Study of the Safety and Effectiveness of GSK6097608 in Participants With Advanced Solid Tumors

This first-time-in-human (FTIH) study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of escalating doses of GSK6097608 given as monotherapy and in combination with dostarlimab in participants with advanced solid tumors. In addition, dostarlimab will be given as monotherapy (Arm D); and in combination with belrestotug (Arm E); and with GSK6097608 + belrestotug (Arm F) in Japanese and Chinese participants. The study may assess the PK/PD cohorts for Arm E and/or Arm F in participants outside of China and Japan. Additionally, dostarlimab will be given in combination with cobolimab in Japanese participants. Drug name mentioned as belrestotug, GSK4428859A and EOS884448 are interchangeable for the same compound. In the rest of the document, the drug will be referred to as belrestotug.


Eligibility Criteria:
Inclusion Criteria:

* Adults 18 years of age or older (or \>=20 years of age in Arm-A Japan, Arm-D Japan, Arm E-Japan, Arm F-Japan, and Arm G-Japan)
* Female participants of childbearing potential must agree to use a highly effective form of contraception
* Histological or cytological documentation of locally advanced, recurrent, or metastatic solid malignancy. Enrollment in PK/PD cohorts will be restricted to participants with histologically or cytologically confirmed diagnosis of 1 or more of the following: non-small-cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), endometrial cancer (EC), colorectal cancer (CRC) (including specified molecular subtypes of these) or an alternative immunogenic tumor type with medical monitor approval
* Disease that has progressed after standard therapy for the specific tumor type, or for which standard therapy has proven to be ineffective, intolerable, or is considered inappropriate, or if no further standard therapy exists
* Participants in a PK/PD cohort (Arms A, B, E and F) must provide fresh tumor biopsies. Biopsies are not required from participants enrolled in Arm D, Arm E, (non-PK/PD cohorts only), Arm F (non-PK/PD cohort only), Arm G or any participant enrolled in mainland China
* Eastern cooperative oncology group (ECOG) performance status (PS) 0 to 1
* Life expectancy of at least 12 weeks
* Adequate organ function as determined by laboratory assessments
* Adequate cardiac ejection fraction as measured by echocardiogram
* Arm A-Japan, Arm D-Japan, Arm E-Japan, Arm F-Japan, and Arm G-Japan only: lives in Japan and is racially Japanese, defined as all biological grandparents being Japanese
* Arm A-China, Arm B-China, Arm D-China, Arm E-China and Arm F-China only (excluding PK/PD cohorts in Arm E and Arm F): is of Chinese descent and lives in China
* Arm D, Arm E, Arm F, and Arm G only: has been deemed suitable for assigned treatment based on assessment by the investigator

Exclusion Criteria:

* Prior anti-cancer treatment including investigational agents, immune checkpoint inhibitors, chemotherapy, targeted therapy, and biological therapy: within 4 weeks or 5 half-lives of the drug, whichever is shorter
* Prior allogenic or autologous bone marrow transplantation or other solid organ transplantation
* Toxicity from previous anticancer treatment, including; greater than or equal to (\>=) Grade 3 immune-mediated toxicity considered related to prior immunotherapy and that led to treatment discontinuation; or toxicity related to prior treatment that has not resolved; or history of myocarditis of any grade during a previous treatment with immunotherapy
* Known additional malignancy that progressed or required active treatment within the last 2 years
* Uncontrolled or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis
* Active autoimmune disease that has required systemic disease-modifying or immunosuppressive treatment within the last 2 years
* Concurrent medical condition requiring the use of systemic immunosuppressive treatment
* Cirrhosis or current unstable liver or biliary disease per investigator assessment
* Active infection requiring systemic treatment, known human immunodeficiency virus infection, or positive test for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV)
* Prolonged QT as measured by electrocardiogram
* Allergen desensitization therapy within 4 weeks of starting study intervention
* History of hypersensitivity to any of the study interventions or their excipients
* Has a history or evidence of cardiac abnormalities within the 6 months prior to enrolment
* Recent history (within 6 months) of uncontrolled symptomatic ascites or pleural effusions
* History of idiopathic pulmonary fibrosis; interstitial lung disease; organizing pneumonia; noninfectious pneumonitis that required steroids, or evidence of active, noninfectious pneumonitis
* Pregnant or lactating woman
* Receipt of live vaccine within 30 days of the start of study intervention
* Receipt of transfusion of blood products or administration of colony-stimulating factors within 14 days before the first dose of study intervention
* Major surgery less than 4 weeks before the first dose of study intervention
* Known drug or alcohol abuse