On February 3, 2021, the U.S. Food and Drug Administration (FDA) granted accelerated approval to tepotinib (Tepmetko®) for adult patients with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition (MET) exon 14 skipping alterations.

FDA Grants Accelerated Approval to Tepotinib for Metastatic NSCLC

Efficacy was demonstrated in a multicenter, nonrandomized, open-label, multicohort study (VISION; NCT02864992) of 152 patients with advanced or metastatic NSCLC with MET exon 14 skipping alterations. Patients received tepotinib 450 mg orally once daily until they experienced disease progression or unacceptable toxicity.

The main efficacy outcome measures were overall response rate (ORR) determined by a blinded independent review committee using response evaluation criteria in solid tumors 1.1 and response duration. Among the 69 treatment-naïve patients, ORR was 43% (95% CI = 32%, 56%) with a median response duration of 10.8 months (95% CI: 6.9, not estimable). Among the 83 previously treated patients, ORR was 43% (95% CI = 33%, 55%) with a median response duration of 11.1 months (95% CI = 9.5, 18.5).

The most common adverse reactions (≥ 20%) were edema, fatigue, nausea, diarrhea, musculoskeletal pain, and dyspnea. Tepotinib can also cause interstitial lung disease, hepatotoxicity, and embryo-fetal toxicity.

The recommended tepotinib dose is 450 mg orally once daily with food.

View full prescribing information for tepotinib.

FDA approved the indication under accelerated approval based on ORR and response duration. Continued approval for the indication is contingent on verification and description of clinical benefit in confirmatory trials. A description of FDA expedited programs is in Guidance for Industry—Expedited Programs for Serious Conditions—Drugs and Biologics.

The review used the Real Time Oncology Review, which streamlined data submission prior to the filing of the entire clinical application. The review also used Assessment Aid and Product Quality Assessment Aid, voluntary submissions from the applicant to facilitate FDA’s assessment.

The review was conducted under Project Orbis, an initiative of FDA’s Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For the application, a modified Project Orbis was undertaken because of the timing of submission to other regulatory agencies. FDA collaborated with Health Canada, Australia’s Therapeutic Goods Administration, and Swissmedic on the review. 

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.  

For assistance with single-patient oncology investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.