-small cell lung cancer

Inclusion criteria

• {"criterion_text":"- 1. Citological or histological diagnosis of non-small-cell-lung cancer (NSCLC) stage III B (not suitable for local treatments with curative intent) or stage IV.\n- 2. Tissue samples available for MET analysis (archivial tissue or tissue collected at study entry); patients without archival tumor tissue or refusing new biopsy at study entry, are eligible if MET mutation is detected in cf-DNA\n- 3. Presence of MET mutations (exon 14 skipping mutation ONLY) detected in tissue or in cf-DNA detected at the local lab or MET amplification (MET/CEP7 ratio > 2.2) detected in the central lab ONLY.\n- 4. Measurable disease according to RECIST criteria version 1.1\n- 5. At least 1 prior line of standard therapy (chemotherapy and/ or immunotherapy)\n- 6. Performance status 0-1 (ECOG)\n- 7. Age ≥18 years\n- 8. Patients potentially fertile using adequate methods of contraception in order to avoid childbearing. Contraceptive methods must be respected by male and female patients and their partners during study treatment period and at least 4 months after completing therapy\n- 9. Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to enrollment: a. ANC ≥ 1500 cells/μL without granulocyte colony-stimulating factor support b. Platelet count ≥ 100,000/μL without transfusion c. Hemoglobin ≥ 9.0 g/dL Patients may be transfused to meet this criterion d. AST, ALT, and alkaline phosphatase ≤ 2.5 × ULN, with the following exceptions: - Patients with documented liver metastases: AST and/or ALT ≤ 5 × ULN - Patients with documented liver or bone metastases: alkaline phosphatase ≤ 5 × ULN. e. Serum bilirubin ≤ 1.25 × ULN f. Patients with known Gilbert disease who have serum bilirubin level ≤ 3 mg/dL may be enrolled g. Calculated creatinine clearance (CRCL) ≥ 45 mL/min or calculated CRCL must be ≥ 60 mL/min\n- 10. Patient compliance to the study procedure\n- 11. Written informed consent"}

Exclusion criteria

• {"criterion_text":"- 1. Tissue sample not available for the central assessing of MET amplification\n- 2. No possibility to assess MET status\n- 3. Absence of any measurable disease according to RECIST criteria\n- 4. Co-existence of driver events, including EGFR mutations, KRAS mutations, ALK rearrangements or ROS-1 rearrangements\n- 5. No prior therapy\n- 6. Concomitant chemotherapy or immunotherapy or radiotherapy\n- 7. Symptomatic brain metastasis\n- 8. Uncontrolled significant inter-current or recent illness, including cardiovascular disorders and gastro-intestinal disorders\n- 9. Major surgery within 2 months before first dose of study treatment\n- 10. Concomitant anti-coagulation with oral anti-coagulants or plated inhibitors\n- 11. History of significant bleeding, trachea-bronchial tree/major blood vessels invading tumors, cavity pulmonary lesions and GI disorders associated with a risk of perforation or fistula formation\n- 12. Diagnosis of another cancer in the last 3 years, except for in situ carcinoma of cervix, breast and bladder or skin carcinoma (squamous or basalioid)\n- 13. Pregnancy or breastfeeding"}

Primary endpoints

• {"endpoint_text":"- Response Rate (RR) (complete + partial responses) of Cabozantinib in NSCLC patients with MET amplification or MET exon 14 skipping mutation pre-treated or not with MET inhibitors.","definition_or_measurement_approach":"Defined as complete + partial responses. Measurable disease is required according to RECIST criteria version 1.1 (RECIST v1.1 mentioned in eligibility)."}

Secondary endpoints

• {"endpoint_text":"- Progression free survival (PFS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Disease Control Rate (DCR: stable disease + partial response + complete response)","definition_or_measurement_approach":"DCR defined in text as stable disease + partial response + complete response."}
• {"endpoint_text":"- Exploratory biomarkers on blood and tissue samples (for each patient enrolled in the study optionally a tissue sample could be provided at disease progression)","definition_or_measurement_approach":"Exploratory biomarker analyses on blood and tissue; optional tissue sample may be provided at disease progression."}

Italy

Earliest CTIS Part Ii Submission Date

23-01-2025

Latest Decision Or Authorization Date

09-01-2026

Processing Time Days

351

Number Of Sites

19

Primary sponsor

Full Name

Fondazione Ricerca Traslazionale

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Italy