A Trial of PEGPH20 in Combination With Avelumab in Chemotherapy Resistant Pancreatic Cancer

Key Inclusion Criteria: * Signed, written IRB/IEC-approved Informed Consent Form * Histologically or cytologically-confirmed pancreatic ductal adenocarcinoma (PDAC). * Accessible tumor for two repeated tumor biopsies. * Progression to first line treatment for locally advanced or advanced disease. Prior adjuvant chemotherapy or chemoradiation therapy for early disease is allowed. * Age ≥18 years. * Radiologically measurable disease per RECIST v1.1. * Performance-status ECOG 0 -2. * Life expectancy ≥ 3 months. * Resolved acute effects of any prior therapy to baseline or Grade ≤1 severity * Screening laboratory: 1. Hematologic: ANC ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin ≥ 9 g/dL 2. Hepatic: Total bilirubin level ≤ 1.5 × the ULN range and AST and ALT levels ≤ 2.5 × ULN or AST and ALT levels ≤ 5 X ULN (for subjects with documented metastatic disease to the liver) 3. Renal: Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula or serum creatinine ≤ 2.0 mg/dL. 4. Albumin ≥2.5 g/dL. 5. Coagulation: PT time and INR within normal limits (+/-15%). PTT within normal limits (+/-15%). * If a subject requires anticoagulation, treatment must be modified to enoxaparin. * Negative serum pregnancy test if female subject is of childbearing potential. * Patients who are willing and able to comply with scheduled visits, treatment plans, laboratory tests, biopsies when required, and other procedures. Exclusion Criteria: * Clinical evidence of DVT, PE, prior history of CVA or history of TIA within 12 months or other known TE event present during the screening period * Current use of megestrol acetate (use within 10 days of Day 1). * Contraindication to heparin as per institutional guidelines. * Another primary cancer within the last 3 years currently requiring antineoplastic treatment within the exception of non-melanoma skin cancer, early-stage prostate cancer, or curatively treated cervical carcinoma in-situ. * Current use of immunosuppressive medication within 2 weeks of study participation, EXCEPT for those listed in protocol * Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent: Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible. * Prior organ transplantation including allogenic stem-cell transplantation. * Active infection requiring systemic therapy. * Known infection with human immunodeficiency virus, Hepatitis B, or Hepatitis C * Known prior severe hypersensitivity to investigational product, hyaluronidase, or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3). * Any history of anaphylaxis or uncontrolled asthma (that is, 3 or more features of partially controlled asthma). * Clinically significant (i.e., active) cardiovascular disease: myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication. * Prior cerebrovascular accident/stroke. * Clinically significant carotid artery disease (e.g. prior carotid surgery, symptomatic and/or requires treatment) * Inability to comply with study and follow-up procedures as judged by the Investigator. * Known alcohol or drug abuse.