Key bioanalytical measurements for antibody-drug conjugate development: PK/PD modelers perspective

摘要

Mathematical modeling can integrate PK, PD and toxicodynamic (TD) data, and can generate and answer key hypotheses. Modeling and simulation techniques can be applied to optimize study design and augment/refine preclini-cal and clinical experimentation. Additionally, modeling can be instrumental in providing a quantitative framework for preclinical to clinical translation of efficacy and safety. The ultimate quality and confidence in these mathematical models depends upon the data used to build or validate them, highlighting the need for high-quality bioanalytical measurements. To support such modeling efforts for antibody-drug conjugates (ADCs), a list of key bioanalytical measurements is presented. Models built using appropriate bioanalytical measurements have been shown to aid in preclinical-to-clinical translation and clinical trial simulations of ADCs [i]. This report highlights that in addition to conventional PK measures, bioanalytical strategies for optimal ADC support also require generation of other drug- and system-specific quantitative measurements (i.e., chemomeasures and biomeasures), at different anatomical levels and drug-development stages.