The Food and Drug Administration (FDA) has granted accelerated approval to Tepmetko® (tepotinib; EMD Serono) for the treatment of adults with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition exon 14 (METex14) skipping alterations.
The approval was based on data from the multicenter, single-arm, open-label, multicohort phase 2 VISION study that evaluated Tepmetko as monotherapy in 152 patients with advanced or metastatic NSCLC with METex14 skipping alterations. Patients received Tepmetko 450mg orally once daily until disease progression or unacceptable toxicity. The major efficacy outcome measure was overall response rate (ORR) as assessed by a blinded independent review committee using RECIST v1.1 and response duration.
Among 69 treatment-naïve patients, the ORR was 43% (95% CI, 32-56) with a median duration of response (DOR) of 10.8 months (95% CI, 6.9-not estimable). The proportion of treatment-naïve patients with a DOR lasting at least 6 and 9 months was 67% and 30%, respectively. Among 83 previously treated patients, the ORR was 43% (95%, 33-55) with a median DOR of 11.1 months (95% CI, 9.5-18.5). The proportion of previously treated patients with a DOR lasting at least 6 and 9 months was 75% and 50%, respectively.
As for safety, the most common adverse reactions (incidence greater than or equal to 20%) reported were edema, fatigue, nausea, diarrhea, musculoskeletal pain, and dyspnea. Interstitial lung disease/pneumonitis and hepatotoxicity were also observed in patients treated with Tepmetko.
“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 primary investigator and Clinical Director, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center. “Tepmetko offers an important and welcome new therapeutic option for patients with metastatic NSCLC harboring these genetic mutations.”
The FDA previously granted Priority Review, Orphan Drug and Breakthrough Therapy designations to Tepmetko for this indication. Continued approval of Tepmetko may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Tepmetko is supplied as 225mg strength tablets in 30- and 60-count boxes.
1. FDA grants accelerated approval to tepotinib for metastatic non-small cell lung cancer. [press release]. Silver Spring, MD: US Food and Drug Administration; February 3, 2021.
2. FDA approves Tepmetko® as the first and only once-daily oral MET inhibitor for patients with metastatic NSCLC with METex14 skipping alterations. [press release]. Rockland, MA: EMD Serono, Inc.; February 3, 2021.
3. Tepmetko [package insert]. Rockland, MA: EMD Serono, Inc.; 2021.