Background: Hyaluronan (HA) can be a constituent of the tumor microenvironment (TME). Accumulation of HA in the TME may result in elevated interstitial pressure, vascular compression, hypoxia, and reduced drug delivery and immune cell access. Pegvorhyaluronidase alfa (PEGPH20; PVHA) enzymatically degrades HA, potentially increasing access and antitumor efficacy of cytotoxic and immuno-therapies. Liquid biopsies may provide a non-invasive approach to predict therapeutic efficacy of PVHA. Methods: Total plasma HA was analyzed as a pharmacodynamic biomarker for PVHA activity in HALO 109-202 (NCT01839487), a Phase 2, open-label, two-stage randomized study of PVHA + nab-paclitaxel + gemcitabine (PAG) vs AG only, in previously untreated patients with Stage IV metastatic PDAC. HA was measured with a liquid chromatography-tandem mass spectrometry (LC-MS/MS) disaccharide assay using baseline plasma samples from Stage 1 (n = 132) and Stage 2 (n = 128) of the study. Results: Lower baseline plasma HA values were significantly correlated with survival outcomes, predicting progression-free survival (PFS) benefit in PVHA-treated patients in Stages 1 and 2, and overall survival (OS) benefit in PVHA-treated patients in Stage 2 (Table). Conclusions: These results support further exploration of a liquid biopsy-based companion diagnostic (CDx) for predicting the therapeutic efficacy of PVHA.

CI, confidence interval; HR, hazard ratio; KM, Kaplan-Meier.