Dose Escalation Study of GSK3326595 in Subjects With Solid Tumors and Non-Hodgkin's Lymphoma

Inclusion Criteria:

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

- Capable of giving signed informed consent

- Able to swallow and retain orally-administered medication - Eastern cooperative
oncology group (ECOG) performance status of 0 to 2 - Diagnosis of one of the
following: 1. Part 1: Histologically- or cytological-confirmed diagnosis of
non-resectable or metastatic solid malignancy. At the time of enrollment, subjects
either: have progressed on prior therapy (radiographic documentation of progression is
adequate for study participation) AND have no standard-of-care therapy that would be
expected to achieve a durable clinical response, OR refuse standard therapy, OR are
not candidates for standard therapy, OR have a disease for which no generally-accepted
standard-of-care exists. 2. Part 2: Histologically- or cytologically-confirmed
diagnosis of metastatic or non-resectable triple-negative breast cancer (TNBC)
(estrogen receptor [ER]-/ progesterone receptor [PR]-/Human Epidermal Growth Factor
Receptor 2 [Her2]-, as defined by local laboratory standards); ER+BC (estrogen
receptor positive [ER+] or progesterone receptor positive [PR+], human epidermal
growth factor receptor 2 negative (Her2-), as defined by local laboratory standards).
NOTE: Subjects in this cohort must have previously received therapy with a
cyclin-dependent kinase (CDK) 4/6 inhibitor or be considered ineligible to receive
therapy with these agents; metastatic or non-resectable transitional cell carcinoma of
the bladder, ureter, or renal pelvis; recurrent GBM. NOTE: Subjects with prior
low-grade glioma with subsequent imaging demonstrating progression to GBM may be
enrolled without confirmatory biopsy on a case-by-case basis after discussion with the
medical monitor; ACC requiring systemic therapy in the opinion of the treating
physician (e.g., for symptomatic disease). NOTE: In order to be eligible for
enrollment, subjects must have shown progression via cross-sectional imaging (e.g., CT
or MRI) compared to prior scan taken at any time in the past; HPV-positive solid tumor
of any primary histology NOTE: (HPV-positive status may be determined locally via any
generally accepted test [e.g., HPV DNA OR p16 immunohistochemistry]). A minimum of 10
subjects must be enrolled with cervical cancer.;or non-Hodgkin's lymphoma. At the time
of enrollment, subjects either: have progressed on prior therapy (radiographic
documentation of progression is adequate for study participation) AND have no
standard-of-care therapy that would be expected achieve a durable clinical response,
OR refuse standard therapy, OR are not candidates for standard therapy.

- Evaluable disease: 1. During Part 1, evaluable disease is required; measurable disease
per RECIST v1.1 is recommended but not required, 2. Subjects enrolled in Part 2 must
demonstrate measurable disease per the disease-specific criteria.

- PK/PD/biomarker/metabolite expansion cohort(s) only: Subjects must consent to pre- and
post-dose tumor biopsies and additional sample collection procedures.

- Food effect sub-study only: Subjects must consent to additional procedures

- All prior treatment-related toxicities must be National Cancer Institute Common
Terminology Criteria for Adverse Events (NCI-CTCAE) version 4 =< Grade 1 (except
alopecia [permissible at any Grade] and peripheral neuropathy [which must be =< Grade
2]) at the time of treatment allocation. - Adequate organ function as per Hematologic,
Hepatic, Renal and Cardiac Laboratory Values

- Reproductive criteria: 1. A male subject with female partner of child bearing
potential must agree to use one of the methods of contraception for the duration
specified in protocol. 2. A female subject is eligible to participate if she is not
pregnant (as confirmed by a negative serum human chorionic gonadotrophin [hCG] test),
not nursing, and at least one of the following conditions apply: Reproductive
potential: subject must agree to follow one of the options and the duration specified
in protocol; Non-reproductive potential defined as i) Pre-menopausal females with one
of the following: Documented tubal ligation, Documented hysteroscopic tubal occlusion
procedure with follow-up confirmation of bilateral tubal occlusion, Hysterectomy,
Documented Bilateral Oophorectomy; ii) Postmenopausal defined as 12 months of
spontaneous amenorrhea with an appropriate clinical profile or females over 60 years
of age. Females on hormone replacement therapy (HRT) and whose menopausal status is in
doubt will be required to use one of the highly effective contraception methods 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 enrollment.

Exclusion Criteria:

- Malignancy attributed to prior solid organ transplant

- Symptomatic or untreated leptomeningeal or brain metastases or spinal cord
compression. Subjects previously treated for these conditions that have had stable
central nervous system (CNS) disease (verified with consecutive imaging studies) for
>1 month , 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. Subject treated with gamma knife
therapy can be enrolled 2 weeks post-procedure as long as there are no post-procedure
complications/they are stable. This criterion does not apply to subjects with GBM
cohort. In Part 1, subjects with GBM may enroll provided that they are on a stable to
decreasing dose of corticosteroids for at least 14 days prior to the first dose of
GSK3326595. In Part 2, subjects with GBM may enroll irrespective of steroid dose.

- Recent prior therapy, defined as 1. Any non-monoclonal anti-cancer therapy within 14
days or 5 half-lives, whichever is longer, prior to the first dose of GSK3326595. Any
nitrosoureas or mitomycin C within 42 days prior to the first dose of GSK3326595.
Prior therapy with biologic agents (including monoclonal antibodies) is permitted so
long as 28 days have elapsed since therapy and all therapy-related AEs have resolved
to =< Grade 1, 2. Any radiotherapy within 14 days or major surgery within 28 days
prior to the first dose of GSK3326595. For subjects in the GBM cohort, subjects must
have completed radiation therapy at least 28 days prior to the first dose of
GSK3326595. 3. Anti-androgen therapies for prostate cancer, such as bicalutamide, must
be stopped 4 weeks prior to enrollment. Second-line hormone therapies such as
enzalutamide or abiraterone should be stopped 2 weeks prior to enrolment. Subjects
with prostate cancer should remain on luteinizing hormone releasing hormone (LHRH)
agonists or antagonists. Subjects with prostate cancer may also remain on low-dose
prednisone or prednisolone [up to 10 milligram (mg)/day] and still be eligible for
this study.

- History of a second malignancy, excluding non-melanoma skin cell cancer within the
last three years. Subjects with second malignancies that were indolent, in situ or
definitively treated may be enrolled even if less than three years have elapsed since
treatment. Consult the GSK Medical Monitor if second malignancies meet the
requirements specified above.

- Current use of a prohibited medication or planned use of any forbidden medications
during treatment with GSK3326595. - 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.

- 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 or within 3 months prior to first dose of study treatment.
Subjects with positive Hepatitis C antibody due to prior resolved disease can be
enrolled only if a confirmatory negative Hepatitis C RNA polymerase chain reaction
(PCR) is obtained.

- Any of the following cardiac abnormalities: 1. 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. 2. Presence of a
cardiac pacemaker, 3. Baseline Corrected QT (Fridericia's formula) interval (QTcF)
>=450 millisecond (msec), 4. Uncontrolled arrhythmias. Subjects with rate-controlled
atrial fibrillation for >1 month prior to first dose of study drugs may be eligible.
5. Class II, III or IV heart failure as defined by the New York Heart Association
(NYHA) functional classification system.

- 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.