A drug given “breakthrough designation” by the U.S. Food & Drug Administration (FDA) may offer the best new option in many years for people facing pancreatic cancer, one of the most aggressive types of cancer.
Daraxonrasib targets mutations in the RAS gene, which helps control cell growth — these mutations send signals that fuel cancer cells. KRAS is the most common of these mutations and drives over 90% of pancreatic cancer, which is projected to be the second most deadly cancer in the United States by 2030.
Researchers are running a series of clinical trials to investigate daraxonrasib. They report encouraging results in patients with stage 4, metastatic disease — meaning the cancer has spread to other organs.
“This drug is potentially going to be a landmark shift in how we treat pancreatic cancer,” says gastrointestinal medical oncologist Eileen O’Reilly, MD, of Memorial Sloan Kettering Cancer Center (MSK). “The ability to target RAS mutations that drive so much of pancreatic cancer is huge and has been missing from our treatments.”
Dr. O’Reilly led a phase 1/2 clinical trial of daraxonsarib as part of a larger multidisease trial led by thoracic medical oncologist Kathryn Arbour, MD.
In Dr. O’Reilly’s trial, the patients with pancreatic cancer had not yet received any form of treatment. Chemotherapy is the standard of care treatment for the disease. She reported results from the trial in April 2026 at the Annual Meeting of the American Association of Cancer Research (AACR).
“This is a targeted therapy, given orally once a day. It’s important that we have an option in the future without chemotherapy for patients when they are first treated,” Dr. O’Reilly says. “This may also help a large population of pancreatic cancer patients who are older and have other medical issues that mean they can’t be treated with chemotherapy or decline it. A drug like this could open up new treatment opportunities for them.”
While Dr. O’Reilly was conducting her trial, another MSK study of the drug was underway for patients who were treated with chemotherapy but had stopped responding to it. MSK gastrointestinal medical oncologist Wungki Park, MD, served as the pancreatic cancer lead for the trial, part of an extraordinary clinical and translational research effort by the team at MSK dedicated to caring for people with the disease.
“This could be a paradigm shift in how we treat pancreatic cancer after more than three decades of relying mainly on chemotherapy,” Dr. Park says.
Larger, phase 3 trials comparing the drug to standard-of-care chemotherapy are also underway. Patients with pancreatic cancer and researchers have been encouraged by the early read-outs from these trials, including the highly publicized RASolute 302 trial, which included major involvement by Dr. O’Reilly and the MSK pancreas team.
“For pancreatic cancer, this is moving very rapidly,” Dr. O’Reilly says.
Clinical Trial Results of Daraxonrasib With Untreated Pancreatic Cancer Patients
As an early-phase clinical trial, the primary goals were to ensure that the drug is safe and beneficial to participants in the trial.
- 38 patients were treated.
- The response rate — meaning the number of patients with tumors that showed positive activity from the drug — was 47%.
- Progression-free survival at 6 months — meaning the cancer didn’t get worse — was 71%.
- Overall survival at 6 months was 83%.
Dr. O’Reilly notes that these results need to be extended in larger studies that directly compare the drug with chemotherapy. But, she says, “this drug’s effect on cancer appears to be at least comparable to chemotherapy and maybe even better.”
In combination with results from other trials, “there is obviously a lot of optimism about this approach,” she says.
Fewer Side Effects Than Chemotherapy, Better Quality of Life
In terms of quality of life, “there is unquestionably a shift in a positive direction for patients,” says Dr. O’Reilly, noting that patients appear to have fewer side effects with the drug than chemotherapy.
Because daraxonrasib is taken daily as a pill, it also means patients aren’t required to wear an infusion pack for 48 hours every other week.
“With daraxonrasib, there is often nausea and other gastrointestinal issues at the beginning of treatment, and some patients developed a rash that can be significant and requires management,” she says. One patient on the trial had to stop participating because of side effects associated with the treatment.
But overall, she says, “patients just feel better taking daraxonrasib. They have more good days and spend less time in clinic or hooked up to chemo.”
How RAS Mutations Drive Cancer
The RAS gene helps regulate cell growth. Mutations to the RAS gene can cause out-of-control cell growth — like a broken light switch that’s stuck in the “on” position, these mutations produce a protein that signals cells to grow continuously.
Researchers have known for decades that mutations in the RAS gene can drive cancer. However, scientists long feared that RAS mutations — including the KRAS mutations that drive the vast majority of pancreatic cancer — were “undruggable.”
That’s because their structure makes it difficult for drugs to attach and block their cancer-causing effect.
How Daraxonrasib Blocks RAS Mutations From Driving Pancreatic Cancer
Scientists, however, have recently been able to design drugs that overcome this challenge.
Daraxonrasib essentially locks the growth signal sent by the mutation, causing cancer cells to slow down or stop growing, a process called RAS inhibition.
The drug has also shown activity against several different forms of RAS mutations, including G12D, G12V, G12R, and Q61X mutations. Because of this, the drug is often referred to as a pan-RAS inhibitor. There are RAS targeting drugs that also target some of these individual mutations alone such as G12D and G12V.
“While this is not yet proven, there is a lot of reason to believe that a pan-RAS inhibitor may block the cancer’s ability to develop resistance to the drug over some of the single targeting agents, which would be a big plus,” Dr. O’Reilly says.
One strategy being explored, Dr. O’Reilly says, is combining a pan-RAS inhibitor with another inhibitor narrowly focused on a specific KRAS mutation such as G12D, the most common mutation in pancreatic cancer.
Other Approaches to RAS Driver Cancers at MSK
Another approach to KRAS-driven cancer at MSK is called a KRAS degrader, which is similar to a RAS inhibitor but intervenes differently.
Dr. Park led a novel first-in-human, first-in-class clinical trial for the drug setidegrasib, with results published in March 2026 in the New England Journal of Medicine.
This KRAS degrader “essentially tells the body that it doesn’t need the protein created by the KRAS mutation, so it’s disposed of,” Dr. Park says. This approach showed promising activity in both pancreatic cancer and lung cancer — the lead investigator was Dr. Arbour at MSK.
Another example is the work of MSK gastrointestinal oncologist and early drug development specialist Rona Yaeger, MD. She led clinical trials involving the drug adagrasilb that led to the first FDA approval of a KRAS drug for colorectal cancer.
For Dr. O’Reilly, the possibility that daraxonrasib may successfully target the RAS mutations responsible for so much pancreatic cancer could be life-changing for the people she cares for.
“I’m hopeful these treatments allow the disease to be incorporated into someone’s life,” says Dr. O’Reilly, “as opposed to their life being overtaken by the treatment of cancer.”
KEY TAKEAWAYS
- A new drug called daraxonrasib that is being investigated in clinical trials for pancreatic cancer at Memorial Sloan Kettering Cancer Center (MSK) shows strong early promise as a potential breakthrough in treating this aggressive disease.
- Daraxonrasib works by targeting RAS gene mutations that cause cancer cells to grow uncontrollably, something scientists once feared was impossible to achieve with medication. Early clinical trials show a significant percentage of previously untreated patients responded positively to the drug.
- Unlike traditional chemotherapy, daraxonrasib is taken as daily pills and appears to cause fewer and more manageable side effects. Doctors report that patients generally feel better during treatment including spending less time in medical settings.
- MSK researchers are also developing related drugs that target the same cancer-driving mutations in pancreatic cancer as well as lung and colorectal cancer.
Additional Authors and Disclosures
Additional authors and disclosures can be found in the abstract at the American Association of Cancer Research.