# Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer

Source: https://onco.cc/key-papers/paper-daraxonrasib-pancreatic-n-engl-j-med-2026/  
OnCo record `paper-daraxonrasib-pancreatic-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

Phase 2 or 3 results paper on Daraxonrasib in Pancreatic ductal adenocarcinoma, in New England Journal of Medicine (2026), one of the most cited Europe PMC records with Daraxonrasib in its title.

## Summary

Background: Current therapies offer limited benefit for patients with previously treated metastatic pancreatic ductal adenocarcinoma (mPDAC). Aberrant activation of the RAS pathway is the key driver of PDAC, with oncogenic RAS mutations present in more than 90% of cases. Daraxonrasib is an oral RAS(ON) multiselective, tri-complex inhibitor of the active guanosine triphosphate-bound state of mutant and wild-type RAS.

Methods: In this phase 3, international, open-label, randomized trial, we randomly assigned patients with previously treated mPDAC to receive daraxonrasib or chemotherapy of the investigator's choice. The dual primary end points were overall survival and progression-free survival in the subpopulation of patients with RAS G12 mutations (the RAS G12 population). Key secondary end points included overall survival and progression-free survival in the overall population (which included patients with RAS G12, G13, or Q61 mutations or with no RAS mutation identified) and objective response and patient-reported quality of life in the RAS G12 and overall populations. Safety was also assessed.

Results: A total of 500 patients, including 91.8% with RAS G12 mutations, were randomly assigned to receive daraxonrasib (248 patients) or chemotherapy (252 patients). The median overall survival in the RAS G12 population was 13.2 months with daraxonrasib and 6.6 months with chemotherapy, and the median overall survival in the overall population was 13.2 months and 6.7 months, respectively; the hazard ratio was 0.40 in both populations (P<0.001). The median progression-free survival in the RAS G12 population was 7.3 months with daraxonrasib and 3.5 months with chemotherapy, and that in the overall population was 7.2 months and 3.6 months, respectively; the hazard ratios were 0.45 and 0.49, respectively (P<0.001 for both comparisons). Adverse events that occurred after the start of treatment were reported in all the patients in the daraxonrasib group and in 97.7% of those in the chemotherapy group; the incidence of adverse events of grade 3 or higher was 61.8% and 69.6%, respectively. Treatment-related adverse events that led to treatment discontinuation occurred in 1.2% of the patients in the daraxonrasib group and in 11.2% of those in the chemotherapy group.

Conclusions: Among patients with previously treated mPDAC, treatment with daraxonrasib led to significantly longer overall survival and progression-free survival than chemotherapy. (Funded by Revolution Medicines; RASolute 302 ClinicalTrials.gov number, NCT06625320.).

Indexed on Europe PMC as PubMed record 42223072 (DOI 10.1056/nejmoa2605555). Its title names Daraxonrasib and its text names Pancreatic ductal adenocarcinoma; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Comparative Study, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea "RAS(ON) inhibitors to convert unresectable pancreatic cancer to resectable" and 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/nejmoa2605555
- Authors: O'Reilly EM, Wainberg ZA, Hendifar AE, et al.
- What it means: One of the most cited trial reports Europe PMC returns for Daraxonrasib in Pancreatic ductal adenocarcinoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.
- Caveats: Matched by Daraxonrasib in the title and Pancreatic ductal adenocarcinoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.; Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper.

## Sources

- N Engl J Med 2026: https://doi.org/10.1056/nejmoa2605555
- PubMed: https://pubmed.ncbi.nlm.nih.gov/42223072/
- Europe PMC: https://europepmc.org/article/MED/42223072
- ClinicalTrials.gov NCT06625320: https://clinicaltrials.gov/study/NCT06625320

## Connected records

- trials: [RASolute 302](https://onco.cc/trials/rasolute-302/)
- 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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