A Yale Medicine specialist explains how a new drug targeting a once-‘undruggable’ gene is improving survival for advanced pancreatic cancer.
For patients with advanced pancreatic cancer, a new drug called daraxonrasib is producing a survival gain doctors rarely see: In a large clinical trial, patients who had already tried other treatments lived a median of about 13 months, compared to six to seven months on standard chemotherapy
“Every five to 10 years, there’s a major shift in how we treat pancreatic cancer,” says James Farrell, MD, director of the Yale Center for Pancreatic Diseases. “This is one of those moments. The doubling of survival is huge—that’s never been achieved before.”
Daraxonrasib is currently under review by the Food and Drug Administration (FDA) and could be approved as early as late 2026
What is KRAS, and why does it matter for pancreatic cancer?
About 90% of pancreatic cancers are driven by mutations in a gene called KRAS. For decades, KRAS was considered “undruggable”—meaning researchers couldn’t find a way to block its effects with a medication, says Dr. Farrell, who is also a professor of medicine at Yale School of Medicine
In recent years, drugs that block specific KRAS mutations have come out. But because there are many different KRAS mutations, each of those drugs only helps a small subset of people
Daraxonrasib works differently. It targets a broad range of KRAS mutations at once, rather than just one. That means it could potentially help far more patients than earlier KRAS-targeted drugs. KRAS mutations also occur in other cancers, including lung cancer, where similar targeted therapies have already shown benefit
Why is pancreatic cancer so hard to treat?
Pancreatic cancer is one of the deadliest cancers in the U.S., even though it’s far less common than breast, prostate, colon, and lung cancers. The lifetime risk is about 1.7%, or roughly 1 in 70 people
A few factors make it especially difficult:
- Few early symptoms: Most patients don’t have noticeable symptoms until the disease has already spread.
- Limited surgical options: Only about 15% to 20% of patients are diagnosed early enough for surgery, which offers the best chance at long-term survival. Many others have tumors that can’t be removed because they involve major blood vessels near the pancreas.
- Historically poor survival: The five-year survival rate stayed in the single digits for decades; it has since improved slightly but is still only about 11% to 13%.
“Most patients present with advanced disease, where survival is measured in months rather than years,” Dr. Farrell says
What does this mean for patients right now?
While daraxonrasib is still under FDA review, the agency has allowed limited early access through a special program, so some patients with advanced pancreatic cancer can already receive it
“For patients, it’s reasonable to begin the conversation with their oncologist about whether these drugs or related clinical trials may be appropriate,” Dr. Farrell says
Because pancreatic cancer often progresses quickly, he adds, exploring options early can matter. This is general information, not a substitute for a conversation with your own care team—individual eligibility depends on tumor genetics, prior treatment, and overall health
Is this a cure?
No. Daraxonrasib is not a cure, and expectations should stay measured
“The drug works for a period of time, but the disease is quite crafty,” Dr. Farrell says. “It can find other pathways and continue to grow.”
Over time, many tumors develop resistance to the drug, and not all patients respond to it in the first place. Side effects can include fatigue, nausea, and gastrointestinal symptoms
Even with these limits, experts describe the results as a meaningful step forward for a disease where treatment options have historically been limited
What happens next?
If daraxonrasib is approved, doctors expect it to eventually move into earlier stages of treatment—including for patients whose cancer hasn’t spread yet or who are candidates for surgery
“It will likely move into other settings over time,” Dr. Farrell says. “We’ll begin to see how it performs not just in advanced disease, but in patients earlier in the course of their illness.”
Researchers are also studying several other KRAS-targeted drugs, including in trials underway at Yale Cancer Center. Longer term, Dr. Farrell says, improving early detection and prevention will be just as important to reducing deaths from pancreatic cancer
“This is just the start,” he says. “Now that we know this target can be successfully treated, it opens up the field for other drugs and new approaches.”
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