Sitravatinib and Nivolumab in Urothelial Carcinoma Study

Sitravatinib is an orally-available, potent small molecule inhibitor of a closely related
spectrum of receptor tyrosine kinases (RTKs) including MET, Axl, MERTK, VEGFR family, PDGFR
family, KIT, FLT3, Trk family, RET, DDR2 and selected Eph family members. Nivolumab is a
human IgG monoclonal antibody that binds to the programmed cell death-1(PD-1) receptor and
blocks its interaction with programmed cell death ligand-1 (PD-L1) and PD-L2, releasing PD-1
pathway-mediated inhibition of the immune response including anti-tumor immune response.
Combining an immunotherapeutic PD-L1 checkpoint inhibitor with an agent that has both immune
modulatory and antitumor properties could enhance the antitumor efficacy observed with either
agent alone. Sitravatinib selectively inhibits key molecular and cellular pathways strongly
implicated in checkpoint inhibitor resistance and therefore represents a rational strategy to
enhance or restore anti-tumor immunity when combined with nivolumab, a checkpoint inhibitor
therapy.

Inclusion Criteria:

- Diagnosis of urothelial carcinoma

- Most recent treatment must have included a checkpoint inhibitor

- Adequate bone marrow and organ function

Exclusion Criteria:

- Uncontrolled tumor in the brain

- Unacceptable toxicity with prior checkpoint inhibitor

- Impaired heart function