Activity of CBT-501, a novel humanized anti-PD-1 antibody, in a humanized genetically engineered mouse model of colon carcinoma.

108Background: CBT-501 (Genolimzumab, GB-226) is a novel humanized mAb (IgG4k) against human Programmed Death-1 (PD-1). CBT-501 demonstrated highly specific binding to PD-1 of human (KD= 505 pM) and cynomolgus (KD= 7.2 nM). It did not completely block the binding of nivolumab or pembrolizumab, suggesting a novel epitope. CBT-501 efficiently inhibited the binding of PD-L1/L2 to PD-1 through a competitive action for both human and monkey. It enhanced human T-cell activation in the Mix Lymphocyte Reaction (MLR), as shown by increased release of IL-2 and INF-γ. The Fc-fragment bound to FcRn dose-dependently without any effector function. The PK/PD studies in cynomolgus showed a linear dose exposure, with a T1/2of 115-142 h for single and repeat dosing. The PD-1 receptor occupancy after a single dose was dose-dependent reaching 100% at peak, maintained after multiple dosing and continued for 6 wk after last dose. Single and repeat dose toxicology studies in cynomolgus showed weight gain of the thyroid and mild...