Every single patient with advanced pancreatic cancer who walked into Dr. Zev Wainberg’s office told him they would rather take an experimental medication than endure another round of chemotherapy.
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Wainberg, co-director of UCLA Health’s GI Oncology Program, was leading a clinical trial of a new drug called daraxonrasib. All the study participants previously had chemotherapy that was starting to fail.
“Statistically, I knew only half of them get the pill, and we don’t get to choose,” Wainberg said. “I put a lot of patients on the chemo arm, and none of them are alive anymore.”
“It’s one of the most emotional studies I’ve ever been a part of,” he said.
Enthusiasm around daraxonrasib is reaching a fever pitch. In the phase 3 trial of 500 patients, the drug was shown to double the survival time of patients with advanced pancreatic cancer, a notoriously deadly cancer: 13.2 months, on average, compared to 6.7 months for people who got chemo. On Sunday, Wainberg and his colleagues presented those results at the American Society of Clinical Oncology’s annual meeting in Chicago. The full study was simultaneously published in the New England Journal of Medicine.
When Revolution Medicines, which makes the drug, released the trial’s preliminary findings in April, Dr. Rachna Shroff, chief of the division of hematology and oncology at the University of Arizona Cancer Center in Tucson, said she “started crying tears of joy.”
“It’s that big of a game-changer for those of us who treat pancreatic cancer,” she said. “It’s unprecedented.”
Now, the excitement is spilling over to other types of cancer. Daxaronrasib, which is taken as three pills once a day, works by targeting a mutation in the KRAS gene found across many cancers, including lung, colorectal, ovarian, endometrial and a type of bile duct cancer called cholangiocarcinoma.
“Pancreas cancer may be the first for this drug, but there will be others,” said Dr. Brian Wolpin, who also led research on daraxonrasib and directs the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute. “Now the floodgates open.”
The Food and Drug Administration has already put the drug on a fast track toward approval for pancreatic cancer, and earlier this month said it would permit Revolution Medicines to give it to patients outside of clinical trials in an expanded access program.
Dr. Mark Goldsmith, chief executive officer for Revolution Medicines, declined to provide a timeline for when the company will file for FDA approval. “Our professionals are working literally 24/7 to get this material prepared as quickly as possible,” he said.
Shrinking tumors
Most pancreatic cancers are diagnosed in later stages of the disease, when surgery isn’t an option.
“Even with our best chemotherapies, the average benefit is around 6 months, sometimes as little as weeks or months,” said Dr. Sameek Roychowdhury, a gastrointestinal medical oncologist at the Ohio State University Comprehensive Cancer Center. “It’s barely enough time for families to grasp the situation.”
Just 3% of patients diagnosed with metastatic pancreatic cancer are alive five years later, according to the American Cancer Society.
Debby Orcutt, 71, was diagnosed with stage 4 pancreatic cancer in April 2024. The cancer had already spread to her liver. Prior to her diagnosis, her only symptom had been a nagging pain in her lower left abdomen that got worse at night.
When chemotherapy started failing Orcutt, she enrolled in the clinical trial for daraxonrasib — and was one of the participants who actually got the drug.
Since she began taking the pill in January 2025, the spot on her liver has vanished. And the tumor on her pancreas has shrunk by 80%, according to her oncologist at Dana-Farber.
“I feel great every single day,” said Orcutt, of Spencer, Massachusetts. “I do not dwell on the fact that I have pancreatic cancer.”
Neither Roychowdhury nor Shroff were involved with clinical trials of daraxonrasib, but both have already begun curating a list of patients to get the drug once it’s available.
“There’s not a doubt in my mind that the second it becomes available, I will start using it,” Shroff said.
What is daraxonrasib and how does it work?
Daraxonrasib targets a mutation in a gene called KRAS, which works like an on/off switch controlling how cells grow in the body. The mutation, which is found in more than 90% of pancreatic cancers, causes the switch to get stuck in an “on” position, allowing cancer cells to grow wildly out of control.
Scientists have known for years that if they could target the KRAS mutation, they could wrench that switch from its “on” position.
“It’s been incredibly hard to drug that mutation,” Wolpin said. “That mutated protein is like a round ball, and you just can’t get the drug to stick to it, to block the effect.” It’s only “through some really amazing chemistry work,” he said, that scientists have been able to develop a drug to work on the mutation.
Daraxonrasib is that first drug. It works by pairing up with a protein called cyclophilin A inside cells, acting like a “molecular glue,” Wolpin said, glomming onto the mutated protein.
Studies for similar drugs in the pipeline are underway. Daraxonrasib is not a cure for cancer; tumors eventually figure out a way to grow again. Ideally, oncologists want an arsenal of drugs like it in line to give to patients when they develop resistance.
Revolution Medicine’s Goldsmith said the company has three other such drugs, called RAS inhibitors, in clinical trials, with a fourth due to start later this year.
Daraxonrasib’s effectiveness appears to expand beyond targeting the mutation. Overall survival was 13.2 months for all patients who got the drug, regardless of whether they had the KRAS mutation.
“Based on the data we have now, I think this drug is relevant to all patients with pancreatic cancer, assuming that they have metastatic cancer,” Wolpin said. “This is the first step to show we can stop using so much chemotherapy.”
Right now, chemotherapy is still recommended as a first-line treatment for patients with advanced pancreatic cancer. Other research is underway, Wolpin said, to see whether those patients should get the drug first.
By all accounts, daraxonrasib is much less toxic compared to chemo. Some patients reported vomiting and diarrhea, as well as sores in the mouth and throat. Some developed a blistering rash that looked like a bad sunburn. Former Nebraska senator Ben Sasse, who got the drug in a clinical trial, described the rash as “nuclear” on a New York Times podcast in April.
Debby Orcutt said her side effects from daraxonrasib were minimal, with a slight rash on her hands and what felt like a big canker sore in her mouth. “We’re talking life or death here,” she said. “How can I complain about a little rash?”
Orcutt and her husband of 47 years, Ron Orcutt, met when they were teenagers with part-time jobs at a shopping center. She sold shoes at Thom McAn; he worked at a Zayre department store. She was 17; he was 18. The two still giggle like school kids.
It’s Ron Orcutt who keeps a careful log of his wife’s daily dose of daraxonrasib. He makes certain that she takes the pills at the right time — setting alarms if he has to — because they must be taken on an empty stomach. That’s exactly two hours after the husband and wife have breakfast together.
The reminders are necessary. By then, Debby Orcutt is out the door, helping her grandchildren get to school on time or heading to her latest part-time job wiping down lunchroom tables at a nearby high school. She doesn’t need the work, but it keeps her active.
“You’ve just got to keep going and have faith. Everybody has to live every day like it’s their last,” she said. “I feel like I’ve been given a second chance, and might as well make the most of it.”
