The Food and Drug Administration has granted accelerated approval for tepotinib (TEPMETKO) for the treatment of adults with metastatic non–small cell lung cancer (NSCLC) harboring MET exon 14 skipping alterations.
Tepotinib is the first once-daily oral MET inhibitor approved for this patient population, and the approval applies to both treatment-naive and previously treated patients with NSCLC.
The approval was supported by results from the ongoing phase 2 VISION trial. Tepotinib produced an overall response rate of 43% in both treatment-naive patients (n = 69) and previously treated patients (n = 83) in this trial. The median duration of response was 10.8 months and 11.1 months, respectively.
Results of the primary analysis were published in The New England Journal of Medicine last year.
Study subjects received the recommended dose of 450 mg taken as two 225-mg tablets once daily with food until disease progression or unacceptable toxicity. Adverse reactions occurring in at least 20% of patients included edema, fatigue, nausea, diarrhea, musculoskeletal pain, and dyspnea. Interstitial lung disease, hepatotoxicity, and embryo-fetal toxicity also have been reported with tepotinib.
Continued approval of tepotinib "may be contingent upon verification and description of clinical benefit in confirmatory trials," the FDA stated in an approval announcement.
EMD Serono, the drug's maker, also announced the approval in a press statement, calling tepotinib "an important and welcome new therapeutic option for patients with metastatic NSCLC harboring these genetic mutations."
"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," Paul K. Paik, MD, the VISION primary investigator and clinical director of the thoracic oncology service at Memorial Sloan Kettering Cancer Center in New York, said in the statement.
"There is a pressing need for targeted treatments that have the potential to generate durable antitumor activity and improve the lives of patients with this challenging disease," he added.
Andrea Ferris, president and chief executive officer of the nonprofit LUNGevity Foundation, further noted the "powerful progress" made in recent years with respect to understanding genetic mutations in NSCLC.
"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," she said in the statement.
Tepotinib was approved in Japan in March 2020. The drug previously received breakthrough therapy designation and orphan drug designation from the FDA. A marketing authorization application for tepotinib was validated by the European Medicines Agency in November 2020 for a similar indication, EMD Serono reported, adding that applications "have also been submitted in Australia, Switzerland, and Canada under the FDA's Project Orbis initiative, which provides a framework for concurrent submission and review of oncology medicines among international partners."
Other phase 2 studies of tepotinib are ongoing. The INSIGHT 2 study is designed to test tepotinib in combination with osimertinib in MET amplified, advanced, or metastatic NSCLC with activating EGFR mutations that has progressed following first-line treatment with osimertinib. The PERSPECTIVE study is designed to test tepotinib in combination with cetuximab in patients with RAS/BRAF wild-type left-sided metastatic colorectal cancer with acquired resistance to anti-EGFR antibody targeting therapy due to MET amplification.
For more details on tepotinib, see the full prescribing information.
This article originally appeared on MDedge.com, part of the Medscape Professional Network.
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Cite this: FDA Grants MET Inhibitor Tepotinib Accelerated Approval for NSCLC - Medscape - Feb 04, 2021.