The FDA has granted accelerated approval to tepotinib (Tepmetko®, EMD Serono) for patients with metastatic non-small cell lung cancer (NSCLC) with mesenchymal-epithelial transition (MET) exon 14 skipping alterations.
"A splice-site mutation that results in a loss of transcription of exon 14 in the oncogenic driver MET occurs in 3% to 4% of patients with NSCLC," wrote the investigators of the phase 2 VISION trial (NCT02864992) in their September publication in The New England Journal of Medicine, led by first author Paul K. Paik, MD, Clinical Director of the Thoracic Oncology Service at Memorial Sloan Kettering Cancer Center. "We evaluated the efficacy and safety of tepotinib, a highly selective MET inhibitor, in this patient population."
VISION, a single-arm, non-randomized trial on which the approval was based, enrolled 152 patients with advanced or metastatic NSCLC with confirmed MET exon 14 skipping alterations, including 69 treatment-naive patients and 83 patients with previously treated disease. Patients received 450 mg of tepotinib once daily until disease progression or unacceptable toxicity, for a primary end point of objective response in patients who had undergone at least nine months of follow-up and duration of response.
Tepotinib produced an overall response rate of 43% in treatment-naive patients, with a median duration of response of 10.8 months. Among previously treated patients, the overall response rate was 43%, with a median duration of response of 11.1 months. Responses lasting at least 6 months occurred in 67% of treatment-naïve patients and 75% of previously treated patients, and responses lasting at least 9 months occurred in 30% of patients in the treatment-naive group and 50% of those in the previously treated disease group.
"Among patients with advanced NSCLC with a confirmed MET exon 14 skipping alteration, the use of tepotinib was associated with a partial response in approximately half the patients," concluded Dr. Paik and colleagues.
According to the prescribing information, the most common any-grade adverse events experienced by at least 20% of patients receiving tepotinib included edema (70%), fatigue (27%), nausea (27%), diarrhea (26%), musculoskeletal pain (24%), and dyspnea (20%). Serious adverse events, experienced by 45% of patients; those occurring in at least 2% of patients included pleural effusion (7%), pneumonia (5%), edema (3.9%), dyspnea (3.9%), general health deterioration (3.5%), pulmonary embolism (2%), and musculoskeletal pain (2%). Grade 3/4 laboratory abnormalities occurring in at least 2% of patients included decreased lymphocytes, decreased albumin, decreased sodium, increased gamma-glutamyltransferase, increased amylase, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), and decreased hemoglobin. Treatment discontinuation due to adverse events occurred in 20% of patients. Dose interruptions due to adverse events occurred in 44%, while dose reductions occurred in 30%. The prescribing information for tepotinib includes warnings for interstitial lung disease, hepatotoxicity, and embryo-fetal toxicity.
The recommended dose of tepotinib is 450 mg taken orally once daily with food.
Image credit: Yale Rosen. Licensed under CC BY-SA 2.0
For More Information
US Food & Drug Administration (2021). FDA grants accelerated approval to tepotinib for metastatic non-small cell lung cancer. Available at https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-tepotinib-metastatic-non-small-cell-lung-cancer