Pembrolizumab and Enobosarm in Treating Patients With Androgen Receptor Positive Metastatic Triple Negative Breast Cancer
Condition: Androgen Receptor Positive; Estrogen Receptor Negative; HER2/Neu Negative; Metastatic Triple-Negative Breast Carcinoma; Progesterone Receptor Negative; Stage IV Breast Cancer AJCC v6 and v7
MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms
Intervention: Enobosarm; Laboratory Biomarker Analysis; Pembrolizumab
Intervention description: Given PO; Correlative studies; Given IV
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies the side effects and how well pembrolizumab and enobosarm work in
      treating patients with androgen receptor positive triple negative breast cancer that has
      spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies,
      such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere
      with the ability of tumor cells to grow and spread. Androgen can cause the growth of breast
      cancer cells. Hormone therapy using enobosarm may fight breast cancer by blocking the use of
      androgen by the tumor cells. Giving pembrolizumab and enobosarm may work better than
      pembrolizumab alone in treating patients with androgen receptor positive triple negative
      breast cancer.
    

Eligibility criteria:

        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 =< 1

          -  Life expectancy 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 =< 10% positive tumor nuclei),
                  progesterone receptor (PR) negative (PR expression =< 10% positive tumor nuclei)
                  and HER2 negative breast cancer by IHC and /or fluorescence in situ hybridization
                  (FISH)

          -  Androgen receptor positive (AR+)

               -  Defined as >= 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 (=< grade 2) and alopecia

          -  Female (childbearing potential): use an adequate method of birth control (except
             hormonal contraception) or be surgically sterile, or abstain from heterosexual
             activity for the course of the study through 120 days after the last dose of study
             medication

               -  Childbearing potential defined as not being surgically sterilized or have not
                  been free from menses for > 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 upper limit of normal (ULN) OR direct bilirubin =< ULN
             if total bilirubin levels > 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) =< 2.5 x ULN OR =<
             5.0 x ULN if liver metastases present (within 14 days prior to day 1 of protocol
             therapy)

          -  Serum creatinine =< 1.5 x ULN OR creatinine clearance (if measured or calculated per
             institutional standard; glomerular filtration rate [GFR] can also be used in place of
             creatinine or creatinine clearance [CrCl]) >= 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 systemic treatment in the past 2 years
             (replacement therapies for hormone deficiencies are allowed)

          -  Known history of human immunodeficiency virus (HIV), hepatitis B or hepatitis C

          -  History of pneumonitis (non-infectious) that required steroids or current pneumonitis

          -  Diagnosed with or treated for cancer within the previous two years, other than breast
             cancer or non-melanoma carcinoma of the skin

          -  Unable to swallow capsules

          -  Currently on bisphosphonate or denosumab with elevated serum calcium levels corrected
             for albumin/ionized calcium levels outside of institutional normal limits

          -  Female: pregnant or lactating

          -  Concomitant medical condition that precludes adequate study treatment compliance or
             assessment, or increases subject risk, in the opinion of the investigator, such as but
             not limited to:

               -  Myocardial infarction or arterial thromboembolic events within 6 months prior to
                  baseline or severe or unstable angina, New York Heart Association (NYHA) class
                  III or IV disease, or a QTCB (corrected according to Bazett's formula) interval >
                  470 msec; serious uncontrolled cardiac arrhythmia grade II or higher according to
                  NYHA; uncontrolled hypertension (systolic > 150 and/or diastolic > 100 mm Hg)

               -  Acute and chronic active infectious disorders and non-malignant medical illnesses
                  that are uncontrolled or whose control may be jeopardized by the complications of
                  this study therapy

               -  Impairment of gastrointestinal function or gastrointestinal disease that may
                  significantly alter the absorption of study drugs (e.g., ulcerative disease,
                  uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome)

          -  Prospective participants who, in the opinion of the investigator, may not be able to
             comply with all study procedures (including compliance issues related to
             feasibility/logistics)