First Time in Humans (FTIH) Study of GSK3368715 in Subjects With Solid Tumors and Diffuse Large B-cell Lymphoma (DLBCL)

Inclusion Criteria:

- Subject must be >=18 to years of age inclusive, at the time of signing the informed
consent.

- Diagnosis of one of the following; Part 1 (Dose Escalation): Histologically- or
cytological-confirmed diagnosis of solid tumor malignancy that is metastatic or
non-resectable; have received all standard treatment options or are no longer eligible
for additional standard treatment options. Evaluable disease that may be measured
directly by the size of the tumor or can be evaluated by other methods. Part 2 (Dose
Expansion): Cohort 2A & 2B: The availability of archival tumor tissue, or willingness
to undergo a fresh biopsy to determine MTAP status. Local MTAP or Cyclin Dependent
Kinase Inhibitor 2A (CDKN2A) results are acceptable for enrolment, but must be
confirmed through central laboratory testing. . Cohort 2A: Histologically- or
cytological-confirmed diagnosis of DLBCL; relapse or refractory disease after at least
1 but not more than 4 lines of prior therapy; at least 1 measurable site of disease
according to the Lugano Classification. The site of disease must be greater than 1.5
centimeter (cm) in the long axis regardless of short axis measurement or greater than
1.0 cm in the short axis regardless of long axis measurement, and clearly measurable
in 2 perpendicular dimensions. Cohort 2B: Pancreatic Cancer: Histologically or
cytologically confirmed adenocarcinoma of the pancreas; unresectable, locally advanced
(Stage III), or metastatic (Stage IV) disease; relapsed or refractory disease after at
least 1 prior line of approved, systemic therapy; at least 1 measurable tumor lesion
per RECIST 1.1. NSCLC: histologically or cytologically confirmed NSCLC; stage IV
disease; tested for presence of echinoderm microtubule-associated protein-like 4-
anaplastic lymphoma kinase (EML4-ALK) rearrangement; received at least 2 prior lines
of approved, systemic therapy, of which 1 therapy has to be a platinum containing
regimen or failed a first-line platinum-containing regimen in combination with an
anti- progressive disease (PD1) monocloncal antibody and refused a second-line regimen
despite being informed about the different therapeutic options and their specific
clinical benefit by the investigator; the content of this informed consent discussion
including the therapeutic options reviewed by the investigator need to be documented
and the subject needs to sign a specific consent form; at least 1 measurable tumor
lesion per RECIST 1.1. Transitional cell carcinoma of the Urothelium: histologically
or cytologically confirmed transitional cell carcinoma (TCC) of the urothelium
(urinary bladder, urethra, ureter or renal pelvis) including mixed pathology with
predominantly (that is [i.e.], > 50 percent of the histopathology sample) TCC with the
exception of neuroendocrine or small cell carcinoma; unresectable, locally advanced
(T4b) or metastatic (lymph node or visceral) disease; relapsed or refractory disease
after at least 1 prior line of approved systemic therapy; at least 1 measurable tumor
lesion per RECIST 1.1.

- Adequate organ function as defined by: Absolute neutrophil count (ANC) with a
laboratory value of >=1.5 times 10^9 per liter (L); Hemoglobin with a laboratory value
of >=9 grams per deciliter (g/dL) for solid malignancy and >=8 g/dL for Non-Hodgkin's
lymphoma; Platelets with a laboratory value of >=100 times 10^9/ L; prothrombin time/
International Normalization Ratio (PT/INR) and partial thromboplastin time (PTT) with
a laboratory value of <=1.5 times upper limit of normal (ULN), unless subject is
receiving systemic anticoagulation (Hematologic); Albumin with a laboratory value of
>=2 g/dL, total bilirubin with a laboratory value of <=1.5 times ULN, alanine
aminotransferase (ALT) with a laboratory value of <=2.5 times ULN or <5 times ULN is
acceptable for subjects with documented liver metastases/tumor infiltration (Hepatic);
calculated creatinine clearance by Chronic Kidney Disease Epidemiology Collaboration
(CKD-EPI) equation or measured from 24 h urine with a laboratory value of >= 50
milliliters per min (mL/min) (Renal); Ejection fraction with a laboratory value of
>=Lower limit of normal (LLN) by echocardiogram (minimum of 50 percent)/ multigated
(radionuclide) angiogram (MUGA), Electrocardiogram (ECG): corrected QT (QTc) interval
using Fridericia's formula (QTcF) with a laboratory value of <450 milliseconds (msec)
(Cardiac).

- Eastern cooperative oncology group (ECOG) performance status of 0 or 1.

- Able to swallow and retain orally-administered medication.

- Availability of a biopsy of the tumor tissue obtained at any time from the initial
diagnosis to study entry.

- A female subject is eligible to participate if she is not pregnant or breastfeeding,
and at least one of the following conditions applies; is not a woman of childbearing
potential (WOCBP) or is a WOCBP and using a contraceptive method that is highly
effective, with a failure rate of <1 percent, during the intervention period and for
at least 120 days, corresponding to the time needed to eliminate any study
intervention(s) (example given [e.g.], 5 terminal half-lives) after the last dose of
study intervention. The investigator should evaluate the effectiveness of the
contraceptive method in relationship to the first dose of study intervention. A WOCBP
must have a negative highly sensitive pregnancy test (urine as required by local
regulations) within 7 days before the first dose of study intervention. The
investigator is responsible for review of medical history, menstrual history, and
recent sexual activity to decrease the risk for inclusion of a woman with an early
undetected pregnancy. Male subjects are eligible to participate if they agree to the
following during the intervention period and for at least 100 days, corresponding to
time needed to eliminate study intervention(s) (e.g., 5 terminal half-lives) plus 90
days after the last dose of study intervention: Refrain from donating sperm plus
either: Be abstinent from heterosexual or homosexual intercourse as their preferred
and usual lifestyle (abstinent on a long term and persistent basis) and agree to
remain abstinent or must agree to use contraception/barrier as detailed below; agree
to use a male condom and should also be advised of the benefit for a female partner to
use a highly effective method of contraception as a condom may break or leak when
having sexual intercourse with a woman of childbearing potential who is not currently
pregnant; agree to use male condom when engaging in any activity that allows for
passage of ejaculate to another person.

- Capable of giving signed informed consent.

Exclusion Criteria:

- History of malignancy other than the disease under study. 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.

- Primary central nervous system (CNS) tumors, Glioblastoma multiforme (GBM),
symptomatic or untreated leptomeningeal or brain metastases or spinal cord
compression. Subjects previously treated for these conditions that have had stable CNS
disease (verified with consecutive imaging studies) for >1 months, are asymptomatic
and off corticosteroids, or are on stable dose of corticosteroids for at least 1 month
prior to study Day 1 are permitted. Stability of brain metastases must be confirmed
with imaging. Subjects treated with gamma knife therapy can be enrolled 2 weeks
post-procedure as long as there are no post-procedure complications/they are stable.

- Any severe or uncontrolled systemic diseases (e.g., unstable or uncompensated
respiratory, hepatic, renal, cardiac disease, or clinically significant bleeding
episodes, or active infection).

- Any serious and/or unstable pre-existing medical, 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.

- Any clinically significant gastrointestinal (GI) abnormalities that may alter
absorption such as malabsorption syndrome or major resection of the stomach and/or
bowels.

- History of known human immunodeficiency virus (HIV) infection or positive HIV test
result at screening.

- Presence of hepatitis B surface antigen (HBsAg) or positive hepatitis C antibody test
result at screening to first dose of study intervention.

- Any of the following cardiac abnormalities: Uncontrolled high blood pressure; any
history of coronary artery disease, including acute coronary syndromes, myocardial
infarction, unstable angina, and history of coronary angioplasty, or stenting;
presence of a cardiac pacemaker or implanted defibrillator; atrioventricular
(AV)-block (including 1st degree AV block if PR >250 msec, and other more advanced
forms of AV block), right bundle branch block (RBBB), left bundle branch block (LBBB),
and any fasicular hemiblocks; A QRS interval at Screening or Baseline >100 msec;
subjects with any symptomatic or sustained arrhythmias (past or present), including
but not limited to: Atrial fibrillation, Atrial flutter, Ventricular tachycardia,
Ventricular fibrillation, Supraventricular tachycardia; Current or past congestive
heart failure; Evidence of a left ventricular ejection fraction below the
institutional lower limit of normal on Screening echocardiogram; Evidence of
significant structural heart disease on echocardiography at Screening (including any
valvular disease greater than "mild" in severity); Cardiac troponin > upper limit of
the reference range at Screening.

- Treatment with any local or systemic anti-neoplastic therapy or investigational
anticancer agent within 14 days or 4 half-lives, whichever is longer, up to a maximum
wash-out period of 28 days prior to initiation of study drug administration.
Anti-androgen therapies for prostate cancer, such as bicalutamide, must be stopped 28
days prior to first dose of GSK3368715. Second-line hormone therapies such as
enzalutamide or abiraterone should be stopped 14 days prior to enrolment. Subjects
with prostate cancer may remain on luteinizing hormone-releasing hormone (LHRH)
agonists or antagonists and/or low-dose prednisone or prednisolone (up to 10
milligrams per day [mg/day]). Nitrosureas and mitomycin C must be stopped within 42
days prior to first dose of GSK3368715.

- Allogeneic hematopoietic stem-cell transplantation.

- Toxicities from previous anti-cancer therapies have not resolved to Baseline or
National Cancer Institute (NCI) CTCAE V4.0. <=Grade 1 (except fatigue and alopecia
[permissible at any grade] and peripheral neuropathy [which must be <= Grade 2]) at
the time of starting study intervention.

- Radiotherapy within 14 days before the initiation of study drug administration (with
the exception of palliative radiotherapy for pain which can be used any time before
the first dose of study therapy).

- Major surgery (i.e. requiring general anesthesia) within 3 weeks before screening, or
not fully recovered from major surgery, or major surgery planned during study
participation. Planned surgical procedures to be conducted under local anesthesia are
allowed.

- Prior organ transplantation.

- Concurrent anti-coagulation therapy. Treatment with low-molecular heparin is allowed.

- Current use of a prohibited medication or planned use of any forbidden medications
during intervention with GSK3368715.

- History of sensitivity to any of the study medications, or components thereof or a
history of drug or other allergy that, in the opinion of the investigator or Medical
Monitor, contraindicates their participation.