NEJM Publishes Phase 1/2 Data for Daraxonrasib as FDA Authorizes Expanded Access for Metastatic Pancreatic Cancer

Overview

The New England Journal of Medicine published Phase 1/2 clinical data on May 6, 2026, for daraxonrasib (RMC-6236), an oral RAS(ON) multi-selective inhibitor, in patients with previously treated advanced RAS-mutant pancreatic ductal adenocarcinoma (PDAC). The results, from a trial led by researchers at Dana-Farber Cancer Institute, showed promising antitumor activity and a manageable safety profile that supported the ongoing pivotal Phase 3 RASolute 302 trial. according to Dana-Farber Cancer Institute

Separately, on May 1, 2026, the U.S. Food and Drug Administration issued a “safe to proceed” letter authorizing Revolution Medicines to initiate an Expanded Access Program (EAP) for daraxonrasib in patients with previously treated metastatic PDAC who have no comparable or satisfactory alternative therapy and cannot participate in a clinical trial. FDA

As previously reported, the company announced in April 2026 that the Phase 3 RASolute 302 trial had met its primary and key secondary endpoints, with median overall survival of 13.2 months on daraxonrasib versus 6.7 months on chemotherapy.

What We Know

• NEJM Phase 1/2 publication (May 6, 2026): The open-label, multicenter Phase 1/2 trial (RMC-6236-001) enrolled 168 patients with advanced RAS-mutant PDAC who had received one or more prior lines of chemotherapy. At the 300 mg daily dose selected for Phase 3, approximately 30 percent of patients with one prior line of treatment achieved an objective response. Across all patients, approximately 90 percent experienced disease control (tumor reduction or stabilization). Median duration of response exceeded 8 months for those with one prior therapy. Dana-Farber Cancer Institute

• Safety profile: Treatment-related adverse events occurred in 96% of patients (grade ≥3 in 30%). The most common were rash, inflammation in the mouth (stomatitis/mucositis), nausea, diarrhea, vomiting, and fatigue. “With supportive medicines, the drug was well-tolerated by the majority of patients,” said first author Dr. Brian M. Wolpin of Dana-Farber. Dana-Farber Cancer Institute

• FDA Expanded Access authorization (May 1, 2026): The FDA received the EAP request from Revolution Medicines on April 28 and signed the “safe to proceed” letter on April 30, announcing it publicly on May 1. “Granting the request two days after receiving the expanded access application reflects the FDA’s strong commitment to facilitate early access to therapies for serious and life-threatening conditions, including pancreatic cancer,” said FDA Commissioner Marty Makary, M.D., M.P.H. FDA

• EAP now available: As of early May 2026, an Expanded Access Program is available for eligible adult patients with previously treated metastatic PDAC. Access is physician-initiated only; licensed U.S. physicians can request on behalf of patients via the company’s expanded access policy and clinicaltrials.gov (NCT07573215). Revolution Medicines stated it is “moving as quickly as possible to ensure safe and equitable access to daraxonrasib for eligible patients in the United States.” PanCAN

• Mechanism and context: Daraxonrasib is the first RAS(ON) multi-selective inhibitor tested in clinical trials for pancreatic cancer. It acts as a molecular glue with cyclophilin A to block signaling of mutant and wild-type RAS proteins. RAS mutations (primarily KRAS) drive more than 90% of pancreatic cancers and were long considered “undruggable.” Dana-Farber Cancer Institute

• Regulatory and presentation plans: Daraxonrasib holds FDA Breakthrough Therapy Designation, Orphan Drug Designation, and a Commissioner’s National Priority Voucher (CNPV) intended to accelerate review. Full mature Phase 3 data from RASolute 302 will be presented by Dr. Wolpin in a plenary session at the 2026 ASCO Annual Meeting on May 31. PanCAN FDA

• Expert perspective: “If supported by data from future clinical trials, daraxonrasib would be a targeted therapy relevant to nearly all patients with advanced pancreatic cancer,” said Dr. Brian Wolpin, director of the Hale Family Center for Pancreatic Cancer Research at Dana-Farber. PanCAN Chief Scientific and Medical Officer Anna Berkenblit, M.D., MMSc, noted the results represent “a real opportunity to bring new hope for people facing this disease.” Dana-Farber Cancer Institute PanCAN

What We Don’t Know

• Mature subgroup analyses (specific RAS variants such as G12D/V/R), exact patient numbers enrolled in RASolute 302, and full progression-free survival and objective response rate data from the Phase 3 trial remain to be presented at ASCO on May 31, 2026.

• The precise timing of the New Drug Application (NDA) submission to the FDA under the CNPV voucher and the duration of any priority review are not yet disclosed.

• Long-term outcomes, quality-of-life data, and how daraxonrasib will be positioned relative to first-line therapies or combinations are still under investigation in additional trials (e.g., RASolute 303 in first-line metastatic PDAC).

• Real-world uptake of the EAP will depend on site activation timelines and physician awareness; while the program is now authorized and listed on clinicaltrials.gov, access is rolling out in a controlled manner.

Analysis

The May 2026 developments mark important milestones in translating the April Phase 3 topline success into both scientific validation and patient access. Publication of the supporting Phase 1/2 data in the New England Journal of Medicine provides the peer-reviewed foundation that regulators and clinicians rely on, while the FDA’s rapid two-day turnaround on the EAP request underscores the agency’s willingness to act swiftly for a disease with historically poor second-line options.

Daraxonrasib’s multi-selective RAS(ON) mechanism offers a potential option relevant to the vast majority of pancreatic cancer patients, a significant shift from earlier allele-specific inhibitors. If the Phase 3 data presented at ASCO confirm the topline survival benefit and the EAP successfully bridges patients to approval, this could represent one of the most meaningful advances for metastatic pancreatic cancer in recent years. The coming weeks—particularly the May 31 ASCO plenary and any NDA filing—will determine how quickly these findings translate into approved treatment and broader availability.