RMC-6236
Overview
RMC-6236 is an investigational pan-RAS/KRAS inhibitor (RAS(ON) inhibitor) in clinical development for KRAS-driven malignancies, including pancreatic ductal adenocarcinoma (PDAC). Unlike allele-selective covalent KRAS G12C inhibitors, RMC-6236 is designed to inhibit multiple oncogenic KRAS variants.
Evidence in the corpus
- The MSK PDAC 2024 cohort (n=2,336) authors cite RMC-6236 as part of an emerging pan-RAS / KRAS-multi inhibitor pipeline. They argue that randomized trials of RAS inhibitors such as RMC-6236 should stratify both intervention and control arms by KRAS mutant-allele dosage (shallow copy-number gains present in ~20% of diploid KRAS-mutant PDAC), since dosage independently predicts shorter OS (HR_adj=1.7 in non-WGD subset, p=3.5×10⁻⁷) and may modify treatment response. PMID:39753968
- In that cohort, ~78% of PDAC patients carried KRAS G12D, G12V, G12R, G12A, or G12S alterations meeting OncoKB level 3A criteria based on the emerging RAS-inhibitor pipeline, making the actionable landscape highly relevant to pan-RAS agents like RMC-6236. PMID:39753968
Resistance mechanisms
- Not reported in corpus.
Cancer types (linked)
Sources
- PMID:39753968 — Zhu et al. 2024, MSK PDAC cohort (pdac_msk_2024); KRAS dosage stratification rationale for pan-RAS inhibitor trials.
This page was processed by crosslinker on 2026-05-04.