An experimental drug from Revolution Medicines has proven broadly effective against an aggressive and tough-to-treat pancreatic tumor in a highly anticipated study result that could quickly change medical practice.
Revolution disclosed in April that the drug, daraxonrasib, nearly doubled survival compared to standard chemotherapy in a Phase 3 trial. At the American Society of Clinical Oncology meeting on Sunday, study investigators provided fuller details experts described as “unprecedented” and “landscape changing.”
Revolution’s primary study objective was to test whether daraxonrasib could benefit pancreatic cancer patients whose disease had spread despite a previous treatment and whose tumors were driven by a particular “RAS G12” mutation. But it also evaluated daraxonrasib’s effects on the entire trial population as a secondary outcome, too.
Data presented at ASCO show Revolution’s drug extended survival by a median of 13.2 months among all recipients. By comparison, those who got chemotherapy and had RAS G12 mutations lived a median of 6.6 months. And that figure was comparable — 6.7 months — for all treated with chemo.
The benefits were similarly stark on measures of disease progression. For people with a RAS G12 mutation, daraxonrasib held tumors in check for a median of 7.3 months. For all drug recipients, that number was 7.2 months. Both numbers doubled the 3.5 month and 3.6 month median survival observed, respectively, among those groups of chemo recipients.
“These results are landscape-changing for metastatic pancreatic cancer patients with a KRAS mutation,” said Rachna Shroff, hematology and oncology chief at the University of Arizona Cancer Center, in a statement provided by ASCO. “We are seeing unprecedented survival and efficacy in second-line treatment with an expected safety profile.”
The data also mark the first time “any patients with pancreatic cancer” had lived a median of more than a year following a drug intervention in a clinical trial, said Alan Sandler, Revolution’s chief development officer.
“And this is in the second-line setting,” in “the all-comer population,” he added.
The drug’s impact was so broadly strong, in part, because enrollees who got daraxonrasib felt better almost immediately, added Pashtoon Kasi, a gastrointestinal oncology specialist at City of Hope and a study investigator.
“We saw an improvement in patients' pain and tumor markers within a week or two of starting treatment. That's how quickly things worked,” Kasi said.
Daraxonrasib is the latest step forward in what’s been a yearslong scientific push to develop medicines that can successfully target the “KRAS” mutations known to drive many cancers. That quest first yielded drugs now known as Lumakras and Krazati, which affect a specific type of KRAS mutation and haven’t become big sellers. Daraxonrasib works differently, binding to the protein in its active, or “on,” state and switching it off.
The therapy’s progress treating pancreatic cancer — a notoriously deadly tumor and tough target for drugmakers — has vaulted Revolution into the biotechnology sector’s upper echelon. The company went public at $17 per share in 2020. Its stock price has climbed nearly ten-fold since, giving Revolution a comparable market capitalization to industry heavyweights like Biogen.
Some analysts believe daraxonrasib could have a more than $10 billion overall market opportunity in pancreatic cancer alone. Revolution could begin generating sales faster than usual, as it’s already been awarded a “national priority” voucher that would speed up its U.S. review once an application is submitted.
