Effect of imprime PGG on innate immune-activating pharmacodynamic changes in a phase I clinical study in healthy human volunteers.

33Background: Imprime PGG (Imprime) is currently in clinical development as combination therapy with checkpoint inhibitors. Imprime, a yeast-derived, soluble β-1,3/1,6 glucan is a Pathogen Associated Molecular Pattern (PAMP) that complexes with endogenous anti-beta glucan antibodies (ABA) and activates innate immune effector cells to trigger the anti-cancer immunity cycle. In this study, we sought to investigate the immunopharmacodynamic (IPD) responses of Imprime in healthy human subjects. Methods: Group 1 (n=12) received a single IV infusion of Imprime 4 mg/kg, Group 2 (n=12) received three weekly infusions of 4mg/kg Imprime. Group 3 (n=12) received infusions of 4 mg/kg or 2 mg/kg Imprime on weeks 1, 2 and 5. In groups 1 and 2, six subjects each received premedication with diphenhydramine 50 mg IV and dexamethasone 8 mg IV. IPD changes were measured at various times before, during and after Imprime administration. Results: Peak levels of complement activation products, C5a and SC5b-9 were detected at th...