Vabametkib (ABN401), a selective type I c-MET TKI, posts 55% ORR in METex14 NSCLC and pivots to 350mg BID

Vabametkib (ABN401) is an oral, highly selective type I c-MET tyrosine kinase inhibitor being developed for MET-dysregulated solid tumors; this Phase 2, multicenter, open-label study enrolled NSCLC with MET exon 14 skipping confirmed by NGS (NCT05541822), treating with 800mg QD (n=42 efficacy; median age 76; treatment-naïve and previously treated cohorts). Blinded independent central review (BICR) showed ORR 55% overall (52% treatment-naïve; 57% previously treated), median DoR 14.5 months (19.9 vs 11.7 months), and median PFS 8.8 months (10.2 vs 7.3 months)—broadly in the same ballpark as approved MET TKIs tepotinib (VISION: ORR ~51%, mPFS ~11 months) and capmatinib (GEOMETRY mono-1: ORR ~68% 1L and ~41% pretreated; mDoR ~9.7 months in pretreated). TRAEs occurred in 89% with Grade ≥3 TRAEs in 11% (no Grade 4); common TRAEs were nausea (75%), diarrhea (34%), hypoalbuminemia (25%), rash (18%), vomiting (18%), and edema (16%), with Grade ≥3 pneumonitis 4.5%; dose reductions (22.7%) and interruptions (36.4%) were frequent, and exposure–response/PK simulation suggested BID dosing better maintained EC90 coverage, leading to selection of an alternative 350mg BID regimen for continued development.