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.