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RASONQUE + gemcitabine + nab-paclitaxel is an investigational combination regimen consisting of daraxonrasib (Rasonque), an oral, multi-selective RAS(ON) inhibitor, combined with the standard-of-care chemotherapies gemcitabine and nab-paclitaxel (Abraxane). Developed by Revolution Medicines, this combination is designed to treat patients with first-line metastatic pancreatic ductal adenocarcinoma (PDAC). Daraxonrasib acts as a molecular glue that binds to cyclophilin A and active, GTP-bound RAS (including wild-type and mutant KRAS, NRAS, and HRAS) to form a tri-complex, thereby blocking downstream RAS signaling. Gemcitabine is a nucleoside metabolic inhibitor, and nab-paclitaxel is an albumin-bound formulation of paclitaxel that inhibits microtubule depolymerization. The FDA granted Breakthrough Therapy Designation to this combination for treatment-naive metastatic PDAC based on promising efficacy and safety data from the Phase 1/2 RMC-GI-102 trial. It is currently being evaluated in the global Phase 3 RASolute 303 trial as a first-line treatment for metastatic PDAC.
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