Investigational Drug
RMC-6236
TrialFetch AI Analysis
Show TrialFetch AI Analysis
Overview
RMC-6236—also called daraxonrasib, RAS inhibitor A122, and, in the United States, Rasonque—is an oral, multiselective RAS inhibitor developed by Revolution Medicines. Although originally investigational, it received FDA approval on August 26, 2026, for adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or are not candidates for multiagent systemic therapy. Its use in lung cancer and other settings remains investigational. (fda.gov)
Mechanism of action
Daraxonrasib is a noncovalent RAS(ON) tri-complex inhibitor. It first binds cyclophilin A; the resulting complex binds active, GTP-bound mutant and wild-type RAS proteins, disrupting interactions with downstream effectors and suppressing RAS–MAPK signaling. Unlike allele-specific inhibitors, it is designed to act across multiple KRAS, NRAS and HRAS variants. (pmc.ncbi.nlm.nih.gov)
Efficacy
In the randomized phase 3 RASolute 302 trial, 500 patients with previously treated metastatic pancreatic adenocarcinoma received daraxonrasib or investigator-selected chemotherapy. In the overall population:
- Median overall survival was 13.2 vs 6.7 months (hazard ratio 0.40).
- Median progression-free survival was 7.2 vs 3.6 months (hazard ratio 0.49).
- Objective response rates were 33.2% vs 11.8%.
Results were similar in the prespecified RAS G12-mutated population. (nejm.org)
Earlier phase 1–2 pancreatic-cancer data at 300 mg showed a 35% response rate among 26 second-line patients with RAS G12 mutations, with median response duration of 8.2 months. (doi.org)
In a phase 1–2 study involving 136 patients with previously treated RAS-mutant non-small-cell lung cancer, response rates ranged from 31% to 37% across dose groups up to 300 mg daily. These findings are preliminary, and daraxonrasib is not FDA-approved for lung cancer. (pubmed.ncbi.nlm.nih.gov)
Safety
In RASolute 302, grade 3 or higher adverse events occurred in 61.8% of daraxonrasib-treated patients versus 69.6% with chemotherapy. Treatment-related toxicity caused discontinuation in 1.2% versus 11.2%, respectively. Important toxicities include dermatologic reactions, stomatitis or oral mucositis, diarrhea, gastrointestinal perforation and interstitial lung disease/pneumonitis. (nejm.org)
In the NSCLC phase 1–2 study, 54% experienced grade 3 or higher adverse events; common events included rash, diarrhea, nausea, vomiting and stomatitis. Four grade 5 events were reported, although the abstract does not indicate that all were treatment-related. (pubmed.ncbi.nlm.nih.gov)
Further reading
- Phase 3 RASolute 302 results — New England Journal of Medicine
- Phase 1–2 pancreatic-cancer results — New England Journal of Medicine
- NSCLC phase 1–2 study — PubMed
- Preclinical mechanism and translational evaluation — Nature
- FDA approval summary
Last updated: Sep 2026
Active trials using RMC-6236
Found 6 active trials using this drug:
TrialFetch AI summary: Adults with previously treated advanced pancreatic ductal adenocarcinoma or NSCLC harboring MTAP loss and a RAS mutation receive oral vopimetostat (TNG462), an MTAP-selective PRMT5 inhibitor, plus either daraxonrasib (RMC-6236), a multi-variant RAS inhibitor, or zoldonrasib (RMC-9805), a KRAS G12D inhibitor. Prior RAS-targeted therapy, PRMT5 inhibitors, or MAT2A inhibitors are excluded.
ClinicalTrials.gov ID: NCT06922591
TrialFetch AI summary: Adults with unresectable locally advanced or metastatic pancreatic ductal adenocarcinoma and homozygous MTAP deletion receive AMG 193, an MTA-cooperative PRMT5 inhibitor, with gemcitabine/nab-paclitaxel or modified FOLFIRINOX. A separate cohort with RAS-mutant disease and prior systemic therapy receives AMG 193 with RMC-6236, a multiselective RAS(ON) inhibitor.
ClinicalTrials.gov ID: NCT06360354
TrialFetch AI summary: Adults with unresectable or metastatic colorectal cancer or metastatic pancreatic ductal adenocarcinoma receive oral RMC-6236, a multiselective active-RAS inhibitor, combined with fluorouracil-based chemotherapy and bevacizumab, cetuximab with or without mFOLFOX6, or gemcitabine plus nab-paclitaxel. In RAS G12D-mutant cohorts, the active-RAS G12D inhibitor RMC-9805 is given with or without RMC-6236 alongside the corresponding regimens.
ClinicalTrials.gov ID: NCT06445062
TrialFetch AI summary: This study enrolls previously treated adults with locally advanced or metastatic RAS-mutated NSCLC, with additional cohorts for KRAS G12C-mutated solid tumors and KRAS G12D-mutated NSCLC. It evaluates active RAS inhibitors—KRAS G12C–targeted RMC-6291, multi-variant RAS–targeted RMC-6236, and KRAS G12D–targeted RMC-9805—in mutation-specific combinations with pembrolizumab, with or without platinum/pemetrexed chemotherapy.
ClinicalTrials.gov ID: NCT06162221
TrialFetch AI summary: Adults with locally advanced or metastatic KRAS G12D-mutant solid tumors after progression on or intolerance to standard therapy receive oral zoldonrasib (RMC-9805), an active KRAS G12D inhibitor, alone or with daraxonrasib (RMC-6236), an active pan-RAS inhibitor. Both drugs form cyclophilin A–mediated complexes to disrupt RAS signaling.
ClinicalTrials.gov ID: NCT06040541
TrialFetch AI summary: Adults with previously treated advanced solid tumors and ECOG 0–1 are eligible for genotype-defined cohorts with KRAS, NRAS, or HRAS mutations; a separate cohort includes RAS–wild-type pancreatic ductal adenocarcinoma. All patients receive oral daraxonrasib (RMC-6236), a multiselective RAS(ON) inhibitor that blocks signaling by active RAS.
ClinicalTrials.gov ID: NCT05379985
