‘Grand Slam’ Pancreatic Cancer Drug Wins FDA Approval

The FDA approved the first-in-class RAS inhibitor daraxonrasib (Rasonque) for metastatic pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer.

The approval stipulates use in adults with PDAC previously treated with at least one prior systemic regimen or that is ineligible for multiagent systemic therapy. The oral drug targets multiple isoforms of RAS, a driver mutation for most patients with PDAC.

“This drug showed unprecedented results in an area of high unmet need,” said Angelo de Claro, MD, the director of FDA’s Oncology Center of Excellence, in a statement. “The approval was granted 6.5 months before the user fee deadline, demonstrating the FDA’s commitment to accelerating the approval of new cancer treatments for patients with serious and life-threatening conditions.”

Principal support for the approval came from the RASolute 302 trial, which showed that second-line treatment with the RAS inhibitor doubled median overall survival (OS) versus investigator’s choice of chemotherapy in metastatic PDAC associated with RAS G12 mutations (13.2 vs 6.7 months, P<0.001). Patients randomized to daraxonrasib also had a greater than twofold improvement in progression-free survival (PFS), a secondary endpoint (7.3 vs 3.5 months, P<0.001).

The magnitude of the OS and PFS benefits were similar in the overall study population, which included patients with less common RAS mutations.

“These results support daraxonrasib as the new standard of care for patients with previously treated metastatic pancreatic cancer,” said Brian Wolpin, MD, of Dana-Farber Cancer Institute in Boston, who presented the findings at the American Society of Clinical Oncology (ASCO) meeting earlier this year.

“I’ve heard this study described as a home run,” said ASCO’s chief medical officer Julie Gralow, MD, at the meeting. “I would actually say it’s a grand slam.”

Also discussing the study, Rachna Shroff, MD, of the University of Arizona Cancer Center in Tucson, said the RASolute 302 results provide “proof of principle that targeting the RAS signaling pathway is critical in the treatment of pancreatic cancer.”

“RASolute 302 literally checks all of the boxes when we think about relevant and important and meaningful clinical outcomes,” she added. “This is such an incredibly impactful study for our patients.”

Skin rash was the most common treatment-related adverse event (TRAE) with daraxonrasib (85.5% of patients). The most frequent grade ≥3 TRAEs with daraxonrasib were rash (13.7%) and stomatitis (12%). TRAEs leading to treatment discontinuation occurred in 1.2% of the daraxonrasib arm and 11.2% of the chemotherapy arm.

Following a preliminary review of the RASolute 302 data, the FDA announced in early May that drugmaker Revolution Medicines could make daraxonrasib available through an expanded access program in collaboration with authorized prescribers.