Exploration of the antibody–drug conjugate clinical landscape

Abstract

ABSTRACTThe antibody–drug conjugate (ADC) field has undergone a renaissance, with substantial recent developmental investment and subsequent drug approvals over the past 6 years. In November 2022, ElahereTM became the latest ADC to be approved by the US Food and Drug Administration (FDA). To date, over 260 ADCs have been tested in the clinic against various oncology indications. Here, we review the clinical landscape of ADCs that are currently FDA approved (11), agents currently in clinical trials but not yet approved (164), and candidates discontinued following clinical testing (92). These clinically tested ADCs are further analyzed by their targeting tumor antigen(s), linker, payload choices, and highest clinical stage achieved, highlighting limitations associated with the discontinued drug candidates. Lastly, we discuss biologic engineering modifications preclinically demonstrated to improve the therapeutic index that if incorporated may increase the proportion of molecules that successfully transition to regulatory approval.

Keywords

• Antibody–drug conjugate
• ADC
• payload
• linker
• drug-to-antibody ratio
• site-directed conjugation