TEPOTINIB for Non-small cell lung cancer (MET exon 14‑mutated)

Inclusion criteria

• {"criterion_text":"- 1.\tInformed, written and signed consent: -\tPatients must have signed and dated the written informed consent form approved by the ethics committee in accordance with the legal and institutional framework. -\tIt must have been signed before protocol-related procedures that are not part of normal patient management are performed. Patients should be willing and able to adhere to the schedule of visits, treatment and laboratory tests.\n- 10.\tAdequate biological function: -\tCreatinine clearance ≥ 30 ml/min; -\tNeutrophils ≥ 1500/mm3; -\tPlatelets ≥100,000/mm3; -\tHaemoglobin ≥ 8 g/dL; -\tLiver enzymes < 3x ULN except for patients with liver metastases (< 5x ULN); -\tTotal bilirubin ≤ 1.5 x ULN except for patients with proven Gilbert's syndrome (≤ 5 x ULN) or patients with liver metastases (≤ 3.0 ULN).\n- 11.\tProtected adults may participate in the study if they are capable of making decisions regarding their medical treatment in accordance with the guardianship judgment.\n- 12.\tFor women of childbearing potential (including women who have had a tubal ligation), serum pregnancy test must be performed and documented as negative within 14 days prior to C1D1.\n- 13.\tWomen of childbearing potential must remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for at least 6 months after the last dose of study drugs. Women must refrain from donating eggs during this same period. A woman is considered to be of childbearing potential if she is post-menarcheal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries or uterus). Examples of contraceptive methods with a failure rate of <1% per year include bilateral tubal ligation, male sterilization, established proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. Hormonal contraceptive methods must be supplemented by a barrier method plus spermicide. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g. calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.\n- 14.\tMen with female partners of childbearing potential or pregnant female partners, must remain abstinent or use a condom during the treatment period and for at least 6 months after the last dose of study treatment to avoid exposing the embryo. Men must refrain from donating sperm during this same period. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g. calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.\n- 15.\tPatient covered by a national health insurance.\n- 2.\tHistologically proven advanced NSCLC.\n- 3.\tPresence of a METex14 mutation (based on local testing). Detection of METex14 mutation should be performed on a tissue sample if available. In case no tissue sample is available, detection of METex14 on a liquid biopsy is authorized. The sponsor should be consulted if there is any doubt about the nature of the mutation.\n- 4.\tEvidence of disease progression after at least one prior line of treatment including either a platinum-based chemotherapy or an anti-PD(L)1 agent or both.\n- 5.\tHas received no more than 2 prior lines of treatment.\n- 6.\tECOG Performance Status 0-3.\n- 7.\tBrain metastases are allowed. If immediate local treatment is required, inclusion is possible once the latter is complete.\n- 8.\tStage IIIB or IIIC non irradiable or stage IV (8th classification TNM, UICC 2015)\n- 9.\tAge ≥ 18 years."}

Exclusion criteria

• {"criterion_text":"- 1.\tPrior treatment with a MET inhibitor (including crizotinib).\n- 2.\tPresence of another known driver oncogene alteration (including EGFR, HER2, KRAS, BRAF mutations or ALK, ROS1, RET fusions). In case of detection of any other driver alteration, inclusion should be discussed with the sponsor.\n- 3.\tECOG Performance Status 4.\n- 4.\tKnown hypersensitivity to tepotinib or its excipients.\n- 5.\tHistory of cancer within 3 years or active cancer except those with a negligible risk of metastasis or death, or those treated curatively. If a patient does not fulfil this criterion but the investigator considers that the benefit/risk balance is in favour of inclusion in the study, please contact IFCT.\n- 6.\tInability to comply with study or follow-up procedures.\n- 7.\tPregnant, lactating, or breastfeeding women.\n- 8.\tAny disease, 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, that may affect the interpretation of the results, or that may render the patient at high risk from treatment complications.\n- 9.\tHistory of idiopathic pulmonary fibrosis or active pneumonitis on chest computed tomography (CT) scan at screening. History of radiation pneumonitis in the radiation field (fibrosis) is permitted."}

Primary endpoints

• {"endpoint_text":"- Progression-free survival (PFS) assessed by independent review committee according to RECIST 1.1.","definition_or_measurement_approach":"PFS assessed by independent review committee according to RECIST 1.1."}

Secondary endpoints

• {"endpoint_text":"- Hierarchical analysis #1: Quality of life: change from baseline to week 6 in QLQ-C30 global health status/Quality of life (GHS/QOL) score, using the EORTC QLQ-C30 questionnaire with lung cancer module QLQ-LC29), tested if the primary endpoint (PFS) shows statistical significance.","definition_or_measurement_approach":"Change from baseline to week 6 in QLQ-C30 GHS/QOL score using EORTC QLQ-C30 with QLQ-LC29; hierarchical testing contingent on primary endpoint significance."}
• {"endpoint_text":"- Hierarchical analysis #2: Overall survival, tested if the primary endpoint (PFS) and the first secondary endpoint (QoL) both show statistical significance.","definition_or_measurement_approach":"Overall survival; hierarchical testing contingent on prior endpoints' significance."}
• {"endpoint_text":"- Objective Response Rate according to RECIST1.1.","definition_or_measurement_approach":"Objective response rate evaluated per RECIST 1.1."}
• {"endpoint_text":"- Duration of response.","definition_or_measurement_approach":"Duration of response measured from first documented response to progression or death."}
• {"endpoint_text":"- Second progression-free survival (PFS2) and Time to next treatment or death (TNT-D).","definition_or_measurement_approach":"PFS2 and time to next treatment or death as defined in protocol (times from randomization to respective events)."}
• {"endpoint_text":"- Incidence, nature, and severity of adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0).","definition_or_measurement_approach":"AEs graded per NCI CTCAE v5.0; incidence, nature and severity recorded."}
• {"endpoint_text":"- Number of cycles for each arm","definition_or_measurement_approach":"Number of treatment cycles administered per arm as recorded in treatment administration records."}
• {"endpoint_text":"- Number of treatment dose modification and interruption.","definition_or_measurement_approach":"Count and description of dose modifications and interruptions per arm."}

France

Earliest CTIS Part Ii Submission Date

07-05-2025

Latest Decision Or Authorization Date

11-06-2025

Processing Time Days

35

Number Of Sites

30

Number Of Participants

133

Primary sponsor

Full Name

Intergroupe Francophone De Cancerologie Thoracique

Organisation Type

Patient organisation/association

Country Of Registered Address

France