Lazertinib (3rd-gen EGFR TKI) matches osimertinib in 1L EGFR-mutant NSCLC—no PFS advantage in MARIPOSA

Lazertinib is a CNS-penetrant, third-generation EGFR tyrosine kinase inhibitor (TKI) engineered for mutant EGFR selectivity (and chosen for combination with the EGFR-MET bispecific antibody amivantamab partly due to lower wild-type EGFR toxicities). In the randomized, double-blind Phase 3 MARIPOSA exploratory head-to-head, treatment-naïve EGFR exon19del/L858R advanced NSCLC patients received lazertinib (n=216) or osimertinib (n=429): median PFS was 18.5 vs 16.6 months (HR 0.98, 95%CI 0.79–1.22; p=0.86), ORR 83% vs 85% with similar median DoR (16.6 vs 16.8 months), and interim OS was NR in both arms (HR 1.00, 95%CI 0.73–1.38). Safety was mostly grade 1–2 EGFR-inhibition AEs in both arms; lazertinib had lower QT prolongation—efficacy looks broadly in-family with historical 1L osimertinib benchmarks (e.g., FLAURA mPFS 18.9 months; mOS 38.6 months), while note that lazertinib monotherapy was included as a “component contribution” arm and is not the US-approved 1L regimen (the FDA-approved use is lazertinib + amivantamab).