Multinational phase 3 trial of amivantamab plus lazertinib for previously untreated EGFR-mutated advanced non-small cell lung cancer

The multinational phase 3 MARIPOSA trial randomized patients with previously untreated EGFR-mutated advanced NSCLC 2:2:1 to the combination of amivantamab (EGFR-MET bispecific antibody) and lazertinib (third-generation EGFR-TKI) or osimertinib or lazertinib. The primary endpoint was progression-free survival in the amivantamab-lazertinib group as compared with the osimertinib group, as assessed by blinded independent central review. The median PFS was significantly longer in the amivantamab-lazertinib group than in the osimertinib group (23.7 versus 16.6 months; HR 0.70; p<0.001). Objective response was seen in 86% versus 85%; the median duration of response was 25.8 months with amivantamab-lazertinib and 16.8 months with osimertinib. In a planned interim overall survival analysis of amivantamab-lazertinib versus osimertinib, the HR for death was 0.80 (95% CI 14.8-18.5). The incidence of discontinuation due to treatment-related adverse events was 10% with amivantamab-lazertinib and 3% with osimertinib. The authors conclude that amivantamab-lazertinib showed superior efficacy to osimertinib as first-line treatment in EGFR-mutated advanced NSCLC.