Pembrolizumab and Pelareorep in Treating Patients With Advanced Pancreatic Cancer

Inclusion Criteria

• •Patients must have histologically confirmed advanced (unresectable or metastatic) pancreatic adenocarcinoma, documented objective radiographic progression and have failed or not tolerated first-line therapy.
• •* Note: First-line therapy denotes systemic chemotherapy for advanced pancreatic adenocarcinoma. Only one line of therapy is permitted in this setting. Intolerant to first line therapy are patients that have developed \>= grade 3 adverse events related to first line therapy and treating physician deems continuing of systemic chemotherapy would be detrimental to patient.
• •Patients must have confirmation of an existing formalin-fixed paraffin-embedded (FPPE) tumor sample from archival tissue or from a fresh biopsy of a primary or metastatic lesion at baseline, either as a block or unstained slides for performance of correlative studies.
• •* Note: Patients must undergo a fresh biopsy if archival tissue is not available.
• •Patients must have measurable disease as defined by RECIST v 1.1.
• •Any major surgery (except biopsies) must have occurred at least 28 days prior to first day of study treatment.
• •Patients must have an Eastern Cooperative Oncology Group (ECOG) performance score =\< 1.
• •Patients must have a life expectancy of \>= 6 months.
• •Absolute neutrophil count (ANC) \>= 1,500 /mcL (with or without growth factor use).
• •Platelets \>= 100,000 / mcL.
• •Hemoglobin \>= 9 g/dL, OR \>= 5.6 mmol/L with (if clinically indicated)/without transfusion or erythropoietin \[EPO\] dependency).
• •Serum creatinine =\< 1.5 x upper limit of normal (ULN), OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) \>= 60 mL/min for subject with creatinine levels \> 1.5 x institutional ULN.
• •* (Note: creatinine clearance should be calculated per institutional standard.)
• •Serum total bilirubin =\< 1.5 x ULN, OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 x ULN.
• •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN, OR =\< 5 x ULN for subjects with liver metastases.
• •Albumin \>= 2.5 mg/dL.
• •International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 x ULN unless subject is receiving anticoagulant therapy. For patients on anticoagulant therapy, PT/INR must be within therapeutic range.
• •Activated partial thromboplastin time (aPTT) =\< 1.5 x ULN unless subject is receiving anticoagulant therapy. For patients on anticoagulant therapy, PT/INR must be within therapeutic range
• •Thyroid-stimulating hormone (TSH), thyroxine (T4) and corticotropin (ACTH) within normal range (prior to registration).
• •Proteinuria within institutional normal or =\< grade 1 OR urinary protein \< 1 g/24 hours (hr) (prior to registration).
• •Female subject of childbearing potential must have a negative urine or serum pregnancy within 7 days of registration. It is to be repeated on day 1 of study treatment, before infusion, if it is done greater than 3 days of day 1. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test is required. Female subjects of childbearing potential must be willing to use an adequate method of contraception (willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity), for the course of the study through 120 days after the last dose of study medication. Should a female patient become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• •* Note: A female of childbearing potential (FOCBP) is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• •* Has not undergone a hysterectomy or bilateral oophorectomy
• •* Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for \> 12 months).
• •Male subjects of childbearing potential must agree to use an adequate method of contraception or be surgically sterile or abstain from heterosexual activity, starting with the first dose of study therapy through 120 days after the last dose of study therapy.
• •Patients must have signed an informed consent indicating that the patient is aware of the neoplastic nature of their disease and have been informed of the procedures of the protocol, the experimental nature of the therapy, alternatives, potential benefits, side effects, risks, and discomforts.
• •Patients must be willing and able to comply with scheduled visits, the treatment plan, and laboratory tests.