Introduction
M1:M2-polarised, tumour
CLEAR CELL RENAL CELL CARCINOMA, TUMOUR
Sitravatinib, an orally available tyrosine kinase inhibitor (TKI), targets key receptors involved in clear cell renal cell carcinoma (ccRCC) biology including the vascular endothelial growth factor receptor (VEGFR) family, c-MET, and the TAM (TYRO3, AXL, and MER) family. This not only inhibits angiogenesis but may mitigate immunosuppressive effects in the tumour microenvironment (TME) by reducing levels of myeloid-derived suppressor cells (MDSCs) and T regulatory (Treg) cells, and increasing the ratio of M1:M2-polarised macrophagesRadical or partial nephrectomy is the current standard-of-care for locally advanced ccRCCWe hypothesised that the combination of neoadjuvant sitravatinib with nivolumab would yield beneficial immunomodulatory responses in patients with ccRCC. This Phase 2 pilot study evaluated the efficacy and safety of neoadjuvant sitravatinib monotherapy lead-in, followed by the addition of nivolumab in patients undergoing nephrectomy for locally advanced ccRCC. The initial lead-in course of sitravatinib monotherapy facilitated exploratory correlative biomarker analyses to enhance our understanding of the mechanisms of action of sitravatinib and nivolumab.