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.