Daraxonrasib (RMC-6236) Clinical Trials (June 2026): ASCO 2026 RASolute 302 Plenary + 4 Phase 3 Trials in the Revolution Medicines pan-RAS(ON) Franchise

Last updated: June 9, 2026 (post-ASCO 2026)

📌 ASCO 2026 Plenary (May 31, 2026, Abstract LBA5) — RASolute 302 readout: The pivotal Phase 3 RASolute 302 trial (NCT06625320; Active, not recruiting) of daraxonrasib monotherapy vs investigator's choice of chemotherapy in previously treated metastatic pancreatic ductal adenocarcinoma (PDAC) was presented in the ASCO 2026 Plenary by Brian M. Wolpin, MD, MPH (Dana-Farber). In the ITT population (n≈500): median overall survival 13.2 months with daraxonrasib vs 6.7 months with chemotherapy (HR 0.40, p<0.0001) — a 60% reduction in risk of death. Median PFS 7.2 vs 3.6 months. ORR 31.6% vs 11.2%. In the RAS G12-mutant subgroup: median OS 13.2 vs 6.6 months, PFS 7.3 vs 3.5 months, ORR 33.2% vs 11.8%. Grade 3+ AEs 43.6% (daraxonrasib) vs 57.5% (chemo); discontinuation for AEs 1.2% vs 11.2%. This is the first Phase 3 in metastatic PDAC across any line to report median OS > 1 year. The PDAC RASolute 302 registrational trial is not in the actively-recruiting list below — it is currently Active, not recruiting.

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 June 2026.

Mechanism of action:

Daraxonrasib is a noncovalent 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. The binding interface uses residues conserved across canonical RAS isoforms (KRAS, NRAS, HRAS) and across the major oncogenic mutational hotspots, so a single drug has activity across G12X variants (G12D, G12V, G12C, G12R) and Q61X variants, in addition to wild-type RAS. 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 only against the G12C variant.

Regulatory status:

FDA approvals: none yet. Daraxonrasib is investigational.
FDA designations: Fast Track designation for advanced pancreatic ductal adenocarcinoma (PDAC) and for previously-treated metastatic NSCLC. Breakthrough Therapy Designation in PDAC.
Phase 3 status: the pivotal RASolute 302 (NCT06625320) in previously treated metastatic PDAC is the source of the ASCO 2026 LBA5 plenary readout (status: Active, not recruiting). Three additional Phase 3 trials are actively recruiting: RASolute 303 (1L metastatic PDAC), RASolute 304 (adjuvant resected PDAC), and RASolve 301 (previously treated RAS-mutated NSCLC). Revolution Medicines' companion G12D-selective compound zoldonrasib (RMC-9805) is also in a Phase 3, RASolute 305 (NCT07621718), in 1L KRAS G12D-mutant metastatic PDAC.
Anticipated first approval: based on the RASolute 302 PDAC plenary readout, regulatory filings are expected to follow; the first approval — likely in previously treated metastatic PDAC — is anticipated 2026–2027.

Active Research Directions in 2026

Pivotal Phase 3 readout in pretreated PDAC (ASCO 2026) — RASolute 302 (NCT06625320) was presented in the ASCO 2026 Plenary (Abstract LBA5, May 31, 2026). Daraxonrasib monotherapy doubled median OS vs investigator's choice chemotherapy in previously treated metastatic PDAC (13.2 vs 6.7 months, HR 0.40, p<0.0001). This is the first Phase 3 in metastatic PDAC across any line to report median OS > 1 year. The trial is now Active, not recruiting.
Registrational Phase 3s in 1L and adjuvant PDAC (recruiting) — RASolute 303 (NCT07491445; 1L metastatic + chemo backbone) and RASolute 304 (NCT07252232; adjuvant resected) extend the PDAC franchise to earlier lines. 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.
Registrational Phase 3 in previously treated RAS-mutant NSCLC — RASolve 301 (NCT06881784) tests daraxonrasib vs docetaxel in patients with previously treated advanced RAS-mutated NSCLC (target enrollment ~420 patients; enrollment continuing through 2026 per the Revolution Medicines Q1 2026 update). 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.
Companion G12D-selective compound now in Phase 3 — Zoldonrasib (RMC-9805), the KRAS G12D-selective RAS(ON) inhibitor, entered Phase 3 in RASolute 305 (NCT07621718): zoldonrasib + investigator's choice chemotherapy (mFOLFIRINOX or GnP) vs placebo + chemotherapy in 1L metastatic KRAS G12D-mutated PDAC.
Combination with checkpoint immunotherapy — NCT07397338 tests 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) extends 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; FDA Breakthrough Therapy Designation in previously treated KRAS G12C-mutant NSCLC. Trial: NCT06128551 (elironrasib + daraxonrasib monotherapy and combination in KRAS G12C-mutated solid tumors).
- Zoldonrasib (RMC-9805) — KRAS G12D-selective; INN-assigned. Phase 1 NCT06040541 in advanced KRAS G12D-mutant solid tumors. Phase 3 RASolute 305 (NCT07621718) in 1L metastatic KRAS G12D PDAC.
- RMC-5127 — KRAS G12V-selective. Trial: NCT07349537 (advanced KRAS G12V-mutant solid tumors).
External-sponsor RAS and synthetic-lethal compounds in trials adjacent to the Revolution Medicines franchise:
- ASP5834 (Astellas) — Phase 1 RAS dose-finding study NCT07094204.
- AN9025 (Adlai Nortye) — Phase 1 RAS-mutant solid-tumor study NCT07252479 (multi-RAS targeting).
- TNG462 (Tango Therapeutics; Revolution Medicines collaborator) — MTAP-deletion-selective synthetic-lethal PRMT5 inhibitor co-developed with daraxonrasib in NCT06922591 (PDAC + NSCLC combinations).
- BMS-986504 (Bristol Myers Squibb) — MTAP-deletion-selective PRMT5 inhibitor (MountainTAP-5, NCT07492680; Phase 2; status: Not yet recruiting). This is not a pan-RAS inhibitor but is included here because MTAP-deletion biology overlaps with RAS-driven cancers.

Trials by Setting

Phase 3 Pivotal Trials (4 trials; 3 recruiting + 1 active/not-recruiting)

NCT06625320 — RASolute 302 (Phase 3; Active, not recruiting): Daraxonrasib monotherapy vs investigator's choice of standard-of-care chemotherapy in patients with previously treated metastatic PDAC. This is the source of the ASCO 2026 Plenary LBA5 readout (May 31, 2026): median OS 13.2 vs 6.7 months (HR 0.40, p<0.0001), median PFS 7.2 vs 3.6 months, ORR 31.6% vs 11.2% in the ITT population (~500 patients). Lead sponsor: Revolution Medicines.
NCT07491445 — RASolute 303 (Phase 3; Recruiting): 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 first-line metastatic-setting trial. Lead sponsor: Revolution Medicines.
NCT07252232 — RASolute 304 (Phase 3; Recruiting): 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. Lead sponsor: Revolution Medicines.
NCT06881784 — RASolve 301 (Phase 3; Recruiting): Daraxonrasib vs docetaxel in patients with previously treated advanced RAS-mutated NSCLC (target ~420 patients). Lead sponsor: Revolution Medicines.

Companion-Compound Phase 3 (1 recruiting)

NCT07621718 — RASolute 305 (Phase 3; Recruiting): Zoldonrasib (RMC-9805, KRAS G12D-selective) + investigator's choice of chemotherapy (mFOLFIRINOX or gemcitabine + nab-paclitaxel) vs placebo + chemotherapy in 1L metastatic KRAS G12D-mutant pancreatic adenocarcinoma. Lead sponsor: Revolution Medicines.

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

NCT05379985 — RMC-6236-001 (Phase 1/2; Recruiting): Foundational study of daraxonrasib in patients with advanced solid tumors harboring specific RAS mutations (KRAS G12 / NRAS / HRAS). The Phase 1/2 data from this study (presented at ASCO/ESMO 2024-2026 and AACR 2026) is the basis for the Phase 3 program. Lead sponsor: Revolution Medicines.
NCT06128551 — Phase 1/2; Recruiting: Elironrasib (RMC-6291, KRAS G12C-selective RAS(ON) inhibitor) and daraxonrasib as monotherapies and in combination in participants with advanced KRAS G12C-mutant solid tumors. Lead sponsor: Revolution Medicines.
NCT07397338 — Phase 1/2; Recruiting: 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. Lead sponsor: Revolution Medicines (collab: Summit Therapeutics).
NCT06162221 — Phase 1/2; Recruiting: RAS(ON) inhibitors in patients with advanced RAS-mutated NSCLC (the Phase 1/2 precursor to RASolve 301). Lead sponsor: Revolution Medicines.

Pan-GI / Solid Tumor Cross-Indication (2 recruiting)

NCT06445062 — Phase 1/2; Recruiting: RAS(ON) inhibitors in patients with gastrointestinal solid tumors (PDAC, CRC, biliary, gastric). Lead sponsor: Revolution Medicines.
NCT07252479 — Phase 1; Recruiting: AN9025 (Adlai Nortye, oral RAS inhibitor) in participants with advanced/metastatic solid tumors harboring RAS mutations. External sponsor (not part of the Revolution Medicines RAS(ON) franchise).

Variant-Selective Companion Compounds (Revolution Medicines RAS(ON) franchise; 2 Phase 1 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 — Zoldonrasib (RMC-9805, KRAS G12D-selective) in participants with KRAS G12D-mutant solid tumors (Phase 1; Recruiting). KRAS G12D is the dominant variant in PDAC (~40%) and is a major target for the RAS(ON) franchise. Lead sponsor: Revolution Medicines.
NCT07349537 — RMC-5127 (KRAS G12V-selective) in patients with advanced KRAS G12V-mutant solid tumors (Phase 1; Recruiting). Lead sponsor: Revolution Medicines.

External RAS-Adjacent / Synthetic-Lethal Approaches (3 trials; 2 recruiting + 1 not yet recruiting)

NCT07094204 — ASP5834 (Astellas) Phase 1 dose-finding study in adults with solid tumors (Recruiting).
NCT06922591 — TNG462 (Tango Therapeutics; collaboration with Revolution Medicines), an MTAP-deletion-selective synthetic-lethal PRMT5 inhibitor, in combination with daraxonrasib in PDAC and NSCLC (Phase 1/2; Recruiting). Tests the MTAP-deletion + RAS-mutant synthetic-lethal hypothesis.
NCT07492680 — BMS-986504 (Bristol Myers Squibb, MountainTAP-5; Phase 2; Not yet recruiting): monotherapy and combinations in advanced/metastatic solid tumors with homozygous MTAP deletion. Note: BMS-986504 is an MTAP-deletion-selective agent (per the official protocol), not a pan-RAS inhibitor. Included here because of MTAP/RAS biology overlap.

Showing the daraxonrasib-related and RAS(ON)-franchise trials in the ClinTrialFinder corpus as of June 2026 (post-ASCO refresh). All NCT IDs, phases, sponsors, and recruitment status above are verified against the corpus. 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 multi-selective:

KRAS mutation (any G12X or Q61X variant: G12D, G12V, G12C, G12R, Q61H/K/L/R, 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), zoldonrasib (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) and NCT06162221 (Phase 1/2 NSCLC).
Tumor type: the PDAC Phase 3s (RASolute 302 pretreated, RASolute 303 1L, RASolute 304 adjuvant) 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

Phase 3 safety data from RASolute 302 (ASCO 2026 Plenary LBA5) and Phase 1/2 data from RMC-6236-001 (ASCO/ESMO 2024-2026, AACR 2026):

Phase 3 RASolute 302 high-level safety (vs investigator's choice chemo, n≈500): Grade 3+ adverse events 43.6% (daraxonrasib) vs 57.5% (chemotherapy); treatment discontinuation due to AEs 1.2% vs 11.2%. Daraxonrasib was generally better tolerated than standard chemotherapy in this population.
Rash and stomatitis (most common treatment-related events leading to dose reduction in RASolute 302) — dermatologic and mucosal toxicity reflecting on-target RAS pathway inhibition in normal skin and oral epithelium. Generally manageable with topical or oral steroids, oral care, and dose modifications. Patients should expect close dermatology and oral-care monitoring.
Other gastrointestinal effects — nausea, vomiting, diarrhea. Standard supportive care (antiemetics, antidiarrheals) 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(ON) 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 303 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 noncovalent tri-complex inhibitor that binds the active GTP-bound (ON) state of canonical RAS isoforms (KRAS, NRAS, HRAS) — including the major oncogenic G12X (G12D, G12V, G12C, G12R) and Q61X variants — together with cyclophilin A to form an inactive ternary complex. At the 2026 ASCO Annual Meeting (May 31, 2026 Plenary Session, Abstract LBA5), the pivotal Phase 3 RASolute 302 trial (NCT06625320) reported median OS 13.2 vs 6.7 months for daraxonrasib vs chemotherapy in previously treated metastatic PDAC (HR 0.40, p<0.0001) — a 60% reduction in risk of death. No brand name yet; investigational, no FDA approvals as of June 2026.

What cancers and trial settings is daraxonrasib being tested in?

Four Phase 3 trials of daraxonrasib are listed in our corpus: RASolute 302 (NCT06625320, Active not recruiting) — the pivotal trial in previously treated metastatic PDAC (the basis of the ASCO 2026 LBA5 plenary readout); RASolute 303 (NCT07491445, Recruiting) — daraxonrasib monotherapy and daraxonrasib + GnP vs standard chemotherapy in first-line metastatic PDAC; RASolute 304 (NCT07252232, Recruiting) — daraxonrasib vs SOC observation as adjuvant after resected PDAC; and RASolve 301 (NCT06881784, Recruiting) — daraxonrasib vs docetaxel in previously treated RAS-mutated NSCLC. A fifth franchise Phase 3 — RASolute 305 (NCT07621718, Recruiting) — tests the G12D-selective companion zoldonrasib (RMC-9805) + chemo in 1L KRAS G12D PDAC. 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), zoldonrasib (G12D, NCT06040541), and 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 binding interface uses residues conserved across RAS isoforms and across oncogenic mutational hotspots, so daraxonrasib has multi-selective activity across G12X variants (G12D, G12V, G12C, G12R) and Q61X variants, in addition to wild-type RAS, and across KRAS, 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?

In the Phase 3 RASolute 302 trial reported at ASCO 2026 (Abstract LBA5), Grade 3+ adverse events occurred in 43.6% of the daraxonrasib arm vs 57.5% of the chemo arm, and treatment discontinuation for AEs was 1.2% vs 11.2% — daraxonrasib was generally better tolerated than standard chemotherapy. The most commonly reported events from the RMC-6236-001 Phase 1/2 study and 2024-2026 ASCO/ESMO/AACR presentations include rash (the most common, reflecting on-target RAS inhibition in normal skin), stomatitis, nausea, vomiting, diarrhea, fatigue, decreased appetite, and liver enzyme elevations. Patients enrolling in daraxonrasib trials should expect close laboratory, dermatology, and oral-care monitoring. Combination-specific toxicities depend on the partner regimen (chemotherapy backbone in RASolute 303; 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), zoldonrasib (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.

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