Analyses of Nivolumab Exposure and Clinical Safety Between 3-mg/kg Dosing and 240-mg Flat Dosing in Asian Patients with Advanced Renal Cell Carcinoma in the Real-World Clinical Setting.

We aimed to identify the clinical characteristics related to increased nivolumab exposure in Japanese patients with renal cell carcinoma (RCC) in real-world clinical setting. Eleven patients were treated with the originally approved nivolumab dosing regimen of 3 mg/kg every 2 weeks (Q2W) (3-mg/kg group) and 8 patients with a flat dose of 240 mg Q2W (flat dosing group). Trough concentrations (C) until the fifth cycle were measured by sandwich enzyme-linked immunosorbent assay using anti-nivolumab monoclonal antibody established by the Autonomously Diversifying Library system. Mean C at four cycles of nivolumab were significantly higher in the flat dosing group than in the 3-mg/kg group. In an analysis of covariates related to nivolumab concentration, serum albumin (Alb) was significantly lower in the 3-mg/kg group than in the flat dose group. C correlated significantly with serum Alb at all cycles. In conclusion, serum Alb was a potential clinically relevant covariate for nivolumab pharmacokinetics in Japanese RCC patients. Further studies should verify whether serum Alb affects nivolumab efficacy and toxicity.