Antibody–Drug Conjugates: Clinical Strategies and Applications

Antibody-drug conjugates (ADCs) have created a new paradigm for novel anticancer drug development, as evidenced by a large development pipeline. With both the specificity of the large-molecule monoclonal antibody and the potency of the small molecule cytotoxic drug, ADCs have tremendous potential to be part of the future of cancer precision medicine as well as cancer combination therapies. This chapter highlights current thinking around clinical development strategies for ADCs from first-in-human (FIH) dose and schedule selection to key assessments needed to support registration and approval. Pharmacometric strategies are integrated across all stages of ADC development. Physiologically based pharmacokinetic (PBPK) models have been proposed and some have been applied in preclinical and clinical ADC development. To date, quantitative systems pharmacology (QSP) models have primarily been used to explore questions around ADC optimization, preclinical dosing, and to generate translational predictions between preclinical species and humans by mechanistic extrapolation.