Telisotuzumab vedotin (c-Met ADC) shows similar activity with or without MET amplification in 2L+ EGFR-WT NSQ NSCLC

Telisotuzumab vedotin (Teliso-V) is a c-Met–directed antibody–drug conjugate linking telisotuzumab to the MMAE microtubule inhibitor payload; this retrospective LUMINOSITY (Phase 2; NCT03539536) subgroup analysis evaluated whether baseline MET amplification (FISH and/or ctDNA) altered outcomes in previously treated (2L+) non-squamous EGFR-WT NSCLC with c-Met protein overexpression (IHC SP44 3+ in ≥25% tumor cells; n=108 tested; 76 efficacy-evaluable with MET-amp results). MET amp was present in 34% overall (37/108) and enriched in high c-Met OE (3+ ≥50%: 45% [26/58] vs intermediate 3+ 25–49%: 22% [11/50]); across all c-Met OE (3+ ≥25%), ORR was 39% with MET amp (N=23) vs 28% without MET amp (N=53) and median PFS was 8.02 vs 5.26 months, with a “durable” subgroup signal noted (79% of patients with PFS ≥10 months had MET GCN ≥10 and/or high c-Met OE). Safety was described as having no new signals in the MET-amp subgroup; efficacy looks directionally better than common post-platinum benchmarks like docetaxel alone (historically low-teens ORR) and roughly in the range of docetaxel+ramucirumab in unselected 2L NSCLC (ORR ~23%, median PFS ~4.5 months), though this is a non-randomized biomarker-selected comparison.