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Optimal Dosage Justification for Datopotamab Deruxtecan in HR-Positive/HER2-Negative Breast Cancer Through
Zoey Tang1, KyoungSoo Lim1, Yu Jiang1
1Clinical Pharmacology and Quantitative Pharmacology, AstraZeneca, Gaithersburg, Maryland, USA.
Clinical and Translational Science
|February 15, 2026
Summary
Model-informed drug development validated the 6 mg/kg dose of datopotamab deruxtecan (Dato-DXd) every 3 weeks for HR+/HER2- breast cancer, showing improved tumor control and progression-free survival.
Area of Science:
- Oncology
- Pharmacometrics
- Clinical Pharmacology
Background:
- Project Optimus is advancing dose selection and optimization in oncology.
- Model-informed drug development (MIDD) is crucial for validating drug dosages.
Purpose of the Study:
- To validate the optimal dose of 6 mg/kg every 3 weeks (Q3W) for datopotamab deruxtecan (Dato-DXd).
- To support patients with HR-positive/HER2-negative breast cancer (HR+/HER2- BC).
Main Methods:
- Utilized MIDD approaches.
- Developed a Tumor Growth Inhibition (TGI)-Progression-Free Survival (PFS) modeling framework.
- Conducted virtual trial simulations at various Dato-DXd dose levels.
Main Results:
- Simulations indicated that 6 mg/kg Q3W Dato-DXd offers superior tumor control.
- The 6 mg/kg Q3W dose demonstrated improved PFS compared to lower doses in HR+/HER2- BC patients.
- Established a relationship between PK exposure, tumor dynamics, and PFS.
Conclusions:
- The 6 mg/kg Q3W dose of Dato-DXd is validated as optimal for HR+/HER2- BC.
- Highlights the significance of advanced modeling in dose optimization.
- Emphasizes the role of MIDD in oncology drug development.
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