For forty years the central driver of pancreatic cancer, the KRAS mutation, ran ahead of every targeted drug anyone could draw to chase it. Generations of medicinal chemists wrote “undruggable” in print and meant it. On the last Sunday of May, in a plenary hall in Chicago, Brian Wolpin of Dana-Farber Cancer Institute put up the curve that ended the run, in a trial whose median follow-up was 8.5 months and whose sponsor’s finances had already been wired for a two-billion-dollar bet from one of the more cold-eyed houses in oncology royalty.

The trial was RASolute 302, run by Revolution Medicines and published the same week in the New England Journal of Medicine. Five hundred patients with metastatic pancreatic ductal adenocarcinoma who had already failed first-line treatment were randomized to either daraxonrasib, an oral once-daily RAS(ON) inhibitor that binds both mutant and wild-type active RAS, or one of four investigator’s-choice second-line chemotherapies: gemcitabine plus nab-paclitaxel, liposomal irinotecan with 5-FU and leucovorin, modified FOLFIRINOX, or FOLFOX. The drug arm lived a median of 13.2 months. The chemo arm lived 6.7. The hazard ratio was 0.40, a 60 percent reduction in the risk of dying inside the trial window, and per the sponsor it is the first time median overall survival has cleared one year in a Phase 3 trial of any line of PDAC therapy.

Tumors shrank in 31.6 percent of patients on daraxonrasib against 11.2 percent on chemotherapy, with progression-free survival running 7.2 months versus 3.6, again roughly doubled. The second-line response rate in this disease has lived under 15 percent for a decade; the drug landed at almost a third.

Toxicity ran the other direction from the usual pattern. Targeted oral oncology drugs almost always pay for their survival edge in side effects: more rash, more diarrhea, more dose interruptions than the chemo they replace. Daraxonrasib did not. Grade 3 or worse treatment-related adverse events showed up in 43.6 percent of the drug arm and 57.5 percent of the chemo arm. Only 1.2 percent of patients on the drug discontinued for side effects, against 11.2 percent on chemo. A skin rash hit more than 86 percent of the daraxonrasib group, which is the kind of number that usually drags a discontinuation curve down with it; here, most of them stayed on the drug anyway.

Set that against the baseline. Five-year survival for metastatic pancreatic cancer in the United States runs around 3 percent. The second-line median has been stuck in the six-to-nine-month range for ten years. The prior KRAS-targeted drugs, sotorasib and adagrasib, only hit the G12C variant, which shows up in maybe one or two percent of pancreatic tumors and almost never gets these patients into the trial. Daraxonrasib hits the broader G12 family, the engine actually running most of the disease.

The number the room did not spend much time on was 8.5. That is the median follow-up, in months. It means half the patients in the trial had been observed for less than that when Wolpin showed his curves. Survival data this fresh drifts. The 13.2-month median can stretch as patients still alive keep living, or it can compress as the early responders die off and the harder cases catch up. The trial was open-label, because you cannot blind an oral pill against an IV chemo infusion, a defensible compromise but a compromise nonetheless. The benefit is large enough that the direction is not in doubt. The exact size of it, eighteen months from now, is.

The other thing the room did not spend much time on was the money, and the money had already arrived. Last summer Royalty Pharma signed a funding agreement with Revolution Medicines for up to two billion dollars: a synthetic royalty of up to 1.25 billion tied to net sales of daraxonrasib and a related Revolution program, plus a senior secured loan of up to 750 million tied to FDA approval and net-sales milestones. The royalty tiers top out near 7.8 percent of net sales. Royalty Pharma did not get rich missing on oncology blockbusters, and a 7.8-percent tiered royalty is not the deal you write against a niche label. It is what you sign when you are pricing in multi-billion-dollar annual sales. The check was placed before Phase 3 read out. The data confirmed it.

The U.S. price has not been set, and Revolution Medicines sets it; nobody at Dana-Farber does. Targeted oral oncology drugs in this class do not arrive cheaply, and the financing terms above are the most honest preview of where the launch price is going to land.

On May 1, the FDA granted expanded access for daraxonrasib, letting patients take the unapproved drug outside the trial while the application is prepared. Revolution Medicines has also said it will use a Commissioner’s National Priority Voucher to file, the new pilot program in which top-of-stack review compresses the standard PDUFA clock, which targets roughly ten months for a new molecular entity, into a stated 1-to-2-month window. The agency’s first CNPV approval, an antibiotic, cleared in two months. If the CNPV holds for this drug, daraxonrasib reaches stage four pancreatic cancer patients six to twelve months earlier than the standard review would have allowed. For a disease whose median survival even with the drug is just over a year, six to twelve months is most of the margin.

None of which makes daraxonrasib a cure. The overall trial population was still mostly dying inside the follow-up window; the drug bought time, not rescue. The five-year picture for metastatic pancreatic cancer remains brutal. A treatment that adds six and a half months at the median is, by any honest accounting, a turn in a road that has not had one in a generation, and also six and a half months. It is the kind of result a careful reader sits with for a minute before deciding what kind of celebration is appropriate.

Thirteen-point-two is still thirteen-point-two. The wall moved.

Sources

  1. NEJM – Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer, RASolute 302 (2026)
  2. Revolution Medicines – RASolute 302 plenary presentation press release
  3. ASCO Post – Daraxonrasib Nearly Doubles Survival in Previously Treated Metastatic Pancreatic Cancer (2026)
  4. Royalty Pharma – Funding agreements with Revolution Medicines for up to $2 billion
  5. FDA – Expanded Access for Investigational Pancreatic Cancer Drug (May 2026)
  6. FDA – Commissioner’s National Priority Voucher (CNPV) Pilot Program
  7. ScienceDaily – Cracking an ‘undruggable’ pancreatic cancer target (2026)