Tepotinib vs Standard Treatment in Patients With Advanced MET Exon 14 Mutated Non-Small Cell Lung Cancer Previously Treated

1. Informed, written and signed consent:

* Patients must have signed and dated the written informed consent form approved by the ethics committee in accordance with the legal and institutional framework.

* It 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.

2. Histologically proven advanced NSCLC.

3. Presence 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.

4. Evidence 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.

5. Has received no more than 2 prior lines of treatment.

6. ECOG Performance Status 0-3.

7. Brain metastases are allowed. If immediate local treatment is required, inclusion is possible once the latter is complete.

8. Stage IIIB or IIIC non irradiable or stage IV (8th classification TNM, UICC 2015)

9. Age ≥ 18 years.

10. Adequate biological function:

* Creatinine clearance ≥ 30 ml/min;

* Neutrophils ≥ 1500/mm3;

* Platelets ≥100,000/mm3;

* Haemoglobin ≥ 8 g/dL;

* Liver enzymes \< 3x ULN except for patients with liver metastases (\< 5x ULN);

* Total bilirubin ≤ 1.5 x ULN except for patients with proven Gilbert's syndrome (≤ 5 x ULN) or patients with liver metastases (≤ 3.0 ULN).

11. Protected adults may participate in the study if they are capable of making decisions regarding their medical treatment in accordance with the guardianship judgment.

12. For 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.

13. Women 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.

14. Men 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.

15. Patient covered by a national health insurance.

What this study is about