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, ineligible for, or otherwise unsuitable for platinum-based therapy and anti-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 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) OX40, inducible T-cell co-stimulator (ICOS) agonist 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 anti-PD-1/PD-L1 therapy.