FDA approves RAS-targeted drug for metastatic pancreatic cancer
The US Food and Drug Administration (FDA) has approved Revolution Medicines’ Rasonque (daraxonrasib) once-daily oral tablets, for the treatment of adults with metastatic pancreatic adenocarcinoma (PDAC).
It is approved in patients who have received at least one prior systemic therapy or who are not candidates for multiagent systemic therapy.
The drug is the first targeted cancer medicine to be approved from a new class of RAS(ON) multi-selective and mutant-selective inhibitors.
Pancreatic cancer is among the most challenging malignancies, frequently presenting with a late diagnosis, aggressive biology and limited responsiveness to conventional treatments. RAS, a key growth control switch in human cells, is the main cause of pancreatic cancer, which is characterised by excessive RAS signalling.
The approval of Rasonque is for adults with metastatic PDAC with or without an identified RAS tumour mutation and does not require use of a companion diagnostic test.
“The FDA approval of Rasonque is a monumental step forward for patients with pancreatic cancer and for the oncology field. For the first time, patients have an approved targeted medicine designed to directly inhibit the main cause of pancreatic cancer, RAS, which has been one of the most intractable disease targets since its discovery decades ago,” said Dr Mark Goldsmith, Chief Executive Officer and Chairman of Revolution Medicines.
He added: “The unprecedented results of the global Phase III trial position Rasonque to become the new standard of care for patients with metastatic pancreatic cancer under an approved label that supports real-world clinical decision-making. This approval further validates our bold RAS(ON) inhibitor strategy that includes multi-selective and mutant-selective approaches targeting a major driver of pancreatic cancer and multiple other cancers.”
The RASolute 302 clinical trial
The FDA approval is based on data from RASolute 302, a global, randomised Phase III trial evaluating Rasonque versus investigator’s choice of cytotoxic chemotherapy in patients with previously treated metastatic PDAC. The trial met all primary and key secondary endpoints in both the RAS G12 mutant population and the overall intent-to-treat (ITT) population, which included patients with or without an identified tumour RAS mutation.
In the ITT population, Rasonque reduced the risk of death by 60% compared with chemotherapy, with a hazard ratio (HR) of 0.40. The median overall survival was 13.2 months with Rasonque compared to 6.7 months for chemotherapy. Rasonque also showed significant improvements in progression-free survival (PFS) with an HR of 0.49. The median PFS was 7.2 months with Rasonque compared to 3.6 months with chemotherapy. Results were generally consistent in the RAS G12 population.
“I believe daraxonrasib is well positioned to become a new standard of care for adults with metastatic pancreatic cancer who have already received at least one systemic therapy or who are not candidates for multiagent systemic therapy. For decades, despite RAS being the main driver and potential drug target for pancreatic cancer, physicians have largely relied on intravenous cytotoxic chemotherapy to treat this aggressive disease. This approval gives physicians the confidence that directly inhibiting RAS can make a striking difference for patients and provides a critically needed new approach to treating patients with metastatic pancreatic cancer,” commented Brian Wolpin, Director of the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute, and principal investigator for the RASolute 302 trial.