Amivantamab (EGFR/MET bispecific) + Lazertinib (EGFR TKI) Suppresses MET/EGFR Resistance vs Osimertinib, Extends 2L PFS

Amivantamab is an IV bispecific antibody targeting EGFR and MET, combined here with lazertinib, a 3rd-gen EGFR tyrosine kinase inhibitor; this MARIPOSA (Phase 3; NCT04487080) brief report used paired baseline/EOT ctDNA (Guardant360) to profile acquired resistance after 1L amivantamab–lazertinib vs 1L osimertinib in previously untreated EGFR ex19del/L858R advanced NSCLC. At EOT, common on-target/off-target resistance events were lower with amivantamab–lazertinib, including MET amplification (3.4% vs 13.1%; nominal p=0.002) and secondary EGFR mutations (1.4% vs 7.6%; nominal p=0.01), with no signal of compensatory increases in other “known” pathways. Among patients who received a first subsequent therapy, median 2L PFS improved to 8.4 vs 5.3 months (HR 0.72; nominal p=0.02), and those with “unknown” (ctDNA-undetected) resistance had longer 2L PFS than those with known resistance (7.4 vs 4.6 months; HR 0.63; nominal p=0.01)—a meaningful directional lift vs the typical ~4–6 month median PFS often seen with post-osimertinib chemotherapy-based approaches in unselected EGFRm NSCLC.