A Phase 2 Study of Sitravatinib in Combination with Nivolumab in Patients with Advanced or Metastatic Urothelial Carcinoma (516-003)

This is a study involving an investigational (experimental) drug called sitravatinib, given in combination with the immunotherapy nivolumab (also known as OPDIVO®).

Sitravatinib is designed to block specific proteins that are thought to cause tumors to grow and to prevent growth of new blood vessels that help cancer tumors to grow and spread. In addition, research indicates that sitravatinib may help stimulate a patient’s immune system, improving its ability to recognize and attack cancer cells.

Nivolumab is an FDA approved, prescription drug that belongs to a class of drugs known as checkpoint inhibitors; specifically, nivolumab is an inhibitor of the Programmed Cell Death (or PD 1). Cancers can have extra signal molecules (PD-L1 molecules) on their surface that make the immune system accept them as normal, helping the cancer cells avoid attack by the immune system. Nivolumab can block these signal molecules, allowing the immune system to recognize and attack cancer cells.

This study will evaluate whether the combination of immune system stimulation caused by sitravatinib and improved recognition of tumor cells caused by nivolumab results in more anti tumor activity (tumor shrinkage) than would be expected with either agent used alone.

Patients will be grouped into cohorts based upon the following:

• Whether or not patients were previously treated with or were ineligible for platinum-based chemotherapy
• Whether or not patients were previously treated with a checkpoint inhibitor or another type of immunotherapy
• Whether or not patients were treated with an antibody-drug conjugate (ADC)

Study cohorts may include 9 - 45 patients depending on the cohort assignment and on how much anti-tumor activity is seen in a cohort. Up to a maximum of 330 patients across approximately 27 study sites in the United States are expected to participate in this study.