A Mechanistic Physiologically‐Based Pharmacokinetic Platform Model to Guide Adult and Pediatric Intravenous and Subcutaneous Dosing for Bispecific T Cell Engagers

Bispecific T cell engagers (Bi‐TCEs) have revolutionized the treatment of oncology indications across both liquid and solid tumors. Bi‐TCEs are rapidly evolving from conventional intravenous (i.v.) to more convenient subcutaneous (s.c.) administrations and extending beyond adults to also benefit pediatric patients. Leveraging clinical development experience across three generations of Bi‐TCE molecules across both liquid and solid tumor indications from i.v./s.c. dosing in adults and pediatric subjects, we developed a mechanistic‐physiologically‐based pharmacokinetic (PBPK) platform model for Bi‐TCEs. The model utilizes a full PBPK model framework and was successfully validated for PK predictions following i.v. and s.c. dosing across both liquid and solid tumor space in adults for eight Bi‐TCEs. After refinement to incorporate physiological ontogeny, the model was successfully validated to predict pediatric PKs in 1 month –