This study looks at squamous cell carcinoma of the head and neck, which is a type of cancer that affects areas such as the throat, mouth, voice box, and surrounding tissues. The study focuses on cases where the cancer has either come back after treatment or has spread to other parts of the body, and where the tumor shows a specific marker called PD-L1. The treatments being tested include GSK4381562, GSK6097608, GSK4428859, and dostarlimab, which are all given through a vein as infusions. These medications work with the body’s immune system to help fight cancer cells. The study will compare different combinations of these treatments to see how well they work against the cancer.

The purpose of the study is to evaluate how well these new combinations of immune system treatments work compared to dostarlimab alone in people with this type of cancer that shows the PD-L1 marker. The main measure of success will be looking at how many people experience either complete disappearance of their tumors or significant shrinking of their tumors during treatment. Participants will be assigned randomly to receive one of the treatment combinations, and the study will follow them for up to 24 months to track how their cancer responds.

During the study, participants will receive their assigned treatment through infusions into a vein, and doctors will regularly check how the tumors are responding using imaging scans and physical examinations. Tissue samples from the tumor will be needed to confirm that the cancer meets the study requirements and to check for the PD-L1 marker. The study is designed as an open-label trial, which means both the participants and their doctors will know which treatment is being given. This is a platform study using a master protocol, which means it is set up in a way that allows testing of multiple treatment combinations at the same time.