Baseline Plasma Ha In Pda Versus Healthy Subjects And Effects Of Pegph2o On Plasma Ha In Pda Subjects Treated With Gem/Nab.

e15699Background: PEGylated recombinant human hyaluronidase (PEGPH20) degrades stromal and tissue hyaluronan (HA) in preclinical pancreatic ductal adenocarcinoma (PDA) models. From an ongoing phase 2 randomized study in subjects with Stage IV PDA treated with PEGPH20, gemcitabine (GEM) and nab-paclitaxel (NAB), we report plasma HA disaccharide concentrations at baseline and post PEGPH20 to evaluate: 1) differences in baseline plasma HA as compared to healthy volunteers, and 2) the kinetics of HA changes post PEGPH20. Methods: Baseline plasma HA from 68 PDA subjects and 24 healthy volunteers was compared using an unpaired Student’s t-test. The entire plasma HA time course of each subject in the phase 2 study was modeled using Non-Linear Mixed Effect modeling (NLME). The dynamics of plasma HA was captured with an indirect response model with zero order input and saturable output from the plasma compartment. Changes to plasma HA post dosing were driven by the enzymatic activity of the recombinant human hyalu...