Crizotinib in patients (pts) with MET-amplified non-small cell lung cancer (NSCLC): Updated safety and efficacy findings from a phase 1 trial.

Abstract

9062 Background: MET amplification (amp) has been reported in a subset of NSCLC with the frequency varying depending on the definition used. Crizotinib, an ALK/ROS1/MET inhibitor approved in ALK- or ROS1-positive NSCLC, also has proven clinical activity in cases of MET exon 14 alterations and MET amp. Here we present an updated analysis of crizotinib in pts with low, medium (med), and high (hi) levels of MET amp in advanced NSCLC. Methods: In this ongoing, open-label, multicenter, phase 1 trial (NCT00585195), MET amp was locally tested; pts with MET/CEP7 ratios ≥1.8 were eligible. Pts received crizotinib 250 mg BID and were assigned to categories based on low (≥1.8–≤2.2), med ( > 2.2– < 5), or hi (≥5) MET/CEP7 ratios. The latter 2 thresholds were revised to > 2.2– < 4 and ≥4; data were then reanalyzed to better delineate predictive biomarkers of response. Selected endpoints included best overall response (BOR) per RECIST v1.0, time to tumor response (TTR), progression-free survival (PFS), duration of response (DOR) and safety. Results: At data cutoff (31 Oct 2017), 40 pts were treated; 3 had no MET amp. Baseline characteristics were comparable among the revised amp categories. Median TTR was 8.0 wk (range, 7.1–9.1). BOR, DOR, and PFS are shown in the. 3 MET hi pts remain on treatment. The adverse event profile in this cohort was consistent with the established safety profile of crizotinib. Conclusions: Pts with NSCLC with hi MET amp (MET/CEP7 ≥4) showed clinically meaningful antitumor activity with rapid and durable responses. Crizotinib was generally well tolerated. Coincidence with MET exon 14 alterations and other targets of crizotinib is being explored. Clinical trial information: NCT00585195.MET/CEP7 Category Low (N =3) Med (N =14) Hi (N =20) Response evaluable n = 3 n = 14 n = 20 Objective response rate, %a (95% CI) 33.3 (0.8, 90.6) 14.3 (1.8, 42.8) 40.0 (19.1, 63.9) Complete response, n 0 0 2 Partial response, n 1 2 6 Stable disease, n 0 4 6 Progressive disease (PD), n 1 4 3 Early death, n 1 3 1 Indeterminate, n 0 1 2 Median DOR, mo (range)b 12.1 (12.1–12.1) 3.7 (3.7–3.7) 5.5 (3.3–25.8) Median PFS, mo (95% CI)c 1.8 (0.8, 14.0) 1.9 (1.3, 5.5) 6.7 (3.4, 7.4) aResponse-evaluable populationbObjective responderscBased on Kaplan-Meier method