FDA approves daraxonrasib for metastatic pancreatic cancer following landmark clinical trial led by Dana-Farber
The U.S. Food and Drug Administration (FDA) has approved daraxonrasib, an oral multi-selective RAS(ON) inhibitor, for adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or are not candidates for multiagent systemic therapy. The approval is based primarily on the results from the pivotal randomized phase 3 RASolute 302 trial comparing daraxonrasib to chemotherapy as second-line therapy for patients with metastatic pancreatic cancer, led by Brian Wolpin, MD, MPH, director of the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute.
"For many years, researchers believed that successfully targeting RAS had the potential to transform the treatment of pancreatic cancer, but therapeutically blocking RAS signaling proved extraordinarily challenging,” said Wolpin, who is also director of the Gastrointestinal Cancer Center at Dana-Farber. “The FDA approval of daraxonrasib represents a landmark advance for patients with metastatic pancreatic cancer. The nearly doubling of median overall survival time seen with this targeted treatment represents meaningful progress for patients where new treatment options are urgently needed."
Daraxonrasib is the first approved targeted therapy in pancreatic cancer designed to inhibit RAS, the major cancer-driving pathway in the disease. It works as a molecular glue that together with another protein, cyclophilin A, blocks the signaling of RAS proteins. More than 90 percent of patients with pancreatic cancer have cancer-driving mutations in the KRAS oncogene within the RAS family of genes.
The phase 3 RASolute 302 study, presented by Wolpin at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, and published in the New England Journal of Medicine, enrolled 500 patients with metastatic pancreatic cancer in North America, Europe and Asia. All patients were previously treated with one line of chemotherapy for metastatic disease. Patients were randomized to receive daraxonrasib or a second line of chemotherapy.
Patients who received daraxonrasib showed a substantial improvement in overall survival compared to those treated with chemotherapy. In the overall study population, daraxonrasib reduced the risk of death by 60%, with a hazard ratio of 0.40. Median overall survival was 13.2 months with daraxonrasib compared to 6.7 months with chemotherapy. There was also a reduction in the risk of cancer progression observed among these patients, with a median progression-free survival of 7.2 months compared to 3.6 months with chemotherapy.
In the overall study population of the phase 3 RASolute 302 study, the objective response rate was 31.6 percent with daraxonrasib and 11.2 percent with chemotherapy. Among patients with a known RAS G12 mutation, 33.2 percent of those who received daraxonrasib experienced substantial tumor shrinkage or disappearance compared to 11.8 percent of those receiving chemotherapy.
No new safety signals with daraxonrasib were observed compared to an earlier report from the phase 1/2 trial, also led by Dr. Wolpin and previously published in New England Journal of Medicine. The most common side effects were rash, inflammation in the mouth, nausea and diarrhea.
"The FDA approval of daraxonrasib is an important milestone for patients with pancreatic cancer and a testament to the power of sustained investment in scientific discovery and clinical research,” said Benjamin L. Ebert, MD, PhD, president and CEO of Dana-Farber. “Dana-Farber is proud to have helped lead preclinical and clinical research that made this advance possible, and we remain committed to developing the next generation of treatments that bring new hope to patients and families facing this devastating disease."
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer and one of the deadliest forms of cancer. About 65,000 people in the United States are diagnosed with PDAC each year, and more than 50,000 die from the disease despite current standard treatments. Because pancreatic cancer often causes few or no symptoms in its early stages, about 80% of patients are diagnosed after the cancer has invaded tissues around the pancreas or spread to other parts of the body, when treatment options are more limited. For patients with metastatic pancreatic cancer, the five-year relative survival rate is approximately 3% in the United States.
"For patients and families facing metastatic pancreatic cancer, this approval represents an advance that has been long awaited and long deserved. It shows how relentlessly studying the biology of cancer leads to new treatments that help patients, even for the most difficult to treat of cancer types. The future is now filled with promise, as the Hale Center team and the field at large build on this approval to identify further approaches that provide durable disease responses and more cures. This is an unprecedented time, and we look forward to the daraxonrasib approval heralding the start of a new era in pancreatic cancer treatment," said Wolpin.
Reference:
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