First-in-Human Phase I/IB Dose-Finding Study of Adagrasib (MRTX849) in Patients With Advanced KRAS G12C Solid Tumors (KRYSTAL-1)

PURPOSE Adagrasib (MRTX849) is an oral, highly selective, small-molecule, covalent inhibitor of KRAS G12C . We report results from a phase I/IB study of adagrasib in non–small-cell lung cancer, colorectal cancer, and other solid tumors harboring the KRAS G12C mutation. MATERIALS AND METHODS Patients with advanced KRAS G12C -mutant solid tumors were treated with adagrasib 150 mg orally once daily, 300 mg once daily, 600 mg once daily, 1,200 mg once daily, or 600 mg orally twice a day using an accelerated titration design, which transitioned to a modified toxicity probability interval design when a predefined degree of toxicity was observed or target adagrasib exposure was achieved. Safety, pharmacokinetics, and…