PEGPH20 Plus Nab-Paclitaxel Plus Gemcitabine Compared With Nab-Paclitaxel Plus Gemcitabine in Participants With Stage IV Untreated Pancreatic Cancer

A Phase 2, Randomized, Multicenter Study of PEGPH20 (PEGylated Recombinant Human Hyaluronidase) Combined With Nab-Paclitaxel Plus Gemcitabine Compared With Nab-Paclitaxel Plus Gemcitabine in Subjects With Stage IV Previously Untreated Pancreatic Cancer

This study is designed to compare the treatment effect of PEGPH20 combined with nab-paclitaxel (NAB) and gemcitabine (GEM) [PAG] to NAB and GEM [AG] in participants with Stage IV previously untreated pancreatic ductal adenocarcinoma (PDA).

The study will have 2 run-in phases, one for each formulation of PEGPH20 (original and new formulations), and a Phase 2 portion. The 2 run-in phases will evaluate the safety and tolerability of the PAG treatment using the original and new succinic acid PEGPH20 formulation, respectively, compared with AG treatment. Phase 2 will have 2 stages due to a partial clinical hold that occurred from April through July 2014. The participants will be randomized in 3:1 for the run-in phases. The first stage will randomize participants in a 1:1 ratio. The second stage will randomize participants in a 2:1 ratio (PAG:AG).

This is an open-label study. To minimize bias to the progression-free survival endpoint, disease progression will be based on the assessment of the Central Imaging Reader (CIR). Determination of clinical progression by the Investigator without corresponding CIR confirmation will be documented with the relevant signs and symptoms.

Key Inclusion Criteria:

• Signed Informed consent.
• Histologically confirmed Stage IV PDA with documented disseminated neoplasm to liver and /or lung. Must have archival or fresh tissue (block /slides) available pre-dose.
• One or more metastatic tumors measurable on computed tomography (CT) scan per RECIST v.1.1 , excluding the primary pancreatic lesion.
• No previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease.
• Karnofsky Performance Status greater than or equal to (≥) 70%.
• Life expectancy ≥3 months.
• Age ≥18 years.
• Screening laboratory values of hemoglobin, platelets, absolute neutrophil count (ANC), bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum creatinine, serum albumin, prothrombin time/international normalized ratio (INR), and partial thromboplastin time (PTT) within specified values/criteria per protocol prior to dosing.

Key Exclusion Criteria:

• Non-metastatic PDA.
• Evidence of deep vein thrombosis (DVT), pulmonary embolism (PE), or other known thromboembolic event present during screening period.
• Known central nervous system involvement or brain metastasis.
• New York (NY) Heart Association Class III or IV cardiac disease or myocardial infarction within the past 12 months.
• Prior history of cerebrovascular accident or transient ischemic attack.
• Pre-existing carotid artery disease.
• Active, uncontrolled bacterial, viral, or fungal infection requiring systemic therapy.
• Current use of megestrol acetate (use within 10 days of Day 1).
• Known infection with human immunodeficiency virus, Hepatitis B, or Hepatitis C.
• History of another primary cancer within the last 3 years with the exception of non-melanoma skin cancer, early state prostate cancer, or curatively-treated cervical cancer in-situ.
• Contraindication to heparin as per National Comprehensive Cancer Network (NCCN) guidelines.
• Previous major bleed (bleeding requiring transfusion of red blood cells) on low-molecular weight heparin (LMWH).
• Any other disease, metabolic dysfunction, physical examination finding or clinical laboratory finding that leads to reasonable suspicion of disease or condition that contraindicates the use of an investigational drug, that may affect interpretation of results, or render the participant at a high risk of treatment complications.