Daraxonrasib, also known as RMC-6236, is an investigational oral targeted therapy being studied for metastatic pancreatic ductal adenocarcinoma, particularly cancers driven by RAS mutations such as KRAS G12D, G12V, and G12R. Published in the New England Journal of Medicine and presented at ASCO 2026, results from the Phase 3 RASolute 302 trial showed that daraxonrasib improved survival compared with standard chemotherapy in patients with previously treated metastatic pancreatic cancer. Although these results are encouraging, daraxonrasib is still investigational and has not yet been approved by the FDA.
What is daraxonrasib?
Daraxonrasib is an oral RAS(ON) inhibitor designed to target active RAS signaling, a major cancer-driving pathway in pancreatic cancer. This is important because most pancreatic cancers are driven by RAS pathway alterations, and KRAS mutations have historically been difficult to target with drugs. Daraxonrasib is being studied as a once-daily pill, which may make it different from many standard pancreatic cancer treatments that require intravenous chemotherapy.
ASCO update: RASolute 302 Phase 3 results
The RASolute 302 trial enrolled 500 patients with previously treated metastatic pancreatic ductal adenocarcinoma and compared oral daraxonrasib with the investigator’s choice of standard chemotherapy. Patients in the study had received one prior line of therapy, which included either a fluoropyrimidine-based or gemcitabine-based regimen. In the RAS G12-mutant group, median overall survival was 13.2 months with daraxonrasib compared with 6.6 months with chemotherapy, representing a statistically significant reduction in the risk of death. Median progression-free survival was 7.3 months with daraxonrasib compared with 3.5 months with chemotherapy in the RAS G12-mutant group.
The response rate was also higher with daraxonrasib, with objective responses reported in 33.2% of patients with RAS G12-mutant disease compared with 11.8% of patients treated with chemotherapy. Patient-reported outcomes also favored daraxonrasib, with longer time before worsening of pain and longer time before deterioration in global health status and quality of life.
Safety and side effects
In RASolute 302, grade 3 or higher treatment-related side effects occurred in 43.6% of patients treated with daraxonrasib and 57.5% of patients treated with chemotherapy. The most common serious treatment-related side effects with daraxonrasib included rash and stomatitis, while chemotherapy was more commonly associated with low blood counts such as neutropenia, anemia, and thrombocytopenia. Treatment discontinuation due to treatment-related side effects occurred in 1.2% of patients receiving daraxonrasib compared with 11.2% of patients receiving chemotherapy.
How can patients get daraxonrasib now?
Daraxonrasib is not yet commercially available because it remains investigational. The Phase 3 RASolute 302 trial is listed as active but not recruiting, so new patients may not be able to enroll in that specific study. However, an Expanded Access Program has been opened to provide daraxonrasib to eligible adults with previously treated metastatic pancreatic adenocarcinoma who have no comparable or satisfactory alternative therapy and cannot participate in an ongoing daraxonrasib clinical trial.
Patients may be eligible for expanded access if they are 18 or older, have metastatic pancreatic ductal adenocarcinoma, have evidence of active disease progression, have received at least one prior line of systemic therapy in the metastatic setting, and have an ECOG performance status of 0 or 1. Patients must also be able to take oral medications and have adequate bone marrow, kidney, liver, and coagulation function. The program is intended for patients who are ineligible for or unable to enroll in another daraxonrasib clinical trial, and additional inclusion and exclusion criteria may apply. ClinicalTrials.gov lists the sponsor contact as Revolution Medicines Study Director, phone 1-844-2-REVMED, email medinfo@revmed.com.
Questions to ask your doctor
Patients interested in daraxonrasib should ask whether their tumor has been tested for RAS mutations, including KRAS G12 mutations such as G12D, G12V, or G12R. They should also ask whether they have received the type of prior treatment required for daraxonrasib access, whether they meet general health and organ-function requirements, and whether a clinical trial or expanded access program is the best path. It may also be helpful to ask: “Am I eligible for the daraxonrasib expanded access program?”, “Can your office contact Revolution Medicines on my behalf?”, “Would I need additional tumor or blood testing?”, “What are the expected side effects?”, and “What standard treatment options remain available if I cannot access daraxonrasib?”
Bottom line
Daraxonrasib is one of the most closely watched investigational drugs in pancreatic cancer because Phase 3 data presented at ASCO showed longer survival, delayed disease progression, higher response rates, and favorable patient-reported outcomes compared with standard chemotherapy in previously treated metastatic disease. Until regulatory approval occurs, the most realistic ways to access daraxonrasib are through an open clinical trial, if available, or through the expanded access program for eligible patients who cannot join a trial.
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References
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 May 7;394(18):1790-1802.
