ideasIdea
RAS(ON) inhibitors to convert unresectable pancreatic cancer to resectable
If daraxonrasib shrinks metastatic tumours this well, use it before surgery to make more locally advanced tumours operable.
Surgery remains the only cure. Only ~20% present resectable; another ~30% are borderline or locally advanced. Response rates with daraxonrasib and zoldonrasib combinations exceed those of FOLFIRINOX, and ctDNA clearance is frequent.
Confidence
35%–60%likelyOnCo editors (initial estimate), 2026-09-07 · Depends on RASolute 302 confirmation and resectability conversion.
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.
What would test it
Randomised phase 2 with R0 resection as primary and DFS/OS secondary; pathologic response and ctDNA clearance as biomarkers.
Maturity
early clinical