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 of integrating advanced modeling techniques into the dose optimization paradigm.
Tang et al. (Sun,) studied this question.