Daraxonrasib Earns FDA Orphan Drug Designation in Pancreatic Cancer

The oral, multiselective inhibitor daraxonrasib (RMC-6236) has been awarded orphan drug designation by the FDA for the treatment of pancreatic cancer.¹

“We are gratified the FDA has granted [o]rphan [d]rug [d]esignation to daraxonrasib for the treatment of pancreatic cancer, a devastating disease with limited therapeutic options and representing a large unmet medical need,” said Mark A. Goldsmith, MD, PhD, chief executive officer and chairman of Revolution Medicines, in a press release.¹ “RAS driver mutations are present in nearly all pancreatic cancer cases, underscoring the urgent need for innovative therapies that target this critical driver of disease progression.”

The FDA grants orphan drug designation to drugs that show potential to prevent, diagnose, or treat a rare disease or condition.² As a potent, direct, multiselective RAS(ON) inhibitor, daraxonrasib is designed to target oncogenic RAS mutations implicated in several tumor types including pancreatic ductal adenocarcinoma (PDAC), where a vast majority of patients harbor RAS mutations.³

With this designation, Revolution Medicines, the sponsor, is now qualified for incentives including tax credits, exemption from user fees, and a potential 7 years of market exclusivity following approval.

What studies are investigating daraxonrasib?

The phase 1/1b RMC-6236-001 trial (NCT05379985) is a single-arm dose-escalation and dose-expansion study assessing the safety, tolerability, pharmacokinetics, and preliminary clinical activity of daraxonrasib in adult pretreated patients harboring specific RAS-mutant advanced solid tumors.⁴

Promising safety and preliminary efficacy data from this trial, presented at the 2025 Gastrointestinal Cancers Symposium, supported the agent’s FDA breakthrough therapy status designation in July 2025. Among 22 patients with second-line metastatic PDAC and KRAS 612X mutations who received daily 300-mg doses of daraxonrasib, the median progression-free survival (PFS) was 8.8 months (95% CI, 8.5–not evaluable).⁵ Other notable figures from this data included objective response rates of 36% and 27% in the KRAS G12X-mutant and broader RAS-mutant population at the 300-mg dose, respectively, with respective disease control rates of 91% and 95%. The trial is expected to complete in June 2026.

Furthermore, the agent is being investigated in the global, multicenter, randomized, open-label phase 3 RASolute 302 trial (NCT06625320).⁶ With an estimated completion date of December 2027, this trial is measuring the safety and efficacy of daraxonrasib against standard-of-care chemotherapy in patients with previously treated metastatic PDAC. The study’s primary end points are PFS and overall survival (OS) in the KRAS G12X-mutant population, while secondary end points include all-population PFS and OS, as well as objective response, time to deterioration, objective response per investigator, duration of response, time to response, adverse events, and pharmacokinetics in the RAS-mutant and overall populations.

Looking ahead, the sponsor has announced plans to launch 2 additional phase 3 trials which will study daraxonrasib in first-line metastatic PDAC and in the adjuvant setting for resectable PDAC.¹

REFERENCES:

1. 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 27, 2025. https://tinyurl.com/3ecwszen

2. Designating an Orphan Product: Drugs and Biological Products. US Food & Drug Administration. Updated August 12, 2024. Accessed October 27, 2025. https://tinyurl.com/5n77pu2w

3. Lee JK, Sivakumar S, Schrock AB, et al. Comprehensive pan-cancer genomic landscape of KRAS altered cancers and real-world outcomes in solid tumors. NPJ Precis Oncol. 2022;6(1);91. doi:10.1038/s41698-022-00334-z.

4. Study of RMC-6236 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS. ClinicalTrials.gov. Updated November 14, 2024. Accessed October 27, 2025. https://clinicaltrials.gov/study/NCT05379985

5. Garrido-Laguna I, Wolpin B, Park W, et al. Safety, efficacy, and on-treatment circulating tumor DNA (ctDNA) changes from a phase 1 study of RMC-6236, a RAS(ON) multi-selective, tri-complex inhibitor, in patients with RAS mutant pancreatic ductal adenocarcinoma (PDAC). J Clin Oncol. 2025, 43(suppl 4):722.doi:10.1200/JCO.2025.43.4_suppl.722

6. Phase 3 Study of Daraxonrasib (RMC-6236) in Patients With Previously Treated Metastatic Pancreatic Ductal Adenocarcinoma (PDAC) (RASolute 302). ClinicalTrials.gov. Updated September 16, 2025. Accessed October 27, 2025. https://www.clinicaltrials.gov/study/NCT06625320