This clinical trial is focused on studying treatments for urothelial cancer, a type of cancer that affects the bladder and other parts of the urinary system. The study involves participants who have not received prior treatment for their cancer, which is either not removable by surgery or has spread to other parts of the body. The trial will test the effectiveness of a combination of two medications, nivolumab and ipilimumab, compared to standard chemotherapy treatments. Chemotherapy is a common cancer treatment that uses drugs to kill cancer cells. The medications nivolumab and ipilimumab are given as infusions, which means they are administered directly into the bloodstream through a vein.

The purpose of the study is to compare how well patients live with the combination of nivolumab and ipilimumab versus standard chemotherapy. The study will also look at how these treatments affect patients who cannot receive a specific chemotherapy drug called cisplatin, and those whose cancer cells have a protein called PD-L1. PD-L1 is a protein that can help cancer cells hide from the immune system. The study will involve regular visits to the clinic for treatment and monitoring, and participants will receive either the combination of nivolumab and ipilimumab or standard chemotherapy, which may include drugs like carboplatin, cisplatin, or gemcitabine.

Participants will be randomly assigned to one of the treatment groups, and some may receive a placebo, which is a substance with no active medication. The study will continue for a period of time to observe the effects of the treatments on overall survival and quality of life. The results of this study will help determine the best treatment options for patients with untreated, unresectable, or metastatic urothelial cancer.