The FDA has issued a “safe to proceed” letter to Revolution Medicines, permitting the initiation of an expanded access treatment protocol (EAP) for daraxonrasib (RMC-6236) for patients with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC).1
Per FDA regulations, expanded access to investigational drugs for treatment purposes is permitted for larger populations under a treatment protocol or treatment investigational new drug application. The expanded access request was received by the FDA on April 28, 2026, and signed on April 30, 2026.
“Granting the request 2 days after receiving the expanded access application reflects the FDA’s strong commitment to facilitate early access to therapies for serious and life-threatening conditions, including pancreatic cancer,” FDA Commissioner Marty Makary, MD, MPH, stated in a news release. “Having taken care of many patients with metastatic cancer, I am hopeful that today’s action will improve the lives of patients suffering from this disease.”
On April 13, 2026, Revolution Medicines shared its intention to submit a new drug application for daraxonrasib under the Commissioner’s National Priority Voucher pilot program. Of note, the FDA previously granted a national priority voucher to daraxonrasib in October 2025. Daraxonrasib also received prior FDA breakthrough therapy and orphan drug designations for patients with previously treated metastatic PDAC harboring KRAS G12 mutations.2,3
What data have been reported with daraxonrasib to date?
The oral, potent, RAS(ON) multi-selective inhibitor generated statistically significant and clinically meaningful improvements in progression-free survival (PFS) and overall survival (OS) benefits vs standard chemotherapy in patients with metastatic PDAC, according to data from the first interim analysis of the phase 3 RASolute 302 trial (NCT06625320).4
RASolute 302 is an ongoing, global, randomized, controlled trial enrolling patients with previously treated PDAC harboring various RAS mutations, such as KRAS G12D, G12V, and G12R, as well as those with no identified RAS mutation.
In the intention-to-treat (ITT) population, daraxonrasib produced a median OS of 13.2 months compared with 6.7 months with chemotherapy (HR, 0.40; P < .0001). Regarding safety, daraxonrasib was generally well tolerated and had a manageable safety profile, according to investigators. No new safety signals were reported.
Notably, all PFS and OS end point data from the first interim analysis were considered final; and results will be presented at the 2026 ASCO Annual Meeting.
"We've never seen data like this presented in pancreatic cancer,” Shubham Pant, MD, MBBS, said in an interview with OncLive®. “The last [dataset] to be this impactful was when FOLFIRINOX [leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin] was compared against gemcitabine, which was more than a decade ago. This is going to be practice-changing...not only for those of us in academic medicine, but for our community oncologists who treat a majority of the patients with pancreatic cancer.”
Additionally, results from a pair of phase 1/2 datasets evaluating daraxonrasib as first-line therapy for metastatic PDAC were presented at the 2026 AACR Annual Meeting.5,6 In the GI-102 platform study (NCT06445062), daraxonrasib in combination with gemcitabine and nab-paclitaxel (Abraxane) produced an overall response rate (ORR) of 58% (95% CI, 41%-73%) and a disease control rate (DCR) of 90% (95% CI, 76%-97%) in treated patients (n = 40). At the 6-month landmark analysis, the PFS rate was 84% (95% CI, 68%-93%), and the OS rate was 90% (95% CI, 76%-96%).
FDA Grants Expanded Access to Daraxonrasib in Previously Treated PDAC
- The FDA has issued a rapid “safe to proceed” decision for an expanded access protocol of daraxonrasib in previously treated metastatic PDAC.
- Daraxonrasib previously demonstrated significant OS improvements vs chemotherapy in the phase 3 RASolute 302 trial, with a manageable safety profile.
- The ongoing phase 3 RASolute-303 study is evaluating daraxonrasib with or without chemotherapy vs chemotherapy alone in frontline metastatic PDAC.
Daraxonrasib was also active in the monotherapy cohort study (NCT05379985). Among efficacy-evaluable patients with RAS-mutant metastatic PDAC (n = 38), the ORR was 47% (95% CI, 31%-64%) and the DCR was 92% (95% CI, 79%-98%). In the all-RAS patient population (n = 40), the Kaplan-Meier estimates for the 6-month PFS and OS rates were 71% (95% CI, 53%-83%) and 83% (95% CI, 67%-92%), respectively. PFS and OS data remained immature at the data cutoff. Toxicity profiles for both the monotherapy and combination regimens were manageable and consistent with prior reports.
"[These are] smaller cohorts, but the [results] were very promising,” Pant said. “If you would have told me a few years ago that I could [potentially] give a pill to my patients with metastatic pancreatic cancer, and [approximately] 50% of them would show response, [I would have been] very excited. That would have been unheard of.”
What’s next for daraxonrasib in PDAC?
Daraxonrasib with or without chemotherapy will be compared with chemotherapy alone as first-line treatment for patients with metastatic PDAC in the phase 3 RASolute-303 trial (NCT07491445).7
Approximately 900 patients are planned for enrollment. Eligible patients are required to have confirmed metastatic PDAC regardless of RAS mutation status, with an ECOG PS of 0 or 1 and no previous exposure to systemic therapy for metastatic disease. Upon enrollment, patients will be randomly assigned 1:1:1 to receive 300 mg of daraxonrasib as monotherapy; 200 mg of daraxonrasib plus gemcitabine/nab-paclitaxel on days 1 and 15 of a 28-day cycle for up to 6 months followed by daraxonrasib monotherapy at 300 mg; or gemcitabine/nab-paclitaxel alone on days 1, 8, and 15 of a 28-day cycle. RAS mutation status is required for stratification.
The study’s coprimary end points are PFS and OS; key secondary end points comprise ORR, DOR, safety, and patient-reported outcomes.
References
- FDA permits expanded access for investigational pancreatic cancer drug. FDA. May 1, 2026. Accessed May 1, 2026. https://www.fda.gov/news-events/press-announcements/fda-permits-expanded-access-investigational-pancreatic-cancer-drug
- Revolution Medicines announces FDA breakthrough therapy designation for daraxonrasib in previously treated metastatic pancreatic cancer with KRAS G12 mutations. News Release. Revolution Medicines, Inc. June 23, 2025. Accessed May 1, 2026. https://ir.revmed.com/news-releases/news-release-details/revolution-medicines-announces-fda-breakthrough-therapy
- Revolution Medicines’ RAS(ON) Multi-Selective Inhibitor Daraxonrasib Granted U.S. FDA Orphan Drug Designation in Pancreatic Cancer. News release. Revolution Medicines. October 27, 2025. Accessed October May 1, 2026. https://ir.revmed.com/news-releases/news-release-details/revolution-medicines-rason-multi-selective-inhibitor
- Daraxonrasib demonstrates unprecedented overall survival benefit in pivotal phase 3 RASolute 302 clinical trial in patients with metastatic pancreatic cancer. News release. Revolutions Medicines. April 13, 2026. Accessed April 13, 2026. https://ir.revmed.com/news-releases/news-release-details/daraxonrasib-demonstrates-unprecedented-overall-survival-benefit
- O'Reilly EM, Wolpin B, Pant S, et al. Daraxonrasib monotherapy as first-line (1L) treatment for patients with metastatic pancreatic adenocarcinoma (mPDAC). Presented at: 2026 AACR Annual Meeting; April 17–22, 2026; San Diego, CA. Abstract LB337.
- Wolpin BM, Musher BL, Manji GA, et al. Daraxonrasib plus chemotherapy (CT) as first line (1L) treatment for patients (Pts) with metastatic pancreatic adenocarcinoma (mPDAC). Presented at: 2026 AACR Annual Meeting; April 17–22, 2026; San Diego, CA. Abstract LB407.
- Study of daraxonrasib and daraxonrasib + GnP as first-line treatment in patients with metastatic pancreatic adenocarcinoma (RASolute 303). ClinicalTrials.gov. Updated April 4, 2026. Accessed May 1, 2026. https://clinicaltrials.gov/study/NCT07491445
