# Daraxonrasib in Previously Treated Advanced RAS -Mutated Pancreatic Cancer

Source: https://onco.cc/key-papers/paper-nct05379985-n-engl-j-med-2026/  
OnCo record `paper-nct05379985-n-engl-j-med-2026` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Published report from the trial registered as NCT05379985, in New England Journal of Medicine (2026), chosen as the most cited paper whose own text cites the registry id.

## Summary

Background: Current therapies for patients with pancreatic ductal adenocarcinoma (PDAC) provide modest benefit. Activating RAS mutations occur in more than 90% of PDAC tumors. Daraxonrasib (RMC-6236) is an oral RAS(ON) multiselective inhibitor that targets guanosine triphosphate-bound mutant and wild-type RAS.

Methods: In this phase 1-2 study, we evaluated daraxonrasib in patients with advanced solid tumors with activating RAS mutations. Patients received 10 to 400 mg of daraxonrasib orally once daily; 300 mg was selected as the phase 3 dose. The primary end point was safety. Pharmacokinetics and antitumor activity were secondary end points. This report focuses on the 168 study patients with previously treated RAS -mutated PDAC.

Results: Among the 168 patients with PDAC who received daraxonrasib at a dose of 300 mg or less, treatment-related adverse events of any grade were reported in 96%; such events of grade 3 or higher were reported in 30%. Treatment-related adverse events that occurred in at least 10% of the patients included rash, diarrhea, nausea, stomatitis or mucositis, vomiting, and fatigue. In a subgroup of 26 patients with RAS G12 mutations who were treated with second-line daraxonrasib at a dose of 300 mg, an objective response to therapy was reported in 35% (95% confidence interval [CI], 17 to 56). The median duration of response was 8.2 months (95% CI, 3.8 to not evaluable), with median values of 8.5 months for progression-free survival and 13.1 months for overall survival. Among the 38 patients with RAS G12, G13, or Q61 mutations, 29% (95% CI, 15 to 46) had an objective response. The median duration of response was 8.2 months (95% CI, 3.8 to 8.8), with median values of 8.1 months for progression-free survival and 15.6 months for overall survival.

Conclusions: Daraxonrasib was associated with treatment-related adverse events of grade 3 or higher in one third of patients with previously treated RAS -mutated PDAC; antitumor activity was also reported. (Funded by Revolution Medicines; RMC-6236-001 ClinicalTrials.gov number, NCT05379985.).

Indexed on Europe PMC as PubMed record 42090791 (DOI 10.1056/nejmoa2505783). Its abstract cites the registry id NCT05379985, which is how it was matched to this trial; no figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: New England Journal of Medicine
- Year: 2026
- DOI: 10.1056/nejmoa2505783
- Authors: Wolpin BM, Park W, Garrido-Laguna I, et al.
- What it means: This is the paper Europe PMC returns for registry id NCT05379985 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
- Caveats: Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.

## Sources

- N Engl J Med 2026: https://doi.org/10.1056/nejmoa2505783
- PubMed: https://pubmed.ncbi.nlm.nih.gov/42090791/
- Europe PMC: https://europepmc.org/article/MED/42090791
- ClinicalTrials.gov NCT05379985: https://clinicaltrials.gov/study/NCT05379985

## Connected records

- trials: [Study of RMC-6236 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS](https://onco.cc/trials/nct05379985/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- ideas: [RAS(ON) inhibitors to convert unresectable pancreatic cancer to resectable](https://onco.cc/ideas/idea-ras-inhibitor-neoadjuvant-pdac/)

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