On February 15, the U.S. Food and Drug Administration (FDA) granted traditional approval to the kinase inhibitor tepotinib (Tepmetko) for adult patients with metastatic non–small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition (MET) exon 14–skipping alterations. The agent is directed against MET.
VISION Trial
Tepotinib was previously granted accelerated approval for this indication on February 3, 2021, based on initial overall response rate and duration of response in the VISION trial (ClinicalTrials.gov identifier NCT02864992), a multicenter, nonrandomized, open-label, multicohort study. The conversion to traditional approval was based on an additional 161 patients and an added 28 months of follow-up time to assess duration of response.
Efficacy was demonstrated in a total of 313 patients with metastatic NSCLC harboring MET exon skipping alterations. Patients received tepotinib at 450 mg once daily until disease progression or unacceptable toxicity.
The primary efficacy measures were overall response rate and duration of response, determined by a blinded independent review committee. Among 164 treatment-naive patients, the overall response rate was 57% (95% confidence interval [CI] = 49%–65%), with 40% of responders having a duration of response lasting 12 months or longer. Among 149 previously treated patients, the overall response rate was 45% (95% CI = 37%–53%), with 36% of responders having a duration of response lasting 12 months or longer.
The most common adverse reactions (occurring in ≥ 20% of patients receiving tepotinib) were edema, nausea, fatigue, musculoskeletal pain, diarrhea, dyspnea, decreased appetite, and rash.
The recommended tepotinib dose is 450 mg orally once daily with food.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was granted Breakthrough and Orphan Drug designations.
