Efficacy and Safety of GTx-024 in Patients With Androgen Receptor-Positive Triple Negative Breast Cancer (AR+ TNBC)

Inclusion Criteria:

- Able and willing to give voluntary, written and signed, informed consent

- Women ≥ 18 years of age

- Women with TNBC who have received at least one but no more than two prior chemotherapy
regimens for TNBC

- Confirmation of AR+ (defined as ≥ 10% nuclear AR staining by immunohistochemistry
[IHC]) TNBC in either the primary or metastatic lesion, assessed during the screening
period by a local laboratory or by medical history

- TNBC confirmed by medical history as: human epidermal growth factor receptor 2
[HER2]-negative (confirmed by IHC 0, 1+ regardless of fluorescence in situ
hybridization [FISH] ratio; IHC 2+ with FISH ratio lower than 2.0 or HER2 gene copy
less than 6.0; FISH ratio of 0, indicating gene deletion, when positive and negative
in situ hybridization [ISH] controls are present); estrogen receptor (ER) negative
(confirmed as ER expression less than or equal to 1% positive tumor nuclei);
progesterone receptor negative (confirmed as progesterone receptor expression less
than or equal to 1% positive tumor nuclei)

- Availability of paraffin embedded or formalin fixed tumor tissue; OR, a minimum of 10
and up to 20 slides of archived tumor tissue for central laboratory confirmation of AR
status and molecular subtyping. Metastatic tumor tissue is preferred when possible

- Subjects must have either measurable disease or bone-only non-measurable disease,
evaluable according to RECIST 1.1

- Subjects with bone metastases should be treated with intravenous bisphosphonates or
subcutaneous denosumab (or investigator preferred standard of care) prior to and
during the trial, unless there is a contraindication or subject intolerance to these
therapies

- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at the time of
screening and enrollment

- Negative pregnancy test in women of childbearing potential (premenopausal or less than
12 months of amenorrhea post-menopause, and who have not undergone surgical
sterilization), no more than 7 days before the first dose of study treatment

- For women of childbearing potential who are sexually active, agreement to use a highly
effective, non-hormonal form of contraception during and for at least 6 months after
completion of study treatment; OR, a fertile male partner willing and able to use
effective non-hormonal of contraception (barrier method of contraception in
conjunction with spermicidal jelly, or surgical sterilization) during and for at least
6 months after completion of study treatment

- Adequate organ function as shown by:

- Absolute neutrophil count ≥ 1,000 cells/mm3

- Platelet count ≥ 100,000 cells/mm3

- Hemoglobin ≥ 9 g/dL

- Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5
Upper Limit of the Normal range (ULN) (or ≤ 5 if hepatic metastases are present)

- Total serum bilirubin ≤ 2.0 × ULN (unless the subject has documented Gilbert
Syndrome)

- Alkaline phosphatase levels ≤ 2.5 × ULN (≤ 5 × ULN in subjects with liver
metastasis)

- Serum creatinine < 2.0 mg/dL or 177 μmol/L

- International normalized ratio (INR), activated partial thromboplastin time
(aPTT), or partial thromboplastin time (PTT) < 1.5 × ULN (unless on anticoagulant
treatment at screening)

- Able to swallow capsules

- Any toxicity from prior chemotherapy has resolved or Grade 1 (NCI-CTCAE, Version 4.0)

Exclusion Criteria:

- Life expectancy < 4 months;

- Subjects with radiographic evidence of central nervous system (CNS) metastases as
assessed by computerized tomography (CT) or magnetic resonance imaging (MRI) that are
not well controlled (symptomatic or requiring control with continuous corticosteroid
therapy [e.g., dexamethasone]). Note: Subjects with CNS metastases are permitted to
participate in the study if the CNS metastases are medically well controlled prior to
screening (as assessed by the Investigator) after receiving local therapy
(irradiation, surgery, etc.)

- Radiotherapy within 14 days prior to first dose of study treatment

- Have, in the judgment of the Investigator, a clinically significant concurrent illness
or psychological, familial, sociological, geographical, or other concomitant condition
that would not permit adequate follow-up and compliance with the study protocol

- Positive hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection at screening

- Positive human immunodeficiency virus (HIV) infection at screening

- Prior treatment with any anti-androgens, including but not limited to, enzalutamide
and bicalutamide

- Major surgery within 28 days of the first dose of study treatment

- Be currently taking or have previously taken testosterone, methyltestosterone,
oxandrolone (Oxandrin®), oxymetholone, danazol, fluoxymesterone (Halotestin®),
testosterone-like agents (such as dehydroepiandrosterone, androstenedione, and other
androgenic compounds, including herbals), or anti-androgens

- Treatment with any of the following hormone replacement therapies, unless discontinued
at least 14 days prior to the first dose of study treatment:

- Estrogens

- Megesterol acetate

- Treatment with any investigational agent within 28 days before the first dose of study
treatment

- Another active cancer (excluding adequately treated basal cell carcinoma or cervical
intraepithelial neoplasia [CIN]/cervical carcinoma in situ or melanoma in situ). Prior
history of other cancer is allowed as long as there is no active disease within the
prior 5 years

- Subject has a 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)

- Current treatment with intravenous bisphosphonate or denosumab with elevated serum
calcium corrected for albumin or ionized calcium levels outside institutional normal
limits at screening

- History of non-compliance to medical regimens

- Subjects unwilling to or unable to comply with the protocol procedures as assessed by
the Investigator

- Concurrent participation in another therapeutic clinical trial