Daraxonrasib granted breakthrough designation for pancreatic cancer
FDA status pertains to treatment of KRAS-driven form of disease
Daraxonrasib, Revolution Medicines’ RAS inhibitor candidate for the treatment of people with advanced, or metastatic, pancreatic cancer with KRAS G12 mutations, has been granted breakthrough therapy designation by the U.S. Food and Drug Administration (FDA).
The designation was supported by data from the Phase 1 trial (NCT05379985). It showed that patients with pancreatic ductal adenocarcinoma (PDAC) harboring KRAS G12 mutations whose disease had progressed after prior therapy achieved a median of 8.8 months of survival without disease progression when treated with daraxonrasib at a dose of 300 mg once daily. PDAC is the most common form of pancreatic cancer.
Revolution Medicines is currently enrolling patients with previously treated metastatic PDAC in the global Phase 3 RASolute 302 trial (NCT06625320), which is being conducted at sites across the U.S., Europe, and Japan. The study is intended to serve as the pivotal trial to support potential regulatory approval of daraxonrasib.
“We look forward to substantially completing enrollment of the RASolute 302 study this year to enable an expected readout in 2026, and should the results support it, working closely with the FDA and other regulatory agencies around the world to bring daraxonrasib to patients as quickly as possible,” Mark A. Goldsmith, MD, PhD, CEO and chairman of Revolution Medicines, said in a company press release.
Daraxonrasib being developed for other cancer types
Pancreatic cancer is a type of cancer that begins in the pancreas, an organ involved in digestion and blood sugar control. PDAC begins in the cells lining the ducts that carry digestive enzymes out of the pancreas.
Due to the lack of early symptoms and detection methods, most patients are diagnosed with PDAC at a metastatic stage, when it has spread to other parts of the body. G12 mutations in the KRAS gene, which encodes a protein involved in cell growth and division, are present in about 85% of the people with PDAC.
Daraxonrasib is an oral inhibitor of the active form of RAS, a family of proteins that includes KRAS. It works by blocking the interaction of KRAS with its downstream effectors. It does so by targeting mutated forms of RAS proteins, including G12 mutations.
The open-label Phase 3 trial is expected to enroll 460 adults with metastatic PDAC with mutations in RAS genes. They must have been previously treated with one prior line of chemotherapy with a gemcitabine- or a 5-fluorouracil-based regimen. Patients with G12, G13, or Q61 mutations in KRAS, NRAS, or HRAS genes may be included.
Participants are randomly assigned to receive daraxonrasib or standard of care chemotherapy. The trial’s main goal is to assess progression-free survival, defined as the time until disease progression, and overall survival.
Secondary measures include changes in health-related quality of life, time and duration of complete or partial response to the treatment, and the treatment’s safety and pharmacokinetics, or how the therapy moves through the body.
The treatment is also being developed for other types of cancer, including non-small cell lung cancer and colorectal cancer.
The breakthrough therapy designation is intended to accelerate the development and review of new treatment candidates for serious conditions and demonstrate substantial improvement over available therapies. The designation provides benefits like intensive guidance from the FDA and potential eligibility for priority review.
