Study design
cancer, tumor, PD‐L1
ONCOLOGY, CANCER, TUMOR, CPS
This multicenter, open‐label, randomized phase III study enrolled patients at 175 hospitals and cancer centers in 29 countries, including 22 centers in China. Patients were initially randomized to receive nivolumab plus ipilimumab or chemotherapy alone at a 1:1 ratio. Amendments to the protocol resulted in randomization at a 1:1:1 ratio to nivolumab plus chemotherapy (XELOX [capecitabine and oxaliplatin] or FOLFOX [oxaliplatin, leucovorin and 5‐fluorouracil]), nivolumab plus ipilimumab or chemotherapy alone; subsequently, the nivolumab plus ipilimumab treatment group was closed, and patients were randomized in a 1:1 manner to treatment with nivolumab plus chemotherapy or chemotherapy alone. Patients were randomized with interactive web response technology in block sizes of six. Once informed consent was obtained from the patient, they were enrolled and assigned to treatment. A treatment allocation list was generated by the sponsor. Web registration was implemented by a third party, and the sequence of assignment was concealed until treatment allocation was complete. Investigators were not blinded to treatment allocation since the trial was open label.Stratification factors were tumor cell PD‐L1 expression (≥1% vs <1% including indeterminate), Eastern Cooperative Oncology Group performance status (ECOG PS; 0 vs 1), chemotherapy type (XELOX vs FOLFOX) and region (Asia vs United States and Canada vs rest of world). All patients in the Chinese subgroup analysis were Asian. Additional amendments to the protocol resulted in patients with PD‐L1 CPS ≥5 being the primary population although patients continued to be enrolled regardless of PD‐L1 expression.