Study to Evaluate Exicorilant (CORT125281) in Combination With Enzalutamide in Patients With Metastatic Castration-Resistant Prostate Cancer

Exicorilant is a selective glucocorticoid receptor (GR) antagonist. In this study, exicorilant will be administered orally in combination with enzalutamide to patients with mCRPC to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of the regimen. The study consists of 2 phases: a dose-determination phase and an expansion phase. The dose determination phase is designed to determine dose-limiting toxicities and the RD of exicorilant plus enzalutamide in patients with mCRPC. Once the recommended dosing regimen has been determined, the following expansion cohorts will be enrolled and treated with exicorilant plus enzalutamide at the RD level. Abiraterone-Resistant Cohort: Patients who have progressed during treatment with abiraterone, and have received no other androgen receptor (AR)-blocking therapies. AR Antagonist-Resistant Cohort: Patients who have progressed during treatment with enzalutamide or other second-generation AR inhibitors. The effect of food on exicorilant PK will be assessed in a portion of the patients enrolled in the Expansion Phase. The 2 expansion cohorts will be enrolled in parallel. In each phase of the study, routine assessments of safety and tolerability will be performed and samples will be collected to determine standard PK parameters for exicorilant, enzalutamide, and their major metabolites. PD, quality of life evaluations and preliminary evaluations of antitumor activity of exicorilant with enzalutamide will be performed throughout the study.