Study of Pembrolizumab in Locally Advanced Esophageal Adenocarcinoma

This is a randomized, multicenter phase II study of pembrolizumab in combination with chemotherapy and chemoradiation in locally advanced esophageal adenocarcinoma to examine the safety and efficacy of the combination of pembrolizumab with chemotherapy and chemoradiation in locally advanced esophageal adenocarcinoma as assessed by 1 year disease free survival rate. The investigators primary aim is to examine the safety and efficacy of pembrolizumab in both pre-operative treatment paradigms for esophageal/GEJ carcinoma. The specific rationale for the investigators study design is rooted in three unanswered questions: 1. does the addition of an immune check-point inhibitor (pembrolizumab) enhance the efficacy of cytotoxic therapy (chemotherapy with chemoradiation) as determined by response rates, nodal down-staging and 1 year disease free survival in comparison to historical controls, 2. what are the pathological effects of combining pembrolizumab with chemotherapy alone, and 3. what are the molecular (PD-L1 expression), immunological (TILs extent) and gene-expression signatures associated with the efficacy of pembrolizumab in the neoadjuvant setting.