Multicenter phase 1 trial of aminvantamab plus lazertinib for EGFR-mutant advanced non-small cell lung cancer after relapse on osimertinib

Patients with EGFR-mutated non-small cell lung cancer often develop resistance to standard third-generation EGFR TKIs. Cohort E of the multicenter phase 1 CHRYSALIS trial evaluated the combination of the EGFR-MET bispecific antibody amivantanab and the third-generation EGFR TKI lazertinib for EGFR-mutated advanced NSCLC in chemotherapy naïve patients after progression on osimertinib. The safety profile of the combination was generally consistent with previous experience of each agent alone, with 4% of patients experiencing grade 3 or higher adverse events. The figure shows the antitumor activity of the combination. The investigator-assessed overall response rate was 36% (95% CI 22-51). The median duration of response was 9.6 months, and the median progression-free survival was 4.9 months. High EGFR and/or MET expression were potential predictive biomarkers of response. The authors conclude that the amivantamab-lazertinib regimen for EGFR-mutated advanced NSCLC in the post-osimertinib and chemotherapy-naïve setting had durable clinical activity.