Zoldonrasib (RMC-9805) Hits 61% ORR in KRAS-G12D–Mutant NSCLC Dose-Expansion presented at AACR

Zoldonrasib is an oral, RAS(ON) G12D-selective “tri-complex” inhibitor that locks mutant KRAS to cyclophilin A. In the Phase 1 RMC-9805-001 study (NCT06040541), 18 heavily pre-treated NSCLC patients with KRAS G12D mutations received the recommended 1,200 mg QD dose: investigator-assessed ORR was 61% (11/18; 1 CR, 10 PR) with an 89% disease-control rate; median time-to-response was 1.4 mo and median time on treatment 2.6 mo. Across 90 solid-tumor patients treated at this dose, treatment-related AEs were mainly grade 1–2 (nausea 39%, diarrhea 24%, vomiting 18%, rash 12%); only two grade 3 events (2%) occurred, with no grade 4/5 toxicity or dose-limiting events reported.

https://aacrjournals.org/cancerres/article/85/8_Supplement_2/CT019/762489/Abstract-CT019-Preliminary-safety-and-antitumor