TPS4144 Background: The majority of patients (pts) with gastroesophageal cancer present with inoperable or metastatic disease and there is a strong need for efficient and tolerable first-line (1L) treatment. Oxaliplatin-based regimens like FOLFOX have become one standard of care. However, median survival is still below 12 months. Results from trials using nivolumab plus ipilimumab treatment of subjects with advanced/metastatic GC and GEJ cancers demonstrated clinical activity, in pts whose tumors did or did not express PD-L1; in addition, nivolumab alone and in combination with ipilimumab demonstrated clinical benefits in various other tumor types. Based on this clinical experience, the AIO-STO-0417 trial (Moonlight) has been designed to evaluate the combination of chemotherapy with two checkpoint inhibitors in first-line therapy of pts with gastroesophageal adenocarcinoma. Methods: This is a prospective, multicenter, randomized, investigator-initiated phase II trial. Pts with Her2-negative, inoperable, advanced or metastatic gastric or esophagogastric junction cancer will be randomized 1:1 to 1L treatment with FOLFOX (Oxaliplatin 85 mg/m²; Leucovorin 400 mg/m²; 5FU 400 mg/m² on d1 of each treatment cycle and 5FU 1200 mg/m² continuous infusion over 24 hrs d1 and d2) every 2 weeks plus Nivolumab 240 mg every 2 weeks and Ipilimumab 1mg/kg every 6 weeks (Arm A) or FOLFOX alone (Arm B). Primary endpoint of the trial is progression-free survival based on the ITT population. Main secondary endpoints are overall survival, objective response rate, Safety and Quality of life (EORTC QLQ-C30). 118 pts (59 per arm) will be enrolled to provide 80% power for detecting an average HR of 0.68 using the log rank test at a one-sided type I error of 10%. At the date of submission, (Feb 2019), 28 of planned 118 pts are randomized. Clinical trial information: NCT03647969.