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CA209577 is a phase 3, randomized, double-blind, placebo controlled study of adjuvant nivolumab in subjects with resected esophageal cancer (EC), or gastroesophageal junction (GEJ) cancer who have received chemoradiother-apy(CRT) followed by surgery. Over the last 30 years in Western Europe, North America and Australia there has been a dramatic shift in the histological subtypes of EC from squamous cell to adenocarcinoma.This has been at-tributed to a decline in smoking and an increase in adeno-carcinoma risk factors including obesity, gastroesophageal reflux disease (GERD) and Barrett’s esophagus. Adeno-carcinoma of the lower esophagus or gastroesophageal junction has increased dramatically amongst both men and women in the last 3 decades and its incidence is increasing faster than any other solid tumor in the Western world. CRT followed by surgery (trimodality therapy) is now considered as a standard of care for the local and locoregional EC and GEJ cancers in the US and EU, and also a treatment option in Asia including Japan. However, only 25-30% of subjects whose tumors have a pathological complete response (pCR) and those subjects have been shown to have a survival benefit with a 50% of 5 year survival rate.The remaining 70-75% of subjects whose tumors did not achieve pathological complete response (non-pCR) have a significantly worse survival with a 37% of 5 year survival rate, and much worse for lymph node positive sub-jects where the median survival is only 9 months and 5 year survival is 17%. There is no established standard of care in the adjuvant setting in subjects who have received CRT followed by surgery and no clinical trials have been performed in this patient population for many years. Thus there is a significant medical need for novel treatment strategies in both EC and GEJ cancers which represents a major health care problem and whose prevalence is in-creasing rapidly. Immunotherapeutic approaches recently have demonstrated clinical efficacy in several advanced cancer types, including melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC). In addi-tion to advanced cancers, immunotherapy has also recent-ly demonstrated a clinical benefit in adjuvant setting. Ipili-mumab, a fully human monoclonal antibody that blocks CTLA-4 to augment anti-tumor immune responses, provid-ed a clinically and statistically significant improvement in recurrence free survival (RFS) compared to placebo in stage III melanoma, and was recently approved by FDA. The preliminary data from Nivolumab monotherapy in heavily pre-treated GC (Gastric Cancer), GEJ and adeno-carcinoma esophageal cancer (AEC) patients showed du-rable anti-tumor activity with 12 % objective response rate (ORR), and the duration of response (DCR) was 7 months. In addition, in the squamous esophageal cancer (SEC) patients, nivolumab also showed durable anti-tumor activity with 17.2% ORR. These results are promising for the ad-vanced GC and EC patients where there is a paucity of treatment options and, in fact, demonstrate more activity than ramucirumab which has recently been approved for 2L or 3L treatment in advanced GC or GEJ cancer. An immunotherapy approach is plausible in the adjuvant setting in EC or GEJ cancer, considering the lack of effective treatment options, clinical activity in the adjuvant setting in melanoma as well as several advanced solid tumors, and the promising preliminary results with PD-1/PD-L1 block-ade in the advanced GC and EC patients.