Revolution Medicines announced that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for daraxonrasib as a once-daily oral monotherapy for adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy.
According to the company’s press release, the recommendation is supported by the Phase 3 RASolute 302 trial, which demonstrated statistically significant improvements in overall survival and progression-free survival compared with chemotherapy. In the overall study population, daraxonrasib reduced the risk of death by 60% at the prespecified primary analysis.
The positive opinion follows an expedited phased review under the EMA’s Cancer Medicines Pathfinder project. A final decision from the European Commission remains pending. If approved, daraxonrasib would become the first broad RAS-targeted treatment option in the European Union for adults with metastatic pancreatic adenocarcinoma.
Mark A. Goldsmith, chief executive officer and chairman of Revolution Medicines, highlighted the RASolute 302 findings and said the company continues to work with regulatory authorities to pursue additional approvals and broaden access, he said:
“Today’s positive CHMP opinion marks a major step toward making RASONQUE available to eligible adults with metastatic pancreatic cancer in the European Union.”
RASolute 302 Meets Primary and Key Secondary Endpoints
RASolute 302 is a global, randomized Phase 3 trial comparing daraxonrasib with the investigator’s choice of cytotoxic chemotherapy in patients with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC).
The study met all primary and key secondary endpoints in both the RAS G12 mutant population and the overall intent-to-treat population. The latter included patients with or without an identified tumor RAS mutation.
The primary analysis was presented at the 2026 American Society of Clinical Oncology Annual Meeting, with simultaneous publication in The New England Journal of Medicine.
Overall Survival Reached 13.2 Months at the Primary Analysis
In the overall intent-to-treat population, median overall survival was 13.2 months with daraxonrasib, compared with 6.7 months with chemotherapy. The hazard ratio for death was 0.40 (95% confidence interval [CI], 0.30-0.53; p<0.0001), corresponding to a 60% reduction in the risk of death.
The 95% confidence interval for median overall survival was 10.0 months to not estimable in the daraxonrasib group and 5.8-8.0 months in the chemotherapy group.
Safety Findings and Adverse Reactions
The most common adverse reactions with daraxonrasib were diarrhea (63.1%), acneiform dermatitis (62.4%), stomatitis (55.5%), nausea (50.8%), vomiting (41.6%) and fatigue (33.2%).
Separately, the U.S. prescribing information summarized in the release reported serious adverse reactions in 30% of patients and permanent discontinuation due to adverse reactions in 2.9%. Warnings include skin toxicity, oral disorders, diarrhea, gastrointestinal perforation, interstitial lung disease/pneumonitis and embryo-fetal toxicity. Gastrointestinal perforation (0.9%) and ILD/pneumonitis (2.4%) each included one fatal event.
Progression-Free Survival Also Improved
Median progression-free survival was 7.2 months with daraxonrasib, compared with 3.6 months with chemotherapy.
The hazard ratio for progression or death was 0.49 (95% CI, 0.38-0.64; p<0.0001). The confidence intervals for median progression-free survival were 5.7-7.5 months and 2.9-4.2 months, respectively.
Results were generally consistent in the RAS G12 mutant population, the company reported.
Overall survival analysis reported median overall survival of 12.4 months with daraxonrasib versus 6.7 months with chemotherapy, with a hazard ratio of 0.49 (95% CI, 0.39-0.62). Revolution Medicines described these findings as generally consistent with the prespecified primary analysis.
An Oral Treatment Targeting Active RAS
Daraxonrasib, developed by Revolution Medicines, is an oral RAS(ON) multi-selective inhibitor that targets RAS proteins in their active, GTP-bound state. Its activity encompasses mutant and wild-type forms of KRAS, NRAS and HRAS, providing a broader approach to RAS inhibition than therapies directed at a single mutation. OncoDaily
Daraxonrasib works through a tri-complex mechanism. It first binds to cyclophilin A, a chaperone protein; this complex then engages active RAS and blocks its interaction with downstream signaling proteins. The approach is particularly relevant to pancreatic ductal adenocarcinoma, where RAS mutations occur in more than 90% of tumors.
The U.S. Food and Drug Administration approved daraxonrasib on August 26, 2026, for adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or are not candidates for multiagent systemic therapy. The approval was supported by the randomized Phase 3 RASolute 302 trial.
Daraxonrasib is also being evaluated through a global Phase 3 registrational program in PDAC and metastatic RAS-mutant non-small cell lung cancer.
The company reported that the U.S. Food and Drug Administration approved daraxonrasib on August 26, 2026, for adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or who are not candidates for multiagent systemic therapy. At the time of the announcement, the treatment remained investigational outside the United States.
Pancreatic Cancer Burden in Europe
Pancreatic adenocarcinoma is the most common form of pancreatic cancer. The release describes it as a malignancy characterized by late diagnosis, aggressive biology, and limited responsiveness to available treatments.
Approximately 147,000 people are diagnosed with pancreatic cancer in Europe each year, while five-year survival remains below 10%, according to figures cited in the release.
Early-stage disease often causes few or no symptoms. Approximately 80% of patients are diagnosed after the cancer has spread, when treatment options are more limited.
European Commission Decision to Follow
The CHMP recommendation concerns daraxonrasib monotherapy for adults with metastatic pancreatic adenocarcinoma after at least one prior systemic therapy.
If granted, the centralized marketing authorization would be valid across all European Union member states and the European Economic Area countries Iceland, Norway and Liechtenstein. The United Kingdom and Switzerland have separate regulatory processes.
Daraxonrasib received orphan medicinal product designation for pancreatic cancer and high-priority status under the EMA’s Cancer Medicines Pathfinder project because of its potential to address a significant unmet need.
Read further on OncoDaily: Eileen M. O’Reilly and RASolute 302: A Rare Survival Advance in Pancreatic Cancer.
