Daraxonrasib (RMC-6236) Clinical Trials (May 2026): 15 Recruiting Trials Across the Revolution Medicines pan-RAS(ON) Franchise

Last updated: May 25, 2026

🗓️ At ASCO 2026 (May 29 – June 2, Chicago): Updated data from the Phase 1/2 RMC-6236-001 study in advanced RAS-mutated solid tumors (NCT05379985), and the related RAS(ON) franchise compounds (elironrasib for G12C, RMC-9805 for G12D), are widely anticipated topics. Revolution Medicines' RAS(ON) program is one of the highest-profile oncology stories of 2026 because it is the first pan-RAS inhibitor class to reach Phase 3 — addressing variants (G12D, G12V, G12R) that the first-generation G12C-only inhibitors (sotorasib, adagrasib) cannot.

About Daraxonrasib

Drug profile:

Daraxonrasib (development code RMC-6236) is an investigational oral, first-in-class pan-RAS(ON) multi-selective inhibitor developed by Revolution Medicines. There is no brand name yet — daraxonrasib remains investigational and has no FDA approvals as of May 2026.

Mechanism of action:

Daraxonrasib is a tri-complex inhibitor: it simultaneously binds (i) the active, GTP-bound ('ON') state of RAS proteins and (ii) the chaperone protein cyclophilin A, assembling an inactive ternary complex that prevents RAS from engaging downstream effectors like RAF and PI3K. This locks the active RAS conformation in a non-signaling state. Critically, the binding surface is the GTP-bound state shared across multiple RAS isoforms — so a single drug has activity against KRAS G12C, G12D, G12V, G12R, G13D, as well as NRAS and HRAS. This is fundamentally different from the first-generation RAS(OFF) inhibitors (sotorasib, adagrasib), which bind only the inactive GDP-bound state of KRAS G12C specifically and therefore work in only the G12C variant.

Regulatory status:

FDA approvals: none yet. Daraxonrasib is investigational.
FDA designations: Fast Track designation for treatment of advanced pancreatic ductal adenocarcinoma (PDAC) and for previously-treated metastatic NSCLC. Breakthrough Therapy Designation in PDAC.
Phase 3 status: 3 Phase 3 trials are actively recruiting (RASolute 302 first-line metastatic PDAC; RASolute 304 adjuvant resected PDAC; RASolve 301 RAS-mutated NSCLC) — see Recruiting Trials below.
Anticipated first approval: based on the RASolute 302 or RASolute 304 PDAC Phase 3 readouts, expected 2027 at the earliest.

Active Research Directions in 2026

First registrational Phase 3s in PDAC — RASolute 302 (1L metastatic + chemo backbone) and RASolute 304 (adjuvant resected) are the two pivotal trials. PDAC is the lead indication because (a) over 90% of pancreatic cancers carry a KRAS mutation, (b) G12D is the dominant variant in PDAC (~40%) and is not addressable by G12C-only therapy, and (c) PDAC has the highest unmet need of any major cancer.
First registrational Phase 3 in NSCLC — RASolve 301 (NCT06881784) tests daraxonrasib in patients with advanced RAS-mutated NSCLC. While the G12C subset of NSCLC has approved RAS(OFF) inhibitors (sotorasib, adagrasib), daraxonrasib expands coverage to non-G12C KRAS variants and to NRAS / HRAS-mutant NSCLC.
Combination with checkpoint immunotherapy — NCT07397338 is testing the RAS(ON) inhibitors (daraxonrasib + companion compounds) in combination with ivonescimab (PD-1 × VEGF bispecific) in solid tumors. RAS inhibition is hypothesized to reverse the immune-cold microenvironment characteristic of RAS-driven tumors.
Pan-GI solid-tumor expansion — NCT06445062 (RAS(ON) inhibitors in GI solid tumors) and NCT06360354 (anvumetostat combinations) extend the franchise into colorectal, biliary, gastric, and other GI cancers where KRAS mutations are common.
Companion variant-selective compounds (the rest of the RAS(ON) franchise):
- Elironrasib (RMC-6291) — KRAS G12C-selective RAS(ON) inhibitor. Trial: NCT06128551 (elironrasib + daraxonrasib monotherapy and combination in KRAS G12C-mutated solid tumors).
- RMC-9805 — KRAS G12D-selective. Trial: NCT06040541 (advanced KRAS G12D-mutant solid tumors).
- RMC-5127 — KRAS G12V-selective. Trial: NCT07349537 (advanced KRAS G12V-mutant solid tumors).
- RMC-7977 (pan-RAS multi-targeted) and RMC-5552 (mTORC1) — earlier-stage research; co-administered with daraxonrasib in some studies to address resistance mechanisms.
External-sponsor RAS(ON) compounds in trials adjacent to the Revolution Medicines franchise:
- BMS-986504 (Bristol Myers Squibb) — pan-RAS(ON) inhibitor in NCT07492680 (combination Phase 1/2). BMS-986504 also appears as a partner compound on the pancreatic-cancer landscape page.
- ASP5834 (Astellas) — dose-finding study NCT07094204.
- TNG462 (Tango Therapeutics) — MTAP-deletion-selective synthetic-lethal inhibitor co-developed with daraxonrasib in NCT06922591 (PDAC + NSCLC combinations).

Recruiting Trials by Setting

Phase 3 Pivotal Trials (3 recruiting)

NCT07491445 — RASolute 302 (Phase 3): Daraxonrasib monotherapy and daraxonrasib + gemcitabine / nab-paclitaxel (GnP) vs standard-of-care chemotherapy as first-line treatment in patients with metastatic pancreatic ductal adenocarcinoma. The registrational metastatic-setting trial of the pan-RAS(ON) inhibitor.
NCT07252232 — RASolute 304 (Phase 3): Daraxonrasib vs SOC observation as adjuvant treatment in patients with resected pancreatic ductal adenocarcinoma following neoadjuvant and/or adjuvant chemotherapy. The registrational adjuvant-setting trial. Note: RASolute 302 + 304 testing the same drug in both first-line metastatic AND adjuvant resected settings simultaneously is unusual and reflects Revolution Medicines' confidence in the Phase 1/2 data.
NCT06881784 — RASolve 301 (Phase 3): Daraxonrasib in patients with advanced RAS-mutated non-small cell lung cancer.

Phase 1 / 2 — Daraxonrasib Monotherapy and Combinations (4 recruiting)

NCT05379985 — RMC-6236-001 (Phase 1/2): Foundational study of daraxonrasib in patients with advanced solid tumors harboring specific RAS mutations (KRAS G12X / NRAS / HRAS). The Phase 1/2 data from this study (presented at ASCO/ESMO 2024-2025) is the basis for the Phase 3 program.
NCT06128551 — Phase 1b/2: Elironrasib (RMC-6291, KRAS G12C-selective RAS(ON) inhibitor) and daraxonrasib as monotherapies and combination therapy in participants with KRAS G12C-mutated solid tumors.
NCT07397338 — RAS(ON) inhibitors in combination with ivonescimab (PD-1 × VEGF bispecific) in patients with solid tumors. Tests the hypothesis that RAS inhibition can sensitize RAS-driven tumors to checkpoint immunotherapy.
NCT06162221 — RAS(ON) inhibitors in patients with advanced RAS-mutated NSCLC (the Phase 1/2 precursor to RASolve 301).

Pan-GI / Solid Tumor Combinations (3 recruiting)

NCT06445062 — RAS(ON) inhibitors in patients with gastrointestinal solid tumors (PDAC, CRC, biliary, gastric).
NCT07252479 — Evaluation of RAS inhibitor treatment in participants with advanced or metastatic solid tumors.
NCT06360354 — Anvumetostat (PRMT5 inhibitor) in combination with other therapies in participants with advanced solid tumors — includes daraxonrasib as one of the partner agents.

Variant-Selective Companion Compounds (RAS(ON) franchise; 3 recruiting)

Daraxonrasib is the pan-RAS(ON) parent compound. Revolution Medicines also develops mutation-specific RAS(ON) inhibitors in parallel; these companions are often combined with daraxonrasib in studies.

NCT06040541 — RMC-9805 (KRAS G12D-selective) in participants with KRAS G12D-mutant solid tumors. KRAS G12D is the dominant variant in PDAC (~40%) and is a major target for the RAS(ON) franchise.
NCT07349537 — RMC-5127 (KRAS G12V-selective) in patients with advanced KRAS G12V-mutant solid tumors.
NCT07094204 — ASP5834 (Astellas pan-RAS) dose-finding study in adults with solid tumors.

External Combinations and Synthetic-Lethal Approaches (2 recruiting)

NCT06922591 — TNG462 (MTAP-deletion-selective synthetic-lethal inhibitor) in combination with daraxonrasib in PDAC and NSCLC. Tests the MTAP-deletion + RAS-mutant synthetic-lethal hypothesis.
NCT07492680 — (Not yet recruiting as of May 2026) BMS-986504 (Bristol Myers Squibb pan-RAS) monotherapy and combinations.

Showing the 15 currently-recruiting RAS(ON) franchise trials in the ClinTrialFinder corpus (plus 1 not-yet-recruiting). Earlier-phase and investigator-initiated combinations may not all be listed. View the latest daraxonrasib search on ClinicalTrials.gov.

Patient Selection and RAS Biomarker Testing

Eligibility for daraxonrasib trials is driven by RAS mutation status — and the specific variant matters less than for the G12C-only inhibitors, since daraxonrasib is pan-selective:

KRAS mutation (any variant — G12C, G12D, G12V, G12R, G13D, Q61, others): the primary eligibility marker for most daraxonrasib trials. Confirmed by tumor tissue NGS (next-generation sequencing) or liquid biopsy (ctDNA). The companion variant-selective compounds (elironrasib G12C, RMC-9805 G12D, RMC-5127 G12V) have stricter variant-specific eligibility.
NRAS / HRAS mutations: daraxonrasib also has activity against NRAS-mutant cancers (relevant in melanoma, AML, some NSCLCs) and HRAS-mutant cancers (relevant in salivary, urothelial, head & neck). Trials including these mutations: NCT05379985 (Phase 1/2 RMC-6236-001), NCT06162221, NCT07252479.
Tumor type: the PDAC Phase 3s (RASolute 302, 304) are PDAC-specific. The NSCLC Phase 3 (RASolve 301) is NSCLC-specific. The cross-tumor Phase 1/2 studies are open across many solid tumors with RAS mutations.
Comprehensive genomic profiling is recommended (e.g., Foundation Medicine, Tempus, Guardant360) — knowing your specific RAS variant determines which combination or trial arm you may be best suited for.
Prior RAS-targeted therapy: some trials enroll RAS-inhibitor-naive patients only; others (resistance / sequencing studies) require prior sotorasib or adagrasib. Check the specific trial protocol.

Side Effects and Practical Considerations

Daraxonrasib's safety profile is still being characterized as an investigational agent. Reported events from the Phase 1/2 RMC-6236-001 study and ASCO/ESMO 2024-2025 presentations:

Rash (most common) — dermatologic toxicity reflecting on-target RAS pathway inhibition in normal skin. Generally manageable with topical or oral steroids and dose modifications. Patients should expect close dermatology monitoring.
Gastrointestinal effects — nausea, vomiting, diarrhea, stomatitis (mouth sores). Standard supportive care (antiemetics, antidiarrheals, oral care) is used.
Fatigue and decreased appetite — common across the dose range.
Liver enzyme elevations — observed in some patients; routine LFT monitoring required.
Class effect considerations: as a first-in-class pan-RAS inhibitor, daraxonrasib hits a pathway active in many normal tissues (skin, GI epithelium). The toxicity profile broadly resembles other on-target oncogenic-signaling inhibitors (e.g., MEK inhibitors, EGFR inhibitors), but with its own pattern.
Combination-specific toxicities — daraxonrasib + gemcitabine/nab-paclitaxel (the RASolute 302 backbone) adds standard chemotherapy toxicities (myelosuppression, neuropathy, alopecia). Daraxonrasib + ivonescimab adds immune-related event risk.
Long-term safety — still being characterized; ongoing follow-up across the Phase 3 program will further define the profile.

Frequently Asked Questions

What is daraxonrasib (RMC-6236)?

Daraxonrasib (development code RMC-6236) is an investigational oral, first-in-class pan-RAS(ON) multi-selective inhibitor developed by Revolution Medicines. It is a tri-complex inhibitor that binds the active GTP-bound (ON) state of multiple RAS isoforms — KRAS G12C, G12D, G12V, G12R, G13D, NRAS, HRAS — together with cyclophilin A to form an inactive ternary complex. This 'RAS(ON)' mechanism is fundamentally different from the first-generation 'RAS(OFF)' inhibitors (sotorasib, adagrasib) that bind only the inactive GDP-bound state of KRAS G12C specifically. Daraxonrasib was the first pan-RAS(ON) inhibitor to enter Phase 3. No brand name yet; investigational, no FDA approvals as of May 2026.

What cancers and trial settings is daraxonrasib being tested in?

Three Phase 3 trials are recruiting: RASolute 302 (NCT07491445) — daraxonrasib monotherapy and daraxonrasib + GnP vs standard chemotherapy in first-line metastatic PDAC; RASolute 304 (NCT07252232) — daraxonrasib vs SOC observation as adjuvant after resected PDAC; and RASolve 301 (NCT06881784) — daraxonrasib in advanced RAS-mutated NSCLC. Plus combinations with ivonescimab (PD-1/VEGF bispecific, NCT07397338), pan-GI tumor studies (NCT06445062), the foundational Phase 1/2 study (NCT05379985), and the companion variant-selective compounds elironrasib (G12C, NCT06128551), RMC-9805 (G12D, NCT06040541), RMC-5127 (G12V, NCT07349537).

How is daraxonrasib different from sotorasib or adagrasib?

Sotorasib (Lumakras) and adagrasib (Krazati) are "RAS(OFF)" inhibitors — they bind the inactive GDP-bound conformation of KRAS G12C specifically, and target only the G12C variant (~13% of NSCLC, ~3-4% of CRC). Daraxonrasib is a "RAS(ON)" inhibitor — it binds the active GTP-bound conformation and assembles a ternary complex with cyclophilin A, blocking downstream signaling. The RAS(ON) mechanism is variant-agnostic: daraxonrasib has activity across KRAS G12C, G12D, G12V, G12R, G13D and across NRAS and HRAS. This is particularly important in pancreatic cancer, where over 90% of tumors carry a KRAS mutation but G12D is the dominant variant (~40%) — not addressable by G12C-only therapy.

What are the main side effects of daraxonrasib?

As an investigational agent, the safety profile is still being characterized. Reported events from the Phase 1/2 RMC-6236-001 study and ASCO/ESMO 2024-2025 presentations include rash (the most common, reflecting on-target RAS inhibition in normal skin), nausea, vomiting, diarrhea, stomatitis, fatigue, decreased appetite, and liver enzyme elevations. Patients enrolling in daraxonrasib trials should expect close laboratory and dermatology monitoring. Combination-specific toxicities depend on the partner regimen (chemotherapy backbone in RASolute 302; immunotherapy in the ivonescimab combination).

Find Daraxonrasib and RAS(ON) Trials Matched to Your Situation

Use ClinTrialFinder's AI-powered matching to find daraxonrasib (RMC-6236), elironrasib (G12C), RMC-9805 (G12D), RMC-5127 (G12V), and other RAS-targeted trials based on your specific cancer, KRAS / NRAS / HRAS mutation, prior treatments, and biomarker context.

Find Matching Trials

This page is for information only and is not medical advice. ClinTrialFinder helps you find clinical trials that may match your situation, but enrollment decisions and treatment choices should always be made with your oncologist or healthcare team. Trial eligibility, recruitment status, and treatment details can change — verify directly with the trial sponsor or on ClinicalTrials.gov before acting on any information here.