Dr. Le on the Rationale for Tepotinib in METex14-Mutant NSCLC

Xiuning Le, MD, PhD, assistant professor, Department of Thoracic/Head and Neck Medical Oncology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, discusses the rationale for tepotinib (Tepmetko) in MET exon 14 skipping (METex14)—mutant non–small cell lung cancer (NSCLC).

While the role of targeted therapy has grown significantly in lung cancer treatment over the past 2 decades, METex14 mutations are a relatively new oncogenic driver, says Le. If the exon 14 is “skipped out” because of the mutation, the MET signaling keeps going, which drives the cancer cells to grow, explains Le; that cancer cell growth results in the development of lung cancer.

Tepotinib is a small molecule inhibitor that targets intracellular part of MET alterations, says Le. The agent has been optimized to target METex14 as well as MET amplification, and it has proved to be very potent in cell cultures. In patients, tepotinib has been shown to elicit 99% target engagement, adds Le.

Based on this promise, investigators set out to examine the oral, highly selective MET inhibitor in patients with locally advanced or metastatic NSCLC who harbor METex14 skipping mutations identified through liquid or tissue biopsy in the phase 2 VISION trial. Findings from the trial that were recently presented at the 2020 ASCO Virtual Scientific Program demonstrated durable clinical activity and manageable toxicity with tepotinib in this patient population.