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 lesionson 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/antagonisttherapy 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 studytreatment.

• 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 28days prior to the start of study treatment.

• Use of herbal products or alternative therapies that may decrease PSA levels or thatmay have hormonal anti-prostate cancer activity within 28 days prior to the start ofstudy treatment or plans to initiate during the study.

• Intervention with any chemotherapy, investigational agents, or other anti-cancerdrugs within 28 days of the first dose of study treatment.

• Use of radium-223 dichloride or other radioligand/radiopharmaceutical within 28 daysprior to the start of study treatment.

• Received limited-field palliative bone radiotherapy >5 fractions and/or anyradiotherapy 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 andstable for the last 28 days before signing of informed consent.

• Spinal cord compression.

• Diagnosis of another clinically significant malignancy within the previous 3 yearsother than curatively treated non-melanomatous skin cancer or superficial urothelialcarcinoma 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 withinthe past 12 months, cerebral vascular accident, brain metastases, and brainarteriovenous malformation.

• Concurrent disease or any clinically significant abnormality.

• Known or suspected hypersensitivity to any components of the formulation used forEPI-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 CYP3Aand CYP2B6.

• Use of granulocyte colony stimulating factor within 7 days prior to screeninglaboratories.

• Not a candidate for enzalutamide treatment.

• Patients with rare hereditary problems of fructose intolerance.