A model-based dose selection and pharmacokinetic (PK) bridging approach was applied to support development of pembrolizumab SC (pembrolizumab with berahyaluronidase alfa for subcutaneous administration) from intravenous (IV) administration. Methodology, results and conclusions will be discussed in this presentation. The MIDD Webinar Series, coordinated by Yash Kapoor and Fulya Akpinar Singh, is a series of webinars focused on shaping the future of drug development and regulatory decision-making sponsored by the ISoP Education Committee. Topics range from MIDD approaches in regulatory submission to pharmacometrics topics that are at the core of model development.

Pediatric dose optimization is constrained by small cohorts and sampling limits. We applied Bayesian Forecasting to select the RP2D for pediatric patients with ALK-fusion tumors. An established PopPK model using adult data as prior in combination with real-time PK monitoring during Cycle 1 guided dose confirmation and/or adjustments. Doses were selected to match the adult steady-state therapeutic exposures. Model‑predicted doses achieved target exposure without adjustment in all 14 patients ≥20kg; 4/5 patients

IVIG co-administration with monoclonal-antibodies/bispecifics is common across autoimmunity, immunodeficiencies, and transplantation. These therapies undergo FcRn-mediated recycling, raising potential for PK-PD interactions. Mechanistic IgG-disposition model utilized to investigate how IVIG dose/timing, and IgG dynamics influence IgG behavior and PK/PD outcomes. Model well-described total/endogenous-IgG kinetics across autoimmune/transplantation. It recapitulated reduced tesidolumab exposure with IVIG in transplantation, explaining associated PD alterations. Model examined IVIG supplementation in multiple-myeloma receiving teclistamab, and rituximab-IVIG co-therapy for transplant desensitization. Simulations revealed IVIG co-therapy alters mAb PK-PD depending on IVIG-regimen, IgG-pool and exposure-response-relationship of the mAb. Model provides mechanistic framework for MIDD and prospective management of IgG interactions. The MIDD Webinar Series, coordinated by Yash Kapoor and Fulya Akpinar Singh, is a series of webinars focused on shaping the future of drug development and regulatory decision-making sponsored by the ISoP Education Committee. Topics range from MIDD approaches in regulatory submission to pharmacometrics topics that are at the core of model development.