FDA Approves Daraxonrasib (Rasonque), First-in-Class RAS(ON) Inhibitor for Metastatic Pancreatic Cancer
核心洞察
The FDA approved daraxonrasib, sold as Rasonque (搜索) by Revolution Medicines, for adults with metastatic pancreatic adenocarcinoma (搜索) after at least one prior systemic therapy.
In the phase III RASolute 302 trial, median overall survival nearly doubled to 13.2 months with daraxonrasib versus 6.7 months with chemotherapy in 500 previously treated patients.
The oral once-daily multiselective RAS (搜索)(ON) inhibitor targets KRAS (搜索) mutations that drive tumor growth in more than 90% of pancreatic cancer (搜索) cases, a target long considered undruggable.
The U.S. Food and Drug Administration has approved daraxonrasib (Rasonque (搜索)), a first-in-class multiselective RAS (搜索)(ON) inhibitor, for adults with metastatic pancreatic adenocarcinoma (搜索) who have received at least one prior systemic therapy or are not candidates for multiagent systemic therapy. The agency granted the approval to Revolution Medicines, Inc., and regulators noted they cleared the drug more than six months ahead of their target date.
The decision makes daraxonrasib the first approved therapy to target a mutated protein that fuels tumor growth in the majority of pancreatic cancers — an approach that had eluded drugmakers for decades because the protein's structure made it difficult for drugs to bind.
Survival Nearly Doubled in Phase III Trial
The approval was based on data from the phase III RASolute 302 trial, presented by Brian M. Wolpin, MD, MPH, of the Dana-Farber Cancer Institute during the Plenary Session at the 2026 ASCO Annual Meeting and published simultaneously by O'Reilly et al in The New England Journal of Medicine.
In the company-funded study, which randomly assigned 500 patients whose metastatic cancer had stopped responding to prior treatment, patients receiving daraxonrasib lived a median of 13.2 months compared with 6.7 months for chemotherapy recipients — a near doubling of median overall survival. Patients on the new treatment also experienced fewer severe side effects.
"This drug showed unprecedented results in an area of high unmet need," said R. Angelo de Claro, MD, Director of the FDA's Oncology Center of Excellence. "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 Long-Undruggable Target
Daraxonrasib is an oral agent taken once daily that targets multiple forms of RAS (搜索), a key driver of tumor growth in most patients with pancreatic adenocarcinoma. The drug targets mutations in the RAS gene family, which normally regulates cell growth; KRAS (搜索) mutations are especially critical in fueling pancreatic cancer (搜索). A structure that made it hard for drugs to stick to the mutated proteins meant this cancer driver was long considered "undruggable."
Revolution Medicines' drug uses what is essentially a molecular glue to bind with multiple KRAS (搜索) subtypes. The Redwood City, California-based drugmaker is studying its technology for several other forms of cancer, including lung cancer (搜索).
The most common side effects of daraxonrasib are rash, diarrhea, stomatitis, nausea, fatigue, vomiting, abdominal pain, edema, decreased appetite, and hemorrhage. Earlier reports of the trial also cited skin rash, mouth sores, diarrhea and other digestive issues.
High Unmet Need in a Deadly Disease
Pancreatic cancer (搜索) is among the most deadly forms of the disease, in large part because it is hard to detect before it starts spreading to other organs. The American Cancer Society estimates about 67,000 new cases will be diagnosed in the United States this year and more than 52,000 people will die from the disease, with a five-year overall survival rate of 13%.
According to the National Cancer Institute, approximately 90% to 95% of those 67,000 annual U.S. cases are pancreatic adenocarcinoma. Despite representing roughly 3.2% of all cancer diagnoses, pancreatic adenocarcinoma accounts for a disproportionately high share of cancer deaths owing to its typically late detection, aggressive disease course, and historically limited treatment options.
"This is not a cure, it's one more option for these patients," said Dr. Pashtoon Kasi of City of Hope Orange County (搜索), a California-based cancer center. "But it's the best option we've ever had."
Regulatory Designations and Expanded Access
The FDA granted daraxonrasib Breakthrough Therapy and Orphan Drug designations, and the application received Priority Review for this indication. It was also reviewed under the Commissioner's National Priority Voucher pilot program, which is intended to help accelerate review of therapies that address national public health priorities.
The drug garnered public attention earlier this year when former Sen. Ben Sasse, R-Neb., described on CBS' "60 Minutes" how he has had less pain while taking it. A surge in public interest led the FDA to allow "expanded access," before the drug's official approval, for patients who met certain criteria.
"It is our fundamental duty to deliver more cures and meaningful treatments to patients as quickly as possible," the FDA's acting commissioner, Kyle Diamantas, said in a statement.
Broader Implications for RAS-Directed Therapy
Unlike other cancers that have benefited from a variety of chemotherapy alternatives, pancreatic cancer (搜索) has been harder to tackle. Doctors who treat pancreatic cancer hope the drug may usher in more new options for other forms of cancer, with scores of experimental drugs in development.
"I think this has opened doors for many other companies," Kasi said. "Downstream I think there are going to be a lot more trials looking at this approach in other tumor types."