Pembrolizumab and Fractionated External Beam Radiotherapy (EBRT) in Patients With Non-Hodgkin Lymphoma (NHL)

Study Drug Administration and EBRT:

If you are found to be eligible for this study, you will have a CT scan while lying still on
your back. This is called a "CT simulation." You will not be injected with a contrast agent
(part of the normal CT process) during the CT simulation. After you complete the CT
simulation, your radiation oncologist will need about 1 week for radiation therapy planning
before you begin your radiation therapy treatment.

You will receive EBRT 1 time each day for a total of either 12 or 22 treatments, depending on
the type of NHL you have.

EBRT is considered part of your standard care. You will be given a separate consent form
which will discuss this procedure and its risks in greater detail.

Starting the day after you begin EBRT, you will receive pembrolizumab by vein over about 1
hour, every 21 days for up to 35 doses.

Study Visits:

Each cycle of pembrolizumab treatment is 21 days.

On Day 1 of Cycle 1, you will have a physical exam.

On Day 1 of Cycles 2-16:

- You will have a physical exam.

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

- Every 2 cycles (Cycles 2, 4, 6, and so on), part of this blood sample will also be used
to check your thyroid function.

- Every 4 cycles (Cycles 2, 6, 10, and so on), part of this blood sample will also be used
to check the status of your immune system.

- During Cycle 4 only, you will have a CT scan to check the status of the disease.

- During Cycle 5 only, urine will be collected for routine tests.

- During Cycle 8 only, you will have a PET/CT scan to check the status of the disease.

At any time, if your doctor thinks it is needed, you may have a bone marrow biopsy and
aspirate and/or a CT or PET/CT scan to check the status of the disease.

Length of Study:

You may take pembrolizumab for up to 35 doses, which may take about 2 years. You will no
longer be able to receive the 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 once you have completed follow-up.

End-of-Treatment Visit:

After you stop receiving the study drug(s):

- You will have a physical exam.

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

- If your doctor thinks it is needed, you will have a PET/CT scan to check the status of
the disease.

Long Term Follow-Up:

About 30 days after your End-of-Treatment visit:

- You will have a physical exam.

- Blood (about 2 tablespoons) will be drawn for routine tests, thyroid function testing,
and immune system testing.

- Urine will be collected for routine tests.

Every 3 months for 1 year, and then every 6 months after that until you start a new therapy,
the disease gets worse, or the study ends:

- You will have a physical exam.

- Blood (about 2 tablespoons) will be drawn for routine tests, thyroid function testing,
and immune system testing.

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

Inclusion Criteria:

1. Have at least one site of lymphomatous disease amenable to external beam radiation
therapy (EBRT)

2. Have at least one non-contiguous lesions that is distinct from the radiation candidate
lesion that is able to be evaluated radiographically or clinically.

3. Be willing and able to provide written informed consent/assent for the trial.

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

5. Have measurable disease (>/= 1.5 cm in the longest diameter for nodal or extranodal
disease)

6. Be willing to provide tissue from a newly obtained core or excisional biopsy of a
tumor lesion. 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 the Sponsor.

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

8. Demonstrate adequate organ function as defined below, all screening labs should be
performed within 10 days of treatment initiation. *HEMATOLOGICAL: Absolute neutrophil
count (ANC) = >/=1,000 /mcL; Platelets = >/=50,000 / mcL; Hemoglobin = >/=8 g/dL or
>/=5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment)
*RENAL: Serum creatinine OR Measured or calculated creatinine clearance (creatinine
clearance should be calculated per institutional standard) (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: Serum total
bilirubin = bilirubin levels > 1.5 ULN;

9. Inclusion #8 cont'd: aspartate aminotransferase (AST) serum glutamic-oxaloacetic
transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamic pyruvic
transaminase (SGPT) = Albumin = >/=2.5 mg/dL *COAGULATION: International Normalized Ratio (INR) or
Prothrombin Time (PT) = as long as PT or PTT is within therapeutic range of intended use of anticoagulants;
Activated Partial Thromboplastin Time (aPTT) = receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of
intended use of anticoagulants

10. 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.

11. Female subjects of childbearing potential must be willing to use an adequate method of
contraception as outlined - Contraception, for the course of the study through 120
days after the last dose of study medication. Note: Abstinence is acceptable if this
is the usual lifestyle and preferred contraception for the subject.

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

Exclusion Criteria:

1. Has had prior radiation therapy to the potential radiation target such that additional
radiation therapy is considered unsafe by the treating radiation oncologist

2. Has a history of allogeneic stem cell transplantation

3. Has a diagnosis of active scleroderma or lupus or any other autoimmune disease that by
the opinion of the treating radiation oncologist would put the patient at unacceptable
risk of toxicity.

4. 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.

5. 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.

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

7. Hypersensitivity to pembrolizumab or any of its excipients

8. 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.

9. 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.

10. 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.

11. Has known active central nervous system (CNS) lymphoma or lymphomatous 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.

12. 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 (eg., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.

13. Has history of (non-infectious) pneumonitis that required steroids, evidence of
interstitial lung disease or active, non-infectious pneumonitis.

14. Has an active infection requiring systemic therapy.

15. 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.

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

17. 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.

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

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

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

21. 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.