On February 3, the US Food and Drug Administration (FDA) granted accelerated approval to tepotinib — a selective, orally administered mesenchymal-epithelial transition (MET) inhibitor — for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with MET exon 14 skipping alterations.1
This approval was based on findings from the phase 2 VISION trial (ClinicalTrials.gov Identifier: NCT02864992) that evaluated the safety and efficacy of tepotinib 500 mg in patients with advanced or metastatic NSCLC and a MET exon 14 skipping alterration.2 These alterations are found in up to 4% of patients with NSCLC and are generally detected in patients aged 70 years and older.
After an overall minimum follow-up in 99 of 152 patients who received tepotinib on the VISION protocol, an independent review determined the response rate to be 46% (95% CI, 36-57), with a median response duration of 11.1 months (95% CI, 7.2-not estimable). Furthermore, results were similar regardless of whether METvariants were detected using liquid or tissue biopsy.
There was, however, a noted incidence of adverse events, with 11% of patients permanently discontinuing treatment on trial.
Xiuning Le, MD, PhD, assistant professor in the department of thoracic/head and neck medical oncology at The University of Texas MD Anderson Cancer Center in Houston, Texas, and one of the study’s authors, discussed the future of tepotinib in the treatment of NSCLC.
What was the rationale for treating patients with MET exon 14 skipping alterations with tepotinib?
Tepotinib is a targeted therapy that inhibits MET. This gene is a recently discovered driver of a subset of lung cancers; when exon 14 gets skipped in this gene, the cells in question start to grow uncontrollably, and tepotinib targets these gene alterations to restore gene function.
This skipping alteration occurs in approximately 3% of patients with NSCLC, and the discovery of the alteration has opened a new door of treatment options relying on MET inhibition. Providers across the country are now asked to check for MET changes. Even though we only learned about this variant within the past decade, the FDA has approved 2 drugs in the past 12 months alone. It has been a big year in this area.
What is also exciting about this therapy is that because patients with the variants in question tend to be older than 70 years of age, a targeted therapy option that relies only on a daily oral dose is hugely preferable to heavily toxic chemotherapies. In addition, the FDA approval of tepotinib is even for patients who have previously received other therapies.
The recently approved MET inhibitors, including tepotinib, are also more selective than older MET inhibitors; they are both more targeted and more potent.