Pembrolizumab and BL-8040 in Metastatic Pancreatic Cancer

Study Drug Administration:

Cycle 1 is 14 days (2 weeks). Cycles 2 and beyond are 21 days (3 weeks).

If you are found to be eligible to take part in this study, on Days 1-5 and 8-12 of Cycle 1,
you will receive BL-8040 as an injection under the skin. After Cycle 1, you will receive
BL-0840 on Days 1, 4, 8, and 11 of each cycle. You will not receive BL-08040 during Days
15-21.

On Day 1 of Cycles 2 and beyond, you will receive pembrolizumab by vein over about 30
minutes. You will not receive pembrolizumab during Cycle 1.

You will be given standard drugs (such as hydrocortisone and diphenhydramine) to help
decrease the risk of side effects. You may ask the study staff for information about how the
drugs are given and their risks.

Length of Treatment:

You may receive pembrolizumab and BL-8040 for about 1 year. You will no longer be able to
receive treatment if the disease gets worse, if intolerable side effects occur, or if you are
unable to follow study directions.

Study Visits:

On Days 1 and 8 of each cycle:

- You will have a physical exam.

- Blood (about 1 tablespoon) will be drawn for routine tests.

Before each dose of BL-8040, blood (about 1 tablespoon) will be drawn for routine tests.

One (1) time during Week 4 and every 3 weeks after that:

°Blood (about 1 tablespoon) and urine will be collected for routine tests.

On Days 1 and 4 of Week 1 and then one (1) time during Weeks 3 and 6, and if the disease
appears to be responding to the study drugs, blood (about 5 tablespoons) will be drawn for
biomarker and tumor marker testing.

During Week 6, you will have a tumor biopsy to learn if the study drug has had any affect on
the disease. The study doctor will discuss with you what type of biopsy you will have.

Every 9 weeks, you will have an MRI or CT scan.

End-of-Treatment Visit:

Within 1 week after your last dose of study drugs:

- You will have a physical exam.

- You will have a CT or MRI to check the status of the disease.

- Blood (about 5 tablespoons) will be drawn for routine, tumor marker, and biomarker
testing.

Follow-Up Visits:

About 30 days after the last dose of study drugs, you will be called by a member of the study
staff to ask how you are doing and if you have had any side effects. This call should last
about 5-10 minutes.

About every 10 weeks after your last dose of study drugs, you will have a CT scan or MRI and
a physical exam. This will continue unless the disease gets worse or you start a new
anti-cancer treatment.

Every 12 weeks, you will be called by a member of the study staff to ask how you are doing.
Each call should last about 5-10 minutes. You will continue to have these calls unless you
withdraw from the study or the study ends, whichever happens first.

Inclusion Criteria:

1. Have histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma
based on pathology report

2. Be willing and able to provide written informed consent for the trial.

3. Be =/> 18 years of age on day of signing informed consent.

4. Have measurable disease based on RECIST 1.1 Target lesions situated in a previously
irradiated area are considered measurable if progression has been demonstrated in such
lesions.

5. Have documented objective radiographic progression after stopping treatment with
first-line therapy and have not yet begun second line therapy. Note: the same image
acquisition and processing parameters should be used throughout the study for a given
subject.

6. Be willing to provide tissue from a newly obtained core or excisional biopsy of a
tumor lesion from a metastatic site. Newly-obtained is defined as a specimen obtained
up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom
newly-obtained samples cannot be provided (e.g. inaccessible or subject safety
concern) may submit an archived specimen only upon agreement from Merck. The specimen
must be from a biopsy site that would be accessible for at least one subsequent biopsy
after initiation on the trial.

7. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
Performance Scale.

8. Have a predicted life expectancy of greater than 3 months.

9. Demonstrate adequate organ function defined as follows: (All screening labs should be
performed within 10 days of treatment initiation); a) Hematological - Absolute
neutrophil count (ANC) =/>1,000/mcL, Platelets =/>100,000 / mcL, Hemoglobin =/>9 g/dL
or =/>5.6 mmol/L without transfusion or EPO dependency (within 14 days of assessment);
b) Renal - Serum creatinine OR Measured or calculated creatinine clearance (should be
calculated per institutional standard) (GFR can also be used in place of creatinine or
CrCl) =/<1.5 X upper limit of normal (ULN) OR =/>60 mL/min for subject with creatinine
levels =/< 1.5 X institutional ULN; c) Hepatic - Serum total bilirubin =/< ULN OR
Direct bilirubin =/< ULN for subjects with total bilirubin levels > ULN, AST (SGOT)
and ALT (SGPT) =/< 1.5 X ULN, Albumin =/>3.3 mg/dL in the absence of dehydration

10. (Continuation of criteria # 9) d) Coagulation International Normalized Ratio (INR) or
Prothrombin Time (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. Have a negative urine or serum pregnancy test within 72 hours prior to receiving the
first dose of study medication (Cycle 1, Day 1) (female subjects of childbearing
potential). If the urine test is positive or cannot be confirmed as negative, a serum
pregnancy test will be required.

12. Female subjects of childbearing potential must be willing to use an adequate method of
contraception. Contraception, for the course of the trial through 120 days after the
last dose of trial drug. Note: Abstinence is acceptable if this is the usual lifestyle
and preferred contraception for the subject. Male subjects of childbearing potential
must agree to use an adequate method of contraception. Contraception, starting with
the first dose of trial therapy through 120 days after the last dose of trial therapy.

Exclusion Criteria:

1. Has 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. Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy, herbal/complementary oral or
IV medicine, or used an investigation device within 4 weeks of the first dose of
treatment.

3. 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.

4. Had a solid organ or hematologic transplant.

5. Has active autoimmune disease that has required systemic treatment in past 2 years
(i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive
drugs). 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.

6. Has a diagnosed additional malignancy within 1 year prior to first dose of study
treatment with the exception of curatively treated basal cell carcinoma of the skin,
squamous cell carcinoma of the skin and/or curatively resected in situ cervical and/or
breast cancers.

7. Has radiographically detectable (even if asymptomatic and/or previously treated)
central nervous system (CNS) metastases and/or carcinomatous meningitis as assessed by
PI and radiology review.

8. Subjects excluded if there is a history of (non-infectious) pneumonitis that required
steroids, evidence of interstitial lung disease, or active, non-infectious
pneumonitis.

9. Has an active infection requiring systemic therapy.

10. 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, including
dialysis.

11. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.

12. 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.

13. Has received prior immunotherapy with agents that target PD-1, PD-L1, PD-L2, CTLA-4,
OX-40, or CD-137 agents, or if the subject has previously participated in Merck
pembrolizumab clinical trials.

14. Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).

15. Has known Hepatitis B or Hepatitis C

16. Has received a live vaccine within 30 days of planned start of study therapy (Cycle 1,
Day 1). Note: The killed virus vaccines used for seasonal influenza vaccines for
injection are allowed; however intranasal influenza vaccines (e.g., FluMist®) are live
attenuated vaccines and are not allowed.

17. Has a known history of active TB (Bacillus Tuberculosis)

18. Unable to tolerate a contrast enhanced CT or MRI for staging/restaging purposes

19. Hypersensitivity to pembrolizumab or any of its excipients.

20. 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 events
due to such agents administered more than 4 weeks earlier.

21. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
within 2 weeks prior to study Day 1 or who has not recovered (i.e., =/< Grade 1 or at
baseline) from adverse events due to a previously administered small molecule agent.
a. Note: Subjects with =/< Grade 2 neuropathy or alopecia are an exception to this
criterion and may qualify for the study. b. Note: If subject received major surgery,
they must have recovered adequately from the toxicity and/or complications from the
intervention prior to starting therapy.

22. Patients requiring beta blockade are disqualified from participating in this study.

23. Patients who, in the estimation of the treating physician or primary investigator,
have had a clinical deterioration of their ECOG performance within the month prior to
enrollment.

24. The use of natural or synthetic cannabinoids.

25. Patients with 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.