A new cancer therapy known as daraxonrasib was recently approved by The Food and Drug Administration for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who have tried at least one other systemic therapy, representing the most significant treatment breakthrough in decades for a common but highly lethal form of pancreatic cancer.
Results from the phase 3 RASolute 302 clinical trial demonstrating daraxonrasib’s efficacy were published in the New England Journal of Medicine (NEJM) in May and shared during a plenary session at the American Society of Clinical Oncology’s 2026 annual meeting. The investigators found that patients who took the oral therapy had a median survival of 13.2 months — almost twice the 6.7-month survival of those receiving chemotherapy.
“Pancreatic cancer has long been one of the most difficult cancers to treat, and for decades we have seen only incremental progress," says Gulam Manji, M.D., Ph.D., director of gastrointestinal medical oncology and co-director of The Pancreas Center at NewYork-Presbyterian and Columbia, who was the principal investigator for Columbia and co-author of the NEJM publication. “To see a therapy nearly double overall survival in a phase 3 study is remarkable.”
Dr. Gulam Manji served as the Columbia principal investigator of the clinical trial that demonstrated daraxonrasib’s efficacy.
Building on Foundational Preclinical Research
Pancreatic cancer has long been considered one of the most challenging cancers to treat, in part because mutations in the RAS gene family — and particularly in the KRAS gene — are the cause of more than 90% of pancreatic tumors. For decades, researchers were unable to effectively target KRAS because its smooth structure does not provide binding pockets for drugs to latch onto, leaving many in the research community to believe it was “undruggable.”
Daraxonrasib belongs to a new class of therapies known as RAS(ON) multiselective inhibitors. Rather than target a single KRAS mutation, these inhibitors act like a molecular glue, enveloping RAS proteins and suppressing the signals that drive mPDAC.
Kenneth Olive, Ph.D., director of GI translational research at Columbia’s Herbert Irving Comprehensive Cancer Center and professor of medicine at Columbia, spearheaded the research evaluating the drug compound using his renowned "mouse hospital” model, which treats mice with pancreatic cancer using the same practices and protocols used on human patients and enrolls them in randomized therapeutic trials. This effort expanded across multiple institutions and culminated in a landmark 2024 Nature study.
Dr. Kenneth Olive’s research in advanced mouse models provided evidence that RAS inhibition was both effective and tolerable for patients.
The research demonstrated that daraxonrasib could selectively target pancreatic tumor cells while largely sparing normal tissue. This addressed longstanding concerns that broad-spectrum RAS inhibition would be too toxic for patients, providing strong evidence that this approach could be both effective and tolerable — a critical step toward advancing the drug into later-stage clinical testing.
“By unleashing a consortium of scientists on this problem, we were able to examine active RAS inhibition in every major class of model for pancreatic cancer, and this inhibitor performed really well in all,” Dr. Olive says.
Changing the Standard of Care
Those preclinical findings were paralleled in the results of the RASolute 302 trial, in which 500 patients with mPDAC who already underwent a first-line treatment were randomly assigned to receive daraxonrasib or chemotherapy. In addition to longer median overall survival, daraxonrasib had better progression-free survival — 7.2 months vs. 3.6 months for chemotherapy — and reduced the risk of death by 60%.
These outcomes and federal approval mark major milestones in decades of efforts to target KRAS and could help change the standard of care for a cancer that measures survival in weeks rather than months. Says Dr. Manji, “FDA approval of daraxonrasib is a watershed moment, providing patients with pancreatic cancer a much-needed effective therapy while opening the door for scientists to develop next-generation agents and transformative combination strategies.”
A version of this article originally appeared on Columbia’s Herbert Irving Comprehensive Cancer Center newsroom.
