Daraxonrasib Clears FDA as First RAS-Targeted Pancreatic Cancer Drug

The FDA approved daraxonrasib (Rasonque; Revolution Medicines), an oral RAS inhibitor, for adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or who are not candidates for multiagent systemic therapy.¹ The decision marks the first approval of a targeted therapy for this form of pancreatic cancer and arrives 6.5 months ahead of the drug's user fee deadline.

How the Drug Works

Daraxonrasib, taken as a once-daily tablet, targets multiple forms of RAS, a protein that drives tumor growth in most patients with pancreatic adenocarcinoma. The cancer arises from cells lining the pancreatic ducts and accounts for 90% to 95% of the roughly 67,000 new pancreatic cancer cases diagnosed annually in the United States, according to the National Cancer Institute. Although pancreatic adenocarcinoma makes up only about 3.2% of all cancer diagnoses, it causes a disproportionate share of cancer deaths because it is usually caught late, progresses aggressively, and has historically had few effective treatments.

Trial Data Behind the Approval

The approval rests on a randomized, open-label, multicenter trial of 500 adults with previously treated metastatic pancreatic adenocarcinoma. Patients who received daraxonrasib had a median overall survival of 13.2 months, compared with 6.7 months among those who received standard chemotherapy. Acting FDA Commissioner Kyle Diamantas, JD, called the approval a critical new option for patients facing “an extraordinarily difficult and historically hard-to-treat cancer.” Angelo de Claro, MD, director of the FDA’s Oncology Center of Excellence, said the results were unprecedented for a disease with such high unmet need.

Those figures track closely with what investigators reported when the underlying phase 3 RASolute 302 trial (NCT06625320) data were first presented in the plenary session at the 2026 American Society of Clinical Oncology meeting in May.² The trial showed a 60% reduction in the risk of death among patients with a RAS G12 mutation, and oncologists described the results as “landscape-changing” and “transformative,” with one expert noting she “started crying in the clinic” upon reading the data. The data also showed a near doubling of progression-free survival (PFS) with patients on daraxonrasib experiencing a median PFS of 7.3 months (RAS G12 mutation) and 7.2 months (overall cohort) compared with 3.5 months (RAS G12) and 3.6 months (overall) on chemotherapy. Plus, daraxonrasib had a more tolerable safety profile relative to chemotherapy.

A Faster Path to Approval

Daraxonrasib received Breakthrough Therapy and Orphan Drug designations along with Priority Review, and its application was evaluated under the FDA Commissioner’s National Priority Voucher pilot program, intended to speed review of therapies addressing national public health priorities.¹ In May, the agency issued a “safe to proceed” letter allowing sponsor Revolution Medicines to open expanded access to the investigational drug ahead of approval.

Safety Profile

The most common adverse effects reported with daraxonrasib were rash, diarrhea, stomatitis, nausea, fatigue, vomiting, abdominal pain, edema, decreased appetite, and hemorrhage. The pivotal trial noted that discontinuation due to adverse effects was far less common with daraxonrasib than with chemotherapy, and that rash and stomatitis, rather than the neutropenia, anemia, fatigue, and neuropathy typical of cytotoxic regimens, were the dominant toxicities.²

What Comes Next

For a disease long considered resistant to targeted approaches—RAS mutations were regarded as “undruggable” for decades—the approval gives clinicians a new oral option for second-line treatment and adds to broader interest in whether RAS-directed therapy could eventually move earlier in the treatment sequence. Additional trials of daraxonrasib in earlier lines of pancreatic cancer, as well as in RAS-mutated lung and colorectal cancers, are already underway, and Revolution Medicines CEO Mark A. Goldsmith, MD, PhD, suggested the drug’s mechanism could ultimately reshape pancreatic cancer from a rapidly fatal disease into one that is more chronically managed.²

References

1. FDA approves first in class targeted therapy for metastatic pancreatic cancer. News release. FDA. August 26, 2026. Accessed August 26, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-class-targeted-therapy-metastatic-pancreatic-cancer
2. Caffrey M. RASolute 302 brings a “transformative” moment in pancreatic cancer: a 60% improvement in overall survival. AJMC. May 31, 2026. Accessed August 26, 2026. https://www.ajmc.com/view/rasolute-302-brings-a-transformative-moment-on-pancreatic-cancer-a-60-improvement-in-overall-survival