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The first drug against the KRAS protein nearly doubled survival in pancreatic cancer in 2026, but on its own it holds the disease for months, not years. Trials are now testing it in combination with a second RAS drug and with chemotherapy, and earlier in the disease; the open questions are which combination, in which order, and what works when the tumour escapes.
RASolute 302 (500 patients, second line) gave daraxonrasib a median survival of 13.2 against 6.7 months (hazard ratio 0.40) and approval in August 2026. The chemistry (Holderfield 2024) inhibits active mutant and wild-type RAS together, so the drug is agnostic to allele but carries wild-type-RAS toxicity (rash, stomatitis); the G12D-selective zoldonrasib spares normal tissue and, combined with daraxonrasib, is meant to close the wild-type and secondary-mutation escape routes (the pairing record g12d-plus-pan-ras). The registry now holds RASolute 303 (first line, alone or with gemcitabine and nab-paclitaxel, 900 estimated, primary completion June 2028), RASolute 309 (zoldonrasib plus daraxonrasib against chemotherapy in G12D disease, 400, March 2029), RASolute 304 (adjuvant, 500, May 2029), Incyte's DAWN-303 (G12D inhibitor with chemotherapy, 588, September 2028) and a G12D competitor trial (GFH375). What none of these answers is sequence: whether a patient who progresses on a RAS inhibitor benefits from a different one, whether chemotherapy after RAS inhibition retains its activity, and whether ctDNA clearance can be used to stop or switch early. Resistance through secondary RAS mutations, receptor tyrosine kinase bypass and adaptive feedback is already described in the roadmap's open problems.
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.
The mechanism that let one drug address G12D, G12V and G12R together, which is why the RASolute 302 trial could enrol unselected pancreatic cancer and nearly double survival.
Sotorasib is a guideline-listed later-line option for the 1 to 2 percent of pancreatic cancers with KRAS G12C, and the proof that KRAS in pancreatic cancer is druggable; the larger opportunity lies with inhibitors of G12D and pan-RAS drugs.
Shares CodeBreaK 100: sotorasib in KRAS p.G12C-mutated advanced pancreatic cancer, KRAS roadmap: undruggable → G12C → pan-RAS, KRAS & RAS inhibitors, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question and the tag pancreatic-evidence.
Shares KRAS roadmap: undruggable → G12C → pan-RAS, KRAS mutation subtypes (G12C, G12D, G12V), RAS / RAF / MEK / ERK (MAPK), Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question and the tag pancreatic-evidence.
Shares Study of Daraxonrasib (RMC-6236) in Patients With Resected Pancreatic Ductal Adenocarcinoma (PDAC), FOLFIRINOX / mFOLFIRINOX, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Resectable pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares Gemcitabine + nab-paclitaxel, FOLFIRINOX / mFOLFIRINOX, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Metastatic pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares RAS(ON) inhibitors to convert unresectable pancreatic cancer to resectable, FOLFIRINOX / mFOLFIRINOX, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Resectable pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares FOLFIRINOX / mFOLFIRINOX, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Resectable pancreatic ductal adenocarcinoma, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares Gemcitabine + nab-paclitaxel, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Metastatic pancreatic ductal adenocarcinoma, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares FOLFIRINOX / mFOLFIRINOX, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Resectable pancreatic ductal adenocarcinoma, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.