Pembrolizumab Plus Neoadjuvant Chemotherapy for Locally Advanced EGJ Adenocarcinoma

Inclusion Criteria: 1. Histologically confirmed AEG, Siewert type I or II; 2. Potentially resectable cT3-4a, any N, M0 (AJCC 8 TNM classification); 3. Have a performance status of 0 or 1 on the ECOG Performance Scale; 4. Age 18-75 years old, both men and women; 5. Be willing and able to provide written informed consent/assent for the trial; 6. Demonstrate adequate organ function , all screening labs should be performed within 10 days of treatment initiation; 7. 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; 8. Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion through repeated biopsies. Newly-obtained is defined as a specimen obtained up to 4 weeks (28 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. Exclusion Criteria: 1. Prior therapy (operation, radiotherapy, immunotherapy, or chemotherapy) for AEG; 2. Ineligibility or contraindication for esophagectomy; 3. Has a diagnosis of immunodeficiency or is receiving chronic 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 study drug; 4. 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); 5. Has severe hypersensitivity and adverse events (≥Grade 3) to nivolumab and/or any PD-1/PD-L1 inhibitors.