Lung-MAP S1400I: nivolumab with or without ipilimumab

S1400I was the non-match sub-study of Lung-MAP for patients whose tumours carried none of the platform's targetable alterations and who had not yet received immunotherapy. It randomised 275 patients with previously treated squamous non-small-cell lung cancer to nivolumab plus ipilimumab or nivolumab alone, with overall survival as the primary endpoint.

The trial was stopped for futility at an interim analysis and published in JAMA Oncology in 2021 by Scott Gettinger and colleagues: the combination did not improve overall or progression-free survival or response rate, and grade 3 or worse side effects were more common with ipilimumab. Exploratory analyses did not find a subgroup, including by tumour mutational burden or PD-L1, that clearly benefited.

The result matters because it was produced quickly inside an existing platform rather than by building a new trial, and because it tempered enthusiasm for doublet checkpoint blockade in squamous lung cancer after CheckMate 227 had shown a benefit in a different setting. Lung-MAP's later immunotherapy sub-studies moved to combinations with other classes, such as ramucirumab in S1800A.