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.
PRIMARY OBJECTIVES: I. To evaluate the safety/tolerability of the combination regimen. II. To determine the response rate (complete response \[CR\] or partial response \[PR\] via Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1) of the combination of pembrolizumab with enobosarm (GTx-024) in patients with advanced androgen receptor (AR) positive (+) triple negative breast cancer (TNBC). SECONDARY OBJECTIVES: I. To evaluate clinical outcomes by RECIST 1.1 including clinical benefit rate (CBR) at 24 weeks, progression free-survival (PFS), duration of response (DOR), event free survival (EFS), time-to-treatment failure (TTF); and overall survival (OS). II. To evaluate the role of immune-related response criteria (irRECIST). III. To evaluate the association of AR by immunohistochemistry (IHC) and clinical response. EXPLORATORY OBJECTIVES: I. To evaluate the association of an AR gene expression signature and clinical response. II. To evaluate genomic and phenotypic status of breast tumor. III. To evaluate the effect of the combination therapy on peripheral blood circulating tumor cells (CTCs) and circulating tumor deoxyribonucleic acid (DNA) (ctDNA). IV. To evaluate the effect of combination therapy on tumor-derived exosomes (TEX) and TEX associated immune biomarkers. V. Immune correlatives: Va. To evaluate pre-treatment programmed death ligand 1 (PD-L1) and tumor infiltrating lymphocytes (TILs) as a predictor of response to combination therapy. Vb. To evaluate specific TIL subsets (e.g. CD4, CD8, regulatory T cell \[Treg\] distribution) and other immunological correlatives (e.g. T cell receptor \[TCR\] repertoire analysis) as possible predictors of response. Vc. To evaluate change in TILs as a result of the combination therapy. Vd. To evaluate peripheral blood, immune biomarkers. OUTLINE: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and enobosarm orally (PO) once daily (QD) on days 1-21. Treatment repeats every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 and 90 days, every 3 months, and bi-annually.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
City of Hope Corona
Corona, California, United States
City of Hope Medical Center
Duarte, California, United States
City of Hope Antelope Valley
Lancaster, California, United States
City of Hope Mission Hills
Mission Hills, California, United States
City of Hope Rancho Cucamonga
Rancho Cucamonga, California, United States
City of Hope South Pasadena
South Pasadena, California, United States
City of Hope West Covina
West Covina, California, United States
Response Rate (Complete Response or Partial Response)
Response rate (complete response or partial response) assessed using Response Evaluation Criteria in Solid Tumors version 1.1.
Time frame: Up to 36 months
Progression-free Survival
Progression-free survival assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Kaplan-Meier estimates will be generated.
Time frame: Time to disease progression/relapse or death as a result of any cause, assessed up to 36 months
Clinical Benefit Rate
Clinical benefit rate assessed by immune-related Response Evaluation Criteria in Solid Tumors version 1.1.
Time frame: At 16 weeks
Overall Survival
Overall survival assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Kaplan-Meier estimates will be generated.
Time frame: Time to death as a result of any cause, assessed up to 36 months
Progression-free Survival
Progression-free survival defined as failure of treatment or death as a result of any cause assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Kaplan-Meier estimates will be generated.
Time frame: Up to 1 year
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