Abstract:
Despite 14 FDA approvals, many Antibody-Drug Conjugates (ADCs) fail in late-stage trials due to an imbalance of efficacy and toxicity. Challenges in ADC design such as the choices of target, protein backbone, linker chemistry, cytotoxic payload, and drug-to-antibody ratio (DAR) make for a vast number of combinations that cannot be fully explored experimentally. In this poster we discuss how Model-informed Drug Development (MIDD) approaches can be used to guide the design, development, and clinical application of ADCs, illustrated with Trastuzumab-DM1, Trastuzumab-DXd, and Tisotumab-vedotin case studies.