Study of Gemcitabine + PEGPH20 vs Gemcitabine Alone in Stage IV Previously Untreated Pancreatic Cancer

PEGPH20 is a PEGylated version of human recombinant PH20 hyaluronidase that, in preclinical
studies, has been shown to remove HA from the extracellular matrix surrounding tumor cells by
depolymerizing this substrate. 87% of pancreatic ductal adenocarcinomas (PDA) overexpress HA.
PDA tumor tissue may be especially sensitive to the HA-degradation properties of PEGPH20 and
thus more responsive to the cytotoxic effects of a given dose of gemcitabine. Modifying the
extracellular environment to increase the penetration and efficacy of anti-cancer agents
represents a novel approach to treating pancreatic cancer and may provide important
therapeutic outcomes in patients with Stage IV Previously Untreated Pancreatic Cancer.

This Phase 1B/2 study will assess safety, tolerability, treatment effect, and various PK/PD
endpoints.

Key Inclusion Criteria:

- Patients with histologically confirmed Stage IV adenocarcinoma of the pancrease
previously untreated for metastatic disease

- One or more metastatic tumors measurable on CT scan per RECIST 1.1 criteria

- Life expectancy of at least 3 months

- Signed, written IRB/EC-approved informed consent

- A negative serum pregnancy test, if female

Key Exclusion Criteria:

- Known brain metastasis

- New York Heart Association Class III or IV cardiac disease, myocardial infarction
within the past 12 months

- Active, uncontrolled bacterial, viral, or fungal infection requiring systemic therapy

- Known allergy to hyaluronidase

- Women currently pregnant or breast feeding