Background: Patients with esophageal cancer refractory to multiple treatments have poor outcomes. We assessed the activity of nivolumab, a human monoclonal IgG4 PD-1 immune checkpoint inhibitor antibody, for patients with advanced esophageal cancer. We conducted phase II, single-arm, multi-center trial in JAPAN (JapicCTI-No.142422).Methods: The target population was esophageal cancer patients aged ≥ 20 years with ECOG performance status of 0 or 1, who had received one or more previous treatments and not pre-selected by PD-L1 status. Nivolumab (3 mg/kg IV Q2W) was administered to patients until observing unacceptable toxicity or disease progression assessed at 6 week intervals. The primary endpoint was the proportion of patients with a confirmed objective response assessed by independent review committee according to RECIST 1.1. Planned sample size was 60 patients (P0 = 5, P1 = 15, α = 0.025 (one-side), 1-β = 0.8). Data cutoff, 17 May 2015.Results:We enrolled 65 patients with esophageal carcinoma: median age 62.0 years (range, 49-80 years); male/female, 54/11; ECOG PS 0/1, 29/36, Histological type was squamous in all pts. The median prior regimens was 3.0 (range, 1-8); 44 patients (67.7%) were treated with prior esophagectomy and 44 patients (67.7%) with prior radiation therapy. There were 64 evaluable patients for efficacy, and 11(17.2%) of 64 patients had objective response (CR/PR, 1/10). 16 (25.0%) of 64 patients had stable disease. The median overall survival was 12.1 months in 64 evaluable patients. The incidence of drug-related Serious AEs was 11 events (9/65 patients): Lung infection(2[3.1%]), Dehydration(2[3.1%]), Interstitial lung disease (2[3.1%]), etc. The patients with grade 3 pneumonitis improved with supportive care. There was no treatment-related death. We will introduce the updated efficacy and safety data of this trial. Conclusions: Nivolumab has meaningful activity and a manageable safety profile in pretreated esophageal cancer. These data support the assessment of nivolumab in randomized, controlled, phase III studies of second-line treatment. Funding: ONO Pharmaceutical CO.,LTD. Bristol-Myers Squibb Clinical trial information: 142422.