A Dose Escalation Study to Investigate the Safety, Pharmacokinetics (PK), Pharmacodynamics (PD) and Clinical Activity of GSK525762 in Subjects With Relapsed, Refractory Hematologic Malignancies

Inclusion criteria

- Written informed consent provided.

- Males and females 18 years old or older.

- In Part 1 and, Part 2, subjects must have AML, MM, or NHL. Subjects with AML, are
eligible if they • have relapsed and/or refractory disease, OR are>=65 years of age
and not candidates for or have refused standard chemotherapy. Subjects with multiple
myeloma are eligible if they have progressed despite therapy with an alkylating agent,
proteasome inhibitor, and immunomodulatory agent, either as individual regimens or in
combination. Subjects with NHL are eligible if they have received at least two prior
lines of systemic therapy, including at least one line of immunochemotherapy with an
anti-CD20 antibody (if their tumor expresses CD20).

In Part 2, the NHL cohort will separately enrol subjects with double- and triple hit
lymphoma, so that a minimum of 10 subjects with this subset of disease will be enrolled. To
be eligible for this sub-cohort, tumor sample from the subject must demonstrate
rearrangement and/or overexpression of MYC and either BCL2 and/or BCL6 genes. Evaluation of
double- or triple-hit status may be performed via appropriate local testing, and the
determination of double- or triple-hit diagnosis will be at the discretion of the
investigator and GSK Medical Monitor.

- Subjects with a prior history of stem cell transplant (autologous and/or allogeneic)
are allowed if

- At least 3 months has elapsed from the time of transplant and

- the subject has recovered from transplant-associated toxicities prior to the
first dose of GSK525762, and For subjects with a prior history of allogeneic
transplant,

- the subject has been off systemic immunosuppressive medications (including but
not limited to: cyclosporine, tacrolimus, mycophenolate mofetil, or
corticosteroids) for at least 1 month prior to the first dose of GSK525762.
Topical steroids are permitted

- there are no signs or symptoms of graft versus host disease, other than Grade 1
skin involvement.

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

- Subject must be stable enough to be expected to complete dosing through the DLT
observation period as assessed by 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.

- A female subject is eligible to participate if she is of: Non-childbearing potential
defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or
postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases,
a blood sample with simultaneous follicle stimulating hormone (FSH) > 40
milli-International units per milliliter and estradiol < 40 picograms per milliliter
(< 140 picomole per liter) is confirmatory]. Females on hormone replacement therapy
(HRT) and whose menopausal status is in doubt will be required to use one of the
contraception methods defined in protocol if they wish to continue their HRT during
the study. Otherwise, they must discontinue HRT to allow confirmation of
post-menopausal status prior to study enrolment. For most forms of HRT, at least two
to four weeks will elapse between the cessation of therapy and the blood draw; this
interval depends on the type and dosage of HRT. Following confirmation of their
post-menopausal status, they can resume use of HRT during the study without use of a
contraceptive method; Child-bearing potential and agrees to use one of the
contraception methods for an appropriate period of time (as determined by the product
label or investigator) prior to the start of dosing to sufficiently minimize the risk
of pregnancy at that point. Female subjects must agree to use contraception until at
least 7 months after the last dose of study medication; Negative serum pregnancy test
<= 7 days prior to first study drug dose; 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 5 half-lives of GSK525762 or at least
28 days (whichever is longer) following the last dose of study treatment.

- Male subjects must agree to use one of the methods of contraception specified. This
method must be used from the time of the first dose of study medication until 16 weeks
after the last dose of study medication. In addition, male subjects whose partners are
or become pregnant must continue to use condoms for 7 days after stopping study
medications.

- Adequate organ system function.

- Ability to comply with dietary and tobacco/alcohol abstinence requirements.

Exclusion Criteria

- Haematological malignancy associated with human immunodeficiency virus (HIV) infection
or solid organ transplant or history of known Hepatitis B Antigen or positive
Hepatitis C antibody (confirmed by Recombinant ImmunoBlot Assay [RIBA], if available
or alternately confirmed by Hepatitis C Virus [HCV] Ribonucleic acid [RNA]).

- History or concurrent malignancy of solid tumours, except for below. Exception:
Subjects who have been disease-free for 5 years, or subjects with a history of
completely resected non-melanoma skin cancer or successfully treated in situ carcinoma
are eligible. Subjects with second malignancies that are indolent or definitively
treated may be enrolled even if less than 5 years have elapsed since treatment.
Consult the GSK Medical Monitor if unsure whether second malignancies meet
requirements specified above.

- Currently receiving cancer therapy (chemotherapy, radiation therapy, immuno- therapy,
biologic therapy, hormonal therapy, surgery, and/or tumour embolization).The following
are allowed: Hydroxyurea for proliferative disease, Corticosteroids, Use of
hematopoetic growth factors is permitted at the discretion of the investigator
according to published guidelines (e.g., National Comprehensive Cancer Network (NCCN),
American Society of Clinical Oncology (ASCO), American Society of Hematology (ASH),
etc.). The following are NOT allowed: Investigational anti cancer drug within 2 weeks
prior to the first dose of GSK525762; Major surgery, radiotherapy, or immunotherapy
within 4 weeks of GSK525762 Chemotherapy regimens with delayed toxicity within the
last 4 weeks. Chemotherapy regimens given continuously or on a weekly basis with
limited potential for delayed toxicity within the last 2 weeks.

Nitrosourea or mitomycin C within the last 6 weeks

- Evidence of severe of uncontrolled infection.

- Use of anticoagulants (e.g., warfarin, heparin) at therapeutic levels within 7 days
prior to the first dose of GSK525762. Low dose (prophylactic) low molecular weight
heparin (LMWH) is permitted. In addition, INR must be monitored in accordance with
local institutional practices, as appropriate.

- Current use of a prohibited medication or requires any of these medications during
treatment with the investigational drugs. This includes excluding current medications
known or suspected to be associated QT prolongation. In addition, any subject who is
expected to require a QT prolonging medication while on trial should not be enrolled.

- 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
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.

- Symptomatic or untreated Central nervous system (CNS) disease, Subjects with a history
of CNS disease (leukemia, lymphoma or myeloma) are permitted to enrol if they have
previously received appropriate therapy and CNS remission has been documented. Subject
with primary CNS lymphoma (defined as isolated CNS lymphoma without systemic
involvement) are excluded from study.

- Cardiac abnormalities as evidenced by any of the following: History or current
clinically significant uncontrolled arrhythmias or hypertension; Clinically
significant conduction abnormalities or arrhythmias, subjects with Bundle Branch
Block; Presence of cardiac pacemaker; 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.

- Any of the following ECG findings or assessments including: Baseline QTcF interval
>=450 milliseconds; Clinically significant ECG assessments should be reviewed by the
site cardiologist prior to study entry.

- GSK525762 is a benzodiazepine class molecule. Any serious known immediate or delayed
hypersensitivity reaction(s) to GSK525762 or idiosyncrasy to drugs chemically related
to the investigational drug.

- Evidence of hemoptysis within the last 7 days.

- History of major gastrointestinal bleeding within the last 3 months or any evidence of
active gastrointestinal bleeding excludes the subject.

- Presence of gastrointestinal disease that would significantly affect compound
absorption.