Avelumabis a human anti-PD-L1 IgG1 monoclonal antibody that has shown antitumor activity in early phase studies in advanced/metastaticgastric/gastroesophageal junctioncancer, including asfirst-linemaintenancetherapy. Here, we describe thedesignofJAVELINGastric100(NCT02625610), an open-label, Phase III trial. A total of 499 patients with locally advanced/metastatic HER2-gastric/gastroesophageal junctioncanceradenocarcinoma, who had achieved at least stable disease following 12 weeks offirst-lineoxaliplatin/fluoropyrimidinechemotherapy, have been randomized 1:1 to receiveavelumabmaintenancetherapy or continuechemotherapy. The primary objective is to demonstrate superior overall survival in all randomized patients or in the PD-L1+population. Secondary objectives are to demonstrate superiority for progression-free survival and objective response rate, compare quality of life measures, and determine safety.