FDA approves RASONQUE (daraxonrasib) the first broad RAS-targeted medicine in metastatic pancreatic cancer – Revolution Medicines

Revolution Medicines, Inc. announced that the FDA has approved RASONQUE (daraxonrasib) once-daily oral tablets, for the treatment of adults with metastatic pancreatic adenocarcinoma (PDAC) who have received at least one prior systemic therapy or who are not candidates for multiagent systemic therapy.
RASONQUE represents the first targeted cancer medicine to be approved from a groundbreaking new class of RAS(ON) multi-selective and mutant-selective inhibitors.

Pancreatic cancer is among the most challenging malignancies, frequently presenting with a late diagnosis, aggressive biology and limited responsiveness to conventional treatments. RAS, a key growth control switch in human cells, is the main cause of pancreatic cancer, which is characterized by excessive RAS signaling. The approval of RASONQUE is for adults with metastatic PDAC with or without an identified RAS tumor mutation and does not require use of a companion diagnostic test.

“The FDA approval of RASONQUE is a monumental step forward for patients with pancreatic cancer and for the oncology field. For the first time, patients have an approved targeted medicine designed to directly inhibit the main cause of pancreatic cancer, RAS, which has been one of the most intractable disease targets since its discovery decades ago. The unprecedented results of the global Phase 3 trial position RASONQUE to become the new standard of care for patients with metastatic pancreatic cancer under an approved label that supports real-world clinical decision-making. This approval further validates our bold RAS(ON) inhibitor strategy that includes multi-selective and mutant-selective approaches targeting a major driver of pancreatic cancer and multiple other cancers. We continue to engage with global regulatory authorities with the goal of expanding and accelerating the reach of RASONQUE,” said Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines.

“Today’s landmark approval is the most significant advance we have seen in the fight against pancreatic cancer, a devastating disease. I believe this drug will transform how pancreatic cancer is treated, giving people the opportunity for more time with loved ones, the possibility of a better quality of life and optimism that continued research may lead to even greater advances,” said Anna Berkenblit, M.D., chief scientific and medical officer of the Pancreatic Cancer Action Network (PanCAN). “In addition, an oral pill can offer a less burdensome treatment experience than standard intravenous chemotherapy. PanCAN will continue to empower patients and caregivers with the resources and knowledge they need to advocate for the care they deserve now that RASONQUE is available for doctors to prescribe.”

“I believe daraxonrasib is well positioned to become a new standard of care for adults with metastatic pancreatic cancer who have already received at least one systemic therapy or who are not candidates for multiagent systemic therapy. For decades, despite RAS being the main driver and potential drug target for pancreatic cancer, physicians have largely relied on intravenous cytotoxic chemotherapy to treat this aggressive disease. This approval gives physicians the confidence that directly inhibiting RAS can make a striking difference for patients and provides a critically needed new approach to treating patients with metastatic pancreatic cancer,” added Brian M. Wolpin, M.D., M.P.H., director of the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute, professor of medicine at Harvard Medical School, and principal investigator for the RASolute 302 trial.

RASolute 302: Phase 3 Clinical Trial Results Supporting FDA Approval

The FDA approval of RASONQUE is based on data from RASolute 302, a global, randomized Phase 3 trial evaluating RASONQUE versus investigator’s choice of cytotoxic chemotherapy in patients with previously treated metastatic PDAC. The trial met all primary and key secondary endpoints in both the RAS G12 mutant population and the overall intent-to-treat (ITT) population, which included patients with or without an identified tumor RAS mutation. Results from the RASolute 302 trial were presented at the 2026 American Society of Clinical Oncology Annual Meeting with simultaneous publication in The New England Journal of Medicine.

In the ITT population, RASONQUE reduced the risk of death by 60% compared with chemotherapy, with a hazard ratio (HR) of 0.40 (95% confidence interval [CI]: 0.30–0.53; p<0.0001). The median overall survival was 13.2 months (95% CI: 10.0–NE) with RASONQUE compared to 6.7 months (95% CI: 5.8–8.0) for chemotherapy. RASONQUE also showed significant improvements in progression-free survival (PFS) with an HR of 0.49 (95% CI: 0.38–0.64; p<0.0001). The median PFS was 7.2 months (95% CI: 5.7–7.5) with RASONQUE compared to 3.6 months (95% CI: 2.9–4.2) with chemotherapy. Results were generally consistent in the RAS G12 population.

RASONQUE demonstrated manageable safety and a favorable tolerability profile. The most common (≥ 20%) adverse reactions in patients treated with RASONQUE were rash, diarrhea, stomatitis, nausea, vomiting, abdominal pain, edema, decreased appetite, and hemorrhage. Please see the Important Safety Information for RASONQUE below.

The trial also evaluated patient-reported outcomes in the ITT population, given the high symptom burden that patients with metastatic PDAC experience. Patients who received RASONQUE demonstrated a statistically significant and clinically meaningful delay in time to deterioration (TTD) for global health status and pain when compared to chemotherapy. RASONQUE prolonged the maintenance of global health status and quality of life, with a median TTD of 5.7 months versus 2.6 months with chemotherapy (HR=0.60 [95% CI: 0.46–0.79]; p<0.001). Additionally, RASONQUE delayed the worsening of clinically relevant pain, demonstrating a median TTD of 9.2 months compared to 3.8 months with chemotherapy (HR=0.51 [95% CI: 0.37–0.71]; p<0.001).

About the RASolute 302 Clinical Trial

RASolute 302 (NCT06625320) was a global, randomized Phase 3 registrational clinical trial designed to evaluate the efficacy and safety of RASONQUE as a monotherapy in patients with previously treated metastatic pancreatic adenocarcinoma (PDAC). In the trial, patients were randomized to receive either an oral dose of 300 mg RASONQUE once daily or investigator’s choice of four different cytotoxic chemotherapy regimens, which represented standard of care across the globe. The trial enrolled patients with metastatic PDAC harboring a wide range of RAS variants, including those with RAS G12 mutations (such as G12D, G12V, and G12R), as well as patients without an identified tumor RAS mutation (wild-type).

The primary endpoints of the RASolute 302 trial were progression-free survival (PFS), as assessed by a Blinded Independent Central Review according to RECIST 1.1, and overall survival (OS) in patients with tumors harboring RAS G12 mutations. Secondary endpoints included PFS and OS in all enrolled patients (the intent-to-treat population) encompassing patients with and without identified tumor RAS mutations, as well as objective response rate, duration of response, and patient-reported quality of life.

Citation: Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer. Authors: Eileen M. O’Reilly, M.D., Zev A. Wainberg, M.D., Andrew E. Hendifar, M.D. et al. Published May 31, 2026 N Engl J Med 2026;395:325-337 DOI: 10.1056/NEJMoa2605555 VOL. 395 NO. 4