A Study of Pembrolizumab Monotherapy or in Combination With Other Agents in Patients With Previously Treated Advanced Gastroesophageal Adenocarcinoma

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive pembrolizumab by
vein over about 30 minutes on Day 1 of each 21-day cycle.

Length of Study:

You may receive the study drug(s) for up to about 1 year (17 cycles).

You will no longer be able to receive the study drug(s) if the disease gets worse, if
intolerable side effects occur, or if you are unable to follow study directions.

Study Visits (for all participants):

On Day 1 of each cycle:

- You will have a physical exam.

- Blood (about 1 tablespoon) will be drawn for routine tests, to check the status of the
disease, and for tumor marker testing. If you can become pregnant, part of this sample
will be used for a pregnancy test.

- Urine will be collected for routine tests (Cycles 1, 2, and every even-numbered cycle
after that [Cycles 4, 6, 8 and so on]).

On Day 8 of Cycle 1:

- You will have a physical exam.

- Blood (about 1 tablespoon) will be drawn for routine tests, to check the status of the
disease, and for tumor marker testing.

- Urine will be collected for routine tests.

At Week 6, you will have a core biopsy and blood (about 3 tablespoons) will be drawn for
biomarker testing.

During the first 6 months, you will have an MRI or CT scan every 6 weeks. After that, this
will be done every 12 weeks.

At any time that the study doctor thinks it is needed, you will have an EKG.

If you had a brain scan at screening and the disease appears to completely go away, you will
have another brain scan to confirm this.

If at any time the disease appears to respond to the study drug, blood (about 3 tablespoons)
will be drawn for biomarker testing.

End-of-Treatment Visit:

As soon as possible after your last dose of study drug(s):

vYou will have a physical exam.

- Blood (about 3 tablespoons) will be drawn for routine tests and biomarker testing.

- You will have a CT scan or MRI.

Follow-Up:

About 30 days after the End-of-Treatment Visit:

- Urine will be collected for routine tests.

- Blood (about 1 tablespoon) will be drawn for routine tests and to check the status of
the disease. If you can become pregnant, part of this sample will be used for a
pregnancy test.

If you stop receiving the study drug(s) for reasons other than the disease getting worse, you
will move into follow-up and be checked on every 12 weeks. At these visits:

- Your vital signs will be measured, including your weight and height.

- You will have a CT scan or MRI until you start a new anti-cancer treatment, the disease
gets worse, or the study ends.

Long-Term Follow-Up:

You will be called every 12 weeks and asked about how you are doing. Each call should last
about 5-10 minutes.

Inclusion Criteria:

1. The subject (or legally acceptable representative if applicable) provides written
informed consent for the trial. The subject may also provide consent for Future
Biomedical Research. However the subject may participate in the main trial without
participating in Future Biomedical Research.

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

3. Male and female subjects who are at least 18 years of age on day of signing informed
consent with histologically and cytologically documented diagnosis as gastroesophageal
adenocarcinoma.

4. Histologically and cytologically documented diagnosis as gastroesophageal
adenocarcinoma.

5. Have a documented advanced (metastatic and/or unresectable) gastroesophageal
adenocarcinoma that is incurable and for which prior first-line or later-line SOC
treatments have failed. There is no limit to the number of prior treatment regimens.
Prior neoadjuvant or adjuvant therapy included in initial treatment may not be
considered first- or later-line SOC treatment unless such treatments were completed
less than 12 months prior to the current tumor recurrence.

6. Have submitted an evaluable tissue sample for biomarker analysis from a newly obtained
core, incisional, or excisional biopsy of a tumor lesion not previously irradiated.
The tumor tissue submitted for analysis must be from a single tumor tissue specimen
and of sufficient quantity and quality to allow biomarker study. A newly obtained
tumor specimen, defined as a specimen obtained up to 6 weeks (42 days) prior to
initiation of treatment on Day 1, for biomarker characterization will be required for
enrollment of all subjects. Tissue from tumor progressing at a site of prior radiation
may be allowed for biomarker characterization upon agreement from Merck. 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 Merck

7. Have measurable disease based on RECIST 1.1 as assessed by the Investigator. Lesions
situated in a previously irradiated area are considered measurable if progression has
been demonstrated in such lesions.

8. Have a performance status of 0 or 1 on the ECOG Performance Scale.

9. Life expectancy of greater than 3 months per the judgment of the investigators.

10. Have adequate organ function. Specimens must be collected within 5 days prior to the
start of study treatment. Hematological: Absolute neutrophil count (ANC) >/= 1,500
/mcL, Platelets >/= 100,000/mcL, Hemoglobin >/= 9 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(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 1.5 X ULN OR Direct bilirubin 1.5
ULN, AST (SGOT) and ALT (SGPT) metastases, Albumin: >/= 2.5 mg/dL

11. Inclusion #9 Cont'd: Coagulation: International Normalized Ratio (INR) or Prothrombin
Time (PT) PT or PTT is within therapeutic range of intended use of anticoagulants, Activated
Partial Thromboplastin Time (aPTT) anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use
of anticoagulants. Creatinine clearance should be calculated per institutional
standard.

12. 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.

13. Male and female subjects of childbearing potential must be willing to use an adequate
method of contraception as outlined in Section 5.7.2, 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.

Exclusion Criteria:

1. Is currently participating in or has participated in a study of an investigational
agent or used an investigational device within 4 weeks prior to the first dose of
study treatment. Note: Subjects who have entered the follow-up phase of an
investigational trial may participate as long as it has been 4 weeks after the last
dose of the previous investigational agent.

2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in
dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of trial treatment.

3. Has severe hypersensitivity (>/=Grade 3) to pembrolizumab or any of its excipients.

4. 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.

5. 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.1) Note: Subjects
with If subject received major surgery, they must have recovered adequately from the
toxicity and/or complications from the intervention as determined by the investigators
prior to starting therapy.

6. Has a known additional malignancy that is progressing or requires active treatment.
Note: Subjects with basal cell carcinoma of the skin, squamous cell carcinoma of the
skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have
undergone potentially curative therapy are not excluded.

7. Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Subjects with previously treated brain metastases may participate provided
they are radiological stable (i.e., without evidence of progression for at least 4
weeks by repeat imaging (note that the repeat imaging should be performed during study
screening), clinically stable and without requirement of steroid treatment for at
least 14 days prior to the first dose of trial treatment. This exception does not
include carcinomatous meningitis which is excluded regardless of clinical stability.

8. Has an 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 and is allowed.

9. Has a history of (non-infectious) pneumonitis that required treatment with steroids or
has current pneumonitis.

10. Has an active infection requiring systemic therapy.

11. 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.

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

13. Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the visit through 120 days after the
last dose of trial treatment.

14. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with
an agent directed to another stimulatory or co-inhibitory TCR (e.g., CTLA-4, OX 40,
CD137).

15. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). No HIV
testing is required unless mandated by local health authority.

16. Had a solid organ or hematologic transplant

17. Has a known history of hepatitis B virus (HBV; hepatitis B surface antigen [HBsAg]
reactive) or known active hepatitis C virus (HCV; HCV RNA [qualitative] is detected)
infection. No testing for Hepatitis B and Hepatitis C is required unless mandated by
local health authority.

18. Has received a live vaccine within 30 days prior to the first dose of the trial drug.
Examples of live vaccines include, but are not limited to, the following: measles,
mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
Calmette - Guérin (BCG), and typhoid vaccine.