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

초록

Background Tepotinib is a selective MET tyrosine-kinase inhibitor. We evaluated the efficacy and safety of tepotinib in patients with various solid cancers harboring MET exon 14 skipping mutation (METex14) or MET gene amplification. Methods A phase II, multicenter, single arm study was conducted for patients with advanced or metastatic solid cancers who progressed after standard treatment, harboring either METex14 or MET amplification (gene copy number≥6) detected by tissue–based next generation sequencing (NGS). Tepotinib was administered at a dose of 500mg once daily, until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR), and the secondary end points were progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety profiles. For exploratory analyses, we analyzed gene profile using alphaLiquid® panel, a liquid–based NGS. Results A total of 35 patients were included (METex14, n=24; MET amplification, n=11). In patients with METex14, NSCLC was the most common (21 of 24) while other cancers were more common in patients with MET amplification (8 of 11). At a median follow-up of 19 months, the ORR was 57.6% for all patients, 52.2% for METex14, and 70% for MET amplification. Median PFS was 8 months (95% CI, 4.5-11.5) and median OS was 14 months (95% CI, 7.8-20.2) in all patients. For METex14, the median PFS was 9 months (95% CI, 1.6-13.6), and the median OS was not reached. For MET amplification, the median PFS was 7 months (95% CI, 1.5-12.5) and the median OS was 10 months (95% CI, 5.8-14.2). The ORR of patients with MET dysregulations detected in liquid–based NGS was 81.3% while the ORR of patients without MET dysregulations was 30%. The most frequently reported adverse events were peripheral edema (40.0%), followed by asthenia (28.6%), transaminase elevation (22.9%), and anorexia (22.9%), mostly grade 1 or 2. Conclusions Tepotinib demonstrated promising antitumor activity and manageable toxicity profiles in patients with various solid cancers harboring METex14 or amplification. Detection of MET dysregulations in liquid-based NGS is expected to play a potential role in predicting response of tepotinib.