"This is the first RAS inhibitor evaluated in a large, randomized trial for patients with pancreatic cancer, and it demonstrates how important an impact these novel medicines are likely to have on the treatment of the disease."
— Dr. Brian Wolpin, Dana-Farber Cancer Institute

Daraxonrasib Achieves Landmark Survival Benefit in Metastatic Pancreatic Cancer

A Phase 3 clinical trial has found that the investigational oral drug daraxonrasib significantly increased overall survival in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) compared to standard chemotherapy. The results were presented at the American Society of Clinical Oncology (ASCO) annual meeting and published in the New England Journal of Medicine.

Trial Results

• The randomized trial enrolled 500 patients with metastatic pancreatic cancer who had received one prior line of chemotherapy.
• Patients receiving daraxonrasib had a median overall survival of 13.2 months, compared to 6.6–6.7 months for those receiving chemotherapy.
• Daraxonrasib reduced the risk of death by 60%.
• Patients on daraxonrasib reported less pain and higher quality of life, and many continued treatment beyond the analysis period.

Drug Mechanism

Daraxonrasib is an oral, Ras(On) multi-selective inhibitor. It targets the mutated KRAS protein, which is present in over 90% of pancreatic cancer cases. The drug acts as a molecular glue, binding to cyclophilin A to inhibit the active KRAS protein, blocking cancer growth signals.

Side Effects

Reported side effects included:

• Rash (experienced by 86–90% of patients)
• Stomatitis (mouth sores)
• Diarrhea, nausea, vomiting, and fatigue

Severe side effects occurred in approximately 30% of patients. The drug was described as less toxic than chemotherapy.

Regulatory Status

The U.S. Food and Drug Administration (FDA) granted the drug fast-track status and permitted an expanded access program for eligible patients with previously treated metastatic pancreatic cancer. Revolution Medicines, the developer of daraxonrasib, is preparing an application for regulatory approval but has not provided a specific timeline.

Expert Statements

"This should become a new standard of care for previously treated metastatic pancreatic cancer."
— Dr. Brian Wolpin, Dana-Farber Cancer Institute

"This represents a very large step forward, though it is not a cure."
— Dr. Zev Wainberg, UCLA, study co-lead

"These results are landscape-changing and unprecedented."
— Dr. Rachna Shroff, University of Arizona Cancer Center

"This study is a grand slam."
— Dr. Julie Gralow, ASCO Chief Medical Officer

"A median overall survival exceeding one year in this patient population is really extraordinary."
— Dr. Emil Lou, University of Minnesota

Background

Pancreatic cancer has a five-year survival rate of approximately 13% for all stages and 3% for metastatic disease. An estimated 67,000 new cases and 52,000 deaths are expected in the U.S. in 2025. KRAS mutations, discovered in the 1980s, have historically been considered "undruggable" due to the protein's structure.

Next Steps

Researchers plan to test daraxonrasib as a first-line treatment and in combination with other therapies. Trials are also underway to evaluate the drug in other KRAS-mutated cancers, including lung and colorectal cancers. Revolution Medicines has three additional RAS inhibitors in clinical trials.

Research Funding Context

The development of daraxonrasib was supported in part by the RAS Initiative, a research program funded by the National Cancer Institute. Some researchers noted that federal investment was critical for the underlying basic research on RAS. In 2025, changes to federal research funding processes and grant allocations have been proposed and implemented by the Trump administration, which some observers have expressed concern could affect future medical research.