A new oral treatment for late-stage pancreatic cancer has shown unprecedented results in a major trial, nearly doubling the average survival time for patients compared to those on standard chemotherapy. The announcement from clinical oncology company Revolution Medicines marks a significant potential advance against one of the deadliest forms of cancer.
In the ongoing global Phase 3 trial, known as RASolute 302, patients with previously treated metastatic pancreatic cancer taking a once-daily 300mg dose of the drug daraxonrasib lived for a median of 13.2 months. Those receiving standard chemotherapy lived for a median of 6.7 months. Revolution Medicines stated this represented a 60% reduced risk of death, with a hazard ratio of 0.40.
The Key Target: A Once ‘Undruggable’ Gene
The breakthrough efficacy is tied directly to the drug’s novel mechanism of action. Daraxonrasib is designed to block a gene called RAS, which Revolution Medicines identifies as the driver behind the vast majority of pancreatic cancers. The company describes pancreatic cancer as the most “RAS-addicted of all major cancers,” with over 90% of patients harbouring tumours driven by mutations in RAS proteins.
For decades, the RAS gene has been considered one of the most challenging targets in oncology. Revolution Medicines explains that daraxonrasib works by suppressing RAS signalling through inhibiting the interaction between wild-type and mutant RAS proteins and their downstream effectors. Its proprietary approach uses a tri-complex inhibitor platform to directly target the active, “ON” state of RAS, blocking the oncogenic signals that fuel cancer growth.
This represents a more personalised, targeted approach compared to traditional chemotherapy. Dr. Brian Wolpin, principal investigator for the trial and a professor at Harvard Medical School, said, “I believe that this new approach is a very important advance for the field that I expect will be practice-changing.”
A Manageable but Significant Side Effect Profile
The benefits come with a distinct set of side effects. According to the UK’s clinical trial registry, common side effects of daraxonrasib include rash, vomiting, fatigue, nausea, diarrhoea, constipation, inflammation, mouth sores, liver inflammation, a decrease in red blood cells, scaly skin and effects on the kidneys.
These effects were illustrated vividly by former US Senator Ben Sasse, who publicly disclosed he is taking daraxonrasib after a stage four pancreatic cancer diagnosis. Sasse, 54, called it a “nasty drug” that causes skin integrity issues, but confirmed his tumours had shrunk by 76% since starting treatment.
Revolution Medicines reported the drug was “generally well tolerated, with a manageable safety profile” in the trial. The side effects of standard chemotherapy, as listed by the American Cancer Society, can be similarly broad, including nausea, hair loss, nerve problems, fatigue, and reduced blood cell counts.
The urgent need for new treatments is underscored by stark survival statistics. The Pancreatic Cancer Action Network states pancreatic cancer is the deadliest major cancer, with a five-year survival rate below 20%. In the UK, survival has seen limited improvement over 50 years, with around 4.3% of people surviving a decade or more. Approximately 11,100 new cases are diagnosed annually in the UK, with late diagnosis being a critical issue: 4 in 5 people in England are diagnosed at a stage where curative surgery is not possible.
Revolution Medicines plans to submit the trial data to the US Food and Drug Administration as part of a New Drug Application. The drug has already received FDA Breakthrough Therapy Designation and Orphan Drug Designation for pancreatic cancer, and the company was selected for a new FDA voucher program to expedite promising medicines. To support global development, the company secured a $2 billion funding arrangement with Royalty Pharma.
The company is also conducting additional Phase 3 trials for daraxonrasib, including studies for first-line pancreatic cancer treatment and for non-small cell lung cancer, signalling a broad strategy to target RAS-addicted cancers.