Evaluation of the Effect of Food and Formulation on the Pharmacokinetics of the SHP2 Inhibitor Migoprotafib Within a Phase I Study in Cancer Patients.

Migoprotafib is a potent and selective inhibitor of Src homology-2 domain-containing phosphatase 2 (SHP2) under investigation in Phase I (PhI) trials both as monotherapy and in combination with multiple therapies for patients with metastatic solid tumors. The PhI study reported herein aimed to assess both a new tablet formulation and the impact of a high-fat meal on the pharmacokinetics (PK) of migoprotafib at the recommended Phase II dose (RP2D) of 60 mg in patients. In two distinct cohorts, patients were administered migoprotafib as a tablet or capsule formulation to assess the impact of formulation, or as a tablet under fasted or fed conditions to assess the impact of food. In an evaluation of the effect of formulation in 20 subjects, the geometric mean ratios (GMRs) [90% CI] of the tablet: capsule formulation were 101 [89.8-114], and 103 [86.2-122], for AUC0-∞ and Cmax, respectively. Consumption of a high-fat meal prior to migoprotafib administration resulted in comparable AUC0-∞ and reduced Cmax compared to fasted administration in 17 subjects, with GMRs [90% CI] of 92.2 [74.5-114], and 42.4 [30.6-58.9], for AUC0-∞ and Cmax, respectively. These findings informed subsequent dosing recommendations for migoprotafib in ongoing and future clinical studies.