EORTC 1707 VESTIGE: Adjuvant immunotherapy in patients with resected gastric cancer following preoperative chemotherapy with high risk for recurrence (ypN+ and/or R1)—An open-label randomized controlled phase II study.

Abstract

TPS4156 Background: Gastroesophageal adenocarcinoma (GEA) patients with metastatic lymph nodes (ypN+) or a microscopically incomplete surgical resection (R1) following neoadjuvant chemotherapy are at high risk of disease recurrence. Current practice is to continue with the same perioperative chemotherapy used prior to surgery, despite these suboptimal outcomes. Adjuvant immunotherapy with nivolumab has shown efficacy in poor risk GEA patients following chemoradiotherapy and surgery in the CheckMate 577 trial, and nivolumab and ipilimumab have demonstrated activity in advanced GEA. We hypothesise that high risk (ypN+ and/or R1) post resection GEA patients who are treated with nivolumab and ipilimumab will have better disease free survival than patients who continue with standard post-operative chemotherapy. Methods: VESTIGE is an ongoing, international, open label randomized phase II study designed to evaluate the efficacy of adjuvant nivolumab plus ipilimumab versus standard post-operative chemotherapy in high risk (ypN+ and/or R1) post resection GEA patients. Eligible patients (n=240) will be randomised 1:1 to receive post-operative adjuvant chemotherapy (identical regimen as pre-operatively) or nivolumab 3mg/kg IV q2w plus ipilimumab 1mg/kg IV q6w x 1 year. Key inclusion criteria include ypN+ and/or R1 status following neoadjuvant chemotherapy plus surgery and an adequate pre-specified surgical resection. The primary endpoint of the study is disease free survival, with secondary endpoints of overall survival, safety, toxicity and quality of life. Since start of recruitment in August 2019, the trial has recruited 85 of 240 patients at 18 sites in the Czech Republic, France, Germany, Israel, Italy, Norway, Poland, Spain, and United Kingdom. The VESTIGE translational research programme includes collection of pre-treatment biopsies, post-chemotherapy resection specimens and serial liquid biopsy on treatment to explore biomarkers predictive of immune checkpoint blockade efficacy. Clinical trial information: NCT03443856.