Amivantamab (EGFR–MET bispecific) delivers 32% ORR in METex14 NSCLC—including 19% post–MET TKI

Amivantamab is an intravenous EGFR–MET bispecific antibody with immune cell–directing activity evaluated in the CHRYSALIS trial in advanced MET exon 14 skipping (METex14) NSCLC after progression on or refusal of standard therapy (n=97; 16 treatment-naive; 28 pretreated without prior MET therapy; 53 pretreated with prior MET therapy). ORR was 32% overall (50% treatment-naive; 46% without prior MET therapy; 19% with prior MET therapy), with median DoR 11.2 months (61% of responders ≥6 months), median PFS 5.3 months, and median OS 15.8 months; in METex14 NSCLC, selective MET TKIs in the pre-MET-TKI setting commonly report ORR ~45%–68% and median PFS ~9.7–11.2 months, so amivantamab’s efficacy here looks more “later-line / post-TKI” than best-in-class first-line. Safety was dominated by on-target EGFR/MET effects and administration events (rash 79%, infusion-related reactions 72%; mostly grade 1–2), with reported treatment-related discontinuation ~9% and ILD/pneumonitis ~5% (grade ≥3 ~1%).