Safety, Clinical Activity, Pharmacokinetics (PK) and Pharmacodynamics Study of GSK2879552, Alone or With Azacitidine, in Subjects With High Risk Myelodysplastic Syndromes (MDS)

Inclusion Criteria:

- >=18 years of age and provided signed written informed consent

- Subjects must have IPSS-R high or very high risk myelodysplastic syndromes (MDS) by
World Health Organization (WHO) classification

- Subjects must have failed hypomethylating treatment where "failure" is defined as:
Progression (according to 2006 International Working Group [IWG] criteria) at any time
after initiation of the hypomethylating treatment OR Failure to achieve complete or
partial response or hematological improvement (HI) (according to 2006 IWG) after at
least 4 cycles treatment OR Relapse after initial complete or partial response or HI
(according to 2006 IWG criteria).

- Subjects are not a candidate, or have failed allogeneic stem cell transplantation.
Subjects who underwent allo-transplant in the past are eligible under following
conditions: transplant was >2 year prior to enrolment, and no evidence of active
graft-versus-host disease (GVHD)

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

- Subjects must have a life expectancy of at least 12 weeks, in the opinion of the
investigator.

- Able to swallow and retain orally administered medication and does not have any
clinically significant gastrointestinal abnormalities that may alter absorption such
as malabsorption syndrome or major resection of the stomach or bowels.

- All prior treatment-related toxicities must be National Cancer Institute- Common
Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4.0 <=Grade 1 at the time of
enrollment (except for alopecia).

- Adequate baseline organ function defined by: International Normalization Ratio (INR)
and activated partial thromboplastin time (aPTT) <=1.3xupper limit of normal (ULN);
platelet count (PLT) >=10,000 (transfusions permitted to bring PLT to >10,000); total
bilirubin <=1.5xULN (Isolated bilirubin >1.5xULN is acceptable if bilirubin is
fractionated and direct bilirubin <35% or subject has a diagnosis of Gilbert's
syndrome); Alanine transaminase (ALT) <=2.5xULN; creatinine <=1.5xULN OR calculated
creatinine clearance by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
equation or measured from 24 hour urine >=50 milliliters (mL)/minute (min); and
Ejection fraction >=lower limit of normal (LLN) by Echocardiogram (ECHO) or multigated
acquisition scan (MUGA)

- Women of childbearing potential must have a negative serum pregnancy test within 7
days of first dose of study treatment and agree to use effective contraception during
the study and for 7 days following the last dose of study treatment.

- Men with a female partner of childbearing potential must have either had a prior
vasectomy or agree to use effective contraception from the administration of the first
dose of study treatment until 3 months after the last dose of study treatment to allow
for clearance of any altered sperm.

Exclusion Criteria:

- AML according to world health organization (WHO) criteria (i.e. bone marrow blasts
>20%)

- Active hepatitis B or hepatitis C treatment

- Baseline Montreal Cognitive Assessment (MOCA) score of 22 or lower

- History of or concurrent malignancy of solid tumours, except for below:

Exception: Subjects who have been disease-free for 2 years, or subjects with a history of
completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are
eligible.

- Prior treatment with temozolomide, dacarbazine or procarbazine

- Prior treatment with poly adenosine diphosphate (ADP) ribose polymerase (PARP)
inhibitors (example (e.g.), olaparib, veliparib [ABT-888])

- Currently receiving other anti-cancer therapy (chemotherapy, radiation therapy,
immuno- therapy, biologic therapy, hormonal therapy, surgery, and/or tumour
embolization)

- Received major surgery, radiotherapy, or immunotherapy within 4 weeks of GSK2879552
administration

- Evidence of severe or uncontrolled systemic diseases (e.g., severe/chronic infection,
unstable or uncompensated respiratory, renal, or cardiac disease). Any serious and/or
unstable pre-existing medical (aside from malignancy exception above), 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

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

- Patients with any major bleeding current or within the past 4 weeks. (e.g. recent
gastrointestinal [GI] hemorrhage or neurosurgery).

- Administration of an investigational drug within 14 days or 5 half-lives, whichever is
shorter, preceding the first dose of study treatment(s) in this study.

- Cardiac abnormalities as evidenced by any of the following: clinically significant
uncontrolled arrhythmias or uncontrolled hypertension; 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; baseline
Corrected QT (QTc) interval using Fridericia's formula >450 milliseconds (msec) or
>480 msec in subjects with Bundle Branch Block. QTc value based on single or average
of triplicate ECGs obtained over a brief recording period

- Current use of a prohibited medication including anticoagulants or platelet inhibitors
or expected to require any of these medications during treatment with the
investigational drug

- Consumption of Seville oranges, grapefruit, grapefruit hybrids, grapefruit juice,
pommelos, or exotic citrus fruits, from 1 day prior to the first dose of study
treatment(s) until the last dose of study drug

- Lactating female

- Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to GSK2879552 or lysine-specific demethylase 1 (LSD1) inhibitors
that contraindicates their participation

- Known hypersensitivity to azacitidine or mannitol