On February 3, 2021, the FDA accelerated the approval of oral tepotinib (Tepmetko; EMD Serono) for adults with metastatic non–small-cell lung cancer (NSCLC) harboring MET exon 14 (METex14) skipping alterations. This approval is for treatment-naïve patients as well as for patients who have received previous therapy. Tepotinib is the second MET inhibitor approved by the FDA and should be selected for treatment based on the presence of METex14. The FDA has granted tepotinib breakthrough therapy and orphan drug designations.
“METex14 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 Paul K. Paik, MD, VISION lead investigator and Clinical Director, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY. “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.”
“The availability of a new precision medicine for NSCLC with METex14 skipping alterations advances patient access to targeted treatment and underscores the importance of routine comprehensive biomarker testing for patients with this challenging cancer,” said Andrea Ferris, LUNGevity President and CEO.
The FDA approved tepotinib based on data from the phase 2 clinical trial VISION, a multicenter, nonrandomized, open-label, multicohort study that enrolled 152 patients with advanced or metastatic NSCLC and METex14 skipping alterations. The study included 69 treatment-naïve patients and 83 patients who have received previous therapy. All patients received monotherapy with tepotinib 450 mg orally once daily until disease progression or until unacceptable adverse events. The main efficacy outcome measures were overall response rate (ORR) and duration of response (DOR).
Among the 69 treatment-naïve patients, the ORR was 43% (95% confidence interval [CI], 32%-56%), with a median DOR of 10.8 months (95% CI, 6.9-not estimable). Among the 83 patients who received previous treatment, the ORR was 43% (95% CI, 33%-55%), with a median DOR of 11.1 months (95% CI, 9.5-18.5).
The most common (≥20% of patients) adverse reactions were edema, fatigue, nausea, diarrhea, musculoskeletal pain, and dyspnea. Tepotinib can also cause interstitial lung disease, hepatotoxicity, and embryo-fetal toxicity.
The recommended dose of tepotinib tablets is 450 mg orally once daily.
This approval was based on ORR and DOR data. Continued approval may be contingent on the verification of clinical benefit in confirmatory clinical trials.