October 2010 Halozyme scientists publish results of preclinical animal models showing that enzymatic depletion of tumor HA with PEGPH20 induces anti-tumor responses.
Study 101 investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of PEGPH20 as a single agent, and Study 102 investigated multiple dosing of PEGPH20 in combination with dexamethasone.
Results confirmed the expected mechanism of action of PEGPH20:
- HA plasma levels increased, in a dose-dependent manner, after PEGPH20 administration
- Tumor imaging from subsets of patients pre- and post-administration of PEGPH20 demonstrated that PEGPH20 treatment rapidly restored tumor perfusion and decreased metabolic activity in tumors
- Histochemical analysis of pre- and post-treatment tumor biopsies showed reduced HA staining after one cycle of treatment with PEGPH20
In this Phase 1b clinical study, PEGPH20 was given in combination with gemcitabine for the treatment of patients with untreated stage IV metastatic pancreatic cancer. The overall response rate (complete response + partial response) by RECIST 1.1 criteria was 42% (10 of 24 patients, 95% CI 22-62%) for those treated at therapeutic dose levels of PEGPH20 as assessed by an independent radiology review.
In an exploratory post-hoc analysis of a small subset of patients treated with PEGPH20 with available biopsy samples and HA scores, progression-free survival and overall survival were longer in patients with high levels of tumor HA compared to patients with low levels of tumor HA.
The observation that patients with tumors characterized by high levels of HA may respond better to PEGPH20 leads Halozyme to develop a companion diagnostic to enable pre-selection of these patients.
Ventana CDx IDE granted, allowing Halozyme to use the assay to prospectively identify HA-HIGH patients for study inclusion.