EPI-7386 in Combination with Enzalutamide for the Treatment of Patients with New or Recurrent Metastatic Prostate Cancer

Inclusion Criteria

• Subjects must have histologically or cytologically confirmed prostate adenocarcinoma without small cell or neuroendocrine features (please note: > 10% small cell or neuroendocrine differentiation will be excluded)
• Subjects must have received no prior second-generation antiandrogen therapies for this disease. Androgen deprivation with LHRH agonist/antagonist therapy or history of bilateral orchiectomy that started less than 12 weeks before study enrollment is allowed
• Subjects may have either de novo or recurrent metastatic disease. Presence of metastatic disease at study entry documented by 1 or more lesions – bone, lymph node, soft tissue or visceral metastases - observed by any imaging technique. * Subjects with recurrent disease may have had prior castration if they are still hormone sensitive (no rising prostate specific antigen [PSA] with castrate levels of testosterone) at the time of enrollment
• Age > 18 years. This study will be limited to adults only
• Evidence of metastatic disease by: * Conventional CT of chest, abdomen and pelvis and bone scans OR * Positron emission tomography (PET) scan OR * MRI
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Absolute neutrophil count > 1000/μL at screening * Note: Subjects must not have received any growth factors within 7 days or blood transfusions within 14 days prior to the hematologic laboratory values obtained at screening
• Platelet count > 100 000/μL at screening * Note: Subjects must not have received any growth factors within 7 days or blood transfusions within 14 days prior to the hematologic laboratory values obtained at screening
• Hemoglobin > 8.5 g/dL at screening * Note: Subjects must not have received any growth factors within 7 days or blood transfusions within 14 days prior to the hematologic laboratory values obtained at screening
• Total bilirubin (TBIL) < 2 × the upper limit of normal (ULN) at screening, except subjects with documented Gilbert syndrome who must have a TBIL < 3 mg/dL
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 5 × ULN at screening
• Creatinine clearance ≥ 45 mL/min and/or estimated glomerular filtration rate (eGFR) ≥ 30
• Albumin > 30 g/L (3.0 g/dL) at screening
• Subjects receiving bisphosphonates or other approved bone-targeting therapy (e.g., denosumab) must be on a stable dose for at least 28 days before the start of study treatment
• Subjects of child-producing potential agree to use highly effective contraceptive methods (i.e., barrier contraception measures such as a male condom with spermicide during intercourse) and avoid sperm donation during the study treatment and for 3 months after the last dose of study treatment. A man is considered to be of child-producing potential, unless he has had a bilateral vasectomy with documented aspermia or a bilateral orchiectomy. Partners of patients must also practice approved forms of birth control
• Subjects must have the ability to understand and the willingness to sign a written informed consent form (ICF)
• Members of all races and ethnic groups are eligible for this trial. At least ≥ 20% of enrolled subjects must be of African American descent. (self-reported)

Exclusion Criteria

• Evidence of metastatic castration-resistant prostate cancer (mCRPC)
• Receipt of any other investigational agents
• 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 noninvasive malignancies, as determined by the principal investigator (PI) or CoPI
• Gastrointestinal issues affecting absorption (e.g., gastrectomy)
• Known history of seizure or conditions that may predispose the subject to seizure, including brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain metastases, or brain arteriovenous malformation Subjects with brain metastases/central nervous system (CNS) disease that are treated prior to enrollment will be allowed in this clinical trial
• Known or suspected hypersensitivity to any components of the formulation used for EPI-7386 or enzalutamide
• Use of compounds known to be strong inducers of CYP3A within 30 days prior to start of study drug treatment, and strong inhibitors of CYP2C8 within 14 days of the first dose of study treatment
• Use of narrow therapeutic index sensitive CYP2C8 substrates (e.g., daprobustat, dasabuvir, repaglinide, paclitaxel) or sensitive substrates for CYP3A
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations considered by the Investigator to limit compliance with study requirements