Population pharmacokinetics of the anti-PD-1 antibody camrelizumab in patients with multiple tumor types and model-informed dosing strategy

Chen-yu Wang1, Chang-cheng Sheng2, Guang-li Ma3, Da Xu3, Xiao-qin Liu4, Yu-ya Wang3, Li Zhang5, Chuan-liang Cui6, Bing-he Xu7, Yu-qin Song8, Jun Zhu8, Zheng Jiao1
1 Department of Pharmacy, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China
2 Department of Pharmacy, Guizhou Provincial People’s Hospital, Guiyang 550002, China
3 Department of Clinical Pharmacology, Jiangsu Hengrui Medicine Co. Ltd, Shanghai 222047, China
4 Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai 200041, China
5 Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
6 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing 100036, China
7 Department of Medical Oncology, National Cancer Hospital, Chinese Academy of Medical Sciences, Beijing 100021, China
8 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing 100036, China
Correspondence to: Zheng Jiao:,
DOI: 10.1038/s41401-020-00550-y
Received: 7 July 2020
Accepted: 29 September 2020
Advance online: 5 November 2020


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.
Keywords: camrelizumab; programmed cell death 1 receptor; population pharmacokinetics; Monte Carlo method; dosing regimen

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