Using Virtual Patients to Evaluate Dosing Strategies for Bispecifics With a Bell-Shaped Efficacy Curve.

ABSTRACT: Bispecific antibodies can be broadly divided into two categories: those that are pharmacologically active as either dimers bound to a single target or as trimers bound to both targets, and those that are only active as trimers. Dose selection of trimer-based bispecifics poses a unique challenge, as toxicity increases with dose, but efficacy does not. Instead, trimer-driven bispecifics have a bell-shaped efficacy curve, for which both under- and over-dosing can cause a decrease in efficacy. To address the challenge of dose selection for trimer-based bispecifics, we develop a semi-mechanistic pharmacokinetic/pharmacodynamic model of one such bispecific, teclistamab. By introducing variability in key patient-specific parameters, we find that the currently selected phase II recommended dose of

SUBMITTER: Gevertz JL 

PROVIDER: S-EPMC12706419 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature