FDA Approves Daraxonrasib for Metastatic Pancreatic Adenocarcinoma

Clinical Summary:

• The FDA has approved 300 mg of once-daily oral daraxonrasib for adults with metastatic pancreatic adenocarcinoma who have received at least 1 prior systemic therapy or are not candidates for multiagent systemic therapy. The approval was based on the global, randomized phase 3 RASolute 302 trial comparing daraxonrasib with investigator’s choice of cytotoxic chemotherapy.
• In the intention-to-treat population, daraxonrasib reduced the risk of death by 60% compared with chemotherapy, with median overall survival of 13.2 vs 6.7 months. Median progression-free survival was 7.2 vs 3.6 months, respectively. Daraxonrasib also delayed deterioration in pain and global health status/quality of life.
• The approval introduces the first targeted therapy from the RAS(ON) multi-selective inhibitor class for metastatic pancreatic adenocarcinoma and provides an oral treatment option regardless of whether a tumor RAS mutation has been identified, without requiring a companion diagnostic test.

On August 26, 2026, the US Food and Drug Administration (FDA) approved daraxonrasib (Rasonque; Revolution Medicines) for adult patients with metastatic pancreatic adenocarcinoma who have received at least 1 prior systemic therapy or are not candidates for multiagent systemic therapy.

Daraxonrasib is a once-daily oral RAS(ON) multi-selective inhibitor designed to target multiple forms of RAS, a protein that drives tumor growth in most patients with pancreatic adenocarcinoma. 

This decision was based on results from the phase 3 RASolute 302 trial, a multicenter, open-label trial that randomized 500 patients 1:1 to receive either 300 mg of once daily daraxonrasib or physician’s choice standard chemotherapy. The trial included patients with a broad range of RAS variants, including RAS G12 mutations such as G12D, G12V, and G12R, as well as patients without an identified tumor RAS mutation.

Primary end points included overall survival (OS) and progression-free survival (PFS), as assessed by blinded independent central review, in patients with a RAS G12 mutation and in the overall population. A key secondary end point was safety. 

In the intention-to-treat population, median OS was 13.2 months in the daraxonrasib arm and 6.7 months in the chemotherapy arm, reducing the risk of death by 60% (hazard ratio [HR], 0.4; 95% confidence interval [CI], 0.3 to 0.53; P < .0001). Median PFS was 7.2 months in the daraxonrasib arm and 3.6 months  in the chemotherapy arm (HR, 0.49; 95% CI, 0.38 to 0.64; P < .0001). Results were generally consistent in the RAS G12–mutant population. 

Patient-reported outcomes also favored daraxonrasib. Median time to deterioration in global health status/quality of life was 5.7 months with daraxonrasib compared with 2.6 months with chemotherapy (HR, 0.60; 95% CI, 0.46 to 0.79; P < .001). Median time to worsening of clinically relevant pain was 9.2 vs 3.8 months, respectively (HR, 0.51; 95% CI, 0.37 to 0.71; P < .001).

The most common adverse reactions occurring in at least 20% of patients included rash, diarrhea, stomatitis, nausea, fatigue, vomiting, abdominal pain, edema, decreased appetite, and hemorrhage. 

Dermatologic toxicity occurred in 86% of patients treated with daraxonrasib, including grade 3 events in 10% of patients. Stomatitis occurred in 57%, including grade 3 events in 9%, while diarrhea occurred in 63%, including grade 3 events in 6%. Interstitial lung disease/pneumonitis occurred in 2.4% of patients, including grade 3 events in 0.9% and 1 fatal event. Gastrointestinal perforation occurred in 0.9%, including 1 fatal event.

Serious adverse reactions occurred in 30% of patients receiving daraxonrasib. Adverse reactions led to permanent treatment discontinuation in 2.9% of patients.

Prophylactic measures are recommended to reduce dermatologic toxicity, including topical corticosteroids, emollient creams, limiting sun exposure, use of broad-spectrum sunscreen, and consideration of prophylactic oral antibiotics.

The recommended dose of daraxonrasib is 300 mg orally once daily until disease progression or unacceptable toxicity. 

Daraxonrasib previously received Breakthrough Therapy and Orphan Drug designations and was granted Priority Review for this indication. The application was also reviewed under the FDA Commissioner’s National Priority Voucher pilot program.

In May, the FDA issued a “safe to proceed” letter allowing the sponsor to initiate an expanded access treatment protocol for daraxonrasib, enabling eligible patients to access the investigational therapy prior to approval.

Source:

US Food and Drug Administration. FDA approves first in class targeted therapy for metastatic pancreatic cancer. Accessed on: August 26, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-class-targeted-therapy-metastatic-pancreatic-cancer

Revolution Medicines. US FDA approves Revolution Medicines’ RASONQUE™ (daraxonrasib), the first broad RAS-targeted medicine in metastatic pancreatic cancer. Accessed on: August 26, 2026. https://www.revmed.com/media/news/13366/u-s-fda-approves-revolution-medicines-rasonquetm-daraxonrasib-the-first-broad-ras-targeted-medicine-in-metastatic-pancreatic-cancer