DESTINY-Breast03 Phase 3 Study Results
T-DXD MOA, Bystander Effect, and Rationale for
Targeting HER2-low mBC
T-DXd1,2
1
T-DXd binds
to HER2
Tumor Cell
8:1 drug-to-
antibody ratio
2
T-DXd
internalized
Highly potent
topoisomerase I
Cleavable linker
inhibitor payload
3 Linker cleaved,
releasing
topoisomerase I
inhibitor
5 Tumor
cell death
Daiichi-Sankyo
DESTINY-Breast04
Neighboring
Tumor Cell
4 Topoisomerase I
inhibitor enters
nucleus
6 Membrane-
permeable
payload results
in bystander
effect
Internalization of T-DXd leads to release of the DXd
payload and subsequent cell death in the target tumor cell
and neighboring tumor cells through the bystander effect1,2
T-DXd
HER2 protein
Topoisomerase I inhibitor payload
Adapted with permission from Modi S, et al. J Clin Oncol 2020;38:1887-96. CC BY ND 4.0.
·
Results from a phase 1b study have reported efficacy of T-DXd in heavily pretreated patients
(N = 54) with HER2-low mBC, with a mPFS of 11.1 months and an ORR of 37.0%³
HER2, human epidermal growth factor receptor 2; MOA, mechanism of action; mBC, metastatic breast cancer; mPFS, median progression-free survival; ORR, objective response rate; T-DXd, trastuzumab deruxtecan.
1. Nakada T, et al. Chem Pharm Bull. 2019;67:173-185. 2. Ogitani Y, et al. Clin Cancer Res. 2016;22:5097-5108. 3. Modi S, et al. J Clin Oncol. 2020;38:1887-1896.
ASCO 2022 #LBA3 Plenary Session
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