The US FDA approval of Revolution Medicine’s Rasonque (daraxonrasib) changes the standard of care in second-line pancreatic cancer, as the oral therapy will displace the intensive and complicated-to-administer chemotherapy regimens currently used in practice, revealsGlobalData, a leading intelligence and productivity platform.

Israel Stern, Healthcare Senior Analyst at GlobalData, comments. “Unlike first-generation RAS inhibitors, that only bind to RAS in its off state, daraxonrasib inhibits RAS while it is actively signalling for growth, which is why it is sometimes called RAS(ON). By utilizing a chaperone called CypA, the drug sterically blocks RAS from activating downstream drivers, thus it covers more than 90% of pancreatic cancer patients with various RAS mutations, as well as inhibit the wild-type RAS reactivation that tumors use to develop drug resistance.”

In the RASolute302 study, on which its approval was based, daraxonrasib demonstrated a median overall survival of 13.2 months in the second-line setting, roughly twice the benefit seen with current chemotherapy-based treatments.

Stern continues: “The company wants to be the key player across the pancreatic cancer treatment landscape and running multiple studies to extend daraxonrasib to the frontline setting. The Phase 3 RASolute303 study, evaluating daraxonrasib alone or with gemcitabine plus paclitaxel chemo in the first-line setting, recently began recruiting. Data presented from an earlier study showed a high response rate for dara daraxonrasib in the first line.”

Revolution Medicine plans to initiate RASolute 304 as a monotherapy in adjuvant pancreatic cancer and RASolute 309 in first-line metastatic that combines daraxonrasib with its other pipeline RAS inhibitor, G12D-specific zoldonrasib, to support a fully chemo-free regimen in first line.

Stern concludes: “Revolution Medicine looks to dominate the pancreatic cancer treatment paradigm. It has an ongoing Phase 3 study for RAS-mutant NSCLC and is planning another one evaluating daraxonrasib in combination with Keytruda and chemo. It will expand further with Phase 2 basket study across multiple tumor types.”