This clinical trial is focused on studying treatments for unresectable or advanced melanoma, a type of skin cancer that cannot be removed by surgery or has spread to other parts of the body. The study is testing two treatments: ceralasertib alone and ceralasertib combined with durvalumab (also known as MEDI4736). The purpose of the study is to evaluate how effective these treatments are in patients whose melanoma has not responded to previous treatments that target a protein called PD-(L)1.

Participants in the study will receive either ceralasertib by itself or ceralasertib together with durvalumab. Ceralasertib is taken as a tablet, while durvalumab is given through an infusion, which means it is delivered directly into the bloodstream. The study will last for up to 22 months, during which time the response of the cancer to the treatments will be monitored. Some participants may also be part of a sub-study that involves taking small samples of their tumor tissue to see how the treatments affect certain immune cells.

The trial aims to understand the changes in the tumor and the immune system caused by the treatments. This includes looking at how many patients show a reduction in tumor size and how long any positive effects last. The study will also measure the presence of certain immune cells, like CD8+ T cells, in the tumor before and after treatment. This research could provide valuable insights into new ways to treat melanoma that has not responded to other therapies.