The US FDA has approved Revolution Medicines’ daraxonrasib for adults with previously treated pancreatic cancer, providing a new oral treatment option in the second-line setting.

Daraxonrasib approved after RASolute302 results

The approval was supported by results from the Phase 3 RASolute302 study, in which daraxonrasib demonstrated a median overall survival of 13.2 months in patients receiving second-line treatment.

GlobalData healthcare senior analyst Israel Stern said the approval could alter treatment in second-line pancreatic cancer by offering an oral therapy that could replace some chemotherapy-based regimens.

“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),” Stern said.

Daraxonrasib targets RAS proteins while they are actively signalling and uses cyclophilin A (CypA) to interfere with RAS activation of downstream signalling pathways.

According to Stern, the mechanism means the treatment has potential activity across pancreatic cancers carrying different RAS mutations, as well as against reactivation of wild-type RAS that can contribute to resistance.

Revolution Medicines expands pancreatic cancer programme

Revolution Medicines is also investigating daraxonrasib in earlier stages of pancreatic cancer.

The Phase 3 RASolute303 study is evaluating daraxonrasib alone and in combination with gemcitabine and paclitaxel as a first-line treatment. The study has begun recruiting patients.

Stern said: “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.”

Earlier clinical data have also indicated activity for daraxonrasib in patients receiving first-line treatment, according to GlobalData.

The company plans to investigate daraxonrasib as a monotherapy in the adjuvant setting through the planned RASolute304 study.

Another planned study, RASolute309, will evaluate daraxonrasib alongside Revolution Medicines’ G12D-specific RAS inhibitor zoldonrasib in patients with first-line metastatic pancreatic cancer.

The combination is intended to investigate whether targeting different RAS mutations could provide a chemotherapy-free treatment approach.

Daraxonrasib programme extends beyond pancreatic cancer

Revolution Medicines is also developing daraxonrasib in other RAS-driven cancers.

Stern said the company has an ongoing Phase 3 study investigating daraxonrasib in RAS-mutant non-small cell lung cancer (NSCLC), with a further study planned combining the drug with pembrolizumab (Keytruda) and chemotherapy.

The company also plans to investigate daraxonrasib in a Phase 2 basket study covering multiple tumour types.

The FDA approval therefore represents an expansion of treatment options for previously treated pancreatic cancer while Revolution Medicines continues to evaluate whether the drug can be used earlier in treatment and across other RAS-driven cancers.