A drug that may offer new hope for people facing pancreatic cancer has been authorized by the U.S. Food & Drug Administration (FDA) for expanded access, meaning more patients can take the drug while it is being studied. Pancreatic cancer is one of the most aggressive types of cancer.
The investigational drug daraxonrasib, previously called RMC-6236, targets mutations in a gene called RAS. KRAS is the most common form and drives over 90% of pancreatic cancers. KRAS mutations have been studied for decades, and scientists long feared they were “undruggable” because they’ve proved so difficult to target with available medicines — until recently.
“Daraxonrasib shuts down the growth signals generated by mutated KRAS, which causes pancreatic cancer cells to stop growing,” says gastrointestinal medical oncologist Wungki Park, MD, MS, of Memorial Sloan Kettering Cancer Center (MSK).
“For the first time, we can clinically target the dominant KRAS signals that drive most pancreatic cancers,” he says. “This could be a paradigm shift in how we treat this cancer after more than three decades of relying mainly on chemotherapy.”
Results from a phase 1/ 2 clinical trial investigating daraxonrasib were published in The New England Journal of Medicine, in May 2026. The study found that for most patients in the trial, the cancer did not worsen for 8.5 months. That is longer than what is typically expected on the current standard of chemotherapy for patients whose cancer has spread and who have already received one previous form of treatment.
For many patients in the clinical trial, the results were dramatic. “Some patients reported that their symptoms improved just days after taking the drug,” Dr. Park says. “We do not see that quick response from most chemotherapy regimens.”
The study involved 16 cancer centers in the United States. At MSK, Dr. Park served as the pancreatic cancer lead, working closely with MSK colleagues, including Eileen M. O’Reilly, MD, as well as Rona Yaeger, MD, and Kathryn Arbour, MD, who led efforts in other cancer types.
The clinical trial is one of several simultaneous trials testing daraxonrasib across different settings. The trial is a novel, first-in-human study of this first-in-class targeted therapy, which is known as a RAS(ON) tri-complex inhibitor and was developed by Revolution Medicines.
How Does Daraxonrasib Work?
Dr. Park compares KRAS mutations to a broken traffic light in cancer cells.
“KRAS mutations in pancreatic cancer are like a traffic light stuck on green that keeps signaling cancer cells to divide and multiply,” he says. “Daraxonrasib essentially locks that signal so it can’t get through, causing the cancer cells to slow down or stop growing.”
Clinical Trial Finds That Daraxonrasib Can Help Advanced Pancreatic Cancer
Dr. Park says the clinical trial is likely to “open a new paradigm” in treating a disease that’s becoming the second leading cause of cancer deaths.
All the patients in the trial had stage 4 pancreatic cancer, meaning the cancer had spread to other organs, often the liver, lymph nodes, lining of the abdomen, and lungs. They had all previously received one line of chemotherapy, but it was no longer working.
The trial involved 168 patients, whose ages range from 30 to 86 years old, with an average age of 65 — 45% of patients were female.
- 35% of patients responded to the drug.
- The median length of time with progression free survival was 8.5 months.
- Median overall survival was 13.1 months.
“All the patients in the trial received daraxonrasib as their second line treatment, meaning they had received standard chemotherapy for their metastatic pancreatic cancer,” Dr. Park explains. “With chemotherapy in this setting, we typically see the cancer start to get worse within just a few months.”
Managing Side Effects While Maintaining Quality of Life
As a first-in-human and first-in-class phase 1 clinical trial, the main goal is to determine the appropriate dose for further clinical trials.
Significant side effects affected about one in three patients. Patients experienced rash, nausea, diarrhea, and mouth sores. These were generally manageable but could occasionally be more severe. Medical teams monitored patients closely and provided support care, including medications and guidance to help prevent and actively manage side effects. No patients discontinued treatment because of side effects at the 300-milligram daily dose.
“Our patients and the pancreatic cancer community are thrilled that we finally have a new drug that may significantly extend the time they have to spend with their loved ones,” Dr. Park says. “Many trial participants also enjoy a better quality of life, in part because they don’t have as many debilitating side effects as they do with conventional chemotherapy.”
Dr. Park says the patients he’s treated with daraxonrasib have enjoyed milestones like attending a daughter’s wedding and celebrating a grandchild’s birth. “Some patients are able to do things they simply could not manage before, such as traveling. I feel like I am finally giving my patients the time they deserve with their loved ones,” he says.
How Daraxonrasib Overcomes Multiple Types of KRAS Mutations
The investigators also determined that daraxonrasib was active across several common types of KRAS mutations in pancreatic cancer, including G12D, G12V, G12R, and Q61X mutations.
“KRAS mutations come in several forms,” Dr. Park says. “Daraxonrasib appears to work against many of them, which may allow the drug to help a broader group of patients.”
Dr. Park and other researchers are studying how cancers may adapt to this treatment and how to further improve the drug’s activity over time.
Next Steps for Daraxonrasib
The FDA announced “Breakthrough Therapy” designation for daraxonrasib in June 2025, based on encouraging early results from the phase 1 trial. A few months later, in October, the FDA said they intended to accelerate review of the drug as part of a new pilot program called the Commissioner’s National Priority Voucher. In May 2026, the FDA issued a “safe to proceed” letter, allowing the drug to be used for more patients as it is being tested.
Phase 3 trials of the drug are underway at MSK: Dr. Park is leading a trial for patients with metastatic cancer who have not had previous treatment, and Dr. O’Reilly is leading one for patients who no longer respond to one line of chemotherapy. The goal is to determine if the drug improves survival, including the length of time the disease does not get worse, compared to standard of care chemotherapy.
“This progress is the result of years of close collaboration across many scientists and clinicians within and beyond MSK,” Dr. Park says. “We are hopeful this work will translate into longer and better lives for patients.”
Other MSK Research Targeting KRAS Mutations
MSK is also advancing a range of KRAS-targeted therapies across multiple cancer types, including next-generation inhibitors and other emerging approaches. Ongoing clinical trials are exploring how these treatments can be used alone or in combination to further improve outcomes for patients.
For example, Dr. Yaeger, an MSK gastrointestinal oncologist and early drug development specialist, led clinical trials involving the drug adagrasilb that led to the first FDA approval of a KRAS drug for colorectal cancer.
“MSK is at the forefront of this amazing translational science, and I’m very glad to be part of this team we continue to build,” says Dr. Park. “This is truly helping patients with some of the most aggressive cancers and many more cancers that are RAS-driven, which accounts for about one-fifth of solid tumors.”
Key Takeaways
- A new drug called daraxonrasib is targeting pancreatic cancer in a way never done before. It works by blocking signals emitted by mutations in the KRAS gene, which are responsible for driving over 90% of pancreatic cancer cases — mutations that scientists once feared were impossible to drug.
- In clinical trials, patients with advanced stage 4 pancreatic cancer saw their disease stop progressing for more than 8.5 months, compared to just a few months on standard chemotherapy. Some patients reported feeling better within days of starting the drug, and many experienced fewer side effects than with chemotherapy, allowing them to travel, attend family events, and enjoy a better quality of life.
- The drug works across different types of KRAS mutations, not just one. Think of KRAS mutations as coming in different shapes and colors — daraxonrasib can target nearly all of them, which researchers hope will also make it harder for the cancer to develop resistance.
- The FDA has given daraxonrasib “Breakthrough Therapy” designation and is fast-tracking its review. Larger Phase 3 trial results are also encouraging.
Additional authors, funding, and disclosures can be found in the paper at The New England Journal of Medicine.