Transition of average drug-to-antibody ratio of trastuzumab deruxtecan in systemic circulation in monkeys using a hybrid affinity capture liquid chromatography-tandem mass spectrometry

Hiromi Habara; Hiromi Okamoto; Yoko Nagai; Masataka Oitate; Hideo Takakusa; Nobuaki Watanabe

doi:10.1002/bdd.2371

Transition of average drug-to-antibody ratio of trastuzumab deruxtecan in systemic circulation in monkeys using a hybrid affinity capture liquid chromatography-tandem mass spectrometry

Biopharm Drug Dispos. 2023 Oct;44(5):380-384. doi: 10.1002/bdd.2371. Epub 2023 Aug 3.

Authors

Hiromi Habara¹, Hiromi Okamoto¹, Yoko Nagai¹, Masataka Oitate¹, Hideo Takakusa¹, Nobuaki Watanabe¹

Affiliation

¹ Drug Metabolism & Pharmacokinetics Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan.

PMID: 37534716
DOI: 10.1002/bdd.2371

Abstract

Trastuzumab deruxtecan (T-DXd, DS-8201a) is an antibody-drug conjugate, comprising an anti-HER2 antibody at a drug-to-antibody ratio of 7-8 with the topoisomerase I inhibitor DXd. In this study, the concentrations of antibody-conjugated DXd and total antibody were determined and observed to decrease over time following intravenous administration of T-DXd to monkeys. The drug-to-antibody ratio of T-DXd also decreased in a time-dependent manner, which reached approximately 2.5 in 21 days after administration. It was suggested that antibody-conjugated DXd of T-DXd was relatively stable in vivo compared with that of other reported antibody-drug conjugates.

Keywords: antibody-conjugated DXd; antibody-drug conjugate (ADC); average drug-to-antibody ratio (average DAR); total antibody; trastuzumab deruxtecan (T-DXd, DS-8201a).