GSK3174998 Alone or With Pembrolizumab in Subjects With Advanced Solid Tumors (ENGAGE-1)

Inclusion Criteria:

- Provide signed, written informed consent.

- Male and female subjects, age >=18 years (at the time consent is obtained).

- Histological documentation of locally advanced, recurrent or metastatic solid
malignancy that has progressed after standard therapy appropriate for the specific
tumor type, or for which standard therapy has proven to be ineffective, intolerable,
or is considered inappropriate. Subjects should not have received more than 5 prior
lines of therapy for advanced disease including both standards of care and
investigational therapies. Subjects whose cancers harbor molecular alterations for
which targeted therapy is standard of care should have received health authority
approved appropriate targeted therapy for their tumor types before enrollment.

- Subjects with the following solid tumors are eligible for screening: Non-small cell
lung cancer (NSCLC), Squamous cell carcinoma of the head and neck (SCCHN), Renal cell
carcinoma (RCC), melanoma, bladder, Triple-negative breast cancer (TNBC), and
Colorectal carcinoma displaying microsatellite instability (MSI CRC).

- A biopsy of the tumor tissue obtained at anytime 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. For Part 1B and
Part 2B, any archival tumor specimen must have been obtained within 3 months of
starting study drug.

- Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST)
version 1.1. Palpable lesions that are not measurable by radiologic or photographic
evaluations may not be utilized as the only measurable lesion.

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

- Life expectancy of at least 12 weeks.

- Adequate organ function as defined by System Laboratory Values; Hematologic (Absolute
neutrophil count [ANC] >=1.5x10^9/ liter [L], Lymphocyte count >1,000/cubic millimeter
[mm^3], Hemoglobin >=9 grams/deciliter [g/dL], Platelets >=100x10^9/L), Hepatic (Total
bilirubin <=1.5x upper limit of normal [ULN] [For subjects with Gilbert's Syndrome,
only if direct bilirubin <=35%, <=3.0xULN], alanine aminotransferase [ALT] <=1.5xULN);
Renal (Serum Creatinine <=1.5xULN OR Calculated creatinine clearance [CrCl >50 mL/min)
and Endocrine (Thyroid stimulating hormone [TSH] within normal limits. If TSH is not
within normal limits at baseline, the subject may still be eligible if total T3 or
free T3 and free T4 are within the normal limits.

- QT duration corrected for heart rate by Fridericia's formula (QTcF) <450 msec or <480
milliseconds (msec) for subjects with bundle branch block.

Female subjects and male subjects with female partners of child bearing potential must
comply with adequate contraception requirements from the time of first dose of study
medication until 120 days after the last dose of study medication.

Exclusion Criteria:

- Prior treatment with the following agents (from last dose of prior treatment to first
dose of GSK3174998): Tumor necrosis factor receptor (TNFR) agonists, including OX40,
CD27, CD137 (4-1BB), CD357 (GITR): at any time; Checkpoint inhibitors, including PD-1,
PD-L1, and anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors: within 4 weeks.

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

- Active residual toxicity from prior therapies.

- Secondary malignancy.

- Brain metastases.

- Active autoimmune disease that has required systemic treatment within the last 2
years.

- Active infection, known human immunodeficiency virus infection, or positive test for
hepatitis B surface antigen or hepatitis C.

- Current active liver or biliary disease.

- Acute diverticulitis, inflammatory bowel disease, intra-abdominal abscess, or
gastrointestinal obstruction within the past 6 months.

- Severe hypersensitivity to other monoclonal antibodies (mAbs).

- Recent (within 6 months) history of second degree (Type II) or third degree
atrioventricular (AV) block cardiomyopathy, myocardial infarction, acute coronary
syndromes (including unstable angina), coronary angioplasty, stenting, or bypass
grafting; Class II, III, or IV heart failure, or symptomatic pericarditis.

- Current or history of idiopathic pulmonary fibrosis, interstitial lung disease, or
organizing pneumonia.

- History of (non-infectious) pneumonitis that required steroids or current pneumonitis.

- Uncontrolled symptomatic ascites or pleural effusions within 6 months.