Revolution Medicines’ daraxonrasib doubled overall survival time for previously treated metastatic pancreatic cancer compared with standard chemotherapy, according to late-stage study results presented Sunday at the American Society of Clinical Oncology Annual Meeting (ASCO 2026) and published in The New England Journal of Medicine. Experts hailed the findings as “landscape-changing,” and presenter Brian Wolpin, MD, MPH, of Harvard Medical School and Dana-Farber Cancer Institute, received a standing ovation when he showed the survival data.

Pancreatic cancer is often detected late, when it is difficult to treat, and it has one of the lowest survival rates of all cancer types. Standard treatment typically includes surgery, radiation and chemotherapy, but disease progression and relapse are common. Five-year survival for metastatic pancreatic cancer only around 3%, and some 50,000 people die from this aggressive malignancy each year.

“Few therapies are available for patients with previously treated metastatic pancreatic cancer, and these therapies have modest efficacy and substantial toxicities,” Wolpin said in an ASCO news release. “The RASolute 302 trial was designed to assess a RAS(ON) multi-selective inhibitor as a second-line treatment for patients with metastatic pancreatic cancer, looking to define a new standard of care for these patients that works better and has less side effects than currently available chemotherapies.”

Daraxonrasib is the first RAS(ON) multi-selective inhibitor, which targets a family of RAS oncogenes (KRAS, NRAS and HRAS) that regulate cell growth and drive cancer development. Long considered “undruggable” due to its structure, RAS mutations play a role in around a third of all cancers and 90% of pancreatic cancer. The Food and Drug Administration (FDA) has approved two drugs for lung and colorectal cancer that block a specific KRAS mutation dubbed G12C—Lumakras (sotorasib) and Krazati (adagrasib)—but daraxonrasib has broader activity. It is likely to be relevant for all patients with metastatic pancreatic cancer, according to Wolpin.

In a prior Phase I/II trial, daraxonrasib was generally safe and showed preliminary evidence of efficacy for treatment-experienced patients with metastatic pancreatic cancer, setting the stage for the international Phase III RASolute 302 trial (NCT06625320). Revolution announced top-line results in April, and Wolpin presented the details at the ASCO meeting.

RASolute 302 assessed the efficacy and safety of daraxonrasib monotherapy in 500 patients in North America, Europe and Asia with previously treated metastatic pancreatic ductal adenocarcinoma. The liver was the most common site of metastasis. The median age was approximately 66 years, more than half were men, two thirds were white, about 12% were Asian and about 4% were Black.

The study enrolled people whose tumors carried the RAS variants G12 (92%), G13 or Q61 as well as those without an identified RAS mutation (known as wild-type). A majority had undergone surgery (pancreatectomy or Whipple procedure). The participants were randomly assigned to receive either daily daraxonrasib pills or the investigator’s choice of four different standard IV chemotherapy.

Daraxonrasib demonstrated “statistically significant and clinically meaningful” improvements over chemotherapy. In the study population as a whole, people treated with daraxonrasib had a median overall survival time of 13.2 months, compared with 6.7 months for those on chemotherapy—a 60% improvement. The median progression-free survival time was 7.2 versus 3.6 months, respectively. Objective response rates, indicating tumor shrinkage, were 32% and 11%. Results were similar for the subset of patients with the RAS G12 variant, Wolpin reported.

Looking at patient-reported outcomes, people assigned to daraxonrasib reported significantly slower worsening of cancer-related pain, overall health and quality of life compared with those on chemotherapy.

Daraxonrasib’s safety profile was described as “manageable,” but side effects were common. The most frequently reported treatment-related adverse events in the daraxonrasib group were skin rash and mouth sores, while low blood cell counts were most common in the chemotherapy group. Severe (grade 3 or higher) treatment-related adverse event rates were 44% in the daraxonrasib group and 58% in the chemotherapy group. However, just 1% of daraxonrasib recipients stopped treatment due to adverse events, compared with 11% of placebo recipients.

These results “represent a major milestone” for patients with metastatic pancreatic cancer, Wolpin said in a Revolution Medicines news release. “These results will change how scientists, clinicians and patients think about treatment for pancreatic cancer, and support a new paradigm where RAS(ON) inhibition enters standard of care for patients with previously treated metastatic pancreatic adenocarcinoma.”

Daraxonrasib also shows promise for pancreatic cancer patients starting treatment for the first time. Phase I/II trial results presented at the American Association for Cancer Research Annual Meeting in April showed that first-line daraxonrasib, either alone or in combination with chemotherapy, demonstrated preliminary evidence of durable antitumor activity with  a manageable safety profile. The objective response rates were 47% for daraxonrasib monotherapy and 58% for daraxonrasib plus chemotherapy.

Revolution plans to submit the Phase III data to the FDA and other regulatory authorities for approval. The company has a new type of priority voucher intended to shorten review time to just one to two months. On May 1, the FDA allowed Revolution to start an expanded access treatment protocol for daraxonrasib; physicians can request the drug from the company for eligible patients prior to approval. Daraxonrasib is also being evaluated for other RAS-related malignancies, including non-small-cell lung cancer, and research is ongoing to understand how cancer develops resistance to the drug and what combination regimens might improve its effectiveness.

“These results are landscape-changing for metastatic pancreatic cancer patients with a KRAS mutation. We are seeing unprecedented survival and efficacy in second-line treatment with an expected safety profile,” said ASCO expert Rachna Shroff, MD, of the University of Arizona Cancer Center. “The RAS revolution is here, and this study is proof of principle that targeting KRAS in pancreatic cancer is feasible and effective.”

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