On August 26, 2026, the U.S. Food and Drug Administration (FDA) approved Rasonque (daraxonrasib) for adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or are not candidates for multiagent systemic therapy, introducing the first RAS-targeted therapy approved for pancreatic cancer.
The approval follows one of the standout moments of the 2026 ASCO Annual Meeting. During the Plenary Session, Brian M. Wolpin, MD, MPH, presented the phase 3 RASolute 302 trial, and the overall survival results drew sustained applause and a standing ovation from the audience.
Daraxonrasib, previously known as RMC-6236, is an oral RAS(ON) multi-selective inhibitor developed by Revolution Medicines. The FDA announced the approval on August 26, 2026, just over one month after accepting the new drug application (NDA) on July 22.
Acting FDA Commissioner Kyle Diamantas, J.D., commented on the significance of the approval:
“Today’s approval provides a critical new option for patients facing an extraordinarily difficult and historically hard-to-treat cancer. It is our fundamental duty to deliver more cures and meaningful treatments to patients as quickly as possible. I am immensely proud of the dedicated FDA scientists whose fast, thorough review and relentless commitment made this groundbreaking milestone a reality.”
Targeting RAS in Pancreatic Cancer
RAS alterations are among the defining molecular features of PDAC. More than 90% of PDAC tumors harbor an oncogenic RAS mutation, making the pathway an important therapeutic target but historically a difficult one to inhibit.
Daraxonrasib is an oral, RAS(ON) multi-selective, noncovalent tri-complex inhibitor. Unlike earlier agents designed to target the inactive, GDP-bound RAS state, daraxonrasib targets the active, GTP-bound “ON” conformation of RAS and inhibits signaling between RAS and downstream effectors.
Daraxonrasib targets multiple RAS variants, including mutated KRAS, NRAS, and HRAS proteins with G12, G13, and Q61 alterations, as well as wild-type RAS. The development of a broadly active RAS inhibitor is particularly relevant in PDAC, where treatment options after progression on first-line chemotherapy remain limited.
RASolute 302
The FDA approval was supported by results from RASolute 302 (NCT06625320), a global, randomized, open-label phase 3 trial evaluating daraxonrasib in previously treated metastatic PDAC. The study enrolled 500 patients with an ECOG performance status of 0–1 across 59 sites in six countries. Participants were randomized 1:1 to receive daraxonrasib 300 mg orally once daily or investigator’s choice of chemotherapy.
The trial was presented by Brian M. Wolpin, MD, MPH, during a Plenary Session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and was simultaneously published in The New England Journal of Medicine. In the overall randomized population, median OS was 13.2 months with daraxonrasib compared with 6.7 months with chemotherapy.
Among patients with RAS G12-mutated tumors, median OS was 13.2 versus 6.6 months, corresponding to a hazard ratio of 0.40. Median PFS in the RAS G12-mutated population was 7.3 months with daraxonrasib versus 3.5 months with chemotherapy, while the confirmed objective response rate was 33.2% versus 11.8%, respectively. In the overall population, the OS treatment effect was consistent across the clinical and molecular subgroups evaluated in the study.
Patient-Reported Outcomes and Safety
Beyond improvements in tumor-control and survival endpoints, daraxonrasib significantly delayed deterioration in cancer-related pain as well as global health status and quality of life compared with chemotherapy.
Grade 3 or higher treatment-related adverse events occurred in 43.6% of patients receiving daraxonrasib compared with 57.5% receiving chemotherapy. Treatment-related adverse events leading to discontinuation occurred in 1.2% of patients receiving daraxonrasib versus 11.2% receiving chemotherapy.
The most frequently reported adverse events associated with Rasonque included rash, diarrhea, stomatitis, nausea, fatigue, vomiting, abdominal pain, edema, decreased appetite, and hemorrhage.
This Is Just the Beginning
Following the RASolute 302 presentation at ASCO 2026, OncoDaily spoke with Alan Sandler, MD, Chief Development Officer at Revolution Medicines, about the development of daraxonrasib and the broader potential of RAS(ON) inhibition.
Sandler reflected on the rapid development of daraxonrasib, which moved from first-in-human testing in 2022 to a positive phase 3 trial in 2026. He also emphasized that RASolute 302 represents one step within a broader development program exploring RAS(ON) inhibition across different RAS variants, tumor types, and earlier treatment settings.
For Sandler, the results mark an important milestone, but not the end of the story:
From RASolute 302 to FDA Review
Regulatory momentum followed the phase 3 results. On July 22, 2026, the FDA accepted for review the New Drug Application (NDA) for daraxonrasib for previously treated metastatic PDAC.
Daraxonrasib was selected for the FDA Commissioner’s National Priority Voucher (CNPV) pilot program, which is intended to help accelerate the review of therapies addressing national public health priorities. The FDA had also granted Breakthrough Therapy and Orphan Drug designations, while the application received Priority Review for this indication.
The regulatory pathway had begun even earlier. In May 2026, the FDA issued a “safe to proceed” letter allowing Revolution Medicines to initiate an expanded access treatment protocol, enabling eligible patients to receive daraxonrasib before formal approval.
ESMO Recommended Daraxonrasib Before FDA Approval
While the FDA review was underway, ESMO had already incorporated the RASolute 302 findings into its clinical recommendations.
On August 19, 2026, the ESMO Guidelines Committee published a Clinical Practice Guideline Express Update on daraxonrasib in metastatic pancreatic cancer. The update recommended daraxonrasib monotherapy after failure of chemotherapy in previously treated patients with RAS G12-mutated tumors and ECOG performance status 0–1 [I, A], explicitly noting at the time that the drug had not yet been approved.
ESMO also recommended tumor molecular profiling at diagnosis in all patients with unresectable PDAC to identify clinically actionable genetic alterations such as RAS G12 mutations [II, A; ESCAT I-A].
Just one week later, on August 26, the FDA approved Rasonque. The decision came only 35 days after the NDA was accepted for review and, according to the FDA, 6.5 months before the application’s user fee deadline.
Angelo de Claro, M.D., director of the FDA’s Oncology Center of Excellence, commented:
“This drug showed unprecedented results in an area of high unmet need. The approval was granted 6.5 months before the user fee deadline, demonstrating the FDA’s commitment to accelerating the approval of new cancer treatments for patients with serious and life-threatening conditions.”
A New Targeted Option in Metastatic PDAC
Pancreatic cancer remains one of the malignancies with the poorest long-term outcomes, particularly after development of metastatic disease. Historically, treatment following progression on first-line therapy has relied predominantly on additional cytotoxic chemotherapy, with relatively modest survival benefits.
The FDA approval of daraxonrasib introduces a new molecularly targeted treatment option for this setting and represents the first successful regulatory approval of a RAS-targeted therapy in pancreatic cancer.
The magnitude of benefit observed in RASolute 302—including the reduction in the risk of death in the RAS G12-mutated population, improvement in PFS and response rates, and lower frequency of severe treatment-related toxicity compared with chemotherapy—supports the clinical significance of the approval.
The recent ESMO guideline update also strengthens the role of molecular profiling in unresectable PDAC by recommending testing at diagnosis to identify clinically actionable genetic alterations.
The full information about the approval is available on the official FDA website.