Population Pharmacokinetics of Serplulimab and Quantitative Assessment of Transitioning From Weight-Based to...

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 C_avg and C_max 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.