Exploration of the antibody-drug conjugate clinical landscape

The antibody-drug conjugate (ADC) field has undergone a renaissance, with substantial recent developmental investment and subsequent drug approvals over the past 6 y. 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.

Automated summary

The ADC field has experienced a renaissance with recent investment and regulatory approvals. A total of 260 ADCs have been tested in clinical trials for cancer treatment. This review focuses on FDA-approved ADCs (11), ADCs in clinical trials but not yet approved (164), and discontinued candidates (92). Analysis based on tumor antigen targeting, linker, payload choices, and clinical stage achieved is provided, with discussion on biologic engineering modifications that can improve therapeutic index and increase regulatory approvals.