Tepotinib in Patients with Advanced NSCLC with MET Amplification (METamp)

Abstract

<h3>Purpose/Objective(s)</h3> <i>MET</i>amp, an oncogenic driver occurring in 1–5% of NSCLC cases, confers a poor prognosis and lacks approved targeted therapies. Tepotinib, a highly selective MET inhibitor, provided durable response in advanced NSCLC with <i>MET</i> exon 14 (<i>MET</i>ex14) skipping in VISION Cohort A. VISION Cohort B evaluated tepotinib in patients with advanced NSCLC and <i>MET</i>amp, as detected by a convenient and minimally invasive liquid biopsy (LBx) assay. <h3>Materials/Methods</h3> Patients with advanced NSCLC, ECOG PS 0–1, 0–2 prior therapy lines, <i>EGFR</i>/<i>ALK</i> wild-type status, no <i>MET</i>ex14 skipping, and <i>MET</i>amp by LBx (<i>MET</i> gene copy number ≥2.5) received oral tepotinib 500 mg QD (450 mg active moiety). Primary endpoint was objective response rate (ORR) (RECIST v1.1) by independent review committee (IRC). Duration of response (DOR), progression-free survival (PFS), and safety were secondary endpoints. The data cut-off was July 1, 2020. <h3>Results</h3> Of 24 enrolled patients, the median age was 63.4 years (range 38–73), 21 patients were male (88%), 21 had ECOG PS 1, and 21 were smokers. Seven patients (29%) received tepotinib in first line (1L), 10 (42%) in second line (2L), and seven patients in third line (3L). As of November 2020, treatment was ongoing for >1 year in five patients (1L, n=2; 2L, n=2; 3L, n=1). The ORR was 42% (10/24 patients) overall, 71% (5/7) in 1L, 30% (3/10) in 2L and 29% (2/7) in 3L (Table). The median DOR was not estimable (NE). Five patients (20.8%) discontinued due to adverse events (AEs) considered unrelated to tepotinib. 16 patients reported treatment-related AEs (67%; Grade 3/4 in seven patients [29%]), including peripheral edema (nine patients [38%]; Grade 3/4 in two [8%]), generalized edema (four patients [17%]; Grade 3/4 in two [8%]), and constipation (four patients [17%]; none with Grade 3/4). <h3>Conclusion</h3> In the first study of a MET inhibitor in advanced NSCLC with <i>MET</i>amp prospectively detected by LBx, tepotinib had high and clinically meaningful activity, especially in 1L, and was generally well tolerated. Tepotinib warrants further evaluation in advanced NSCLC with <i>MET</i>amp.