EPI-7386 in Combination with Enzalutamide Compared with Enzalutamide Alone in Subjects with MCRPC

Inclusion Criteria: * Males ≥18 years. * Histologically, pathologically, or cytologically confirmed prostate adenocarcinoma. * Evidence of castration-resistant prostate cancer (CRPC). * Presence of metastatic disease at study entry documented by 1 or more bone lesions on bone scan or by soft tissue disease observed by CT/MRI. * Naïve to second generation anti-androgens. * Evidence of progressive disease defined as 1 or more Prostate Cancer Working Group 3 (PCWG3) criteria. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Ongoing ADT with luteinizing hormone-releasing hormone (LHRH) agonist/antagonist therapy or history of bilateral orchiectomy, with castrate level testosterone. * Serum testosterone ≤1.73 nmol/L (50 ng/dL). * Subjects receiving bisphosphonates or other approved bone-targeting therapy (e.g., denosumab) must be on a stable dose for at least 28 days prior to the start of study treatment. * Demonstrate adequate organ function. Exclusion Criteria: * Biologic anti-cancer therapy within 28 days prior to the start of study treatment. * Use of hormonal agents with anti-tumor activity against prostate cancer within 28 days prior to the start of study treatment. * Use of herbal products or alternative therapies that may decrease PSA levels or that may have hormonal anti-prostate cancer activity within 28 days prior to the start of study treatment or plans to initiate during the study. * Intervention with any chemotherapy, investigational agents, or other anti-cancer drugs within 28 days of the first dose of study treatment. * Use of radium-223 dichloride or other radioligand/radiopharmaceutical within 28 days prior to the start of study treatment. * Received limited-field palliative bone radiotherapy \>5 fractions and/or any radiotherapy within 2 weeks prior to the start of study treatment. * Received a blood transfusion within 28 days of hematologic screening labs. * Known intra-cerebral disease or brain metastasis unless adequately treated and stable for the last 28 days before signing of informed consent. * Spinal cord compression. * Diagnosis of another clinically significant malignancy within the previous 3 years other than curatively treated non-melanomatous skin cancer or superficial urothelial carcinoma and other in situ or non-invasive malignancies. * Gastrointestinal issues affecting absorption. * Significant cardiovascular disease. * Known history of seizure or conditions that may pre-dispose them to seizure, including brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain metastases, and brain arteriovenous malformation. * Concurrent disease or any clinically significant abnormality. * Known or suspected hypersensitivity to any components of the formulation used for EPI-7386 or enzalutamide. * Use of strong inhibitors of CYP2C8. * Use of strong inducers of CYP3A. * Use of narrow therapeutic index sensitive CYP2C8 or sensitive substrates for CYP3A and CYP2B6. * Use of granulocyte colony stimulating factor within 7 days prior to screening laboratories. * Not a candidate for enzalutamide treatment. * Patients with rare hereditary problems of fructose intolerance.