Payload-Based Clinical Pharmacology Review of Approved Antibody-Drug Conjugates: Commonalities and Considerations for...

Antibody-drug conjugates (ADCs) combine the specificity of an antibody with the potency of a cytotoxic drug. Thirteen ADCs, utilizing seven unique cytotoxic payloads and targeting 11 distinct antigens, are currently approved by the US Food and Drug Administration as of June 2025, representing a rapidly growing and highly promising class of anticancer therapeutics. Monomethyl auristatin E is the most frequently used payload (in five approved ADCs), followed by deruxtecan and calicheamicin. It is noted that ADCs using the same linker and payload often share similar PK and catabolism/metabolism characteristics, and thus providing opportunities for their streamlined development provided the applicant owns or has a right of reference of underlying data when it is necessary. In this review, we summarize the key clinical pharmacology considerations by payload class, using approved ADCs as case examples to support development and regulatory approval. We then compare the data and discuss how to leverage prior experience of ADCs, either qualitatively or quantitatively. These data and strategy insights will help researchers to integrate data from platform ADCs that share the same linker-payload and apply broader ADC-related insights, thereby accelerating future ADC developments.