Daraxonrasib Nearly Doubles Survival in Metastatic Pancreatic Cancer Trial

Patients with metastatic pancreatic cancer treated with daraxonrasib lived a median of 13.2 months, almost twice as long as the 6.7 months observed in those receiving second-line chemotherapy, according to a Phase 3 trial at Dana-Farber Cancer Institute.

The global RASolute 302 study, involving 500 participants from North America, Europe, and Asia, demonstrated that daraxonrasib reduced the risk of death by 60 percent. These results will be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting.

All patients enrolled had metastatic pancreatic cancer and had undergone one prior chemotherapy regimen for advanced disease before randomization to either daraxonrasib or chemotherapy treatment.

In addition to improving overall survival, daraxonrasib extended median progression-free survival to 7.2 months compared to 3.6 months with chemotherapy.

Targeting the KRAS oncogene in pancreatic cancer

Pancreatic cancer is among the most lethal cancers, often diagnosed after metastasis. Existing second-line therapies provide limited benefits, with few metastatic patients surviving beyond one year.

Since over 90 percent of pancreatic tumors harbor KRAS oncogene mutations, RAS proteins are a prime target for drug development. Daraxonrasib is an oral multi-selective RAS(ON) inhibitor designed to block signaling from both mutant and non-mutant RAS proteins.

Brian Wolpin, director of the Hale Family Center for Pancreatic Cancer Research and Gastrointestinal Cancer Center at Dana-Farber, stated, “This is the first RAS inhibitor evaluated in a large, randomized trial for patients with pancreatic cancer, and it demonstrates how important an impact these novel medicines are likely to have on the treatment of the disease.”

Investigators noted that survival benefits occurred regardless of patients’ RAS mutation status, indicating potential broad applicability across metastatic pancreatic cancer cases.

Higher tumor response rates observed

The trial revealed that 33.2 percent of patients with known RAS G12 mutations achieved significant tumor shrinkage or disappearance under daraxonrasib treatment, compared to 11.8 percent in the chemotherapy group.

When considering all patients regardless of mutation status, the objective response rate was 31.6 percent with daraxonrasib versus 11.2 percent with chemotherapy.

No unexpected safety issues were reported. Common side effects included rash, mouth inflammation, nausea, and diarrhea, consistent with previous clinical trials.

Wolpin added, “Given its ability to inhibit mutant and non-mutant RAS(ON) proteins, daraxonrasib has a broad applicability that has not been possible before.”

The drug’s approval process is ongoing, but the US Food and Drug Administration recently authorized an expanded access program permitting certain previously treated metastatic pancreatic cancer patients to receive daraxonrasib while regulatory review continues.

The study’s full findings were published in The New England Journal of Medicine.