Perioperative Chemo and Pembrolizumab in Gastric Cancer

Inclusion Criteria

• 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.
• Plan to proceed to surgery following peri-operative chemotherapy based on standard staging studies per local practice.
• 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.
• Be at least 18 years of age on day of signing informed consent.
• 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.
• Have a performance status of 0 or 1 on the ECOG Performance Scale.
• 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.
• 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.
• 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.
• 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.

• 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

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