The Study of Gemcitabine Plus Nab-Paclitaxel in Combination With Pegvorhyaluronidase Alfa (PVHA; PEGPH20) and Pembrolizumab as Front-line Treatment for Metastatic Pancreatic Adenocarcinoma.

Inclusion Criteria: * Male/female participants who are at least 18 years of age on the day of signing informed consent with an untreated metastatic histologically confirmed diagnosis of stage IV pancreatic ductal adenocarcinoma will be enrolled in this study. * Male participants: A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period. * Female participants: A female participant is eligible to participate if she is not pregnant not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 A WOCBP who agrees to follow the contraceptive guidance in during the treatment period and for at least 120 days after the last dose of study treatment. * The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. Patients or their legally authorized representative must be informed of the investigational nature of this study. * Measurable disease on computed tomography (CT) scan and/or MRI per RECIST 1.1 criteria. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. * Willing to undergo a pre-treatment core or excisional biopsy of a tumor lesion not previously irradiated, except for patients with 15 FFPE unstained slides of tumor tissue where a pre-treatment biopsy is optional. If 15 FFPE unstained slides are unavailable a pre-treatment biopsy is only mandatory if it can be obtained via a non-significant risk procedure. Significant risk procedures include (but are not limited to) biopsies of the brain, lung / mediastinum, pancreas, or endoscopic procedures extending beyond the esophagus, stomach, or bowel. Any biopsy via significant risk procedure is optional. For patients who pursue an optional biopsy when a non-significant risk biopsy is possible the optional biopsy will serve as the pre-treatment tissue sample. Biopsy requirements are further outlined in section 7.1.2.7. * Willing to undergo an on-treatment core or excisional tumor biopsy at week 8 (for the first 20 evaluable patients). Biopsy risk requirements for on-treatment biopsies are the same as the pre-treatment biopsy and outlined above and in section 7.1.2.7. * Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to day 1 of treatment. . * Has a life expectancy of ≥ 20 weeks. * Has adequate organ function as defined in the following table (Table 1). Specimens must be collected within 10 days prior to the start of study treatment. Exclusion Criteria: * A WOCBP who has a positive urine pregnancy test within 72 hours prior to the first dose of study treatment (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. * Has received any prior systemic anti-cancer therapy including investigational agents for their metastatic pancreatic ductal adenocarcinoma prior to the first dose of study treatment. This includes any patients that have progressed ≤ 6 months of adjuvant therapy. Note: Participants must have recovered from all Adverse Events (AE) due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible. Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment. * Has received any prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX40, CD137). * Has received prior radiotherapy for metastatic pancreatic ductal adenocarcinoma prior to the first dose of study treatment. * Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. * Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. * Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. * Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. * Has known history of Central Nervous System (CNS) metastases and/or carcinomatous meningitis, regardless of whether or not they have been treated. * Has severe hypersensitivity (≥Grade 3) to gemcitabine, nab-paclitaxel, PVHA or pembrolizumab and/or any of their excipients. * Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. * Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. * Has an active infection requiring systemic therapy. * Has a known history of Human Immunodeficiency Virus (HIV). * Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (HCV) (defined as detectable HCV RNA) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority. * Liver cirrhosis. * Has a known history of active TB (Bacillus Tuberculosis). * Is currently using megestrol acetate or megestrol acetate containing drugs within 10 days of registration. * Has a history of cerebrovascular accident (CVA), transient ischemic attack (TIA) or carotid artery disease requiring intervention / treatment. * Has New York Heart Association Class III or IV cardiac disease (Appendix 5) or myocardial infarction within the past 12 months. * Has known allergy to hyaluronidase. * Has clinical evidence of Deep Vein Thrombosis (DVT), PE or known thromboembolic event present during the screening period. 1. Subjects with superficial vein thrombosis are eligible. 2. Subjects with visceral/splanchnic vein thrombosis are still eligible, if in the opinion of the investigator, the visceral/splanchnic vein thrombosis is primarily associated with the anatomic location of the underlying disease of metastatic pancreatic cancer. * Active bleeding issues or a pathologic condition that is associated with high risk of bleeding. * Unable to tolerate low-molecular weight heparin 1 mg/kg as prophylaxis. * Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. * Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.