CheckMate 227

CheckMate 227 was a large open-label phase 3 programme in previously untreated advanced non-small-cell lung cancer without EGFR or ALK alterations. Part 1 randomised patients by PD-L1 status to nivolumab plus low-dose ipilimumab, nivolumab alone or nivolumab plus chemotherapy (PD-L1 of 1 percent or more), or to nivolumab plus ipilimumab or nivolumab plus chemotherapy (PD-L1 below 1 percent), each against platinum doublet chemotherapy. The co-primary endpoints were progression-free survival in tumours with high mutational burden and overall survival in PD-L1-positive tumours.

Nivolumab plus ipilimumab lengthened overall survival compared with chemotherapy in patients whose tumours expressed PD-L1 at 1 percent or more, and the benefit also appeared in the PD-L1-negative group. The tumour mutational burden endpoint did not translate into an overall survival difference. The combination was approved in the United States in May 2020 for PD-L1-positive disease, and the long-term follow-up has shown a tail of durable survivors in both PD-L1 groups.