Background and Objective <p>Binimetinib is approved for multiple indications at a therapeutic dose of 45 mg twice a day (BID), in combination with encorafenib. A clinical hepatic impairment (HI) study was designed to evaluate the pharmacokinetics (PK), safety, and tolerability of a single oral dose of binimetinib in participants with mild, moderate, and severe HI compared with demographically matched healthy participants with respect to age, gender, and body weight.</p> Methods <p>Participants were enrolled according to National Cancer Institute (NCI) classification criteria for hepatic function based on their total bilirubin and aspartate aminotransferase levels at screening. Participants enrolled into Group 1 (normal hepatic function) were matched to participants enrolled into Groups 2, 3, and 4 (mild, moderate, and severe HI, respectively) with respect to age, gender, and body weight. Dose-normalized PK parameters were evaluated because of a difference in doses for the severe HI group compared to the other groups, with the dose reduction due to the increased exposures observed in the moderate HI group.</p> Results <p>Among 27 PK evaluable participants, changes in binimetinib dose-normalized PK parameters <i>C</i>_max/D and AUC_inf/D were minimal in participants with mild HI compared to the normal hepatic function group. Both the moderate and severe HI groups had significant changes as AUC_inf/D increased by 81% and 111%, respectively, compared to the normal hepatic function group. Unbound AUC_last/D for the moderate and severe HI groups increased by 280% and 248% compared to the normal hepatic function group, respectively.</p> Conclusion <p>Based on these findings on total and unbound exposures, dose reductions are recommended for binimetinib in cancer patients with moderate and severe HI.</p> Clinical Trial Registration <p>ClinicalTrials.gov NCT02050815, registered 29 January 2014.</p>