Azacitidine and Pembrolizumab for Patients With Myelodysplastic Syndrome (MDS)

Study Drug Administration:

Each study cycle is 4 weeks (28 days).

- You will receive azacitidine either by vein over about 10-40 minutes or as an injection
under the skin for 7 days starting on Days 1of each cycle. If you are receiving
azacitidine at a clinic that closes over the weekend, alternate dosing schedules (such
as receiving azacitidine on Days 1-5 and 8-9 of each cycle) are possible.

- You will receive pembrolizumab by vein over about 30 minutes on Day 1 of Cycle 1, and
then every 3 weeks after that.

Length of Study:

You will receive the study drugs for as long as the doctor thinks is in your best interest.
You will no longer be able to take the study drugs if the disease gets worse, if intolerable
side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over after the long-term follow-up period.

Study Visits:

On Day 1 of Cycle 1, or within 72 hours of the first dose of study drugs, if you are able to
become pregnant, blood (about 1 teaspoon) or urine will be collected for a pregnancy test.

On Day 1 of Cycle 1 and then every 3 weeks after that, blood (about 2-3 teaspoons) and urine
will be collected for routine tests and a physical exam performed before the dose of
pembrolizumab.

On Day 1 of every cycle, the following tests and procedures will be performed. The Day 1 of
Cycle 1 tests can be done within 72 hours of the first dose of study drugs.

- You will have a physical exam.

- Blood (about 2-3 teaspoons) will be drawn for routine tests.

On Days 8, 15, and 22 of Cycle 1, blood (about 2-3 teaspoons) will be drawn for routine
tests.

Between Days 22-28 of Cycles 1 and 3 and then 1 time every 3 cycles after that, you will have
a bone marrow biopsy and aspirate to check the status of the disease and for cytogenetic
testing.

If your doctor thinks it is needed, at any point in the study, you may have additional bone
marrow biopsies and aspirations.

End-of-Treatment Visit:

After you stop the study drugs:

°You will have a physical exam.

Follow-Up:

Within 30 days after your last dose of the study drugs, you will be called by a member of the
study team and asked how you are feeling and about any other drugs or treatments you are
receiving. The phone call should last about 10 minutes. You will continue having these calls
every 12 weeks for 1 year and then every year after that.

Inclusion Criteria:

1. Voluntary signed informed consent before performance of any study related procedure
not part of normal medical care indicating that the patient is aware of the
investigation and nature of this study in keeping with Institutional policies and with
the understanding that the consent may be withdrawn with the subject at any time
without prejudice to future medical care.

2. Intermediate 1 (INT-1) or higher risk MDS defined by International Prognostic Scoring
System (IPSS) criteria.

3. More or equal than 18 years of age at the time of signing consent.

4. Patients can or cannot have receive prior therapy with hypomethylating agent but will
be allocated to specific patient cohorts based on their prior exposure. Patients that
had received prior hypomethylating agent therapy should have at least received 6
cycles of therapy and not achieved any response or had progressed after any given
number of cycles.

5. ECOG performance of 0 to 2.

6. Male patients, even if surgically sterilized, should agree to practice effective
barrier contraception for the entire study treatment period and through 120 days after
the last dose of the study treatment or agree to completely abstain from
heterosexually intercourse. Female patients who are postmenopausal for at least one
year before the screening visit or are surgical sterile or if they are of child
bearing potential must have a negative pregnancy test within 72 hours of treatment of
the start date and agree to practice two effective methods of contraception forms at
the same time from the time of signing the informed consent through 120 days of the
last dose of the study treatment or agree to completely abstain from heterosexual
intercourse.

7. Willingness and ability to comply with scheduled visits treatment plans, laboratory
tests and other study procedures.

8. Demonstrate adequate organ function as follows, all screening labs should be performed
within 10 days of treatment initiation. Serum creatinine or measured or calculated
creatinine clearance (GFR can also be used in place of creatinine or CrcL) upper limit of normal (ULN) or >/= 60 mL/min for subject with creatinine levels > 1.5
x institutional ULN. Creatinine clearance should be calculated per institutional
standard. Serum total bilirubin disease or leukemia disease) or direct bilirubin bilirubin levels > 1.5 ULN. AST (SGOT) and ALT (SGPT) due to Gilbert's disease or leukemia disease) or metastases.

9. Female subject of childbearing potential should have a negative urine or serum
pregnancy within 72 hours prior to receiving the first dose of study medication. If
the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
will be required.

10. Female subjects of childbearing potential should be 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. Subjects of
childbearing potential are those who have not been surgically sterilized or have not
been free from menses for > 1 year.

11. Male subjects should 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.

12. Patients must receive a minimum dose of azacitidine of 75mg/(m)(2) dose.

Exclusion Criteria:

1. Significant medical psychiatric cognitive or other conditions that may compromise the
patient ability to understand the patient information to give informed consent to
comply with the study protocol or to complete the study.

2. Any severe or concurrent disease or condition including uncontrolled systemic
infection, congestive heart failure, angina pectoris or cardiac arrhythmia and
autoimmune processes that in the opinion of the investigator would make the patient
inappropriate for study participation.

3. Patients with known hypersensitivity to 5-azacitidine or MK3475 or any of their
excipients.

4. Prior history of stem cell transplantation.

5. For patients in the relapse or refractory cohort, any other therapy not being a
hypomethylating agent after HMA failure or more than 4 months since completion of last
cycle of hypomethylating agent. Please note that hypomethylating agent may include
second generation compounds such as SGI-110, oral decitabine or oral azacitidine and
will also include combinations with investigational agents.

6. Treatment with other investigational agents including chemotherapy, immunotherapy, or
radiation therapy within a month prior to the start of this clinical trial.

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 a known history of active TB (Bacillus Tuberculosis).

10. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
Day 1 or who has not recovered (i.e., due to agents administered more than 4 weeks earlier.

11. 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., baseline) from adverse events due to a previously administered agent. Note: Subjects
with study. Note: If subject received major surgery, they must have recovered adequately
from the toxicity and/or complications from the intervention prior to starting
therapy.

12. Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
skin that has undergone potentially curative therapy or in situ cervical cancer.

13. Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Subjects with previously treated brain metastases may participate provided
they are stable (without evidence of progression by imaging 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 7 days prior to trial treatment. This exception does not include
carcinomatous meningitis which is excluded regardless of clinical stability.

14. Has active autoimmune disease that has required systemic treatment in the 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.

15. Has known history of, or any evidence of active, non-infectious pneumonitis.

16. Has an active infection requiring systemic therapy.

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 pre-screening or screening visit
through 120 days after the last dose of trial treatment.

20. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

21. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

22. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected).

23. Has received a live vaccine within 30 days of planned start of study therapy. Note:
Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
attenuated vaccines, and are not allowed.