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- A phase 3 clinical trial found that daraxonrasib shows promise as a treatment for pancreatic cancer.
- The drug doubled survival time and improved quality of life for people with advanced disease.
- The findings represent a potential breakthrough in pancreatic cancer treatment.
Pancreatic cancer is one of the deadliest types of cancer, but a new medication may offer hope for certain patients.
Results from a phase 3 clinical trial, published in The New England Journal of Medicine and presented at the recent annual meeting of the American Society of Clinical Oncology, showed that the oral medication daraxonrasib outperformed chemotherapy across multiple metrics. In people with metastatic pancreatic cancer, it doubled survival time, improved quality of life, and slowed disease progression.
Pashtoon Kasi, MD, the medical director of gastrointestinal medical oncology at City of Hope Orange County, said buzzwords often used to describe promising studies, such as “game changer” and “groundbreaking,” are actually warranted in this case. “If there is a study where they truly, aptly apply, it’s this one,” he said.
Here’s what to know about the trial results, what they mean for people with pancreatic cancer (and other cancer types), and what comes next for accessing the drug.
What Did the Study Find?
The phase 3 trial—the final stage of testing before a drug can be considered for approval by the Food and Drug Administration— included 500 patients who’d previously been treated for metastatic pancreatic ductal adenocarcinoma (mPDAC), an aggressive form of pancreatic cancer that has spread beyond the pancreas to other organs. This type accounts for the vast majority of pancreatic cancer cases.
Participants were randomly assigned to receive either chemotherapy (252 patients) or daraxonrasib (248 patients), taken as a pill three times a day.
Nearly 92% of participants had a mutation in the KRAS gene, which is part of the RAS gene family that helps regulate cell growth and division. KRAS mutations occur in more than 90% of pancreatic cancers and are found in about 20% of all cancers, including lung and colorectal cancers.
People taking daraxonrasib, regardless of whether they had the KRAS mutation, survived for a median of 13.2 months, nearly twice as long as those who received chemotherapy.
The drug also “doubled the time of cancer growth control, nearly tripled the ability to shrink the cancer, and maintained quality of life better for longer compared to traditional treatment,” said lead study author Eileen O’Reilly, MD, a gastrointestinal medical oncologist at Memorial Sloan Kettering Cancer Center.
Why Daraxonrasib May Improve Pancreatic Cancer Survival
Daraxonrasib works by targeting KRAS as well as other RAS mutations that produce proteins stuck in an activated, or “on” state, driving uncontrolled cell growth, O’Reilly explained.
The drug “binds to an intracellular protein and sticks to activated RAS as a so-called molecular ‘glue,’” she said. “The net effect is to switch off the RAS pathway signaling and stop growth and spread of cancer.”
What Do the Trial Results Mean for People With Pancreatic Cancer?
The trial results come with two limitations that could introduce bias: The study was open-label, meaning patients knew which treatment they were receiving, and it was funded by Revolution Medicines, the drug’s manufacturer, said Tracy Proverbs-Singh, MD, MPH, a gastrointestinal medical oncologist at the John Theurer Cancer Center at Hackensack University Medical Center.
Still, she and other experts said the findings are significant for a patient population with few treatment options. Pancreatic cancer has the lowest five-year survival rate of any major cancer—just 13%—and, unlike several other cancers, it has no approved gene-targeted therapies.
“RAS, which has historically been considered to be ‘undruggable,’ is now in the category of targetable genes in cancer,” O'Reilly said.
Added Kasi: “It’s a big moment for patients with metastatic pancreas cancer who have failed one line of chemotherapy. They now could be getting another line of therapy and could have this pill as an option.”
The findings could also pave the way for revisiting treatments that have shown promise in other cancers but not in pancreatic cancer. Immunotherapy, for example, “may work in combination with KRAS inhibitors,” said Erkut Borazanci, MD, MS, director of oncology at HonorHealth Research Institute in Arizona.
Could Daraxonrasib Treat Other Types of Cancer?
The new findings apply only to metastatic pancreatic cancer. However, O’Reilly said clinical trials examining the value of daraxonrasib “in localized and other settings of pancreas cancer” are underway.
Researchers are also investigating daraxonrasib as a treatment for other cancers fueled by KRAS mutations.
“The findings from the daraxonrasib study have profound and exciting implications for the treatment of many other types of cancer, including colon and lung cancers,” Proverbs-Singh said. “The success in pancreatic cancer serves as a powerful proof-of-concept that could unlock new therapies across oncology.”
Is This Drug Currently Available For Pancreatic Cancer?
The FDA has fast-tracked the approval process for daraxibrasib to treat pancreatic cancer, and O’Reilly said she’s hopeful that the drug will be approved in the coming months.
In the meantime, some patients may be able to access the drug through the FDA’s compassionate use or expanded access programs, which allow certain treatments to be used before formal approval.
In fact, on May 1, the FDA authorized Revolution Medicines to provide daraxonrasib through an expanded access program, which O’Reilly said “is anticipated to provide availability of daraxonrasib to those who most proximally can benefit.”
