FDA Grants Breakthrough Designation for Tepotinib for Lung Cancer With Specific Mutation

The U.S. Food and Drug Administration (FDA) granted breakthrough therapy designation to the oral MET inhibitor tepotinib for patients with metastatic non-small cell lung cancer (NSCLC) who harbor MET exon 14 skipping alterations and progressed after platinum-based cancer therapy.

The FDA’s decision was based on data from the ongoing phase II VISION trial, which assessed the safety and efficacy of tepotinib in this patient population.

Responses observed with tepotinib

An interim analysis included 73 patients with NSCLC with MET exon 14 skipping alterations that were identified via liquid biopsy (n=57) or tissue biopsy testing (n=58). In the liquid biopsy-identified group, there was a 50% overall objective response rate (ORR) according to an independent review committee (median duration of response (DOR) = 12.4 months) and a 55.3% ORR according to the study’s investigators (median DOR = 17.1 months). In the tissue biopsy-identified group, ORRs were 45.1% (median DOR = 15.7 months) and 54.9% (median DOR = 14.3 months), respectively.

Most treatment-related adverse events (AEs) were grade 1 or 2. The most common any-grade AEs reported among 87 safety-evaluable patients were peripheral edema (48.3%), nausea (23%), diarrhea (20.7%), and increased blood creatinine (12.6%).

Four patients discontinued treatment due to AEs, including peripheral edema (n=2), interstitial lung disease (n=1), and nausea and diarrhea (n=1).

Approximately 3% to 5% of patients with NSCLC have alterations of the MET signaling pathway, which results in an aggressive form of the cancer. Tepotinib is also being investigated in the INSIGHT 2 study in combination with the tyrosine kinase inhibitor (TKI) osimertinib in epidermal growth factor receptor (EGFR) mutated, MET amplified, locally advanced or metastatic NSCLC that is refractory to prior EGFR TKI.