Quantitative approaches to drug development

Consolidated insights from academia, industry, and service providers on the topic of in vitro–in vivo correlation/relationship (IVIVC/R) models, including physiologically based biopharmaceutics modeling (PBBM), and their importance in pharmaceutical development and regulatory decision-making. These modeling approaches are transforming drug development by linking biopharmaceutical properties directly to clinical performance. They help accelerate timelines, reduce the need for costly experimental studies and clinical trials, and provide solid justification for regulatory decisions — especially around drug formulation questions.

Datopotamab deruxtecan (Dato-DXd) is a trophoblast cell surface antigen 2 (TROP2) -directed antibody-drug conjugate (ADC) developed for advanced or metastatic solid tumors, including certain types of breast cancer and non-small cell lung cancer. This study introduces the first population PK model for Dato-DXd, which semi-mechanistically links the pharmacokinetics of the ADC to its potent payload, DXd. The results support the rationale for weight-based dosing and validate the key clinical pharmacology label claim for Dato-DXd. The knowledge gained from this work will inform the dosing strategies for future Dato-DXd clinical studies.