EMA’s Review of Daraxonrasib in PDAC Accelerated Under Phased Review Process

The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has initiated a phased review of daraxonrasib, an investigational, oral RAS(ON) multi-selective inhibitor being developed for pancreatic cancer, according to a news release from Revolution Medicines.¹ The phased review process accelerates the assessment of a medicine by evaluating data in phases as they become available, ahead of submission of a full marketing authorization application. The announcement comes as the company nears completion of a rolling submission of a new drug application (NDA) for daraxonrasib to the FDA under the agency’s Commissioner’s National Priority Voucher pilot program.

What prompted the EMA to expedite its review of daraxonrasib?

Daraxonrasib has been designated by the EMA as an orphan medicinal product for the treatment of pancreatic cancer and has been recognized as a high priority under the agency’s Cancer Medicines Pathfinder project based on its potential to address a high unmet medical need. Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, is diagnosed at an advanced or metastatic stage in approximately 80% of patients and carries a 5-year survival rate of approximately 3%.¹

“As our rolling submission of an NDA to the FDA nears completion, we are encouraged by the strong engagement we’ve received from health authorities around the world,” stated Mark A. Goldsmith, MD, PhD, chief executive officer and chairman of Revolution Medicines, in the press release.¹ “The EMA’s decision to include daraxonrasib in its new phased review process is an important step toward making this medicine available to patients globally as quickly as possible. We believe this milestone underscores both the significant unmet medical need in pancreatic cancer and the potential of daraxonrasib to address that need.”

What results from the pivotal RASolute 302 trial support this regulatory momentum?

Previously covered topline findings from the phase 3 RASolute 302 trial (NCT06625320) showed that daraxonrasib nearly doubled median overall survival (OS) compared with standard-of-care chemotherapy in patients with previously treated metastatic PDAC, regardless of RAS mutation status.² Patients treated with daraxonrasib achieved a median OS of 13.2 months vs 6.7 months with chemotherapy (HR, 0.40; P <.0001), alongside statistically significant gains in progression-free survival (PFS). The global, randomized trial enrolled approximately 500 adult patients with PDAC and documented RAS mutations at codon 12, 13, or 61, all of whom were randomly assigned 1:1 to receive 300 mg of oral daraxonrasib once daily or investigator’s choice of standard cytotoxic chemotherapy.³

Updated findings, shared in the plenary session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, showed that daraxonrasib exhibited a manageable safety profile, and patients reported significantly delayed deterioration in cancer-related pain, overall global health status, and quality of life compared with those on chemotherapy.⁴

What earlier trial data set the stage for these results?

The RASolute 302 findings built on earlier data from the phase 1/2 RMC-6236-001 trial (NCT05379985), published in The New England Journal of Medicine, which evaluated daraxonrasib monotherapy in patients with advanced solid tumors harboring activating RAS mutations.⁵ Among 26 patients with RAS G12 mutations who received the 300-mg daily dose in the second-line setting, daraxonrasib produced an objective response rate (ORR) of 35% (95% CI, 17%-56%), a median duration of response of 8.2 months (95% CI, 3.8-not evaluable [NE]), a median PFS of 8.5 months (95% CI, 6.7-10.5), and a median OS of 13.1 months (95% CI, 6.7-10.5). In a broader cohort of 38 patients with any RAS mutation at the same dose, the ORR was 29% (95% CI, 15%-46%), with a median OS of 15.6 months (95% CI, 10.9-NE).

Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 30% of patients across the study. Regarding any-grade TRAEs, rash (90%), stomatitis or mucositis (54%), and diarrhea (52%) were among the most common toxicities; investigators noted these effects were generally manageable with routine clinical interventions.

What combination data has daraxonrasib shown with vopimetostat?

In June 2025, early combination data pairing daraxonrasib with the investigational PRMT5 inhibitor vopimetostat in a phase 1/2 trial (NCT06922591) enrolling patients with MTAP-deleted and RAS-mutant metastatic PDAC was released.⁶ In MTAP-deleted, second- and third-line PDAC, the combination elicited an ORR of 92%, with 11 of 12 possible responses, 9 of which were confirmed. The disease control rate was 100%, and the 6-month PFS rate was 90%. No grade 4 or 5 AEs or serious AEs, and no grade 3 or higher RAS-associated TRAEs were noted at a median follow-up of 5.0 months. Based on these findings, the developers intend to advance the vopimetostat plus daraxonrasib combination into phase 3 development for patients with first-line MTAP-deleted pancreatic cancer.

What is daraxonrasib’s regulatory history, and how does it work?

Daraxonrasib’s regulatory pathway in the US has expanded steadily alongside this data readout. The FDA previously granted daraxonrasib breakthrough therapy designation and orphan drug designation for patients with previously treated metastatic PDAC harboring G12 mutations.⁷ More recently, the agent was subsequently selected for the FDA Commissioner’s National Priority Voucher pilot program, intended to accelerate development and review of therapies aligned with US national health priorities. CancerNetwork also covered the FDA’s decision to issue a “safe to proceed” letter authorizing an expanded access program for daraxonrasib in previously treated metastatic PDAC, permitting the agent’s use in eligible patients ahead of formal approval.⁸

Mechanistically, daraxonrasib works by suppressing RAS signaling through inhibition of the interaction between both wild-type and mutant RAS(ON) proteins and their downstream effectors. It is designed to target cancers driven by a broad range of common RAS mutations, including PDAC, non–small cell lung cancer, and colorectal cancer. It is being advanced through a global phase 3 registrational program comprising 4 trials, including the completed RASolute 302 trial.

References

1. European Medicines Agency expedites assessment of Revolution Medicines’ daraxonrasib under phased review process. News release. Revolution Medicines, Inc. July 7, 2026. Accessed July 8, 2026. https://ir.revmed.com/news-releases/news-release-details/european-medicines-agency-expedites-assessment-revolution
2. Daraxonrasib demonstrates unprecedented overall survival benefit in pivotal phase 3 RASolute 302 clinical trial in patients with metastatic pancreatic cancer. News release. Revolution Medicines Inc. April 13, 2026. Accessed July 8, 2026. https://tinyurl.com/44t5vh5d
3. Phase 3 study of daraxonrasib (RMC-6236) in patients with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC) (RASolute 302). ClinicalTrials.gov. Updated April 27, 2026. Accessed July 8, 2026. https://tinyurl.com/5n8ns7xz
4. 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. Presented at: 2026 American Society of Clinical Oncology Annual Meeting; May 29-June 2, 2026; Chicago, IL.
5. Wolpin BM, Park W, Garrido-Laguna I, et al. Daraxonrasib in previously treated advanced RAS-mutated pancreatic cancer. N Engl J Med. 2026;394(18):1790-1802. doi:10.1056/NEJMoa2505783
6. Tango Therapeutics announces combination of vopimetostat and daraxonrasib demonstrated 92% objective response rate in pancreatic cancer. News release. Tango Therapeutics. June 8, 2026. Accessed July 8, 2026. https://tinyurl.com/yc2j8t9p
7. 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 July 8, 2026. https://tinyurl.com/2zrdrcer
8. FDA permits expanded access for investigational pancreatic cancer drug. News release. FDA. May 1, 2026. Accessed July 8, 2026. https://tinyurl.com/4xbhx3pd