Pembrolizumab and Enobosarm in Treating Patients With Androgen Receptor Positive Metastatic Triple Negative Breast Cancer

Inclusion Criteria

• Documented informed consent
• Willing to provide a sample from a recently obtained (within 42 days prior to initiation of day 1) biopsy of a tumor lesion
• If recently-obtained samples are unavailable an archived metastatic specimen not previously irradiated may be submitted upon agreement from the study principal investigator (PI)
• Eastern Cooperative Oncology Group (ECOG) performance status of = 3 months
• Metastatic triple negative breast cancer (TNBC)
• Measurable disease per RECIST version (v)1.1 criteria: at least 1 lesion of > 10 mm in long axis diameter for non-lymph nodes or > 15 mm in short axis diameter for lymph nodes that is serially measurable according to RECIST 1.1 using computerized tomography, magnetic resonance imaging, or panoramic and close-up color photography
• Histologically proven diagnosis of TNBC per current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline
• Estrogen receptor (ER) negative (ER expression = = 50% nuclear AR staining by immunohistochemistry (IHC) in either the primary or metastatic lesion
• NOTE: research testing of AR status is available at City of Hope (COH) Pathology
• Resolution of grade 2 and above toxicities of most recent therapy except for stable sensory neuropathy (= 1 year
• Male: use and adequate method of contraception with the first dose of study therapy through 120 days after the last dose of study therapy
• Note: abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
• Absolute neutrophil count (ANC) >= 1500/mm^3 (within 14 days prior to day 1 of protocol therapy)
• Platelets >= 100, 000/mm^3 (within 14 days prior to day 1 of protocol therapy)
• Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment) (within 14 days prior to day 1 of protocol therapy)
• Serum total bilirubin = 1.5 x ULN (within 14 days prior to day 1 of protocol therapy)
• Albumin >= 2.5 mg/dL (within 14 days prior to day 1 of protocol therapy)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = = 60 mL/min if creatinine levels > 1.5 x ULN (within 14 days prior to day 1 of protocol therapy)
• Female of childbearing potential only: negative urine or serum pregnancy test; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required (within 14 days prior to day 1 of protocol therapy)

Exclusion Criteria

• Anti-programmed cell death protein-1 (anti-PD-1), PD ligand-1 (PD-L1), PD ligand-2 (PD-L2) agent, an antibody targeting other immuno-regulatory receptors or mechanisms
• Radiotherapy within 14 days prior to day 1 of protocol therapy
• AR targeted agents (including GTx-024, enzalutamide or other AR targeted therapies)
• Investigational agent within 21 days prior to day 1 of protocol therapy
• Hormone replacement therapies (estrogens, megestrol acetate) within 14 days prior to day 1 of protocol therapy
• Live-virus vaccination within 30 days prior to day 1 of protocol therapy
• Systemic cytotoxic chemotherapy, antineoplastic biologic therapy, or major surgery within 21 days of the first dose of trial medication
• Testosterone or testosterone-like agents (methyltestosterone, oxandrolone, oxymetholone, danazol, fluoxymesterone, dehydroepiandrosterone, androstenedione) other androgenic compounds or anti-androgens within 30 days prior to day 1 of protocol therapy
• Chronic systemic steroid therapy or on any other form of immunosuppressive medication
• Unstable or untreated brain/leptomeningeal metastasis
• Clinically active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, or abdominal carcinomatosis (known risks factors for bowel perforation)
• Active central nervous system metastases and/or carcinomatous meningitis
• Severe hypersensitivity reaction to treatment with another monoclonal antibody
• Active autoimmune disease that has required