Background: Advanced or metastatic esophageal squamous cell carcinoma (ESCC) is associated with poor prognosis; new first- line systemic treatment options are needed. Combining immuno-oncology therapies with standard chemo-therapy may represent a promising approach for the treatment of solid tumors. Results from a Phase Ib study evaluating durvalumab with tremelimumab and chemotherapy in patients with advanced or metastatic ESCC are reported.Methods: Adults with advanced or metastatic ESCC who were candidates for first- line platinum- based chemotherapy received durvalumab 1500 mg (Day 1), tremelimumab 75 mg (Day 1), cisplatin 80 mg/m(2) (Day 1) and 5-fluorouracil (5-FU) 800 mg/m(2) (Days 1- 5) in 28 -day cycles until disease progression or discontin-uation due to toxicity. The study consisted of safety run- in (Part A) and expansion (Part B) periods. The primary endpoint was safety. Antitumor activity was an exploratory endpoint.Results: Sixteen patients were enrolled, 6 in Part A and 10 in Part B, and re-ceived a median of 4.0 treatment cycles. All patients were Asian; median age was 65.0 years. All patients experienced adverse events (AEs) related to cisplatin and 5- FU, and 8 (50.0%) patients experienced AEs related to durvalumab and treme-limumab. Grade =3 treatment-related AEs occurred in 7 (43.8%) patients. There were no deaths associated with AEs. Six (37.5%) patients achieved an objective response. Median progression- free survival was 3.75 months, and median overall survival was 9.69 months.Conclusions: Durvalumab with tremelimumab and chemotherapy demonstrated manageable safety and antitumor activity in patients with advanced or metastatic ESCC, warranting further investigation in randomized trials. Registered with ClinicalTrials.gov: NCT02658214.