The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to daraxonrasib in combination with gemcitabine and nab-paclitaxel for the treatment of patients with previously untreated metastatic pancreatic cancer.
Revolution Medicines announced the designation on September 14, 2026. It applies specifically to treatment-naïve metastatic pancreatic adenocarcinoma, marking an effort to move RAS-targeted therapy into the first-line setting.
Daraxonrasib is an oral, multi-selective RAS(ON) inhibitor designed to target the active, cancer-driving state of RAS proteins. The FDA designation covers its use with the widely used chemotherapy combination of gemcitabine and nab-paclitaxel.
The first-line combination remains investigational, and its safety and efficacy for this indication have not yet been established.
Breakthrough Designation Based on RMC-GI-102
The designation was supported by data from the Phase 1/2 RMC-GI-102 trial (NCT06445062), an open-label, multicenter study evaluating RAS(ON) inhibitor combinations in gastrointestinal malignancies.
The relevant cohort included patients with previously untreated, RAS-mutant metastatic pancreatic ductal adenocarcinoma who received daraxonrasib in combination with gemcitabine and nab-paclitaxel.
In previously reported results from 40 patients, the combination produced a confirmed objective response rate of 58%, including one complete response. At the December 1, 2025 data cutoff, median progression-free survival and overall survival had not yet been reached.
The estimated 6-month progression-free survival rate was 84%, while the estimated 6-month overall survival rate was 90%.
The safety profile was described as manageable and generally consistent with the known profiles of the individual treatments. The most common Grade 3 or higher treatment-related adverse events included anemia, decreased neutrophil count, and fatigue.
Alan Sandler, MD, Chief Development Officer at Revolution Medicines, said:
“This Breakthrough Therapy Designation underscores the significant unmet need among patients with previously untreated metastatic pancreatic adenocarcinoma.”
According to Revolution Medicines, this represents the third Breakthrough Therapy Designation for daraxonrasib and the fifth across the company’s portfolio of RAS(ON) inhibitors.
Phase 3 RASolute 303 Trial Underway
Daraxonrasib is now being evaluated in the ongoing Phase 3 RASolute 303 trial (NCT07491445).
The global, randomized, open-label study is designed to enroll approximately 900 patients with previously untreated metastatic pancreatic adenocarcinoma, regardless of tumor RAS genotype. It is comparing three treatment strategies:
- daraxonrasib monotherapy;
- daraxonrasib plus gemcitabine and nab-paclitaxel;
- gemcitabine and nab-paclitaxel alone.
The primary endpoints are progression-free survival and overall survival, with additional endpoints assessing antitumor activity, safety, tolerability, and patient-reported outcomes.
Daraxonrasib Recently Received Its First FDA Approval
The new designation comes shortly after the FDA 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.
FDA Approves Daraxonrasib: First-in-Class RAS Inhibitor for Metastatic Pancreatic Cancer
That approval was based on the Phase 3 RASolute 302 trial (NCT06625320). In the overall study population, median overall survival was 13.2 months with daraxonrasib versus 6.7 months with standard-of-care chemotherapy, corresponding to a hazard ratio of 0.40.
Median progression-free survival was 7.2 versus 3.6 months, while objective response rates were 30% and 11%, respectively.
Daraxonrasib became the first FDA-approved therapy of its class for metastatic pancreatic adenocarcinoma. The newly granted Breakthrough Therapy Designation could now support accelerated development and regulatory review of the drug in combination with chemotherapy for patients receiving their first systemic treatment.
FDA Breakthrough Therapy Designation is intended for therapies for serious or life-threatening conditions where preliminary clinical evidence indicates the potential for substantial improvement over available treatments on one or more clinically significant endpoints.
