Oral Drug Daraxonrasib Nearly Doubles Survival in Advanced Pancreatic Cancer Trial

A new oral drug for metastatic pancreatic cancer produced survival numbers that most oncologists had stopped expecting to see in this disease - and the data, published simultaneously with an ASCO plenary presentation, are now driving a push for rapid regulatory approval.

The Phase 3 RASolute 302 trial, results of which were published May 31 in the New England Journal of Medicine, tested daraxonrasib against standard chemotherapy in 500 patients with previously treated metastatic pancreatic ductal adenocarcinoma recruited from sites across North America, Europe, and Asia. That population matters: these were patients who had already been through one line of treatment and had few options left.

<cite index="11-1">Compared with standard chemotherapy, daraxonrasib nearly doubled overall survival - from 6.7 months to 13.2 months.</cite> <cite index="11-2">The drug reduced the risk of death for metastatic pancreatic cancer patients by 60%.</cite>

To understand why that number landed the way it did in the oncology community, some context helps. <cite index="12-4,12-5">Pancreatic cancer remains one of the deadliest malignancies, with more than half of cases diagnosed after metastasis has already occurred and a five-year relative survival rate of roughly 3% for metastatic disease. Current second-line chemotherapy regimens provide only modest benefit, with a median progression-free survival of three to four months and a median overall survival of six to seven months.</cite>

<cite index="14-3">Pancreatic cancer is the third-leading cause of cancer deaths in the U.S. and kills nearly 53,000 people each year.</cite>

What makes daraxonrasib mechanistically distinct is how it reaches its target. For decades, KRAS - the mutation that drives the vast majority of pancreatic tumors - was considered essentially undruggable because its surface offered no clean binding site for small molecules. <cite index="11-5,11-6">Rather than binding to KRAS directly, daraxonrasib attaches to a molecule called cyclophilin A inside cells, which helps fold proteins into their final three-dimensional structures; that complex then binds to the active KRAS protein and shuts down its ability to signal cancer cells to multiply.</cite>

<cite index="12-7">Unlike earlier KRAS inhibitors that are specific to individual mutations, daraxonrasib can inhibit KRAS activity regardless of the specific variant present, and it demonstrated activity in both RAS-mutant and RAS-wild-type tumors.</cite> That breadth is clinically relevant: not all patients with pancreatic cancer carry the same KRAS variant.

<cite index="17-2">Daraxonrasib is taken orally once daily</cite>, which is a meaningful difference for patients already managing the physical toll of metastatic disease and frequent infusion appointments. <cite index="13-4">Trial investigators reported the drug was generally well tolerated with a manageable safety profile and no unexpected safety findings.</cite>

The results were presented at ASCO by Brian Wolpin, MD, MPH, director of the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute, and published the same day in the New England Journal of Medicine. In a statement included in a Dana-Farber news release, <cite index="13-7">Wolpin called daraxonrasib "the first RAS inhibitor evaluated in a large, randomized trial for patients with pancreatic cancer," adding that it demonstrates "how important an impact these novel medicines are likely to have on the treatment of the disease."</cite>

<cite index="13-5">The results support the use of daraxonrasib as the new standard of care for second-line treatment of metastatic pancreatic cancer,</cite> according to the Dana-Farber release.

Regulatory momentum is already building. <cite index="13-1">On May 1, 2026, the FDA granted permission for Revolution Medicines to initiate an expanded access program for daraxonrasib for patients with previously treated metastatic pancreatic cancer.</cite> <cite index="17-6">Revolution Medicines intends to submit the trial data to global regulatory authorities, including to the U.S. Food and Drug Administration, as part of a future New Drug Application under a Commissioner's National Priority Voucher.</cite>

For patients sitting in an oncologist's office after a first-line treatment has stopped working, that pipeline matters enormously. The expanded access program means some of those patients can reach the drug now, before full approval. How quickly the FDA moves on the NDA - and whether payers fall in line behind whatever label ultimately comes out - will determine whether these survival numbers translate from a trial cohort to the broader population of roughly 53,000 Americans diagnosed with pancreatic cancer each year.

Sources cited:
- New England Journal of Medicine (RASolute 302 trial, May 31, 2026) (https://www.nejm.org/doi/full/10.1056/NEJMoa2605555)
- ASCO Post (https://ascopost.com/news/june-2026/daraxonrasib-nearly-doubles-survival-in-previously-treated-metastatic-pancreatic-cancer/)
- Dana-Farber Cancer Institute news release (https://www.dana-farber.org/newsroom/news-releases/2026/rason-inhibitor-doubles-median-overall-survival-in-results-of-phase-3-trial-for-patients-with-metastatic-pancreatic-cancer)
- Revolution Medicines investor release (IR site) (https://ir.revmed.com/news-releases/news-release-details/daraxonrasib-demonstrates-unprecedented-overall-survival-benefit/)
- ScienceDaily (https://www.sciencedaily.com/releases/2026/06/260604044247.htm)
- UCHealth Today (https://www.uchealth.org/today/new-pancreatic-cancer-drug-daraxonrasib/)