Director/Principal Scientist Genentech, Inc. South San Francisco, California
Antibody-drug conjugates (ADCs) are an important class of biotherapeutics in oncology. To date, eight ADCs have received US Food and Drug Administration (FDA) approval with many more in the early- and late-stage clinical development. ADCs have complex molecular structures consisting of a monoclonal antibody (mAb) covalently bound with a cytotoxic payload through a chemical linker. The cytotoxic payloads, upon releasing from ADCs, are expected to behave like small molecules. As a result, evaluating the drug-drug interaction (DDI) potential associated with payloads is important in clinical development of ADCs. However, given the relatively high potency and low systemic exposure of cytotoxic payloads, DDI consideration for ADCs might be different from traditional small molecules. An IQ ADC working group was formed to collect the data and develop the risk-based payload-mediated DDI strategy. The objective of this presentation is to share the overall findings and provide a working group recommendation for a payload-mediated DDI strategy for ADCs. Specifically, payload-mediated DDI risk will be assessed based on 8 approved ADCS, and an IQ ADC database that includes 26 ADCs with 6 unique payloads. DDI results, and its implications for labeling, will be summarized for the 8 approved ADCs. A decision tree to guide the assessment of payload as a victim will be presented.
Learn the risk-based DDI strategy to support clinical development of ADCs
Learn the clinical approaches to assess payload-mediated DDI of ADCs
Learn the IQ pharma industry perspective on a risk-based, payload-mediated DDI framework for ADCs