Population pharmacokinetics of the anti-PD-1 antibody camrelizumab in patients with multiple tumor t

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Camrelizumab,a programmed cell death 1(PD-1)inhibitor,has been approved for the treatment of patients with relapsed or refractory classical Hodgkin lymphoma,nasopharyngeal cancer and non-small cell lung cancer.The aim of this study was to perform a population pharmacokinetic(PK)analysis of camrelizumab to quantify the impact of patient characteristics and to investigate the appropriateness of a flat dose in the dosing regimen.A total of 3092 camrelizumab concentrations from 133 patients in four clinical trials with advanced melanoma,relapsed or refractory classical Hodgkin lymphoma and other solid tumor types were analyzed using nonlinear mixed effects modeling.The PKs of camrelizumab were properly described using a two-compartment model with parallel linear and nonlinear clearance.Then,covariate model building was conducted using stepwise forward addition and backward elimination.The results showed that baseline albumin had significant effects on linear clearance,while actual body weight affected intercompartmental clearance.However,their impacts were limited,and no dose adjustments were required.The final model was further evaluated by goodness-of-fit plots,bootstrap procedures,and visual predictive checks and showed satisfactory model performance.Moreover,dosing regimens of 200 mg every 2 weeks and 3 mg/kg every 2 weeks provided similar exposure distributions by model-based Monte Carlo simulation.The population analyses demonstrated that patient characteristics have no clinically meaningful impact on the PKs of camrelizumab and present evidence for no advantage of either the flat dose or weight-based dose regimen for most patients with advanced solid tumors.
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