A phase II study of tepotinib in patients with advanced solid cancers harboring MET exon 14 skipping mutations or amplification (KCSG AL19-17)

Abstract

Background: We evaluated the efficacy fi cacy and safety of tepotinib in patients with various solid cancers harboring MET exon 14 skipping mutation (METex14) MET ex14 ) or MET gene amplification. fi cation. Patients and methods: A phase II, multicenter study was conducted in patients with advanced or metastatic solid cancers who progressed after standard treatment, harboring either MET ex14 or MET amplification fi cation detected in tissue-based next-generation sequencing (NGS). The primary endpoint was objective response rate (ORR). For exploratory analyses, we analyzed the gene profiles fi les using plasma NGS test. Results: Thirty-five fi ve patients were enrolled. The ORR was 57.6% for all patients, 52.2% for those with MET ex14, and 70% for those with MET amplification. fi cation. Median progression-free survival (PFS) was 8 months [95% confidence fi dence interval (CI) 4.5-11.5 months] and median overall survival (OS) was 14 months (95% CI 7.8-20.2 months) in all patients. For patients with non-small-cell lung cancer with MET ex14, the median PFS was 9 months (95% CI 4.7-13.4 months) and the median OS was 17 months [95% CI not applicable (NA)-NA]. For patients with MET amplification, fi cation, the median PFS was 7 months (95% CI 1.5-12.5 months) and the median OS was 10 months (95% CI 5.8-14.2 months). The ORR of patients with MET dysregulation detected by plasma NGS was 72.2%, whereas the ORR was 30% in those without detection. The most common adverse events were peripheral edema, asthenia, transaminase elevation, and anorexia, mostly grade 1 or 2. Conclusions: Tepotinib demonstrated consistent antitumor activity in patients with MET ex14, and promising antitumor activity in various cancers with MET amplification. fi cation. Detection of MET dysregulation by plasma NGS may predict the response to tepotinib.