FDA Accepts NDA for Daraxonrasib in Pretreated Metastatic Pancreatic Cancer

The FDA has accepted for review the new drug application (NDA) for daraxonrasib, an oral RAS(ON) multi-selective inhibitor, as a treatment for patients with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC), according to a news release from the developer, Revolution Medicines, Inc.¹

What did the RASolute 302 trial show?

The application is supported by results from the phase 3 RASolute 302 trial (NCT06625320), which evaluated daraxonrasib against standard chemotherapy in this patient population. The trial met all primary and key secondary endpoints, including improvements in overall survival (OS) and progression-free survival (PFS). Notably, when the findings were shared on the plenary stage at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, they earned a standing ovation.² These results were simultaneously shared in the New England Journal of Medicine.³

Specifically, in patients with a RAS G12 mutation, the median OS was 13.2 months (95% CI, 10.0-not estimable) with daraxonrasib vs 6.6 months (95% CI, 5.4-8.2) with chemotherapy (HR, 0.40; 95% CI, 0.30-0.54; P <.0001).

Daraxonrasib also showed a manageable safety profile and no unexpected safety findings. Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 43.6% of the daraxonrasib arm vs 57.5% of the chemotherapy arm; the most frequent with daraxonrasib were rash (14%) and stomatitis (12%). TRAEs led to treatment discontinuation in 1.2% of the daraxonrasib arm and 11.2% of the chemotherapy arm. Patients who received the drug experienced significantly delayed deterioration in cancer-related pain and in overall global health status and quality of life compared with those who received chemotherapy.

“The FDA’s acceptance of the daraxonrasib NDA is an important step in the regulatory review process and brings us closer to the possibility of offering patients a new targeted medicine for previously treated metastatic pancreatic cancer,” stated Mark A. Goldsmith, MD, PhD, chief executive officer and chairman of Revolution Medicines, in the press release.¹ “Daraxonrasib is an oral targeted medicine designed to inhibit RAS, the main cause of pancreatic cancer, and the application is supported by unprecedented results from the phase 3 RASolute 302 trial. These findings underscore the potential for daraxonrasib to become a new standard of care and to help define a new class of RAS‑targeted medicines for this disease.”

What is the RASolute 302 trial design?

Patients enrolled in RASolute 302 were randomly assigned to receive either an oral dose of 300 mg daraxonrasib once daily or 1 of 4 investigator-selected chemotherapy regimens representing standard of care globally. The trial enrolled patients with a wide range of tumor RAS G12 variants, including G12D, G12V, and G12R, as well as patients without an identified tumor RAS mutation.

The dual primary end points were PFS, assessed by blinded independent central review per RECIST 1.1 criteria, and OS in patients with RAS G12–mutated tumors. Secondary end points included PFS and OS across the full intent-to-treat population, along with objective response rate, duration of response, and patient-reported quality of life.

What is daraxonrasib and how does it work?

Daraxonrasib (RMC-6236) is an investigational oral, noncovalent tri-complex inhibitor that suppresses RAS signaling by blocking the interaction between wild-type and mutant RAS(ON) proteins and their downstream effectors. CancerNetwork® spoke with Asfar Azmi, PhD, a professor of oncology at Wayne State University School of Medicine and the director of pancreas cancer research at the Karmanos Cancer Institute in Detroit, Michigan, about daraxonrasib’s mechanism of action.

It is designed to target cancers driven by a broad range of common RAS genotypes, including PDAC, non–small cell lung cancer (NSCLC), and colorectal cancer, and is being evaluated across a global phase 3 registrational program comprising 4 trials, including the completed RASolute 302 trial and 3 additional trials in PDAC and metastatic RAS-mutant NSCLC.

What is daraxonrasib's broader regulatory status?

Daraxonrasib was selected for the FDA Commissioner's National Priority Voucher pilot program, a designation intended to accelerate review of medicines addressing key national health priorities. Additionally, in May 2026, the FDA permitted expanded access, issuing a “safe to proceed” letter for daraxonrasib, which authorized the initiation of an expanded access program for the treatment of patients in this indication.⁴ Daraxonrasib also previously received breakthrough therapy designation and orphan drug designation for previously treated metastatic PDAC. More recently, in July 2026, the European Medicines Agency (EMA)'s Committee for Medicinal Products for Human Use began a phased review of daraxonrasib, allowing data to be evaluated as they become available ahead of a full marketing authorization application submission.⁵ Daraxonrasib holds orphan medicine designation for pancreatic cancer in Europe and has high-priority status under EMA's Cancer Medicines Pathfinder project.

“We look forward to continuing to work closely with the FDA as the agency reviews the application, and with other global regulatory authorities as we advance our efforts to bring daraxonrasib to patients as quickly as possible,” Goldsmith added.¹

References

1. Revolution Medicines' new drug application for daraxonrasib accepted for review by US FDA for previously treated metastatic pancreatic cancer. News release. Revolution Medicines, Inc. July 22, 2026. Accessed July 23, 2026. https://ir.revmed.com/news-releases/news-release-details/revolution-medicines-new-drug-application-daraxonrasib-accepted/
2. Wolpin BM, Wainberg ZA, Hendifar AE, et al. Daraxonrasib, a RAS(ON) multi-selective inhibitor vs chemotherapy in previously treated metastatic pancreatic adenocarcinoma (mPDAC): primary and final analysis from the phase 3 RASolute 302 study. J Clin Oncol. 2026;44(suppl 17):LBA5. doi:10.1200/JCO.2026.44.17_suppl.LBA5
3. 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. doi:10.1056/NEJMoa2605555
4. FDA permits expanded access for investigational pancreatic cancer drug. News release. FDA. May 1, 2026. Accessed July 23, 2026. https://tinyurl.com/4xbhx3pd
5. European Medicines Agency expedites assessment of Revolution Medicines' daraxonrasib under phased review process. News release. Revolution Medicines, Inc. July 7, 2026. Accessed July 23, 2026. https://ir.revmed.com/news-releases/news-release-details/european-medicines-agency-expedites-assessment-revolution