Protocol for a prospective multicenter intervention study (URivo study) assessing biomarkers in patients with previously treated advanced clear cell renal cell carcinoma receiving nivolumab

ABSTRACT

Background:In recent years, immune checkpoint inhibitors have been introduced into routine clinical practice for treating patients with a wide variety of malignant tumors, including advanced renal cell carcinoma (aRCC), resulting in the significant improvement of the prognosis of these patients. However, a reliable biomarker prediciting the clinical course in patients receiving nivolumab has not yet been developed; accordingly, the URivo study was planned to investigate the significance of various candidate biomarkers for aRCC patients treated with nivolumab.Methods:This was designed as a prospective multicenter intervention study, and will include a total of 200 aRCC patients who are scheduled to receive nivolumab followed by treatment with either 1 or 2 tyrosine kinase inhibitors (TKIs). Using resected tumor tissues and serum samples prior to the introduction of nivolumab, the following assessments will be conducted programmed death ligand-1 (PD-L1) and PD-L2 gene copy number gains by fluorescence in situ hybridization, serum concentrations of PD-L1 and PD-L2 by enzyme-linked immunosorbent assay, and expression ofseveral proteins involved in apoptosis, epithelial-mesenchymal transition, signal transduction and immune reaction by immunohistochemical staining. The outcomes of these assays will be evaluated focusing on the association with the response to nivolumab, overall survival, progression-free survival and disease-specific survival.Conclusions: The significance of various types of candidate biomarker, particularly PD-L1 and PD-L2, will be intensively investigated in this study, and this may offer unique information to determine the optimal indication of nivolumab for aRCC patients following the failure of TKIs.Trial RegistrationUMIN000030400; registered April 1, 2018