Amivantamab in Participants With Advanced NSCLC and MET Exon 14 Skipping Mutations: Final Results From the CHRYSALIS Study.

introductionAmivantamab is an EGFR-MET bispecific antibody with immune cell-directing activity. We assessed the safety and efficacy of amivantamab in participants with advanced NSCLC harboring primary MET exon 14 skipping mutations (METex14).

methodsCHRYSALIS enrolled participants with METex14 NSCLC who progressed after or declined standard-of-care therapy. Participants received intravenous amivantamab weekly for 4 weeks and biweekly thereafter. Objective response rate, duration of response (DoR), clinical benefit rate, progression-free survival, overall survival, safety, and circulating tumor DNA were analyzed.

resultsAmong 97 participants, 16 were treatment naive, 28 received prior treatment without MET therapies, and 53 received prior MET therapies. Objective response rate was 32% overall, 50% in treatment-naive participants, 46% in participants without prior MET therapies, and 19% in participants with prior MET therapies. In participants without prior MET therapies, amivantamab activity was observed regardless of co-occurring genomic alterations. Clinical benefit rate was 69% overall, 88% in treatment-naive participants, 64% in participants without prior MET therapies, and 66% in participants with prior MET therapies. Median DoR was 11.2 months; 61% (19/31) of the responders had DoR greater than or equal to 6 months. Median progression-free survival was 5.3 months (95% confidence interval, 4.3-7.0); median overall survival was 15.8 months (95% confidence interval, 14.6-not estimable). Most common adverse events were rash (79%) and infusion-related reactions (72%), most being grades 1 to 2 (52%).

conclusionsThe safety profile was consistent with previous reports of amivantamab in EGFR-mutant NSCLC. Amivantamab demonstrated clinically meaningful and durable antitumor activity in participants with METex14 advanced NSCLC, including those who progressed on prior MET therapies.