Population Pharmacokinetics of SCT510 (a Bevacizumab Biosimilar) and Avastin in Healthy Subjects and Patients with Non-squamous Non-small Cell Lung Cancer.

[BACKGROUND] SCT510 is a proposed biosimilar of bevacizumab (Avastin), a monoclonal antibody that targets vascular endothelial growth factor.

[OBJECTIVE] This analysis aimed to characterize the population pharmacokinetics of SCT510, a bevacizumab biosimilar, and its reference product (Avastin) in healthy subjects and patients with advanced non-squamous non-small cell lung cancer. Secondary objectives were to evaluate the pharmacokinetic similarity between the two drugs and to investigate the effects of factors, including alanine transaminase, creatinine clearance, and age, on their pharmacokinetic profiles.

[METHODS] The population pharmacokinetic model was developed by pooling intensive pharmacokinetic data from a phase I trial in healthy male subjects with sparse pharmacokinetic data from a phase III trial in patients with non-squamous non-small cell lung cancer, utilizing a non-linear mixed-effects modeling (NONMEM) approach.

[RESULTS] A total of 2647 serum concentration data from 399 subjects were included in the population pharmacokinetic analysis. A two-compartment model with linear elimination adequately described the pharmacokinetic data for both SCT510 and Avastin. The final model identified albumin, body weight, creatinine clearance, sex, study drug (SCT510 vs Avastin), and subject type (healthy vs patient) as statistically significant covariates. Furthermore, the analysis confirmed the pharmacokinetic similarity of SCT510 and Avastin, as no substantial differences in exposure were observed after single or multiple doses in either healthy subjects or patients. Finally, covariates such as alanine transaminase, creatinine clearance, and age were found to have no clinically relevant impact on the pharmacokinetics of either drug.

[CONCLUSIONS] SCT510 and Avastin demonstrated comparable population pharmacokinetic profiles, supporting the biosimilarity of SCT510 to its reference product. The analysis also indicated that no clinically relevant differences in exposure were observed for either agent across a wide range of hepatic or renal function, or age. These findings collectively support that no dose adjustment is necessary for these factors.

[CLINICAL TRIAL REGISTRATION] NCT05113511, NCT03792074.