A Phase 2 Clinical Trial of the Combination of Pembrolizumab and Selective Androgen Receptor Modulator (SARM) GTX-024 in Patients With Metastatic Androgen Receptor (AR) Positive Triple Negative Breast Cancer (TNBC)
Overview
- Phase
- Phase 2
- Intervention
- Enobosarm
- Conditions
- Androgen Receptor Positive
- Sponsor
- City of Hope Medical Center
- Enrollment
- 18
- Locations
- 7
- Primary Endpoint
- Response Rate (Complete Response or Partial Response)
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief 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.
Detailed Description
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.
Investigators
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+)
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
Arms & Interventions
Treatment (pembrolizumab, enobosarm)
Patients receive pembrolizumab IV over 30 minutes on day 1 and enobosarm PO QD on days 1-21. Courses repeat every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Enobosarm
Treatment (pembrolizumab, enobosarm)
Patients receive pembrolizumab IV over 30 minutes on day 1 and enobosarm PO QD on days 1-21. Courses repeat every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis
Treatment (pembrolizumab, enobosarm)
Patients receive pembrolizumab IV over 30 minutes on day 1 and enobosarm PO QD on days 1-21. Courses repeat every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Pembrolizumab
Outcomes
Primary Outcomes
Response Rate (Complete Response or Partial Response)
Time Frame: Up to 36 months
Response rate (complete response or partial response) assessed using Response Evaluation Criteria in Solid Tumors version 1.1.
Secondary Outcomes
- Progression-free Survival(Up to 1 year)
- Clinical Benefit Rate(At 16 weeks)
- Overall Survival(Time to death as a result of any cause, assessed up to 36 months)