# RAS(ON) inhibitors to convert unresectable pancreatic cancer to resectable

Source: https://onco.cc/ideas/idea-ras-inhibitor-neoadjuvant-pdac/  
OnCo record `idea-ras-inhibitor-neoadjuvant-pdac` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

If daraxonrasib shrinks metastatic tumours this well, use it before surgery to make more locally advanced tumours operable.

## Summary

The proposal is to give the RAS(ON) inhibitor daraxonrasib, with or without chemotherapy, before surgery for borderline resectable and locally advanced pancreatic ductal adenocarcinoma, to see whether it raises the R0 resection rate compared with mFOLFIRINOX. Surgery remains the only route to cure, yet only a minority of patients present with resectable disease. The rationale is the deep and rapid responses seen with daraxonrasib and zoldonrasib, oral dosing, ctDNA clearance as an early surrogate, and the fact that RASolute 303 and 304 already move the drug earlier. The test would be a randomised phase 2 with R0 resection as the primary endpoint. At an early clinical stage, it addresses the bottleneck of the undruggable drivers.

## Fields

- Kind: Idea
- Last checked: 2026-09-06
- Hypothesis: Neoadjuvant daraxonrasib (± chemotherapy) increases R0 resection rate and 2-year DFS in borderline/locally advanced PDAC compared with mFOLFIRINOX.
- Rationale: Deep, rapid responses; oral dosing; ctDNA as an early surrogate; RASolute 303/304 already move the drug earlier.
- Proposed test: Randomised phase 2 with R0 resection as primary and DFS/OS secondary; pathologic response and ctDNA clearance as biomarkers.
- Maturity: early-clinical

## Sources

- ClinicalTrials.gov NCT06625320: RASolute 302: https://clinicaltrials.gov/study/NCT06625320

## Connected records

- cancers: [Borderline resectable pancreatic ductal adenocarcinoma](https://onco.cc/cancers/borderline-resectable-pdac/), [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/), [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/)
- targets: [KRAS](https://onco.cc/targets/kras/)
- drugs: [Daraxonrasib](https://onco.cc/drugs/daraxonrasib/), [FOLFIRINOX / mFOLFIRINOX](https://onco.cc/drugs/folfirinox/), [Zoldonrasib](https://onco.cc/drugs/zoldonrasib/)
- trials: [RASolute 302](https://onco.cc/trials/rasolute-302/)
- key papers: [Daraxonrasib in Previously Treated Advanced RAS -Mutated Pancreatic Cancer](https://onco.cc/key-papers/paper-nct05379985-n-engl-j-med-2026/), [Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer](https://onco.cc/key-papers/paper-daraxonrasib-pancreatic-n-engl-j-med-2026/), [Daraxonrasib: A Breakthrough in Pancreatic Ductal Adenocarcinoma](https://onco.cc/key-papers/paper-daraxonrasib-pancreatic-cureus-2026/)
- terms: [Neoadjuvant therapy versus surgery first for resectable and borderline resectable pancreatic cancer](https://onco.cc/terms/neoadjuvant-versus-upfront-surgery-pancreatic/)
- roadmaps: [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/)
- ideas: [Chemotherapy before surgery for every resectable pancreatic cancer, settled by the two perioperative trials rather than assumed](https://onco.cc/ideas/idea-pdac-neoadjuvant-chemotherapy-for-all-resectable-disease/), [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/)
- bottlenecks: [The undruggable drivers](https://onco.cc/bottlenecks/b-undruggable-targets/)

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