The FDA has approved Revolution Medicines' daraxonrasib, the first RAS-directed therapy for previously treated metastatic pancreatic adenocarcinoma, based on a phase 3 trial showing a survival benefit over chemotherapy.
The FDA has approved daraxonrasib (brand name Rasonque) for adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or who are not candidates for multiagent chemotherapy, marking the first RAS-directed therapy cleared for the disease.1
The once-daily oral agent, developed by Redwood City, California-based Revolution Medicines, becomes the company's first commercial product since its 2014 founding around the premise that the long-considered undruggable RAS protein family could be therapeutically targeted.
The approval arrived roughly six and a half months ahead of its PDUFA date.
“This drug showed unprecedented results in an area of high unmet need,” said Angelo de Claro, director of the FDA’s Oncology Center of Excellence, adding that the timing “demonstrat[es] the FDA’s commitment to accelerating the approval of new cancer treatments for patients with serious and life-threatening conditions.”1
The approval rests on the phase 3 RASolute 302 trial, a randomized, open-label, multicenter study of 500 adults with previously treated metastatic pancreatic ductal adenocarcinoma. Patients received daraxonrasib or investigator's choice of standard chemotherapy after progressing on a prior fluoropyrimidine- or gemcitabine-based regimen.
Median overall survival reached 13.2 months with daraxonrasib versus 6.7 months with chemotherapy, corresponding to roughly a 60% reduction in the risk of death.2 The trial also met its progression-free survival endpoint. Reported adverse events include rash, diarrhea, stomatitis, nausea, fatigue, vomiting, abdominal pain, edema, decreased appetite, and hemorrhage.1
“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,” said Mark A. Goldsmith, MD, PhD, chief executive officer and chairman of Revolution Medicines, in a press release. “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.”
Pancreatic adenocarcinoma accounts for roughly 90% to 95% of the 67,000 pancreatic cancer cases diagnosed annually in the United States, and despite representing about 3.2% of all cancer diagnoses, it contributes disproportionately to cancer mortality.1 Late detection, aggressive progression, and a narrow chemotherapy backbone—largely FOLFIRINOX or gemcitabine plus nab-paclitaxel regimens—have kept survival gains modest for decades.
A therapy built around a distinct mechanism gives oncologists a second-line option beyond cytotoxic retreatment, a gap that has shaped commercial and reimbursement discussions across the oncology sector for years.
Daraxonrasib is described as a RAS(ON) multiselective inhibitor, engaging the active, guanosine triphosphate-bound state of mutant and wild-type RAS proteins that drive proliferation in more than 90% of pancreatic tumors.2 That distinguishes it from earlier RAS-directed compounds restricted to a single mutation subtype.
Groundwork came from the open-label phase 1/2 RMC-6236-001 study, which enrolled 168 previously treated patients and established the 300-mg dose later carried into RASolute 302.3 The FDA granted the drug Breakthrough Therapy, Orphan Drug, and Priority Review designations, reviewed the application under the
When the inaugural group of CNPV awards were announced, experts noted that Revolution was well set up to achieve the designation for daraxonrasib.
“Market analysts have already noted how Disc Medicine and Revolution Medicines saw their probabilities of approval and valuations jump following voucher awards, precisely because regulatory risk and timing uncertainty fell,” Thani Jambulingam, PhD wrote in an analysis on PharmExec. “Add in the reputational ‘regulatory goodwill’ that comes with being in the inaugural group, and the first wave winners are building a compounding advantage.”
The survival difference is substantial for a disease where incremental gains have been the norm, but the open-label design leaves some findings, particularly progression-free survival assessments, susceptible to reporting bias absent blinded independent review. Cross-trial comparisons with chemotherapy regimens also warrant caution given differences in prior-treatment exposure and patient selection.
Durability beyond the reported median follow-up, performance across specific RAS mutation subgroups, and long-term tolerability of a chronic oral regimen remain open questions that will likely shape post-marketing requirements and formulary evaluations. A related trial combining daraxonrasib with a second RAS(ON) compound in first-line disease is ongoing, which may eventually inform sequencing decisions.
Sources
1. US Food and Drug Administration. FDA Approves First in Class Targeted Therapy for Metastatic Pancreatic Cancer. News release. August 26, 2026.
2. O'Reilly EM, Wainberg ZA, Hendifar AE, et al; RASolute 302 Trial Investigators. Daraxonrasib or chemotherapy in previously treated metastatic pancreatic cancer. N Engl J Med. 2026;395(4):325-337.
3. Wolpin BM, Park W, Garrido-Laguna I, et al; RMC-6236-001 Investigators. Daraxonrasib in previously treated advanced RAS-mutated pancreatic cancer. N Engl J Med. 2026;394(18):1790-1802.
4. National Cancer Institute. Cancer Stat Facts: Pancreatic Cancer. Surveillance, Epidemiology, and End Results Program. Accessed August 26, 2026.
