Perioperative Chemo and Pembrolizumab in Gastric Cancer

Inclusion Criteria: 1. Have previously untreated localized gastric or GE junction adenocarcinoma as defined by T2 or greater primary lesion or the presence of any positive nodes- N+(clinical nodes) without evidence of metastatic disease. 2. Plan to proceed to surgery following peri-operative chemotherapy based on standard staging studies per local practice. 3. Be willing and able to provide written informed consent/assent 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. 4. Be at least 18 years of age on day of signing informed consent. 5. 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. 6. Have a performance status of 0 or 1 on the ECOG Performance Scale. 7. Demonstrate adequate organ function as defined below, all screening labs should be performed within 14 days of treatment initiation. Adequate Organ Function Laboratory Values * 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) * Serum creatinine OR Measured or calculated creatinine clearance (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 * Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN * AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases * Albumin \>2.5 mg/dL * 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 * Creatinine clearance should be calculated per institutional standard. 8. Have a 2D Echocardiogram with left ventricular ejection fraction = or \> 45% in order to receive Epirubicin. Subjects with inadequate EF or other contraindication can proceed on study without the use of Epirubicin. 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 must be willing to use an adequate method of contraception - 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. 11. Male subjects of childbearing potential must agree to use an adequate method of contraception - 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. 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. 2. 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. The use of physiologic doses of corticosteroids (prednisone 10 mf or equivalent) may be approved after consultation. 3. Has a known history of active TB (Bacillus Tuberculosis) 4. Hypersensitivity to pembrolizumab or any of its excipients. 5. Has had any prior chemotherapy, targeted small molecule therapy, or radiation therapy for their current diagnosis. 6. Has a known additional malignancy that is progressing or requires active treatment within 3 years from registration. 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. Subjects with a history of prior malignancy diagnosed and treated greater than 3 years form registration may be considered with consultation of the primary investigator. 7. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. 8. 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. 9. Has known history of prior pneumonitis requiring treatment with steroids, or any evidence of active, non-infectious pneumonitis. 10. Has an active infection requiring systemic therapy which is not expected to have resolved by Cycle 1 Day 1 dosing. 11. Has a history or current evidence of any condition (e.g. known deficiency of the enzyme dihydropyrimidine dehydrogenase \[DPD\]),, 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 pre-screening or screening 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. 15. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). 16. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected). 17. Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor-investigator staff directly involved with this trial, unless prospective IRB approval (by chair or designee) is given allowing exception to this criterion for a specific subject. 18. 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.