FDA Grants Accelerated Approval to Tepotinib for METex14+ NSCLC

The FDA has granted an accelerated approval to tepotinib for the treatment of adult patients with metastatic non–small cell lung cancer who harbor a MET exon 14 skipping alteration.

The FDA has granted an accelerated approval to tepotinib (Tepmetko) for the treatment of adult patients with metastatic non–small cell lung cancer (NSCLC) who harbor a MET exon 14 skipping alteration.1,2

MET exon 14 skipping occurs in approximately 3% to 4% of NSCLC cases, and patients with this aggressive lung cancer are often elderly and face a poor clinical prognosis,” said VISION primary investigator Paul K. Paik, MD, and clinical director, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, in a statement. “There is a pressing need for targeted treatments that have the potential to generate durable anti-tumor activity and improve the lives of patients with this challenging disease. Tepmetko offers an important and welcome new therapeutic option for patients with metastatic NSCLC harboring these genetic mutations.”

The application was reviewed through the FDA’s Real-Time Oncology Review program, as well as through Project Orbis. Continued approval for tepotinib in this indication may be contingent upon verification of clinical benefit in confirmatory trial(s).

Approval for the MET inhibitor is based on findings from the phase 2 open-label, single-arm VISION study (NCT02864992) of single-agent tepotinib as treatment of patients with NSCLC with MET exon 14 skipping alterations, as assessed by liquid and/or tissue biopsy.

The trial showed an overall response rate (ORR) by blinded independent review committee per RECIST 1.1 criteria of 43% (95% CI, 32%-56%) among 69 treatment-naïve patients with a median duration of response (DOR) of 10.8 months (95% CI, 6.9-not estimable [NE]). Among 83 patients who were previously treated, the ORR was also 43% (95% CI, 33%-55%) and the median DOR was 11.1 months (95% CI, 9.5-18.5).

In the study, 152 patients with advanced or metastatic NSCLC and MET exon 14 skipping alterations received treatment with continuous tepotinib. A total of 99 patients were followed for at least 9 months. Of these patients, 66 patients had MET alterations confirmed on liquid biopsy and 60 were confirmed on tissue biopsy. The 99 patients encompassing the efficacy population were known as the combined-biopsy group.3

According to data previously published in the New England Journal of Medicine, the ORR by independent review was 46% (95% CI, 36%-57%) in the efficacy population; in the liquid biopsy group the ORR was 48% (95% CI, 36%-61%) and in the tissue biopsy group the ORR was 50% (95% CI, 37%-63%). By investigator assessment overall, the ORR was 56% (95% CI, 45%-66%) and the liquid biopsy and tissue biopsy response rates were 56% (95% CI, 43%-68%) and 62% (95% CI, 48%-74%), respectively.

The median DOR was 11.1 months (95% CI, 7.2-NE) in the combined-biopsy group, 9.9 months (95% CI, 7.2-NE) in the liquid biopsy group, and 15.7 months (95% CI, 9.7-NE) in the tissue-biopsy group.

By independent review, the median progression-free survival (PFS) was 8.5 months (95% CI, 6.7-11.0) in the combined-biopsy group, 8.5 months (95% CI, 5.1-11.0) in the liquid-biopsy group, and 11.0 months (95% CI, 5.7-17.1) in the tissue-biopsy group.

Patients with brain metastases (n = 11) had an ORR of 55% (95% CI, 23%-83), a median DOR of 9.5 months (95% CI, 6.6-NE), and a median PFS of 10.9 months (95% CI, 8.0-NE).

Adverse events (AEs) of any grade that were considered to be treated related were reported in 89% of all treated patients (n = 152). The most common events were peripheral edema (63%), nausea (26%), diarrhea (22%), blood creatinine increase (18%), and hypoalbuminemia (16%).

Grade ≥3 AEs were reported in 28% of patients, with 2% of these events being grade 4 in severity. The most common grade ≥3 AE was peripheral edema in 7% of patients. Serious AEs considered to be treatment related were observed in 15%.

Treatment-related AEs led to dose reduction in 33% of patients and treatment discontinuation in 11%, these were mostly due to peripheral edema, pleural effusion, or dyspnea.

Twenty-one patients had AEs leading to death during treatment but only 1 death was considered to be related to treatment with tepotinib in a patient with respiratory failure and dyspnea secondary to interstitial lung disease.

Tepotinib is recommended to be administered at 450 mg orally once daily with food.


1. FDA grants accelerated approval to tepotinib for metastatic non-small cell lung cancer. FDA. February 3, 2021. Accessed February 3, 2021. https://bit.ly/3oOIWMO

2. FDA Approves TEPMETKO® as the First and Only Once-daily Oral MET Inhibitor for Patients with Metastatic NSCLC with METex14 Skipping Alterations. News release. EMD Serono. February 3, 2021. Accessed February 3, 2021. https://bit.ly/36FrnZs

3. 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. 2020;383:931-943. doi:10.1056/NEJMoa2004407

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