Trial of Tepotinib compared to Standard Treatment in Patients with Advanced MET exon 14 Mutated Non-Small Cell Lung Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Intergroupe Francophone De Cancerologie Thoracique

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

3 Dec 2025 → ongoing

Decision date (initial)

2025-06-11

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To compare the efficacy of tepotinib versus investigator’s choice in patients with METex14 NSCLC following prior treatment with immunotherapy and/or platinum-based chemotherapy.

Secondary objectives 3

1. To assess quality of life under tepotinib or investigator’s choice treatment in patients with METex14 NSCLC.
2. To assess efficacy of tepotinib or investigator’s choice treatment
3. To assess observance to treatment

Conditions and MedDRA coding

Advanced MET exon 14 Mutated Non-Small Cell Lung Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. 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. 2. Histologically proven advanced NSCLC.
3. 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. 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. 5. Has received no more than 2 prior lines of treatment.
6. 6. ECOG Performance Status 0-3.
7. 7. Brain metastases are allowed. If immediate local treatment is required, inclusion is possible once the latter is complete.
8. 8. Stage IIIB or IIIC non irradiable or stage IV (8th classification TNM, UICC 2015)
9. 9. Age ≥ 18 years.
10. 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. 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. 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. 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. 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. 15. Patient covered by a national health insurance.

Exclusion criteria 9

1. 1. Prior treatment with a MET inhibitor (including crizotinib).
2. 2. Presence 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.
3. 3. ECOG Performance Status 4.
4. 4. Known hypersensitivity to tepotinib or its excipients.
5. 5. History 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.
6. 6. Inability to comply with study or follow-up procedures.
7. 7. Pregnant, lactating, or breastfeeding women.
8. 8. Any 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.
9. 9. History 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival (PFS) assessed by independent review committee according to RECIST 1.1.

Secondary endpoints 8

1. 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.
2. Hierarchical analysis #2: Overall survival, tested if the primary endpoint (PFS) and the first secondary endpoint (QoL) both show statistical significance.
3. Objective Response Rate according to RECIST1.1.
4. Duration of response.
5. Second progression-free survival (PFS2) and Time to next treatment or death (TNT-D).
6. 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).
7. Number of cycles for each arm
8. Number of treatment dose modification and interruption.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 9

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Intergroupe Francophone De Cancerologie Thoracique

Sponsor organisation

Intergroupe Francophone De Cancerologie Thoracique

Address

10 Rue De La Grange Bateliere

City

Paris

Postcode

75009

Country

France

Scientific contact point

Organisation

Intergroupe Francophone De Cancerologie Thoracique

Contact name

Contact

Public contact point

Organisation

Intergroupe Francophone De Cancerologie Thoracique

Contact name

Contact

Locations

1 EU/EEA country · 30 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications