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

Inclusion Criteria

• 18 years and older.
• Patients must sign a written informed consent prior to entering the study.
• Histologically confirmed (either previously or newly biopsied) metastatic unresectable pancreatic adenocarcinoma, including with intraductal papillary mucinous neoplasm.
• 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.
• Previous treatment lines
• 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.
• 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.
• 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
• 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.
• Eastern Cooperative Oncology Group (ECOG) status ≤1.
• Life expectancy of at least 3 months.
• Adequate organ function at Baseline as defined below. All laboratory assessments should be performed within 10 days of treatment initiation
• 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%
• 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
• 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
• 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
• Subjects must use effective contraception:
• 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