Introduction: Amivantamab is an epidermal growth factor receptor (EGFR)-MET bispecific antibody with immune cell-directing activity. We assessed amivantamab's safety and efficacy in participants with advanced non-small cell lung cancer (NSCLC) harboring primary MET exon 14 skipping mutations (METex14).
Methods: CHRYSALIS enrolled participants with METex14 NSCLC who progressed after/declined standard-of-care therapy. Participants received intravenous amivantamab weekly for 4 weeks and biweekly thereafter. Objective response rate (ORR), duration of response (DoR), clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), safety, and circulating tumor DNA were analyzed.
Results: Among 97 participants, 16 were treatment naïve, 28 received prior treatment without MET therapies, and 53 received prior MET therapies. ORR was 32% overall, 50% in treatment-naïve 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. CBR was 69% overall, 88% in treatment-naïve 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 responders had DoR ≥6 months. Median PFS was 5.3 months (95% CI, 4.3-7.0); median OS was 15.8 months (95% CI, 14.6-not estimable). Most common adverse events were rash (79%) and infusion-related reactions (72%), majority being grade 1-2 (52%).
Conclusions: The 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.
Keywords: CHRYSALIS; MET exon 14 skipping mutation; advanced non-small cell lung cancer; amivantamab; prior MET therapies.
Copyright © 2025. Published by Elsevier Inc.