Study of a Combination of GSK1795091 and Immunotherapies in Subjects With Advanced Solid Tumors

Inclusion Criteria:

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

- Histological documentation of advanced solid tumor.

- Archival tumor tissue obtained at any time from the initial diagnosis to study entry.
Although a fresh biopsy obtained during screening is preferred, archival tumor
specimen is acceptable if it is not feasible to obtain a fresh biopsy. Subjects
enrolled in a PK/Pharmacodynamic Cohort must provide a fresh biopsy of a tumor lesion
not previously irradiated during the screening period and must agree to provide at
least one additional on-treatment biopsy.

- Disease that has progressed after standard therapies or for which standard therapy is
otherwise unsuitable (example, intolerance).

- Measurable disease, that is, presenting with at least 1 measurable lesion per Response
Evaluation Criteria in Solid Tumors (RECIST version 1.1).

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

- Life expectancy of at least 12 weeks.

- Adequate organ function.

- In France, a subject will be eligible for inclusion in this study only if either
affiliated to or a beneficiary of a social security category.

- Male or female subjects will be included. A female subject is eligible to participate
if she is not pregnant, not breastfeeding, and at least 1 of the following conditions
applies: a) Not a woman of childbearing potential (WOCBP) OR b). A WOCBP who agrees to
follow the contraceptive guidance during the treatment period and for at least 120
days after the last dose of study treatment.

- Capable of giving signed informed consent which includes compliance with the
requirements and restrictions specified.

Additional Inclusion criteria for Subjects in Part 2a (GSK3174998 expansion) and Part 2b
(GSK3359609 expansion):

- Histological or cytological documentation of squamous cell carcinoma of the head and
neck (SCCHN) (oral cavity, oropharynx, hypopharynx, or larynx) that is recurrent,
locally advanced, or metastatic and is not amenable to curative treatment options,
surgery or definitive chemoradiation therapy.

- Received or ineligible for platinum-based therapy and Programmed death receptor-1
(PD-1)/programmed death-ligand 1 (PD-L1) therapy

- Received no more than 3 prior lines of systemic therapy for metastatic disease.

Additional Inclusion Criteria for Subjects in Part 2c (pembrolizumab expansion):

- Histological or cytological documentation of SCCHN (oral cavity, oropharynx,
hypopharynx, or larynx) that is recurrent, locally advanced, or metastatic and is not
amenable to curative treatment options, surgery or definitive chemoradiation therapy.

- Received or ineligible for platinum-based therapy.

- Received no more than 2 prior lines of systemic therapy for metastatic disease.

Exclusion Criteria:

- Malignancy other than disease under study with the exception of those from which the
subject has been disease-free for more than 2 years and not expected to affect the
safety of the subject or the endpoints of the trial.

- Symptomatic central nervous system (CNS) metastases or asymptomatic CNS metastases
that have required steroids within 2 weeks prior to first dose of study treatment.

- Active autoimmune disease that has required systemic disease modifying or
immunosuppressive treatment within the last 2 years. Replacement therapy (example,
thyroxine or physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency) is permitted.

- Concurrent medical condition requiring the use of systemic immunosuppressive treatment
within 28 days before the first dose of study treatment.

- Known human immunodeficiency virus infection.

- Current unstable liver or biliary disease per investigator assessment defined by the
presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or
gastric varices, persistent jaundice, or cirrhosis.

- Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior
to first dose of study treatment.

- Positive Hepatitis C test result at screening or within 3 months prior to first dose
of study treatment.

- QT interval corrected for heart rate according to Fridericia's formula (QTcF) >450
milliseconds (msec) or QTcF >480 msec for subjects with bundle branch block

- Recent history (within the past 6 months) of acute diverticulitis, inflammatory bowel
disease, intra-abdominal abscess, or gastrointestinal obstruction.

- Recent history of allergen desensitization therapy within 4 weeks of starting study
treatment.

- History of severe hypersensitivity to monoclonal antibodies (mAbs).

- History or evidence of cardiovascular (CV) risk including any of the following: a)
Recent (within the past 6 months) history of serious uncontrolled cardiac arrhythmia
or clinically significant ECG abnormalities including second degree (Type II) or third
degree atrioventricular block. b) Cardiomyopathy, myocardial infarction, acute
coronary syndromes (including unstable angina pectoris), coronary angioplasty,
stenting, or bypass grafting within the past 6 months before enrollment. c) Congestive
heart failure (Class II, III, or IV) as defined by the New York Heart Association
(NYHA) functional classification system. d) Recent (within the past 6 months) history
of symptomatic pericarditis.

- History of idiopathic pulmonary fibrosis, pneumonitis, interstitial lung disease, or
organizing pneumonia, or evidence of active, non-infectious pneumonitis.

- Recent history (within 6 months) of uncontrolled symptomatic ascites or pleural
effusions.

- Any serious and/or unstable pre-existing medical, psychiatric disorder, or other
condition that could interfere with the subject's safety, obtaining informed consent,
or compliance to the study procedures.

- Is or has an immediate family member (example, spouse, parent/legal guardian, sibling
or child) who is investigational site or sponsor staff directly involved with this
trial, unless prospective Institutional Review Board (IRB) approval (by chair or
designee) is given allowing exception to this criterion for a specific subject.

- Prior treatment with the following agents: a) Tumor necrosis factor receptor (TNFR)
agonists, including OX40, cluster of differentiation (CD)27, CD137 (4-1BB), CD357
(glucocorticoid-induced TNFR family-related gene) at any time. b) Prior systemic or
intratumoral therapy with TLR agonist. c) Anticancer therapy or investigational
therapy within 30 days or 5 half-lives of the drug, whichever is shorter. d) Prior
radiation therapy: permissible if at least 1 non-irradiated measurable lesion is
available for assessment according to RECIST version 1.1 or if a solitary measurable
lesion was irradiated, objective progression is documented. A wash out of at least 14
days before start of study treatment for radiation of any intended use to the
extremities for bone metastases and 28 days for radiation to the chest, brain, or
visceral organs is required.

- Prior allogeneic or autologous bone marrow transplantation or other solid organ
transplantation.

- Toxicity from previous treatment including: a) Toxicity Grade >=3 related to prior
immunotherapy and that lead to study treatment discontinuation. b) Toxicity related to
prior treatment has not resolved to Grade <=1 (except alopecia, or endocrinopathy
managed with replacement therapy).

- Received transfusion of blood products (including platelets or red blood cells) or
administration of colony stimulating factors (including granulocyte colony-stimulating
factor [G-CSF], granulocyte macrophage colony-stimulating factor, and recombinant
erythropoietin) within 2 weeks before the first dose of study treatment.

- Major surgery <=4 weeks before the first dose of study treatment. Subjects must have
also fully recovered from any surgery (major or minor) and/or its complications before
initiating study treatment.

- Known drug or alcohol abuse.

- Receipt of any live vaccine within 4 weeks.

Additional Exclusion Criteria for Subjects in Part 2c

- Received prior PD-1/PD-L1 therapy.