Investigational Drug
daraxonrasib
TrialFetch AI Analysis
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Overview
Daraxonrasib (RMC-6236; brand name Rasonque) is an oral cancer drug developed by Revolution Medicines. Although research into additional uses continues, it is no longer investigational for all uses: the US FDA approved it 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. (fda.gov)
Mechanism of action
Daraxonrasib inhibits the active, GTP-bound form of RAS. It binds the cellular protein cyclophilin A; the resulting complex engages RAS and blocks downstream signaling. Its activity spans multiple mutant and wild-type RAS variants rather than a single mutation. (sciencedirect.com)
Efficacy
In the randomized phase 3 RASolute 302 trial, 500 patients with previously treated metastatic pancreatic cancer received daraxonrasib or the investigator’s choice of chemotherapy. Median overall survival was 13.2 versus 6.7 months in the full study population, and median progression-free survival was 7.2 versus 3.6 months, respectively. Objective response rates were 31.6% versus 11.2%. These results concern previously treated metastatic disease; they do not establish benefit in other settings. (pubmed.ncbi.nlm.nih.gov)
A separate early-phase study in previously treated RAS-mutant non-small-cell lung cancer reported tumor responses in more than 30% of patients. That use remains under study. (pubmed.ncbi.nlm.nih.gov)
Safety
In RASolute 302, adverse events of grade 3 or higher occurred in 61.8% of daraxonrasib recipients and 69.6% of chemotherapy recipients; treatment-related adverse events led to discontinuation in 1.2% and 11.2%, respectively. Earlier pancreatic-cancer trial results identified rash, diarrhea, nausea, mouth inflammation, vomiting and fatigue among treatment-related adverse events reported in at least 10% of patients. (pubmed.ncbi.nlm.nih.gov)
Further reading
- Phase 3 pancreatic-cancer trial, New England Journal of Medicine
- FDA approval announcement
- Daraxonrasib discovery and mechanism, Journal of Medicinal Chemistry
Last updated: Sep 2026
Active trials using daraxonrasib
Found 6 active trials using this drug:
TrialFetch AI summary: Adults with previously untreated metastatic KRAS G12D-mutated pancreatic adenocarcinoma and ECOG performance status 0–1 are randomized to oral daraxonrasib plus zoldonrasib or gemcitabine plus nab-paclitaxel. Daraxonrasib inhibits active RAS broadly, while zoldonrasib selectively inhibits active KRAS G12D.
ClinicalTrials.gov ID: NCT07805954
TrialFetch AI summary: Adults with advanced or metastatic solid tumors harboring homozygous MTAP deletion receive BMS-986504, an investigational MTA-cooperative PRMT5 inhibitor, alone or in tumor-specific combinations. Combination cohorts pair it with pumitamig (a PD-L1/VEGF-A bispecific antibody) and chemotherapy; daraxonrasib (a RAS(ON) inhibitor), with or without chemotherapy; nivolumab plus relatlimab; or temozolomide and radiotherapy.
ClinicalTrials.gov ID: NCT07492680
TrialFetch AI summary: Adults with newly diagnosed metastatic pancreatic adenocarcinoma, ECOG 0–1, and no prior systemic therapy for metastatic disease are randomized to first-line daraxonrasib alone, daraxonrasib plus gemcitabine/nab-paclitaxel, or gemcitabine/nab-paclitaxel alone. Daraxonrasib is an oral RAS(ON) inhibitor that targets active, GTP-bound RAS signaling.
ClinicalTrials.gov ID: NCT07491445
TrialFetch AI summary: Adults with ECOG 0–1 and advanced or metastatic RAS-mutant solid tumors are eligible; expansion cohorts include untreated nonsquamous NSCLC and previously treated solid tumors or colorectal cancer. Treatment pairs ivonescimab (PD-1/VEGF-A bispecific antibody) with a RAS(ON) inhibitor—daraxonrasib (multiple RAS variants), elironrasib (KRAS G12C), or zoldonrasib (KRAS G12D)—with selected cohorts adding platinum–pemetrexed, daraxonrasib, or cetuximab.
ClinicalTrials.gov ID: NCT07397338
TrialFetch AI summary: Adults with measurable, advanced KRAS G12V-mutant solid tumors after progression on or intolerance to standard therapy receive RMC-5127 alone or with daraxonrasib or cetuximab; prior direct RAS-targeted therapy is excluded. RMC-5127 is an investigational inhibitor of active KRAS G12V, daraxonrasib inhibits active RAS across multiple variants, and cetuximab targets EGFR.
ClinicalTrials.gov ID: NCT07349537
TrialFetch AI summary: Adults with unresectable locally advanced or metastatic NSCLC harboring a KRAS, NRAS, or HRAS codon 12, 13, or 61 mutation, previously treated with platinum chemotherapy and anti-PD-(L)1 therapy, are randomized to oral daraxonrasib or docetaxel. Daraxonrasib is a RAS(ON) inhibitor that targets active, GTP-bound RAS to block downstream signaling.
ClinicalTrials.gov ID: NCT06881784
