Question of the Day 05-21-25

Which of the following best characterizes the drug-to-antibody ratio (DAR) of trastuzumab deruxtecan?

A. Low DAR = 2 with non-cleavable linker

B. DAR = 3.5 with disulfide linker

C. DAR = 4 with valine-citrulline linker

D. High DAR = 8 with cleavable tetrapeptide linker

E. Variable DAR adjusted by dose level

Answer: D

Explanation:

Trastuzumab deruxtecan (Enhertu®) is accurately characterized by a high drug-to-antibody ratio (DAR) of approximately 8, with its deruxtecan payload (a topoisomerase I inhibitor) attached via an enzymatically cleavable tetrapeptide-based linker (Answer D); this design aims for high potency and payload release within tumor cells.

The other options describe different antibody-drug conjugates (ADCs) or incorrect principles: ado-trastuzumab emtansine (T-DM1) has an average DAR of ~3.5 and a non-cleavable thioether linker (related to A); mirvetuximab soravtansine features an average DAR of ~3.4 and a cleavable disulfide linker (B); and ADCs like tisotumab vedotin often have a DAR of ~4 with a cleavable valine-citrulline linker (C).

Importantly, the DAR is a fixed structural characteristic of an ADC and is not variably adjusted based on patient dosing factors (making E incorrect).

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