Abstract CT213: ORIENT-16: Sintilimab plus XELOX vs placebo plus XELOX as 1st line treatment for unresectable advanced gastric and GEJ adenocarcinoma
Authors: Xu Jianming , Jin Yongshuai , Liu Ying , Zhou Hui , Wang Yan 
Published: August 2019

Background: Gastric cancer is one of the most common malignant tumors worldwide, and the 2nd most common in China. The development of new agents for the treatment of advanced gastric cancer is stagnant. Immunotherapy which inhibits the programmed death 1 (PD-1)/ programmed death ligand 1 (PD-L1) interaction is becoming a new option for treatment of late-stage gastric cancer (GC). Several trials suggest patients with PD-L1 positive expression (Combined Positive Score: CPS ≥ 1) population, especially CPS ≥ 10 population, are most likely to benefit from anti-PD-1 antibody treatment. Emerging data show encouraging efficacy signals of anti-PD-1 antibody in combination with chemotherapy in GC. Sintilimab, a highly selective, fully human, anti-PD-1 monoclonal antibody, was approved for relapsed or refractory Hodgkin Lymphoma in China in 2008. Based on the efficacy signals and the safety profile from a phase 1b trial of sintilimab plus XELOX regimen (oxaliplatin and capecitabine) as first line treatment for unresectable advanced gastric and GEJ adenocarcinoma, we aim to verify the therapeutic potential of sintilimab in combination with chemotherapy in patients with advanced GC/gastroesophageal junction (GEJ) cancer .

Methods: The ORIENT-16 study (NCT: 03745170) is a randomized, double-blind, multi-center, phase III trial conducted in China to evaluate the efficacy and safety of sintilimab or placebo in combination with XELOX as first-line treatment in subjects with recurrent unresectable locally advanced or metastatic GC or GEJ adenocarcinoma. The study will enroll 650 patients. Patients will be randomly assigned in a 1:1 ratio to receive sintilimab every 3 weeks plus XELOX (capecitabine, 1000mg/m2 orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130mg/m2 intravenously on day1 every 3 weeks) or placebo plus XELOX for up to six cycles. Thereafter, the patients will receive maintenance therapy with sintilimab every 3 weeks plus capecitabine (1000mg/m2 orally twice daily for 14 days followed by 7 days off) or placebo plus capecitabine every 3 weeks. Sintilimab will be dosed according to the subject’s bodyweight ( &lt; 60kg, 3mg/kg; ≥ 60kg, 200mg). Stratification factors are ECOG Performance status (0 or 1), liver metastasis (yes or no) and PD-L1 expression score in tumor cells and immune cells (DAKO 22C3: CPS &lt; 10 or ≥ 10). Major eligibility criteria include age between 18 and 75 years; newly diagnosed, recurrent unresectable locally advanced or metastatic G or GEJ adenocarcinoma; at least one evaluable tumor lesion according to RECIST v1.1 criteria; and patients must have fresh tumor tissue or archival tumor tissue for PD-L1 assessment from within 6 months of entrance. Patients with known HER2 positive G or GEJ cancer are excluded. Treatment will be discontinued for disease progression, unacceptable toxicity, patient / physician decision to withdraw or after 24-months of treatment. The primary endpoint is median overall survival assessed in both entire population and in PD-L1 positive (CPS ≥ 10) population of patients. Secondary endpoints include progression free survival, objective response rate, disease control rate,duration of response and safety. Recruitment is currently ongoing in multiple sites in China.

Citation Format: Jianming Xu, Yongshuai Jin, Ying Liu, Hui Zhou, Yan Wang. ORIENT-16: Sintilimab plus XELOX vs placebo plus XELOX as 1st line treatment for unresectable advanced gastric and GEJ adenocarcinoma [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 CT213.