Adjuvant Pembrolizumab for Patients With Locally Advanced Esophageal Squamous Cell Carcinoma at High Risk of Recurrence

Inclusion Criteria

• Be willing and able to provide written informed consent/assent for the trial.
• Be ≥ 20 years of age on day of signing informed consent.
• Be a diagnosed by pathology or cytology with a locally advanced ESCC, which is clinically stage according to the TNM system of the American Joint Committee on Cancer (AJCC) Cancer Staging System (7th edition), fulfilling one of the following criteria as determined by endoscopic ultrasound, computed tomography, bronchoscopy and positron emission tomography:
• T3, N0, M0;
• T4a, N0, M0;
• T1-4a, N1-3, M0.
• Have been treated with preoperative cisplatin-based CRT followed by esophagectomy with lymph node dissection for the locally advanced ESCC (defined by above criteria).
• Have a performance status of 0 or 1 on the ECOG Performance Scale.
• Exhibit at least one risk factor of tumor recurrence in the post-CRT surgical tissues:
• Close (≤1mm) or involved margin;
• Residual tumor cells in lymph nodes with extranodal invasion.
• ypN2 or ypN3.
• Adequate hemogram and organ function:
• Absolute neutrophil count ≥1, 500 /mcL; platelets ≥100,000 / mcL; hemoglobin ≥9 g/dL without transfusion or EPO dependency (within 7 days of assessment)
• Serum creatinine ≤1.5 X upper limit of normal or measured or calculated creatinine clearance ≥60 mL/min; serum total bilirubin ≤ 1.5 X ULN; AST and ALT ≤ 2.5 X ULN; albumin >2.5 mg/dL; international normalized ratio or prothrombin time and activated partial thromboplastin time ≤1.5 X ULN unless subject is receiving anticoagulant therapy
• 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.
• 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.

Exclusion Criteria

• Is diagnosed with adenocarcinoma of esophagus or gastroesophageal junction.
• Has synchronously diagnosed with a squamous cell carcinoma of aero-digestive way, other than esophageal cancer.
• Has prior malignancy, except for: (a) adequately treated basal cell or squamous cell skin cancer; (b) in-situ cervical cancer; (c) previously diagnosed malignancy which have been adequately treated and shown no evidence of recurrence for more than 5 years.
• 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.
• Has a known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• 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 system