Although no peri-operative trials of B7-H3 blockade have yet been reported, early-phase data from recurrent/metastatic disease provide proof-of-concept: in a multicentre phase I/II trial, 18 PD-L1-negative, platinum-refractory HNSCC patients treated with the Fc-optimized B7-H3 monoclonal antibody enoblituzumab (MGA271) plus pembrolizumab achieved an objective response rate of 33% and a disease-control rate of 72%, with grade ≥3 immune-related adverse events in 11% [76]. This evidence concerns the gene CD276 and metastatic neoplasm.