FDA Approves Tepotinib for Metastatic Non-Small Cell Lung Cancer with MET Exon 14 Skipping Alterations

By: Dr. Anish Shah
Bronx-Lebanon Hospital; Bronx, NY

On February 15, 2024, the U.S. Food and Drug Administration granted regular approval to tepotinib (Tepmetko) for adult patients with metastatic non-small cell lung cancer (NSCLC) with MET exon 14 skipping alterations as detected by the VISION trial. In February 2021, the FDA had granted accelerated approval to Tepotinib, a MET inhibitor, based on the VISION phase 2 trial results. The drug showed a significant response rate in both new patients and those who had received prior treatments, with the response lasting several months (median DOR of 10.8 months in new patients while 11.1 months in those who had received prior treatments). The transition from accelerated approval to regular approval was influenced by additional patient data and an extended follow-up period.

Study ID number: NCT02864992

Approval was based on the VISION trial, a single-arm, open-label, multicenter, non-randomized, multicohort study that included 255 patients with advanced or metastatic NSCLC with MET exon 14 skipping alterations confirmed using RECIST v1.1 criteria and an ECOG performance status of 0 or 1. Tepotinib was given orally at a dose of 450 mg once daily until disease progression or intolerable toxicity. The median treatment duration was not specified.

Efficacy was established on the objective response rate (ORR) by RECIST v1.1 criteria as assessed by a blinded independent review committee (BIRC) and the duration of response (DOR). Results of the study showed that in treatment-naive patients, tepotinib induced an ORR of 57% (95% CI, 49%-65%), with 40% of these responders continuing to respond for 12 months or more. Among the previously treated patients, the ORR achieved with tepotinib was 45% (95% CI, 37%-53%), with 36% of these responders experiencing a DOR of at least 12 months.

The study concluded that tepotinib is an effective treatment for patients with metastatic NSCLC with MET exon 14 skipping alterations, showing significant response rates in both treatment-naive and previously treated patients.

Side effects of the medication included serious adverse reactions experienced by 45% of the patients, with three patients experiencing fatal adverse reactions due to pneumonitis, hepatic failure, and dyspnea from fluid overload. Common adverse effects included edema, fatigue, nausea, diarrhea, abdominal pain, constipation, vomiting, musculoskeletal pain, dyspnea, cough, pleural effusion, reduced appetite, and pneumonia.