Revolution Medicines and its RAS inhibitor daraxonrasib stole the show at the American Society of Clinical Oncology’s annual meeting this weekend, as Truist Securities predicts a possible third quarter launch for the pancreatic cancer drug.
After decades of struggle and a month of anticipation, the RAS revolution in pancreatic cancer has officially arrived.
The full data on Revolution Medicines’ knockout pancreatic cancer candidate daraxonrasib was unveiled on Sunday, to multiple rounds of applause, at the American Society of Clinical Oncology’s annual meeting in Chicago. The drug doubled overall survival (OS) and progression-free survival (PFS) and nearly tripled the objective response rate compared to chemotherapy.
“We see this dataset as derisking approval and supporting rapid adoption as the rolling NDA [new drug application] progresses with potential for 3Q26E U.S. launch and broader label flexibility,” Truist Securities wrote in a note to investors on Sunday.
Julie Gralow, ASCO’s chief medical officer, was equally effusive. “It’s a grand slam. It is much more than a home run,” she said during a Saturday press briefing with reporters.
Revolution, meanwhile, is also taking advantage of the momentum to look ahead to the rest of its pipeline. “It validates our entire program of RAS,” Chief Development Officer Alan Sandler told BioSpace in an interview. “And validates it not only for pancreatic cancer but also as we are looking into non-small cell lung cancer and colorectal cancer.”
Revolution stunned the cancer world in April with topline data showing that daraxonrasib nearly doubled overall survival for patients with advanced pancreatic cancer. That was a massive win for a disease with a five-year relative survival rate of 13%. The FDA quickly granted expanded access to the drug.
The global Phase 3 RASolute 302 trial enrolled 500 previously treated patients with metastatic pancreatic ductal adenocarcinoma (mPDAC), evaluating daily oral daraxonrasib versus standard chemotherapy. Overall survival jumped from 6.7 months to 13.2 months and PFS went from a median of 3.6 months for the chemo group to 7.2 months for patients on daraxonrasib.
“To see that degree of improvement, it really struck me,” said Meredith Pelster, associate director of Gastrointestinal Cancer Research at Sarah Cannon Research Institute, who is a RASolute 302 investigator but not an author on the abstract. “It’s just a really hopeful day in a disease that has very unfortunately been characterized by hopelessness for a very long time.”
The overall response rate (ORR) for patients with a RAS G12 mutation was 33.2% with the drug, compared to 11.8% for those on chemo. For all patients, regardless of mutation, daraxonrasib resulted in an ORR of 31.6% compared to 11.2% for the chemo cohort.
Some 43.6% of patients on daraxonrasib experienced a grade 3 or higher treatment-related adverse event (TRAE), compared to 57.5% of patients receiving chemo. Some 14% of patients taking daraxonrasib developed a serious rash and 12% experienced serious stomatitis, or an inflamed or sore mouth. About 1.2% of patients discontinued taking the drug due to TRAEs, compared to 11.2% for patients on chemo, and patient-reported quality of life improved on daraxonrasib vs. chemo.
“It was very consistent with what I think we were expecting,” Pelster told BioSpace. “Although daraxonrasib does have toxicities, the overall quality of life for patients was improved.”
Revolution has shipped the first batch of drug to a clinical site as part of the expanded access program, Sandler said. Phase III trials, including RASolute 303 and RASolve 301, evaluating daraxonrasib in earlier treatment lines and in non-small cell lung cancer (NSCLC), are ongoing. Revolution now has four RAS inhibitors including daraxonrasib and the G12D inhibitor zoldonrasib in various stages in its pipeline.
“Collectively, we view RVMD as well-positioned to capture the RAS space with multiple catalysts ahead,” Truist wrote in a Sunday note.
RAS mutations are found in around 30% of all cancers, Sandler said. “This is just the beginning.”
