Pembrolizumab and PEGPH20 in Treating Patients With Metastatic Pancreatic Cancer

PRIMARY OBJECTIVES: I. To assess the progression free survival duration of patients treated with the combination of pegylated recombinant human hyaluronidase PH20 (PEGPH20) and pembrolizumab. SECONDARY OBJECTIVES: I. To assess the safety and tolerability of the combination of PEGPH20 and pembrolizumab. EXPLORATORY OBJECTIVES: I. To evaluate objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) and Immune-Modified Response Evaluation Criteria in Solid Tumors (iRECIST) criteria, duration of response (DOR), disease control rate (DCR), time to progression (TTP) and progression-free survival (PFS) per RECIST and iRECIST as assessed by M.D. Anderson investigators and overall survival (OS) of the combination of pembrolizumab and PEGPH20. II. To explore the association between PD-L1 expression by immunohistochemistry (IHC), shed PD-L1 level, hyaluronan (HA) levels, somatic gene expression profiling and antitumor efficacy of the combination of pembrolizumab and PEGPH20 based on RECIST 1.1 as well as OS. III. To explore the relationship between genomic variation and response to study treatment. IV. To examine the effect of pembrolizumab and PEGPH20 on immune cell infiltration into tumor. V. To explore the effect of PEGPH20 on serum HA levels, and to compare changes in serum HA with clinical efficacy. VI. To determine the impact of the combination of pembrolizumab and PEGPH20 on circulating immune cells. OUTLINE: Patients receive pembrolizumab intravenously (IV) over 10 minutes on day 1 and pegylated recombinant human hyaluronidase PH20 subcutaneously (SC) on days 1, 8, and 15. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 9 and 12 weeks.