[SS09] Enhancing Drug Development and Patient Care through Model Informed Drug Development

[SS09-03] QSP modeling platform for ADCs: a virtual population pipeline for ADC portfolio comparison

*Pei Luo¹, Katie Link², Bruna Scheuher², Mary E. Spilker², Mike G. Zager², Blerta Shtylla² (1. Pfizer Development China (China), 2. Pfizer Research & Development (United States of America))

Keywords:

ADC,QSP,Virtual Population

Antibody drug conjugates (ADCs) are typically composed of a monoclonal antibody (mAb) backbone covalently attached to a cytotoxic drug known as payload via a chemical linker. Since 1980s, ADCs have arisen in the oncology field from the concept of “magic bullet” by 1908 Nobel laureate Paul Ehrlich. ADCs combine both the advantages of highly specific targeting ability of the antibody with the highly potent killing mechanism of the payload to eliminate cancer cells. To support key decisions regarding dose regimen/schedule optimization & combination therapy assessment, trial design and special populations, we leveraged a published quantitative systems pharmacology (QSP) model to capture ADCs disposition and efficacy in humans [1]. We developed a retrospective virtual population by matching the QSP model output to progression free survival (PFS) and best percentage change in sum of diameters from baseline of phase 2 DESTINY-Breast01 patients following administration of T-DXd [2]. Here, we present a virtual population pipeline which can be leveraged together with published summary data to support ADC portfolio evaluation.

[1] Scheuher, B. et al. (2023) J of Pharmacokin and Pharmacody.
[2] Modi, S. et al. NEMJ 382.7 (2020): 610-621.