LAUSR

TPS708Background: Sitravatinib is a potent oral tyrosine kinase inhibitor that targets multiple receptor tyrosine kinase pathways including the vascular endothelial growth factor (VEGF), c-MET, and the Tyro3, Axl, and MER family. These pathways can allow tumor cells to escape immune surveillance despite immune checkpoint therapy. We therefore hypothesized that combining sitravatinib with the anti-PD1 antibody nivolumab will enhance antitumor immune responses in pts with ccRCC. The present study is designed to determine the optimal dose for this combination using efficacy and toxicity as co-primary outcomes. Methods: This phase I/II trial uses the sequentially adaptive late-onset EffTox design (Jin et al. J Am Stat Assoc 2014), which accounts for potential late-onset toxicities induced by immunotherapy, and allows dose-finding based on both the efficacy and toxicity of each successive dose. Eligible pts have metastatic ccRCC that progressed on prior VEGF-targeted therapy. Each pt receives initially a pre-s...