Amivantamab + Carbo-Paclitaxel Halves Risk of Progression After Osimertinib—Regardless of EGFR or MET Resistance Mechanism

In the phase 3 MARIPOSA-2 trial (NCT04988295) of EGFR-mutant (Ex19del/L858R), which accounts for about 32% of all NSCLC cases%20in%20Europe.), advanced NSCLC patients that had progressed on osimertinib, 131 patients received the EGFR–MET bispecific amivantamab plus carboplatin-paclitaxel (ami-chemo) and 263 received chemotherapy alone. Baseline circulating-tumor-DNA sequencing identified MET amplification in 10% and secondary EGFR C797X/other mutations in 13% of patients in the ami-chemo arm. Ami-chemo improved median PFS from 4.2 mo to 5.9 mo overall (HR 0.49, p<0.001) and did so across resistance subgroups: METamp (HR 0.51), secondary EGFR mutations (HR 0.55), EGFR/MET-independent alterations (HR 0.54), and unknown mechanisms HR (0.31). Benefit persisted even with TP53 co-mutation (HR 0.63). Historical docetaxel ± ramucirumab in the same setting yields PFS ≈ 4–5 mo, underscoring the added value of antibody–chemo pairing here (NCT01168973).