DESTINY-Breast03 Phase 3 Study Results
Patritumab Deruxtecan (HER3-DXd)
•
HER3-DXd is an ADC with 3 components 1-6:
•
•
A fully human anti-HER3 IgG1 mAb (patritumab), covalently linked to
A topoisomerase I inhibitor payload, an exatecan derivative, via
A tetrapeptide-based cleavable linker
7 Key Attributes of HER3-DXd
Payload mechanism of action:
topoisomerase I inhibitor a,1-4
High potency of payload a,1-4
Human anti-HER3
IgG1 mAb1-4
Deruxtecan 1-4
High drug to antibody ratio = 8
a,1,2
Payload with short systemic half-life a,b,2,3
NH
H
Stable linker-payload a,2-4
H3C-
HO-CH3
Cleavable Tetrapeptide-Based Linker
Tumor-selective cleavable linker a,1-5
Topoisomerase I Inhibitor Payload
(DXd)
Bystander antitumor effect a,2,6
HER, human epidermal growth factor receptor; IgG1, immunoglobulin G1; mAb, monoclonal antibody.
a The clinical relevance of these features is under investigation. b Based on animal data.
1. Hashimoto Y, et al. Clin Cancer Res. 2019;25:7151-7161. 2. Nakada T, et al. Chem Pharm Bull (Tokyo). 2019;67(3):173-185. 3. Ogitani Y, et al. Clin Cancer Res. 2016;22(20):5097-5108. 4. Koganemaru S, et al.
Mol Cancer Ther. 2019;18:2043-2050. 5. Haratani K, et al. J Clin Invest. 2020;130(1):374-388. 6. Ogitani Y, et al. Cancer Sci. 2016;107(7):1039-1046.
ASCO 2022 #1002 Oral
Daiichi-Sankyo
83View entire presentation