CD274 and neoplasm: In 2016’s KEYNOTE-012 phase Ib trial, the safety, tolerability, and anti-tumor activity of pembrolizumab were first established in patients with R/M HN scc regardless of PD-L1 expression status, with 17% of patients having grade 3 or 4 adverse events (primarily, transaminitis, hyponatremia, and one case of drug-related rash) [51].