Chemotherapy remains the mainstay systemic treatment for pancreatic ductal adenocarcinoma (PDAC) and the disease continues to hold a dismal prognosis. Most PDACs (>90%) are driven by mutant forms of KRAS, which were historically considered ‘undruggable’; however, recent pharmacological breakthroughs in targeting this protein are providing new hope. Now, new data from a phase I/II trial demonstrate the promising efficacy of daraxonrasib — a novel non-covalent inhibitor that targets the active ‘ON’ conformations of mutant and wild-type KRAS, HRAS and NRAS — in this disease.

In this trial, 168 patients with previously treated advanced-stage KRAS-mutant PDAC (89% KRAS G12-mutant) received daraxonrasib at once-daily oral doses of up to 300 mg. The primary end point was safety, with preliminary antitumour activity as a key secondary end point.