An Expert’s Perspective on What Daraxonrasib Means for the Future of Pancreatic Cancer Care
In This Article
- The phase 3 RASolute 302 clinical trial of daraxonrasib is widely seen as a breakthrough in treating metastatic pancreatic cancer
- Mass General Brigham is taking part in an expanded access program for daraxonrasib while the drug awaits approval from the FDA
- Harsh Singh, MD, a medical oncologist at Mass General Brigham Cancer Institute, believes daraxonrasib will usher in a new generation of safer, more effective therapies for pancreatic cancer
When results of the phase 3 RASolute 302 clinical trial were presented at the 2026 American Society of Clinical Oncology Annual Meeting, oncologists around the world rejoiced. Those in attendance responded with a one-minute standing ovation.
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In the landmark study, patients with metastatic pancreatic ductal adenocarcinoma received either daraxonrasib, an oral tablet administered once daily, or traditional chemotherapy, the standard of care. The investigators found that daraxonrasib outpaced chemotherapy in both overall survival (13.2 to 6.6 months) and progression-free survival (7.2 to 3.6 months).
Harsh Singh, MD, program director, Hepatobiliary and Pancreas Cancers at Mass General Brigham Cancer Institute, is among those who have hailed the results. (He was not involved in the study.)
“This is a transformative change in how we treat pancreatic cancer, and I’m hopeful that daraxonrasib will be a foundation for much, much better therapies to come,” Dr. Singh says. “Government and industry have invested a lot into pancreatic research over the last three decades. Now, we’re seeing the fruit of that investment with a treatment that fundamentally attacks the underlying biology and dependency of pancreatic cancer.”
The U.S. Food and Drug Administration (FDA) granted daraxonrasib expedited review status for metastatic pancreatic cancer in July 2026. Two months earlier, the FDA approved a request from Revolution Medicines, the drug’s manufacturer, to establish an expanded access program (EAP).
Under the EAP, oncologists can apply for access to daraxonrasib for patients with metastatic pancreatic cancer whose disease has progressed following prior treatment. Mass General Brigham Cancer Institute is participating in the program and has consented roughly 50 patients to date.
A unique mechanism of action
According to the American Cancer Society, around 67,500 people in the United States will be diagnosed with pancreatic cancer this year and roughly 53,000 people will die of the disease. A paper published in Cancer Research projected it will become the second-leading cause of cancer-related death in the country by 2030.
Over 90% of pancreatic cancer cases are driven by mutations in the KRAS gene. KRAS mutations, in turn, leave the KRAS protein in an “always-on” state that fuels tumor growth.
Although the association between KRAS and pancreatic cancer (along with other cancers) has been well-established, developing drugs to target the protein has proven to be exceptionally difficult. The reason? The smooth surface of KRAS lacks the tiny pockets that small molecule inhibitors need to establish a foothold and do their work.
KRAS also binds its natural ligand, GTP, with exquisite avidity, making it challenging for drugs to outcompete GTP. (This is unlike most targeted oncogenes, such as EGFR, which bind ligand ATP with less avidity, making ATP competitive inhibitors chemically feasible.)
Daraxonrasib’s unique mechanism of action allows it to succeed where other drugs have not. First, daraxonrasib binds to cyclophilin A, one of the most ubiquitous proteins in the body, to form a bicomplex. Then, the bicomplex binds to KRAS to form a tricomplex.
“This does two things,” Dr. Singh says. “First, it blocks the downstream signals that KRAS was sending to cancer cells to grow. Second, it starts turning the ‘on’ form of KRAS into the ‘off’ form of KRAS. There are other structural chemistry solutions out there for blocking KRAS, but this is the most successful one thus far.”
In addition to superior efficacy, the RASolute 302 trial showed that daraxonrasib had a much more manageable safety profile than chemotherapy. The most frequent grade 3 or higher treatment-related adverse events reported in participants receiving daraxonrasib were rash (14%) and stomatitis (12%).
“Daraxonrasib does have some unique side effects that we’re learning how to manage,” Dr. Singh says. “But overall, it beat chemotherapy in every aspect we could look at.”
‘An exciting and emotional time’
Under the expanded access program, centers must report significant adverse events. No detailed data collection or additional reporting is required.
Mass General Brigham Cancer Institute began dosing patients in July 2026. Dr. Singh appreciates the opportunity to offer daraxonrasib sooner for patients who might not have the luxury of waiting for FDA approval.
“This has been an exciting and emotional time both for patients receiving the drug and prescribers who were frustrated by chemotherapy not working as well as we wanted it to work,” he says. “Being able to give a treatment that offers hope to patients has been extremely rewarding for my colleagues and me.”
While Mass General Brigham Cancer Institute did not have a direct role in the RASolute 302 study, it was involved in several previous clinical trials contributing to the development of daraxonrasib and other KRAS inhibitors. Currently, the institute’s phase 1 program, led by Dejan Juric, MD, has one of the nation’s broadest clinical trial portfolios for targeting KRAS in pancreatic, colorectal, lung, and other cancers. Meanwhile, translational scientists like Ryan B. Corcoran, MD, PhD, and David T. Ting, MD, are making strides in understanding how tumors learn to grow while patients are on KRAS inhibitors so that countermeasures can be developed.
Leon Pappas, MD, PhD, a medical oncologist at Mass General Brigham Cancer Institute, has led a number of phase 1 clinical trials looking at novel KRAS inhibitors.
“This is an exciting time for RAS-targeted therapy development,” he says. “We’re seeing a flurry of activity in drug development and academic research in this space. And Mass General Brigham is playing a leading role in this area by combining cutting-edge translational research and patient-centered care. I'm very optimistic about what the future holds in terms of helping patients with KRAS mutations.”
Dr. Singh also referenced plans to test KRAS inhibitors in patients with localized disease in the hopes of significantly increasing cure rates.
“Daraxonrasib is not the end but really the beginning of a new wave of treatments for pancreatic cancer,” he says. “I believe we’re going to see more KRAS inhibitors that are either more selective or more active, along with combination strategies that build on KRAS inhibitors, to get us to new treatment paradigms unlike we have seen before.”
To request expanded access to daraxonrasib for one of your patients, please call 617-726-5130.