Multinational phase 1-1b trial of amivantamab plus lazertinib for atypical EGFR-mutated advanced non-small cell lung cancer

Efficacy of current treatment options is limited for patients with advanced non-small cell lung cancer (aNSCLC) harboring atypical EGFR mutations, such as S768I, L861Q, G719X. Cohort C of the multinational phase 1-1b CHRYSALIS-2 trial evaluated the combination of amivantamab (EGFR- and MET-directed bispecific antibody) and lazertinib (EGFR TKI) for patients who previously received no more than 2 lines of therapy for aNSCLC with atypical EGFR mutations. The primary endpoint was investigator-assessed objective response rate. The median duration follow-up in the overall population was 16.1 months. The ORR in the overall population was 52% (95% CI 42-62) with a median duration of response 14.1 months (9.5-26.2), median progression-free survival 11.1 months (7.8-17.8) and median overall survival not estimable (22.8 months-NE). Among treatment-naïve participants, the ORR was 57% (95% CI 42-71), with a median DoR 20.7 months (9.9-NE), median PFS 19.5 months (11.2-NE), and median OS NE (26.3-NE). Adverse events were consistent with previous studies and primarily grade 1 and 2. The authors conclude that among participant with atypical EGFR-mutated aNSCLC, the combination of aminvantamab and lazertinib demonstrated clinically meaningful antitumor activity with no new safety signals.