Optimal Dosage Justification for Datopotamab Deruxtecan in HR-Positive/HER2-Negative Breast Cancer Through Model-Informed Drug Development Approaches.

ABSTRACT: Project Optimus has been reforming the dose selection and optimization paradigm in oncology. In this context, model-informed drug development (MIDD) approaches were utilized to validate the optimal dose selection of 6 mg/kg every 3 weeks (Q3W) for datopotamab deruxtecan (Dato-DXd) in patients with HR-positive/HER2-negative breast cancer (HR+/HER2- BC). A Tumor Growth Inhibition (TGI)-Progression-Free Survival (PFS) modeling framework was developed to assess the relationship between Dato-DXd PK exposure, tumor dynamics, and PFS, and support virtual trial simulations at different Dato-DXd dose levels. Simulations suggested that Dato-DXd at 6 mg/kg Q3W provide superior tumor control and improved PFS compared to a lower dose in patients with HR+/HER2- BC. This work underscores the importance o

SUBMITTER: Tang Z 

PROVIDER: S-EPMC12906696 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature