Study Assessing Safety and Efficacy of Combination of BL-8040 and Pembrolizumab in Metastatic Pancreatic Cancer Patients

Inclusion Criteria: 1. 18 years and older. 2. Patients must sign a written informed consent prior to entering the study. 3. Histologically confirmed (either previously or newly biopsied) metastatic unresectable pancreatic adenocarcinoma, including with intraductal papillary mucinous neoplasm. 4. Have measurable disease (≥ 1 measurable lesion) based on Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 as determined by the site study team. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. 5. Previous treatment lines 1. Cohort 1: Have documented objective radiographic progression after stopping treatment with first-line or further therapy, i.e. chemotherapy and or radiotherapy. Surgery not followed with neoadjuvant therapy will not be considered as first-line therapy. 2. Cohort 2: Have documented objective radiographic progression after stopping treatment with first-line, gemcitabine-based chemotherapy. Only primary metastatic patients will be allowed to participate. Patients with previous surgery for their pancreatic cancer will not be allowed to participate. 6. Willing to submit an evaluable tumor tissue sample, preferably from a liver metastasis, unless tumor is considered inaccessible or biopsy is otherwise considered not in the subject's best interest 7. Complete resolution of toxic effect(s) of the most recent prior chemotherapy to Grade 1 or less (except alopecia). If the subject received major surgery or radiation therapy of \> 30 Gy, they must have recovered from the toxicity and/or complications from the intervention. 8. Eastern Cooperative Oncology Group (ECOG) status ≤1. 9. Life expectancy of at least 3 months. 10. Adequate organ function at Baseline as defined below. All laboratory assessments should be performed within 10 days of treatment initiation 1. Hematological: * White blood cell (WBC) ≥ 2,500/mm\^3 * Absolute neutrophil count * Cohort 1: ≥ 1000 /mm\^3 * Cohort 2: ≥ 1500 /mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥9 g/dL or ≥5.6 mmol/L * Hematocrit ≥30% 2. Renal function: • 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 (CrCl) \> 60 mL/min for subject with creatinine levels \>1.5 x institutional ULN 3. Hepatic function: * Total Bilirubin: within institutional normal ranges * Aspartate Aminotransferase/Serum Glutamic Oxaloacetic Transaminase (AST/SGOT) and Alanine Transaminase/Serum Glutamic Pyruvic Transaminase (ALT/SGPT): ≤2.5 x ULN OR ≤5 x ULN for subjects with liver metastases 4. Coagulation: * International Normalized Ratio (INR) or PT: ≤1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants * Activated Partial Thromboplastin Time (aPTT): ≤1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants 11. Subjects must use effective contraception: 1. Female subjects must be of non-childbearing potential or, if of childbearing potential, must have a negative urine or serum pregnancy test within 72 hours prior to taking study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. The serum pregnancy test must be negative for the subject to be eligible. Non-childbearing potential is defined as (by other than medical reasons): * ≥45 years of age and has not had menses for over 2 years * Amenorrhoeic for \> 2 years without a hysterectomy and oophorectomy and a Follicle Stimulating Hormone (FSH) value in the postmenopausal range upon pretrial (Screening) evaluation * Post hysterectomy, bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation at least 6 weeks prior to Screening. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure otherwise the subject must be willing to use two adequate barrier methods throughout the study, starting with the Screening visit through 120 days after the last dose of study therapy. Information must be captured appropriately within the site's source documents 2. Male subjects must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. Exclusion Criteria: 1. Has a pancreatic tumor other than adenocarcinoma, including: acinar cell carcinoma, pancreaticoblastoma, malignant cystic neoplasms, endocrine neoplasms, squamous cell carcinoma, Vater and periampullary duodenal or common bile duct malignancies. 2. For Cohort 2 only: subjects with a bowel obstruction. 3. Has an active infection requiring systemic therapy or has an uncontrolled infection. 4. Has a known additional malignancy that is progressing or requires active treatment. Exceptions are adequately treated basal cell or squamous cell carcinoma that has undergone potentially curative therapy or carcinoma in situ of the cervix. 5. Has an underlying medical condition that would preclude study participation. 6. Has a disease that is suitable for therapy administered with curative intent. 7. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment. 8. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. 9. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at Baseline) from Adverse Event (AE) due to agents administered more than 4 weeks earlier. 10. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or has not recovered (i.e., ≤ Grade 1 or at Baseline) from AE due to a previously administered agent . 11. An active autoimmune disease that has required systemic treatment in the 2 years preceding the study (i.e., with the use of disease-modifying agents, corticosteroids or immunosuppressive drugs). Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed. 12. Has received transfusions of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including Granulocyte Colony Stimulating Factor (G-CSF), Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) or recombinant erythropoietin) within 4 weeks prior to study Day 1. 13. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis. 14. Has a history of interstitial lung disease. 15. O2 saturation \< 92% (on room air). 16. For both Cohorts: Has unstable angina, new onset angina within the last 3 months, myocardial infarction within the last 6 months, and current congestive heart failure New York Heart Association Class III or higher. For Cohort 2: has ventricular arrhythmias or uncontrolled blood pressure, or severe arterial thromboembolic events less than 6 months prior to study initiation. 17. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator. 18. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 19. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the Screening visit through 120 days after the last dose of trial treatment. Women with a positive pregnancy test within 72 hours from Baseline. 20. Has received prior therapy with an anti-Programmed Cell Death Protein 1 (PD-1), anti-Programmed Cell Death-Ligand 1 (PD-L1), or anti-(Programmed Cell Death-Ligand 2 (PD-L2) agent or if the subject has previously participated in Merck MK-3475 clinical trials. 21. Has a positive HIV test at Screening or at any time prior to Screening. Patients without a prior positive HIV test result will undergo an HIV test at Screening, unless not permitted per local regulations. 22. Has known active Hepatitis B (defined as having a positive Hepatitis B surface antigen (HBsAg) test at Screening) or Hepatitis C (defined as having a positive Hepatitis C Virus (HCV) antibody test or a positive HCV RNA test at Screening) 23. Has known history of Chronic Hepatitis B or C 24. Has received a live vaccine within 30 days of the planned start of study therapy. Seasonal flu vaccines that do not contain live virus are permitted. 25. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Note: Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging using the identical imaging modality for each assessment, either MRI or computerized tomography (CT) scan, for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to Baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 14 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. 26. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients. 27. Cohort 2: Has clinical ascites requiring treatment