Revolution Medicines’ pan-RAS inhibitor helped patients with a highly aggressive form of pancreatic cancer live an average of six months longer than chemotherapy, hitting a goal of the phase 3 study.
The late-stage trial enrolled patients with metastatic pancreatic ductal adenocarcinoma (PDAC) for whom previous treatment had failed. These individuals received either a daily oral dose of 300 mg daraxonrasib or a standard-of-care intravenous chemotherapy.
In the overall study population—which included patients with various types of RAS mutations as well as those without—patients on daraxonrasib saw median overall survival (OS) of 13.2 months versus 6.7 months for the chemotherapy cohort, according to an April 13 release.
The primary endpoints of the trial were both OS and progression-free survival (PFS) in patients who specifically have RAS G12 mutations. While Revolution confirmed that the trial hit these primary and key secondary endpoints, the company’s release didn’t offer up any PFS data.
Revolution also said that daraxonrasib was “generally well tolerated, with a manageable safety profile in patients with PDAC and with no new safety signals.”
The biotech said it would be taking the OS and PFS results to regulators as a part of a package for approval. In the U.S., this will involve using the FDA’s new national priority voucher scheme. The data are also slated to be shared at the 2026 American Society of Clinical Oncology meeting at the end of May.
“In this pivotal trial, daraxonrasib as a targeted medicine delivered a dramatic improvement in overall survival in patients with previously treated metastatic pancreatic cancer compared to standard of care chemotherapy, consistent with earlier findings,” Revolution’s CEO Mark Goldsmith, M.D., Ph.D., said in the release.
“These results represent a potentially transformative advance for patients and underscore daraxonrasib’s potential to redefine the treatment landscape,” Goldsmith added. “We are moving with urgency toward global regulatory submissions and remain committed to rapidly advancing this therapy for patients with a broad range of RAS-addicted cancers.”
Revolution has a lot riding on daraxonrasib, which Evaluate rated last month as the most valuable orphan drug currently in development across biopharma. At the time, Evaluate analysts justified the projections of $4 billion in sales in 2032 as reflecting “the considerable unmet need in pancreatic cancer, due in part to the ineffectiveness of immunotherapy in this setting.”
Revolution has already exploited this hype to its advantage, securing a potential funding infusion of up to $2 billion from Royalty Pharma in return for a slice of the profits if daraxonrasib makes it to market.
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Revolution described pancreatic cancer as the most “RAS-addicted of all major cancers,” with RAS mutations accounting for over 90% of all cases. As a multi-selective inhibitor of RAS(ON) proteins, daraxonrasib is designed to treat a wide range of RAS drivers.
Revolution is also running a phase 3 trial of daraxonrasib both as a monotherapy and in combination with chemotherapy in patients with first-line PDAC. The biotech committed to the phase 3 study after reporting an overall response rate of 55% in patients with first-line metastatic PDAC who received daraxonrasib plus chemotherapy.
But Revolution could face competition. In January, Immuneering reported updated data on atebimetinib in first-line pancreatic cancer patients that suggested a 64% OS rate at 12 months. Immuneering has identified safety and tolerability as an area where it thinks the MEK inhibitor may have an edge over daraxonrasib.
Meanwhile, Revolution has another RAS(ON) inhibitor in the clinic in the form of zoldonrasib, which is being tested in a phase 3 study for first-line metastatic PDAC with RAS G12D mutation, and is being readied for a late-stage study in KRAS G12C-mutant non-small cell lung cancer.
