Dose Escalation and Expansion Study of GSK525762 in Combination With Fulvestrant in Subjects With Hormone Receptor-positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Advanced or Metastatic Breast Cancer

Inclusion Criteria:

- Written informed consent provided.

- Females 18 years old and greater (at the time of written consent)

- Histologically or cytologically confirmed diagnosis of advanced or metastatic
adenocarcinoma of the breast.

- Documentation of ER-positive and/or progesterone receptor (PR)-positive tumor (>=1%
positive stained tumor cell nuclei) based on local testing of the most recent tumor
biopsy, using an assay consistent with local standards.

- Documentation of HER2-negative tumor based on local testing of the most recent tumor
biopsy. At the time of writing, HER2-negative tumor is defined as immunohistochemistry
(IHC) score of 0 or 1+, or negative by in situ hybridization defined as a
HER2/chromosome enumeration probe 17 (CEP17) ratio <2 or for single probe assessment
of an average HER2 copy number <4.

- Provision of mandatory screening fresh tumor biopsy sample during the screening
period.

1. Screening biopsy can be waived if a biopsy was collected within 3 months prior to
first dose of study drug and was collected after the last anti-cancer treatment
before coming into this study.

2. Subjects with inaccessible site of biopsy or who have a significant medical risk
of obtaining the biopsy should be discussed with the Medical Monitor if they can
qualify.

3. Bone biopsies are not acceptable. Biopsies should be obtained from bone with
metastatic soft-tissue component. Subjects with bone only disease may be enrolled
upon review by Medical Monitor.

- History of prior therapy that satisfies one of the following criteria:

1. Aromatase inhibitor (AI) failures: Disease that relapsed during treatment or
within 12 months of completion of adjuvant therapy with an AI, OR disease that
progressed during treatment with an AI for advanced/metastatic disease. Prior
ovarian suppression and/or tamoxifen are allowed as long as other criteria are
met.

2. Cyclin-dependent kinase 4/6 (CDK4/6) inhibitor plus AI failures: Disease that
progressed on a CDK4/6 inhibitor plus AI, for advanced/metastatic disease with a
minimum duration of treatment of 12 months (>=12 months) with CDK4/6 inhibitor
plus AI. Subjects with either measurable disease or bone only disease are
allowed. Prior ovarian suppression and/or tamoxifen are allowed as long as other
criteria are met.

- Documented progression on last line of systemic anti-cancer therapy with CDK4/6
inhibitor + AI is required.

- Any menopausal status.

- Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
criteria is required except for subjects with bone only disease.

- All prior treatment- related toxicities must be National Cancer Institute-Common
Terminology Criteria for Adverse Events (NCI-CTCAE) version 4 <= Grade 1 (except
alopecia (permitted at any grade) and peripheral neuropathy (permitted at <= Grade 2)
at the time of treatment allocation.

- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 to 1.

- Adequate organ function.

- Able to swallow and retain orally administered medication.

- A female subject is eligible to participate if she is of: i) Non-childbearing
potential and agrees to use one of the contraception methods, from the time of the
screening pregnancy test until 7 months after the last dose of study medication. ii)
Negative serum pregnancy test <=7 days prior to first study drug dose. iii) Female
subjects who are lactating must discontinue nursing prior to the first dose of study
treatment and must refrain from nursing throughout the treatment period and for at
least 28 days following the last dose of study treatment.

Exclusion Criteria:

- Prior therapy with any Bromodomain and extra-terminal (BET) inhibitor, any selective
estrogen receptor degrader (SERD) including fulvestrant, or inhibitors of the
Phosphoinositide-3-kinase (PI3K)/ serine/threonine-specific protein kinase
(AKT)/Mammalian Target of Rapamycin (mTOR) pathway.

- Prior therapy with more than one line of cytotoxic chemotherapy following diagnosis of
advanced/metastatic disease.

- More than or equal to 3 lines of systemic anti-cancer therapy in the advanced or
metastatic setting.

- Recent prior therapy, defined as:

1. Any investigational or approved non-biologic anti-cancer drug within 14 days or
five half-life (whichever is greater) prior to the first dose of GSK525762 and
fulvestrant.

2. Any nitrosoureas or mitomycin C within 42 days prior to the first dose of
GSK525762 and fulvestrant

3. Any anti-cancer biologic agents within 42 days prior to the first dose of
GSK525762 and fulvestrant

4. Any radiotherapy within 14 days prior to the first dose of GSK525762 and
fulvestrant. If the subject received radiotherapy <90 days prior to study
treatment, the irradiated lesion cannot be the only lesion used for evaluating
response.

5. Any major surgery within 28 days prior to the first dose of GSK525762 and
fulvestrant

- Concomitant active malignancy other than HR+/HER2- breast cancer

- Therapeutic-dose anticoagulation (e.g., warfarin, low-molecular weight heparin [LMWH],
or novel oral anticoagulants) must be discontinued and coagulation parameters must be
normalized prior to the first dose of GSK525762 and fulvestrant. Prophylactic
anticoagulation, with low doses (per standard practice) of agents such as LMWH, direct
thrombin inhibitors, or factor Xa inhibitors is permitted.

- Current use of a prohibited medication or planned use of any forbidden medications
during treatment with GSK525762 and fulvestrant. This includes medications with
significant risk of Torsades de pointes as well as those that are potent inducers or
inhibitors of CYP3A4 enzymes.

- Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated
respiratory, hepatic, renal, cardiac disease, or clinically significant bleeding
episodes). Any serious and/or unstable pre-existing medical (aside from malignancy),
psychiatric disorder, or other conditions that could interfere with subject's safety,
obtaining informed consent or compliance to the study procedures, in the opinion of
the Investigator.

1. Systolic blood pressure higher than 150 millimeters of mercury (mmHg) or
diastolic blood pressure higher than 90 mmHg found on 2 separate occasions
separated by 1 week, despite adequate therapy, will be defined as uncontrolled
hypertension.

2. Uncontrolled diabetes mellitus (despite therapeutic; compliance to intervention)
as defined by a hemoglobin A1c (HbA1c) level more than 8% and/or occurrence of
more than two episodes of ketoacidosis in the 12 months prior to the first dose
of study drug.

- Subjects with advanced/metastatic, symptomatic, visceral spread, that are at risk of
life-threatening complications in the short term including subjects with massive
uncontrolled effusions (pleural, pericardial, peritoneal), pulmonary lymphangitis, and
over 50% of liver involvement in metastases.

- Symptomatic or untreated leptomeningeal or brain metastases or spinal cord
compression.

- Cardiac abnormalities as evidenced by any of the following: Baseline QT interval
corrected by Fridericia's formula (QTcF) interval >=480 milliseconds (msec);
Clinically significant conduction abnormalities or arrhythmias; Presence of cardiac
pacemaker or defibrillator with a paced ventricular rhythm limiting electrocardiogram
analysis; History or evidence of current >=Class II congestive heart failure as
defined by New York Heart Association (NYHA); History of acute coronary syndromes
(including unstable angina and myocardial infarction), coronary angioplasty, or
stenting within the past 3 months. Subjects with a history of stent placement
requiring ongoing antithrombotic therapy (e.g., clopidogrel, prasugrel) will not be
permitted to enroll; Clinically significant cardiomegaly, ventricular hypertrophy, or
cardiomyopathy.

- Current active liver or biliary disease (with the exception of Gilbert's syndrome or
asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease
per investigator assessment).

- Presence of hepatitis B surface antigen (HBsAg) or positive hepatitis C antibody test
result at screening.

- History of known human immunodeficiency virus (HIV) infection.

- Any serious known immediate or delayed hypersensitivity reaction(s) to GSK525762 or
fulvestrant, or idiosyncrasy to drugs chemically related to the investigational drugs.

- Hemoptysis >1 teaspoon in 24 hours within the last 28 days.

- Concurrent use of non-steroidal anti-inflammatory drugs (NSAIDs) (except for cases
where NSAIDs provide benefit over other analgesics and in these cases, consideration
should be given to the prophylactic administration of a proton pump inhibitor) and
high dose aspirin (allowed up to <=100 milligrams orally daily).

- Subjects with history of known bleeding disorder(s) including clinically significant
hemorrhage (e.g., gastrointestinal, neurologic), within the past 6 months.

- Any clinically significant gastrointestinal abnormalities that may alter absorption,
such as malabsorption syndrome, chronic gastrointestinal disease, or major resection
of the stomach and/or bowels that could preclude adequate absorption of the study
medication.