Dhaval K. Shah

Aims This study aims to develop a generalized pharmacokinetic (PK) model for monomethyl auristatin E (MMAE)‐based antibody–drug conjugates (ADCs) that can simultaneously capture the PK of multiple ADC analytes commonly measured in the clinic. Methods A comprehensive literature review was conducted to collect PK data on MMAE‐based ADCs from clinical trials. From each study, PK profiles of total antibody, the ADC, conjugated MMAE, and unconjugated MMAE, were extracted. These data were pooled and dose‐normalized to evaluate the generalizability of PK across various ADCs and dose levels. Upon confirming PK generalizability, a generalized PK model for MMAE‐based ADCs was developed using the entire dataset. Furthermore, exposure metrics ( and AUC) reported across the range of doses were combined to establish linear relationships between dose and exposure metrics for MMAE‐based ADCs. Results A total of 109 PK profiles from 18 distinct MMAE‐based ADCs were gathered. The dose‐normalized PK profiles supported the generalizability of PK for MMAE‐based ADCs. A generalized PK model was developed, which enabled capturing the PK data for 4 ADC analytes across all collected MMAE‐based ADCs. A linear relationship between dose and PK exposure metrics was established, enabling the prediction of typical exposure values across different doses for MMAE‐based ADCs. Conclusions This study comprehensively analysed clinical PK data from different valine–citrulline (vc)‐MMAE‐based ADCs. The generalized PK model developed here serves as an important tool for a priori prediction of the PK for multiple ADC analytes in clinical settings and lays the foundation for establishing generalized exposure–response and exposure–toxicity correlations for MMAE‐based ADCs.