This clinical trial is studying renal cell carcinoma, a type of kidney cancer that is advanced and has gotten worse after previous treatment. The study compares two treatment approaches: belzutifan taken by mouth together with zanzalintinib, or belzutifan taken by mouth together with placebo. Zanzalintinib is also known by the code name XL092. The purpose of the study is to see which treatment helps people live longer and keeps the cancer from getting worse for a longer time.

People in the study are assigned by chance to one of the two treatment groups, and neither the study team nor the participants know which treatment is being given. The treatment is taken as tablets over time, with regular study visits during the trial. During these visits, the study team checks for side effects and overall health, and asks about symptoms and daily well-being.

The trial is looking at adults with advanced kidney cancer who have already received treatment with PD-1/L1 and VEGF-TKI medicines, either one after the other or together. PD-1/L1 and VEGF-TKI are types of cancer medicines that act in different ways to slow tumor growth. The study follows participants while they receive treatment and for some time afterward to understand the effects of the medicine combination over time.