Upon joining the study, you will be randomly assigned to one of two treatment groups. This process is similar to flipping a coin and ensures fairness in the study.

You will receive either the combination of belzutifan and zanzalintinib, or cabozantinib alone.

You will begin taking your assigned medication by mouth in the form of tablets.

If you are assigned to the combination group, you will take both belzutifan and zanzalintinib tablets.

If you are assigned to the single medication group, you will take cabozantinib tablets.

All medications are taken orally as tablets or film-coated tablets.

Throughout the study, you will undergo regular imaging scans to evaluate how your kidney cancer is responding to treatment.

These assessments will follow standardized criteria called RECIST 1.1, which is a method used to measure changes in tumor size.

Independent radiologists will review your scans to determine if the disease is stable, improving, or progressing.

Your health will be monitored regularly for any side effects or adverse events related to the treatment.

If you experience any concerning symptoms or side effects, your treatment may be adjusted or stopped.

You will be asked to complete questionnaires at regular intervals to assess your quality of life and how you are feeling.

These questionnaires include the EORTC QLQ-C30, which evaluates your overall health, physical functioning, and ability to perform daily activities.

You will also complete the FKSI-DRS questionnaire, which focuses on symptoms specifically related to kidney cancer.

Your responses will help determine how the treatment affects your daily life and well-being.

You will continue taking your assigned medication as long as the treatment is working and you are not experiencing unacceptable side effects.

The study will monitor how long you remain without disease progression, which is called progression-free survival.

The study will also track overall survival, which measures how long participants live during and after the study.

Your medical team will assess whether your cancer responds to treatment, including whether tumors shrink or disappear.

If your cancer responds to treatment, the duration of that response will be measured to understand how long the benefit lasts.

You will remain in the study until your disease progresses, you experience side effects that require stopping treatment, or the study ends.

The study is expected to continue until December 2031, though your individual participation may be shorter depending on your response to treatment.