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

NCT02971761 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 16131NCI-2016-01759
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 7

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 36 months

Secondary Outcomes (4)

• Progression-free Survival

  Time to disease progression/relapse or death as a result of any cause, assessed up to 36 months

• Clinical Benefit Rate

  At 16 weeks

• Overall Survival

  Time to death as a result of any cause, assessed up to 36 months

• Progression-free Survival

  Up to 1 year

Study Arms (1)

Treatment (pembrolizumab, enobosarm)

EXPERIMENTAL

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.

Drug: Enobosarm; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

Interventions

Enobosarm DRUG

Given PO

Also known as: Gtx-024, Ostarine

Treatment (pembrolizumab, enobosarm)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pembrolizumab, enobosarm)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (pembrolizumab, enobosarm)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (7)

City of Hope Corona

Corona, California, 92879, United States

Location

City of Hope Medical Center

Duarte, California, 91010, United States

Location

City of Hope Antelope Valley

Lancaster, California, 93534, United States

Location

City of Hope Mission Hills

Mission Hills, California, 91345, United States

Location

City of Hope Rancho Cucamonga

Rancho Cucamonga, California, 91730, United States

Location

City of Hope South Pasadena

South Pasadena, California, 91030, United States

Location

City of Hope West Covina

West Covina, California, 91790, United States

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

ostarine; pembrolizumab

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Limitations and Caveats

The trial was stopped early because of the withdrawal of GTx-024 drug supply. Full assessment of activity could not be completed as planned.

Results Point of Contact

• Title: Yuan Yuan, MD, PhD.
• Organization: Department of Medical Oncology, City of Hope

yuyuan@coh.org

626-256-4673

Study Officials

• Yuan Yuan

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2016
• First Posted: November 23, 2016
• Study Start: June 1, 2017
• Primary Completion: October 28, 2020
• Study Completion: August 16, 2022
• Last Updated: February 20, 2024
• Results First Posted: June 10, 2022

Record last verified: 2024-02

Locations

US (7)