Safety Considerations for the Development of Antibody-Drug Conjugates

Antibody-drug conjugates (ADCs) are a novel modality leveraging monoclonal antibody (mAb)-mediated delivery of a cytotoxic payload molecule to its target. Since the drug conjugated to mAb, typically a highly cytotoxic small molecule, can be released unconjugated in plasma and contribute to drug-drug interaction (DDI) potential, both the antibody and small molecule drug component are considered from the perspective of ADC safety.

Numerous chemotherapies utilizing ADCs are being developed for treatment of advanced cancers, however, the regulatory guidance for evaluation of ADC DDI potential is not well established.