On 3 February 2021, the US Food and Drug Administration (FDA) granted accelerated approval to tepotinib (Tepmetko, EMD Serono Inc.) for adult patients with metastatic non-small cell lung cancer (NSCLC) harbouring mesenchymal-epithelial transition (MET) exon 14 skipping alterations.
Efficacy was demonstrated in the VISION study (NCT02864992), a multicentre, non-randomised, open-label, multicohort study enrolling 152 patients with advanced or metastatic NSCLC with MET exon 14 skipping alterations. Patients received tepotinib 450 mg orally once daily until disease progression or unacceptable toxicity.
The main efficacy outcome measures were overall response rate (ORR) determined by a blinded independent review committee using RECIST v1.1 and response duration. Among the 69 treatment naïve patients, the ORR was 43% (95% confidence interval [CI] 32%, 56%) with a median response duration of 10.8 months (95% CI 6.9, not estimable). Among the 83 previously treated patients, the 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% of patients) were oedema, fatigue, nausea, diarrhoea, musculoskeletal pain, and dyspnoea. Tepotinib can also cause interstitial lung disease, hepatotoxicity, and embryo-foetal toxicity.
The recommended tepotinib dose is 450 mg orally once daily with food.
Full prescribing information for Tepmetko is available here.
This indication is approved under accelerated approval based on ORR and response duration. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
This review used the Real-Time Oncology Review, which streamlined data submission prior to the filing of the entire clinical application. The review also used the Oncology Center of Excellence (OCE) Assessment Aid and the Product Quality Assessment Aid, voluntary submissions from the applicant to facilitate the FDA’s assessment.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this application, a modified Project Orbis was undertaken because of the timing of submission to other regulatory agencies. FDA collaborated with Health Canada, Therapeutic Goods Administration (Australia), and Swissmedic on this review.