# Daraxonrasib

Source: https://onco.cc/drugs/daraxonrasib/  
OnCo record `daraxonrasib` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The first drug that blocks all active RAS variants, approved by the FDA in August 2026 for metastatic pancreatic cancer, where KRAS drives 90% of tumours.

## Summary

Daraxonrasib is Revolution Medicines' tri-complex inhibitor. Phase 1/2: median OS ~14.5 months in second-line pancreatic cancer versus historical ~6 months. RASolute 302 (second-line PDAC) supported FDA approval on 26 August 2026 as Rasonque for metastatic pancreatic cancer; RASolute 303 (first-line) and the NSCLC phase 3 (RASolve 301) continue. Rash and stomatitis are the main toxicities.

## Fields

- Kind: Treatment
- Status: approved
- Last checked: 2026-09-04
- Brand: Rasonque
- Code: RMC-6236
- Modality: Small-molecule pan-RAS(ON) inhibitor
- Mechanism: Binds cyclophilin A to form a tri-complex that sterically blocks RAS(ON) from engaging effectors, across G12X/G13X/Q61X and wild-type RAS.
- Approvals: US 2026: Metastatic pancreatic adenocarcinoma after at least one prior systemic therapy, or in adults who are not candidates for multiagent systemic therapy
- Dosing: Oral; 300 mg once daily (phase 3 dose; 200 mg in some cohorts)

## Notes

- Pancreatic cancer, regulators: the Rasonque label (effective 27 August 2026) indicates daraxonrasib 300 mg once daily for metastatic pancreatic adenocarcinoma after at least one prior systemic therapy or in adults who are not candidates for multi-agent chemotherapy, on RASolute 302 (overall population: overall survival 13.2 against 6.7 months, hazard ratio 0.40; progression-free survival by blinded review 7.2 against 3.6 months, hazard ratio 0.49; response 30 against 11 percent; RAS G12 population 13.2 against 6.6 months). Label safety (241 treated): serious adverse reactions 30 percent, discontinuation 2.9 percent, dose interruption 69 percent (rash 27, stomatitis 20 percent), dose reduction 37 percent. No EMA authorisation and no NICE appraisal were listed on 24 September 2026; RASolute 303 (first line) recruits at six UK hospitals and RASolute 304 (adjuvant) at six.
- Pancreatic ductal adenocarcinoma biomarkers: RASolute 302 enrolled on RAS G12, G13 or Q61 mutation or no identified RAS mutation rather than on one allele; 91.8% of the 500 patients carried a G12 allele and the hazard ratio for death was 0.40 in both the G12 and the overall population, so the practical threshold is a RAS-mutant or RAS-unknown tumour rather than a specific variant (O'Reilly 2026).

## Sources

- FDA approval notice: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-daraxonrasib-metastatic-pancreatic-adenocarcinoma
- FDA approval letter, NDA 220910: https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2026/220910Orig1s000ltr.pdf
- FDA prescribing information (label): https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/220910Orig1s000lbl.pdf
- FDA novel drug approvals 2026: https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2026
- Rasonque label (openFDA): indication, RASolute 302 results and adverse reactions: https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22RASONQUE%22
- FDA notice: daraxonrasib for metastatic pancreatic adenocarcinoma (26 August 2026): https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications
- O'Reilly et al., daraxonrasib or chemotherapy in previously treated metastatic pancreatic cancer, RASolute 302 (NEJM 2026): https://doi.org/10.1056/NEJMoa2605555
- Wolpin et al., daraxonrasib in previously treated advanced RAS-mutated pancreatic cancer, phase 1 (NEJM 2026): https://doi.org/10.1056/NEJMoa2505783

## Connected records

- cancers: [Borderline resectable pancreatic ductal adenocarcinoma](https://onco.cc/cancers/borderline-resectable-pdac/), [BRCA or PALB2-mutant pancreatic ductal adenocarcinoma](https://onco.cc/cancers/brca-palb2-pdac/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [KRAS G12C-mutant colorectal cancer](https://onco.cc/cancers/kras-g12c-colorectal/), [KRAS G12C-mutant non-small-cell lung cancer](https://onco.cc/cancers/kras-g12c-nsclc/), [KRAS G12C-mutant pancreatic ductal adenocarcinoma](https://onco.cc/cancers/kras-g12c-pdac/), [Locally advanced unresectable pancreatic ductal adenocarcinoma](https://onco.cc/cancers/locally-advanced-pdac/), [Metastatic pancreatic ductal adenocarcinoma](https://onco.cc/cancers/metastatic-pdac/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Resectable pancreatic ductal adenocarcinoma](https://onco.cc/cancers/resectable-pdac/)
- technologies: [KRAS & RAS inhibitors](https://onco.cc/technologies/kras-inhibitors/)
- targets: [KRAS](https://onco.cc/targets/kras/)
- companies: [Quanta Therapeutics](https://onco.cc/companies/quanta-therapeutics/), [Revolution Medicines](https://onco.cc/companies/revolution-medicines/)
- trials: [A Study of BMS-986504 Monotherapy and in Combination With Other Agents in Participants With Advanced and/or Metastatic Solid Tumors With Homozygous MTAP Deletion (MountainTAP-5)](https://onco.cc/trials/nct07492680/), [CodeBreaK 100 (pancreatic cancer cohort)](https://onco.cc/trials/codebreak-100/), [Phase 2 Study of Daraxonrasib in Recurrent KRAS-Mutant Biliary Tract Cancer](https://onco.cc/trials/nct07793253/), [RASolute 302](https://onco.cc/trials/rasolute-302/), [Study of Daraxonrasib (RMC-6236) in Patients With RAS Mutated NSCLC (RASolve 301)](https://onco.cc/trials/nct06881784/), [Study of Daraxonrasib (RMC-6236) in Patients With Resected Pancreatic Ductal Adenocarcinoma (PDAC)](https://onco.cc/trials/nct07252232/), [Study of Daraxonrasib and Daraxonrasib + GnP as First-line Treatment in Patients With Metastatic Pancreatic Adenocarcinoma](https://onco.cc/trials/nct07491445/), [Study of Elironrasib and Daraxonrasib as Monotherapies and Combination Therapy in Participants With Advanced KRAS G12C Mutant Solid Tumors](https://onco.cc/trials/nct06128551/), [Study of RAS(ON) Inhibitors in Combination With Ivonescimab in Patients With Solid Tumors](https://onco.cc/trials/nct07397338/), [Study of RAS(ON) Inhibitors in Patients With Advanced RAS-mutated NSCLC](https://onco.cc/trials/nct06162221/), [Study of RAS(ON) Inhibitors in Patients With Gastrointestinal Solid Tumors](https://onco.cc/trials/nct06445062/), [Study of RMC-6236 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS](https://onco.cc/trials/nct05379985/), [Study of RMC-9805 in Participants With KRAS G12D-Mutant Solid Tumors](https://onco.cc/trials/nct06040541/), [Study of Zoldonrasib (RMC-9805) Plus Daraxonrasib (RMC-6236) Versus Gemcitabine and Nab-Paclitaxel as First-Line Treatment in Metastatic KRAS G12D-Mut](https://onco.cc/trials/nct07805954/), [Study to Evaluate the Safety, Tolerability & Efficacy of TNG462 in Combination in PDAC & NSCLC Patients](https://onco.cc/trials/nct06922591/)
- key papers: [Concurrent inhibition of oncogenic and wild-type RAS-GTP for cancer therapy](https://onco.cc/key-papers/paper-holderfield-ras-on-multi-selective-inhibitor-nature-2024/), [Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer](https://onco.cc/key-papers/paper-daraxonrasib-pancreatic-n-engl-j-med-2026/), [Ostrem and Shokat: the hidden pocket that made KRAS G12C druggable](https://onco.cc/key-papers/paper-ostrem-kras-g12c-nature-2013/)
- drugs: [Zoldonrasib](https://onco.cc/drugs/zoldonrasib/)
- ideas: [Covalent chemistry for the RAS mutations that still have no drug](https://onco.cc/ideas/idea-bio1-pan-ras-covalent-g12d/), [Off-the-shelf KRAS vaccines after pancreatic cancer surgery](https://onco.cc/ideas/idea-shared-kras-vaccine-adjuvant/), [RAS inhibitor combinations and sequence: pan-RAS plus G12D-selective, plus chemotherapy, and what to give after progression](https://onco.cc/ideas/idea-pdac-ras-inhibitor-combinations-and-sequencing/), [RAS(ON) inhibitors to convert unresectable pancreatic cancer to resectable](https://onco.cc/ideas/idea-ras-inhibitor-neoadjuvant-pdac/)
- pairings: [G12D-selective + pan-RAS(ON) inhibitor (zoldonrasib + daraxonrasib)](https://onco.cc/pairings/g12d-plus-pan-ras/)
- roadmaps: [KRAS roadmap: undruggable → G12C → pan-RAS](https://onco.cc/roadmaps/kras-roadmap/), [Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question](https://onco.cc/roadmaps/pancreatic-roadmap/), [Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall](https://onco.cc/roadmaps/targeted-therapy-roadmap/)
- terms: [Pancreatic cancer drugs in England: NICE appraisals and the Cancer Drugs Fund (September 2026)](https://onco.cc/terms/pancreatic-cancer-uk-drug-access/)
- pathways: [Pancreatic cancer (KEGG map)](https://onco.cc/pathways/pancreatic-cancer-signalling/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/)
- bottlenecks: [The undruggable drivers](https://onco.cc/bottlenecks/b-undruggable-targets/)

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