Model-informed drug development for immuno-oncology agonistic anti-GITR antibody GWN323: Dose selection based on MABEL and biologically active dose.

ABSTRACT: GWN323, an agonistic human anti-GITR (glucocorticoid-induced TNFR-related protein) IgG1 antibody, was studied clinically as an immuno-oncology therapeutic agent. A model-based minimum anticipated biological effect level (MABEL) approach integrating in vitro and in vivo data informed dose selection for the first-in-human (FIH) study. Data evaluated included pharmacokinetics (PK) of DTA-1.mIgG2a (mouse surrogate GITR antibody for GWN323), target-engagement pharmacodynamic (PD) marker soluble GITR (sGITR), tumor shrinkage in Colon26 syngeneic mice administered with DTA-1.mIgG2a, cytokine release of GWN323 in human peripheral blood mononuclear cells, and GITR binding affinity. A PK model was developed to describe DTA-1.mIgG2a PK, and its relationship with sGITR was also modeled. Human GWN323 P

SUBMITTER: Ji Y 

PROVIDER: S-EPMC9468570 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature