FDA Approves Revolution Medicines’ RASONQUE for Metastatic Pancreatic Cancer | iPharmaCenter

The U.S. Food and Drug Administration has approved RASONQUE, also known as daraxonrasib, as a once-daily oral treatment for adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or who are not candidates for multiagent chemotherapy.

The decision marks the first approval of a broad RAS-targeted medicine for this disease. RASONQUE belongs to a new class of RAS(ON) multi-selective and mutant-selective inhibitors designed to suppress RAS signaling in tumors driven by a range of RAS genotypes.

A New Targeted Approach for a Difficult Disease

Pancreatic adenocarcinoma is one of the most challenging cancers to treat. It is often diagnosed at an advanced stage, grows aggressively, and responds poorly to many standard therapies.

RAS proteins act as central regulators of cell growth. In pancreatic cancer, abnormal RAS signaling is a key driver of tumor development. The FDA authorization applies to patients with metastatic disease regardless of whether a specific RAS mutation has been identified, and it does not require a companion diagnostic test.

Phase 3 Trial Shows Large Survival Benefit

The approval was supported by results from the global Phase 3 RASolute 302 study. The trial compared RASONQUE with investigator-selected cytotoxic chemotherapy in adults with previously treated metastatic pancreatic adenocarcinoma.

The study met all primary and key secondary endpoints in both the overall intent-to-treat population and the RAS G12 mutant subgroup.

In the intent-to-treat group, RASONQUE reduced the risk of death by 60% compared with chemotherapy. The hazard ratio was 0.40. Median overall survival was 13.2 months with RASONQUE versus 6.7 months with chemotherapy.

Progression-free survival also improved. The hazard ratio for progression or death was 0.49. Median progression-free survival was 7.2 months with RASONQUE compared with 3.6 months for chemotherapy.

Quality of Life and Symptom Control

The trial also assessed patient-reported outcomes, which are especially important in metastatic pancreatic cancer due to the high symptom burden.

The median time to deterioration for global health status and quality of life was 5.7 months with RASONQUE versus 2.6 months with chemotherapy. For clinically relevant pain, the median time to deterioration was 9.2 months with RASONQUE compared with 3.8 months for chemotherapy.

RASONQUE showed a manageable safety profile and was generally well tolerated in the trial.

About Pancreatic adenocarcinoma

Pancreatic adenocarcinoma accounts for the majority of pancreatic cancer cases. Approximately 55,000 people are diagnosed with this form of the disease in the United States each year, and more than 50,000 die from it under current standard care.

Because early-stage disease often causes few or no symptoms, about 80% of patients are diagnosed after the cancer has spread. For those with metastatic disease, the five-year relative survival rate in the U.S. is approximately 3%.

How RASONQUE Works

RASONQUE is an oral, noncovalent, tri-complex inhibitor that targets multiple forms of RAS, including wild-type and mutant variants of KRAS, NRAS, and HRAS.

The medicine is designed to block the interaction between active RAS(ON) proteins and their downstream effectors, thereby suppressing RAS-driven tumor growth. It is being studied in additional cancers, including non-small cell lung cancer and colorectal cancer, as part of a broader development program.

Regulatory Designations and Access

RASONQUE was selected for the FDA Commissioner’s National Priority Voucher pilot program, which aims to accelerate review of therapies addressing important national health needs. The application was also included in the FDA’s Project Orbis initiative, which supports concurrent review of oncology drugs by multiple international regulators.

The FDA previously granted RASONQUE Breakthrough Therapy Designation and Orphan Drug Designation for previously treated metastatic pancreatic adenocarcinoma. Additional Breakthrough Therapy Designations have been awarded for certain RAS-mutant non-small cell lung cancer populations.

Once-daily oral tablets are now available by prescription in the United States. Revolution Medicines said patient support will be provided through its (ON)Path program, which is intended to help with access, navigation, and treatment-related questions.