Randomized Phase III Trial of mFOLFIRINOX +/- Nivolumab vs. FOLFOX +/- Nivolumab for First-Line Treatment of Metastatic HER2-Negative Gastroesophageal Adenocarcinoma

The purpose of this study is to compare the usual treatment alone to adding a third chemotherapy drug called irinotecan to the usual treatment. The addition of irinotecan to the usual treatment could shrink your cancer and extend your life. But, it could also cause side effects, which are described in the risks section below. This study will help the study doctors find out if this different approach is better, the same, or worse than the usual approach. To decide if it is better, the study doctors will be looking to see if the treatment with mFOLFIRINOX, the three-drug chemotherapy, increases the life of patients by 6 months or more compared to the usual approach with FOLFOX, the two-drug chemotherapy. This chemotherapy drug, irinotecan, is already approved by the FDA for use in stomach and esophagus cancer, but most of the time it is not used until FOLFOX, the standard two-drug chemotherapy, stops working. There will be about 382 people taking part in this study.