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



Status:Recruiting
Conditions:Breast Cancer, Cancer, Cancer, Cancer, Cancer, Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:11/9/2018
Start Date:June 1, 2017
End Date:October 2019

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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)

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. Monoclonal antibodies, such as pembrolizumab, 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 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.

TERTIARY 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. To evaluate pre-treatment programmed death ligand 1 (PD-L1) and tumor infiltrating
lymphocytes (TILs) as a predictor of response to combination therapy.

VI. To evaluate specific TIL subsets (e.g. CD4, CD8, regulatory T cell [Treg] distribution)
and other immunological correlative (e.g. T cell receptor [TCR] repertoire analysis) as
possible predictors of response.

VII. To evaluate change in TILs as a result of the combination therapy.

VIII. 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 courses 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.

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 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

- Platelets >= 100,000/mm^3

- Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO)
dependency (within 7 days of assessment)

- Serum total bilirubin =< 1.5 x upper limit of normal (ULN) OR direct bilirubin =< ULN
if total bilirubin levels > 1.5 x ULN

- Albumin >= 2.5 mg/dL

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN OR =<
5.0 x ULN if liver metastases present

- 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

- 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

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 for, 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)
We found this trial at
11
sites
2000 Circle of Hope Dr
Salt Lake City, Utah 84112
(801) 585-0303
Principal Investigator: Adam Cohen, MD
Phone: 801-587-4725
Huntsman Cancer Institute at University of Utah Huntsman Cancer Institute (HCI) is part of the...
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Columbus, Ohio 43210
Principal Investigator: Daniel Stover, MD
Phone: 614-685-6700
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Columbus, OH
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Corona, California 92879
Principal Investigator: Misagh Karimi, MD
Phone: 626-256-4673
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Duarte, California 91010
Principal Investigator: Yuan Yuan, MD, Phd
Phone: 626-256-4673
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Kansas City, Kansas 66160
Principal Investigator: Anne O'Dea, MD
Phone: 913-588-7750
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44151 15th Street West
Lancaster, California 93534
Principal Investigator: Mohammad Fekrazad, MD
Phone: 626-256-4673
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15031 Rinaldi Street
Mission Hills, California 91345
Principal Investigator: Suzy Melkonian, MD
Phone: 626-256-4673
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Rancho Cucamonga, California 91730
Principal Investigator: Benham Ebrahimi, MD
Phone: 626-256-4673
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Sacramento, California 95817
Principal Investigator: Mili Arora, MD
Phone: 916-734-8614
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South Pasadena, California 91030
Principal Investigator: Christina H. Yeon
Phone: 626-256-4673
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West Covina, California 91790
Principal Investigator: Gargi Upadhyaya, MD
Phone: 626-256-4673
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