Abstract 1498TiP
Background
Systemic chemotherapy is currently still the only option for unresectable locally advanced or metastatic G/GEJ, and the prognosis for these patients is poor with median overall survival (OS) only around 1 year. Pre-clinical studies suggest that anti-VEGF receptor 2 (VEGFR-2) antibody can reprogram the tumor microenvironment away from immunosuppression. The synergistic anti-tumor activities by blockade of PD-1 and VEGFR-2 were also observed in clinical settings. On this basis, ORIENT-106 study is conducted to investigate the efficacy and safety of sintilimab (an IgG4 PD-1 antagonist) plus ramucirumab (an IgG1 VEGFR-2 antagonist) in advanced G/GEJ adenocarcinoma.
Trial design
Patients with unresectable locally advanced or metastatic G/GEJ adenocarcinoma, without prior therapy for advanced disease, who have PD-L1 expression CPS ≥ 10 and are HER2 negative, will be enrolled and randomized in a 1:1 ratio to receive either sintilimab plus ramucirumab every 3 weeks or chemotherapy by investigator’s choice of FP (5-FU plus cisplatin) or CapeOx (Capecitabine plus oxaliplatin) every 3 weeks. Combination chemotherapy is given up to 6 cycles, followed by 5-FU or capecitabine maintenance monotherapy. In the immunotherapy group, treatment beyond progressive disease is allowed. Stratification factors include ECOG performance status (0 or 1), primary tumor location (gastric or GEJ) and measurable lesion (with or without). Primary endpoint is OS. Secondary endpoints include progression free survival, objective response rate, disease control rate, duration of response, assessed by investigator based on RECIST v1.1 and iRECIST criteria, safety profile and PK characteristics. Planned enrollment is approximately 540 patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Innovent Biologics, Inc. and Eli Lilly and Company.
Funding
Innovent Biologics, Inc. and Eli Lilly and Company.
Disclosure
Z. Li, Z. Ma, Y. Liu, Y. Wang, H. Zhou: Full/Part-time employment: Innovent Biologics, Inc. L. Yang, H. Li: Full/Part-time employment: Eli Lilly and Company. All other authors have declared no conflicts of interest.