RNK08954 (oral KRAS G12D inhibitor) posts 38.5% ORR in pretreated KRAS G12D NSCLC

RNK08954 is a potent, selective, oral small-molecule inhibitor of KRAS G12D evaluated in an ongoing first-in-human, multicenter, open-label Phase 1a/1b study (NCT06667544) enrolling solid tumors with KRAS G12D; this interim NSCLC readout includes 47 NSCLC patients, with 39 response-evaluable. At the Jan 20, 2026 data cutoff, ORR was 38.5% (15/39; 95% CI 23.4–55.4) and DCR was 94.9% (37/39), with median DoR not reached; most patients had ECOG 1 (91.5%) and 1–3 prior lines. Safety was dominated by mostly grade 1 GI toxicity (diarrhea 78.7%, nausea 61.7%, vomiting 55.3%); grade 3 TRAEs occurred in 23.4% (grade 3 diarrhea 10.6%), with no grade ≥3 ALT/AST signal and no fatal events—benchmarks to keep in mind in this post-platinum setting include docetaxel+ramucirumab (REVEL) ORR 23% and median PFS 4.5 months (vs docetaxel ORR 14%, PFS 3.0 months), albeit in an all-comers population not selected for KRAS G12D.