A Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of GSK2816126 in Subjects With Relapsed/Refractory Diffuse Large B Cell Lymphoma, Transformed Follicular Lymphoma, Other Non-Hodgkin's Lymphomas, Solid Tumors and Multiple Myeloma

Part 1 Inclusion Criteria

- Provided signed written informed consent

- Males and females >=18 years of age (at the time consent is obtained).

- Tumor type criteria: relapsed/refractory non-Hodgkin's lymphoma (NHL) that meets one
of the following criteria:

- Germinal Center B cell Diffuse large B cell lymphoma (GCB-DLBCL) relapsed or
refractory to at least one prior regimen (e.g., rituximab, cyclophosphamide,
doxorubicin, vincristine, prednisone [R-CHOP]) AND not a candidate for standard
salvage regimens or autologous or allogeneic stem cell transplant. Local confirmation
of lymphoma subtype (e.g. GCB-DLBCL) is allowed for enrollment but must be confirmed
through central laboratory testing.

- Solid tumors that meet the following criteria: Measurable disease by Response
Evaluation Criteria In Solid Tumors 1.1 (RECIST) in at least 1 site. For Castrate
Resistant Prostate Cancer (CRPC) measurable disease can also include Prostate Specific
Antigen (PSA) level. Disease progression with the last line of therapy and at least
one prior standard of care regimens, or tumor for which there is no approved therapy,
or for which standard therapy is unsuitable or refused. Mutation Status: Solid tumor
types, other than prostate, must have a one of the following EZH2 inhibitor
sensitizing mutations as determined via local testing: An activating mutation in EZH2
(Y641F/C/S/H/N, A677V/G, and/or A687V; Loss of a component of the SWI/SNF complex,
including, but not limited to, ARID1A, SMARCB1 (aka SNF5/INI1/BAF47), SMARCA4 (aka
BRG1), or PBRM1 (aka PB1) as determined by molecular testing (bi-allelic loss or
mutation) or immunohistochemistry; Loss of BAP1 (ubiquitin carboxy-terminal hydrolase)
as determined by molecular testing (bi-allelic loss or mutation) or
immunohistochemistry

- CRPC subjects: Must have measurable disease by either: RECIST1.1 or a minimum PSA of 5
nanogram/milliliter; Disease progression on last line of therapy and must have
progressed on abiraterone, enzalutamide, or taxane chemotherapy; Subjects may continue
GnRH agonists; Small cell prostate cancer is eligible

- For all subjects: Availability of archival tissue, or willingness to undergo fresh
biopsy if archival tissue is not available.

- Must have a pre-existing central venous access such as a port, Hickmann catheter or a
peripherally inserted central catheter (PICC line) or be willing and able to have one
inserted.

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

- Men with a female partner of childbearing potential must have either had a prior
bilateral vasectomy with resultant azoospermia, bilateral orchiectomy, or must agree
to use one of the contraception methods listed in protocol from the time of the first
dose of study medication until at least 2 weeks (14 days) after the last dose of study
treatment due to the long elimination phase of study drug.

- A female subject is eligible to participate ifs she is of: Non-child bearing potential
as described in the protocol; OR Child bearing potential and agrees to use effective
contraception as described in the protocol, for an appropriate period of time (as
determined by the product label) prior to the start of dosing to sufficiently minimize
the risk of pregnancy and for at least 2 weeks (14 days) following the last dose of
study treatment. Women of childbearing potential must have a negative serum pregnancy
test within 7 days of first dose of study treatment followed by negative urine or
serum pregnancy test once every 4 weeks (prior to next dose cycle) thereafter.-
Adequate organ system function as defined in the protocol.

Part 2 Inclusion Criteria

- In addition to inclusion criteria listed for Part 1, Part 2 will enroll GCB-DLBCL tFL
and MM subjects only. Relapsed and/or refractory MM or tFL that have failed prior
standard therapy and for which there is no standard salvage regimen

- Lymphoma subjects will be required to undergo EZH2 mutation testing. This will require
availability of archival tissue, or willingness to undergo fresh biopsy, for central
testing of EZH2 mutation status.

- Based on the results of the mutation test, lymphoma subjects may be enrolled in one of
four cohorts: GCB-DLBCL EZH2 mutant cohort: Tumors must contain one, or more, of the
following EZH2 activating mutations: Y641F; Y641N; Y641S; Y641H; Y641C; A677G; and/or
A687V. GCB-DLBCL EZH2 wild type cohort: Tumors that do not contain one of the above
mutations; Subjects with tumors harboring EZH2 mutations other than the seven outlined
above will be enrolled in the EZH2 wild type cohort. tFL EZH2 mutant cohort: Tumors
must contain one, or more, of the following EZH2 activating mutations: Y641F; Y641N;
Y641S; Y641H; Y641C; A677G; and/or A687V. tFL EZH2 wild type cohort: Tumors that do
not contain one of the above mutations; Subjects with tumors harboring EZH2 mutations
other than the seven outlined above will be enrolled in the EZH2 wild type cohort

Part 1 and 2 Exclusion Criteria

- Receiving any cancer therapy within 2 weeks of first dose (including surgery, and/or
tumor embolization) Note: the following are allowed: Corticosteroids to control
systemic or local symptoms, up to a dose of 10 mg prednisone or equivalent daily and
stable for at least 7 days prior to enrollment. Subjects with prostate cancer may
remain on GnRH agonists. Other hormonal therapies (e.g., bicalutamide, abiraterone and
enzlutimide) for prostate cancer must be stopped 4 weeks prior to enrolment.

Note: the following are NOT allowed: Chemotherapy regimens with delayed toxicity within the
last 3 weeks. Nitrogen mustards, Melphalan, Monoclonal antibody or Nitrosourea within the
last 6 weeks.

- Received an investigational anti-cancer drug within 6weeks, or within 5 half-lives
(whichever is shorter) of the first dose of study drug(s). A minimum of 14 days must
have passed between the last dose of prior investigational agent and the first dose of
study drug.

- Current use of a prohibited medication per protocol or expected to require any of
these medications during treatment with study drug.

- Known Human Immunodeficiency Virus, or serological evidence for Hepatitis B (positive
hepatitis B surface antigen [HBsAg]), or chronic Hepatitis C infection. For subjects
who are negative for HBsAg, but Hepatitis B core Antibody [HBcAB] positive, a HBV DNA
(viral load) test will be performed and if negative are eligible. Subjects with
positive Hepatitis C antibody serology with a negative HCV ribonucleic acid (RNA) test
results are eligible.

- Concurrent use of therapeutic warfarin is allowed. However, anticoagulants that do not
have reversal agents available are prohibited.

- Any major surgery, radiotherapy or immunotherapy within the 4 weeks prior to first
dose of study drug, or palliative radiotherapy to a single symptomatic lesion within
the 2 weeks prior to first dose of study drugs.

- Subjects with prior allogeneic transplant are excluded: however, subjects who have
previously received an autologous stem cell transplant are allowed if a minimum of 100
days has elapsed from the time of transplant and the subject has recovered from
transplant-associated toxicities prior to the first dose of GSK2816126

- Unresolved toxicity greater than Grade 1 National Cancer Institute - Common
Terminology Criteria for Adverse Events (NCI-CTCAE) version 4 from previous
anti-cancer therapy, with the exception of alopecia and peripheral neuropathy.
Lymphoma subjects with <= Grade 3 lymphopenia can be enrolled at the discretion of the
investigator.

- Packed red blood cell or platelet transfusion within 7 days of screening laboratory
tests.

- Psychological, familial, sociological or geographical conditions that do not permit
compliance with the protocol.

- Cardiac exclusion criteria: History of acute coronary syndromes (including myocardial
infarction and unstable angina), coronary angioplasty, or stenting within the past 6
months prior to first dose of study drug; QTcF> 450 milliseconds (msec); Uncontrolled
arrhythmias. Subjects with rate controlled atrial fibrillation for >1 month prior to
first dose of study drug may be eligible; Class II, III or IV heart failure as defined
by the New York Heart Association (NYHA) functional classification system.

- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to the study drug or their excipients.

- Pregnant or lactating female.

- Unwillingness or inability to follow the procedures outlined in the protocol.

- Uncontrolled diabetes or other medical condition that may interfere with assessment of
toxicity.

- Central nervous system (CNS) metastases, with the following exception: Subjects who
have previously treated CNS metastases, are asymptomatic, and have no requirement for
steroids at least 14 days prior to first dose of study drug; Subjects with
carcinomatous meningitis are excluded regardless of clinical stability.

- Invasive malignancy or history of invasive malignancy other than disease under study:
any other invasive malignancy from which the subject has been disease-free for more
than 2 years and, in the opinion of the principal investigator and GSK Medical
Monitor, will not affect the evaluation of the effects of this clinical trial
treatment on currently targeted malignancy, can be included in this clinical trial;
Curatively treated non-melanoma skin cancer and any carcinoma-in-situ.