Journal Article

Population Pharmacokinetics of Serplulimab and Quantitative Assessment of Transitioning From Weight‐Based to Flat‐Dosing Strategy

Kwok, Zhihao, Wang, Qingyu, Hu, Chen, Zhou, Liang, Wang, Kun, Shen, Yuanyuan, Xu, Fengyan, Lin, Yaqi, Gao, Yuying

2026

Overview

Serplulimab is a fully humanized anti–PD‐1 monoclonal antibody approved for small‐cell lung cancer and other malignancies. The initial dosing strategy was based on body weight (WT‐based); however, flat‐dosing offers greater convenience and reduced variability. This study characterized the population pharmacokinetics (PopPK) of serplulimab using data from 11 clinical trials and quantitatively evaluated the appropriateness of transitioning from WT‐based to flat‐dose regimens. Serplulimab concentration–time data from 2110 patients were analyzed using nonlinear mixed‐effects modeling. A previously developed two‐compartment model with time‐varying clearance best described the pharmacokinetic (PK) profile. A stepwise forward‐addition and backward‐elimination procedure was used to evaluate covariate effects on PK parameters. Model adequacy was confirmed by diagnostic plots, prediction‐corrected visual predictive checks (pcVPCs), and bootstrap analysis. Simulations compared exposures between 3 mg/kg every 2 weeks (Q2W), 4.5 mg/kg every 3 weeks (Q3W), 200 mg Q2W, and 300 mg Q3W regimens. Body weight and albumin were the main predictors of exposure. Although statistically significant, covariate effects were modest (≤ 20%) and not clinically meaningful, supporting a unified dosing strategy. Simulations showed that flat‐dose regimens achieved exposure comparable to WT‐based dosing, with < 25% differences in median Cavg and Cmax across body‐weight ranges. Exposure–response (E–R) analyses revealed no meaningful association between exposure and outcomes. The PopPK model adequately described serplulimab PK and supports transitioning from WT‐based to flat‐dosing, demonstrating comparable exposure, efficacy, and safety across regimens. Study Highlights What is the current knowledge on the topic? ○Flat‐dosing of monoclonal antibodies can provide comparable exposure as WT‐based dosing while simplifying their clinical use, but quantitative justification is needed for each specific agent. What question did this study address? ○Can flat‐dose regimens of serplulimab achieve similar PK exposure, efficacy, and safety as WT‐based dosing across broad patient populations? What does this study add to our knowledge? ○PopPK and E‐R analyses showed comparable exposure and clinical outcomes between flat and WT‐based dosing, with covariate effects ≤ 20% and not clinically meaningful. How might this change clinical pharmacology or translational science? ○The findings quantitatively support flat‐dosing of serplulimab, reinforcing the shift toward simplified, standardized dosing strategies for monoclonal antibodies in oncology.

• Publisher: John Wiley & Sons, Inc,Wiley
• Subject: Adult / Aged / Antibodies, Monoclonal, Humanized - administration & dosage / Antibodies, Monoclonal, Humanized - pharmacokinetics / Body Weight / Clinical trials / Computer Simulation / Datasets / Dose-Response Relationship, Drug / Drug dosages / Esophageal cancer / E–R analysis / Female / flat‐dosing / HLX10 / Humans / Liver cancer / Lung cancer / Lung Neoplasms - drug therapy / Male / Middle Aged / Models, Biological / Monoclonal antibodies / Nonlinear Dynamics / population pharmacokinetics / serplulimab / Simulation / WT‐based dosing