Tepotinib May Now Be Used to Treat Patients with METex14+ NSCLC, FDA Says

Based on results of the VISION study, the FDA has granted accelerated approval to tepotinib for MET exon 14 skipping altered metastatic non–small cell lung cancer.

Accelerated approval was granted to the highly selective MET inhibitor tepotinib (Tepmetko) for the treatment of adults with metastatic non–small cell lung cancer (NSCLC) and MET exon 14 skipping alterations.1

Results of the phase 2 study VISION study (NCT02864992) served as the basis of the approval and were published in the New England Journal of Medicine in 2020.2

On the trial, patients received 500 mg of tepotinib once daily with a primary outcome of objective response rate (ORR) by independent review among patients with at least 9 months of follow-up. Additionally, response was analyzed according to whether the presence of a MET exon 14 skipping mutation was detected on liquid or tissue biopsy.

The ORR by independent review was 46% (95% CI, 36%-57%), with a median duration of response (DOR) of 11.1 months (95% CI, 7.2-notestimable [NE]) in the combined-biopsy group. ORRs in the liquid (n = 66) and tissue biopsy groups (n = 60) were 48% (95% CI, 36-61) and 50% (95% CI, 37-63), respectively.

Subgroup analyses were recently presented at the International Association for the Study of Lung Cancer 2020 World Conference on Lung Cancer (WCLC) Singapore,3 for which 152 patients had 9 or more months of follow-up and were assessed for efficacy in cohort A and 255 were evaluated for safety in cohorts A and C as of data cut-off of July 1, 2020.

In treatment-naïve patients from cohort A (n = 69), the ORR was 44.9% (95% CI, 32.9%-57.4%), with a median DOR of 10.8 months (95% CI, 6.9-NE). Progression-free survival (PFS) was 8.5 months (95% CI, 6.8-11.3). In previously-treated patients from this cohort (n = 83), the ORR was 44.6% (95% CI, 33.7%-55.9%), median DOR was 11.1 months (95% CI, 9.5-18.5), and median PFS was 10.9 months (95 CI, 8.2-12.7).

Tepotinib was generally well tolerated across therapy lines, with mostly mild-moderate adverse events (AEs) and few discontinuations. The most common treatment-related AE, peripheral edema, was mostly low grade (Grade ≥3, 7%) and rarely led to discontinuation (4%). Other common AEs include nausea, diarrhea, blood creatine increase, and hypoalbuminemia. The safety profile was consistent in patients who received prior IO, study authors found.

The agent previously received priority review designation from the FDA for this indication in April 2020.4

MET [exon 14] skipping alterations drive a particularly aggressive form of NSCLC in a patient population that is generally elderly, facing poor clinical prognosis and in urgent need of new therapeutic options,” Luciano Rossetti, global head of Research & Development for the Biopharma business of Merck KGaA in Darmstadt, Germany, said in a press release at the time of priority review.

The FDA-recommended dose of tepotinib is 450 mg orally once daily with food. Given that the approval is based on ORR from a phase 2 trial, continued approval may be contingent upon verification in a confirmatory trial.


1. FDA grants accelerated approval to tepotinib for metastatic non-small cell lung cancer. FDA. February 3, 2021. Accessed February 3, 2021. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-tepotinib-metastatic-non-small-cell-lung-cancer?utm_medium=email&utm_source=govdelivery

2. Paik PK, Felip E, Veillon R, et al. Tepotinib in Non-Small-Cell Lung Cancer with MET Exon 14 Skipping Mutations. N Engl J Med. doi: 10.1056/NEJMoa2004407.

3. Paik PK, Sakai H, Felip E, et al. Tepotinib in patients with MET exon 14 (METex14) skipping advanced NSCLC: updated efficacy from VISION Cohort A. Presented at: International Association for the Study of Lung Cancer 2020 World Conference on Lung Cancer; January 28-31, 2021; Virtual. Abstract MA11.05

4. FDA Accepts Filing of New Drug Application for Tepotinib for the Treatment of Patients with Metastatic NSCLC with METex14 Skipping Alterations. News release. Published August 25, 2020. Accessed February 3, 2021. https://www.emdgroup.com/en/news/tepotinib-file-acceptance-fda.html