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

Abstract

Objective: Camrelizumab, a programmed cell death 1 (PD-1) inhibitor, has been approved for the treatment of relapsed or refractory classical Hodgkin lymphoma. The aim of this study was to perform a population pharmacokinetics (PK) analysis of camrelizumab to quantify the impact of patient characteristics on PK and to investigate the appropriateness of flat dose in the dosing regimen. Methods: A total of 3298 camrelizumab concentrations from 133 patients from four studies were analyzed using nonlinear mixed effects modeling. Covariate model building was conducted using stepwise forward addition and backward elimination. Monte Carlo simulation was conducted to compare exposures of 200 mg and 3 mg/kg every 2-week regimens. Results: The PK of camrelizumab were adequately described by a two-compartment model with parallel linear and nonlinear clearances. Baseline albumin had significant effects on linear clearance, and weight had effects on inter-compartmental clearance. Moreover, 200 mg and 3 mg/kg regimens provide similar exposure distributions with no advantage to either dosing approach. Conclusion: Population PK analysis provided an integrated evaluation of the impact of albumin and weight on the PK of camrelizumab. It also provided evidence that neither the flat-dose nor the weight-based dose regimen was advantageous over the other for most patients with tumors.

Safety, activity, and pharmacokinetics of camrelizumab in advanced Asian melanoma patients: a phase I study

“…Besides, the expansion cohort of first in human trial conducted in Australia demonstrated that camrelizumab showed manageable toxicity at a fix dose of 200 mg [ 11 ]. Several studies in China have shown that camrelizumab 200 mg showed acceptable safety profile and potential efficacy in various tumors [ 6 , 10 , 16 – 19 ]. Taken together, the fixed dose of 200 mg could be the recommended dose in the further trials.…”

Novel Agents For Relapsed and Refractory Classical Hodgkin Lymphoma: A Review

“…To date, finding novel and highly effective anti-PD-1 agents remains a major challenge worldwide. In China, several anti-PD-1 agents have been approved by the National Medical Products Administration for use in the treatment of r/r cHL from 2018 to 2022, including sintilimab (40,41), tislelizumab (42,43), camrelizumab (44)(45)(46)(47)(48)(49)(50), penpulimab (51), and zimberelimab (52). A summary of these agents is provided in Table 2.…”

“…Camrelizumab is an anti-PD-1 agent that has shown good efficacy against various advanced malignancies ( 44 ). It achieved a high rate of objective response (76.0%; 95% CI, 64.7–85.1) in cHL patients failing or ineligible for ASCT ( 45 ), and the median PFS was 22.5 months and the 36-month OS was 82.7%, according to the latest updates ( 46 ).…”

Reactive capillary hemangiomas induced by camrelizumab in a patient with hepatocarcinoma

“…Camrelizumab, as a treatment for various malignancies, has been approved for the treatment of relapsed or refractory classical Hodgkin lymphoma, nasopharyngeal cancer, and nonsmall cell lung cancer, 1 and it can also be used for hepatocellular carcinoma, 2 esophageal squamous cell carcinoma, 3 gastric cancer, 4 and so forth. Reactive cutaneous capillary endothelial proliferation (RCCEP) is the most common adverse reaction to camrelizumab.…”