Introduction

Introduction to T-DXd

T-DXd Was Designed With 7 Key Attributes
T-DXd is an ADC Composed of 3 Components

T-DXd Was Designed With 7 Key Attributes

Payload MOA: topoisomerase I inhibitor^1,2^,a
High potency of payload^1,2^,a
High drug-to-antibody ratio ≈ 8^1,2^,a
Payload with short systemic half-life^1,2^,a
Stable linker payload^1,2^,a
Tumor-selective cleavable linker^1,2^,a
Bystander antitumor effect^1,3^,a

^aThe clinical relevance of these features is under investigation.

T-DXd is an ADC Composed of 3 Components

T-DXd is an ADC Composed of 3 Components^1,2

A humanized anti-HER2 IgG1 mAb^1,2,4 with the same amino acid sequence as trastuzumab, covalently linked to a topoisomerase I inhibitor payload, an exatecan derivative, via a tetrapeptide-based cleavable linker^1,2

Abbreviations

ADC = antibody-drug conjugate

;

HER2 = human epidermal growth factor receptor 2

;

IgG = immunoglobulin G

;

mAb = monoclonal antibody

;

MOA = mechanism of action

;

T-DXd = trastuzumab deruxtecan

References

1. Nakada T, Sugihara K, Jikoh T, et al. The latest research and development into the antibody–drug conjugate, [fam-] trastuzumab deruxtecan (DS-8201a), for HER2 cancer therapy. Chem Pharm Bull (Tokyo). 2019;67(3):173-185.
2. Ogitani Y, Aida T, Hagihara K, et al. DS-8201a, a novel HER2-targeting ADC with a novel DNA topoisomerase I inhibitor, demonstrates a promising antitumor efficacy with differentiation from T-DM1. Clin Cancer Res. 2016;22(20):5097-5108.
3. Ogitani Y, Hagihara K, Oitate M, et al. Bystander killing effect of DS-8201a, a novel anti-human epidermal growth factor receptor 2 antibody-drug conjugate, in tumors with human epidermal growth factor receptor 2 heterogeneity. Cancer Sci. 2016;107(7):1039-1046.
4. Trail PA, Dubowchik GM, Lowinger TB. Antibody drug conjugates for treatment of breast cancer: novel targets and diverse approaches in ADC design. Pharmacol Ther. 2018;181:126-142.

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