Abstract CT211: ORIENT-15: A randomized, multicenter, double-blind, Phase III study of sintilimab + paclitaxel and cisplatin (TP) versus placebo + TP as first-line treatment in patients with unresectable locally advanced or metastatic esophageal squamous cell carcinoma
Authors: Shen Lin , Lu Zhihao , Xu Linxinyu , Wang Yan , Zhou Hui , Liu Ying 
Published: August 2019

Background: China has the largest population of patients with esophageal cancer in the world. The major histopathological type is squamous cell carcinoma and it accounts for more than 90% of the cases. About 40% esophageal squamous cell carcinoma (ESCC) are PD-L1 positive, however, the prognostic and predictive value of this biomarker remains elusive for this disease. Regardless of PD-L1 status, the median overall survival of patients with advanced or metastatic ESCC is about 10 months, reflecting an unmet medical need for new treatments. Sintilimab is a fully human anti-PD-1 monoclonal antibody that blocks the PD-1/PD-L1,PD-L2 interaction and restores T-cell response thereby destroying tumor cells. Sintilimab has a safety profile consistent with other approved PD-1 antibodies and was approved for relapsed/refractory Hodgkin lymphoma in China in 2018. Recently, comparing to chemotherapy, nivolumab and pembrolizumab significantly improved overall survival in second-line esophageal cancer patients, which suggests the application of PD-1 therapy in first-line ESCC. This randomized, multicenter, double-blind, Phase III study compares the efficacy and safety of sintilimab in combination with paclitaxel and cisplatin (TP) versus placebo with TP as first-line systemic treatment in patients with unresectable, locally advanced or metastatic ESCC in China.

Methods: To be eligible, patients must be between 18 and 75 years of age, not eligible for definitive therapy, have untreated locally advanced recurrent or metastatic ESCC, have at least one measurable lesion, and must provide tumor tissue for PD-L1 assessment (tumor proportion score, TPS by Dako 22 C3) within 6 months prior to entrance. Patients with prior PD-1, PD-L1 or PD-L2 antibody treatment, cisplatin cumulative exposure ≥ 300 mg/m2, or esophageal or tracheal stent placement are excluded. A total of 640 subjects will be randomized in a 1:1 ratio to receive either sintilimab plus TP Q3W or placebo plus TP Q3W until unacceptable toxicity, disease progression, death or withdrawal of consent. Stratifying factors include PD-L1 TPS ≥ 10% or &lt; 10%, liver metastasis or not, and ECOG PS 0 or 1. The primary endpoint is median overall survival assessed in the experimental and control groups in both the entire population and the PD-L1 positive (TPS ≥ 10%) population. The secondary endpoints are PFS, ORR, DCR, DoR and safety. Clinical trial information: NCT03748134.

Citation Format: Lin Shen, Zhihao Lu, Linxinyu Xu, Yan Wang, Hui Zhou, Ying Liu. ORIENT-15: A randomized, multicenter, double-blind, Phase III study of sintilimab + paclitaxel and cisplatin (TP) versus placebo + TP as first-line treatment in patients with unresectable locally advanced or metastatic esophageal squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT211.