CD274 and metastatic melanoma: Vorinostat is an HDAC inhibitor that has shown a higher ORR when combined with pembrolizumab versus pembrolizumab alone (48% versus 25%, P = 0.026) in advanced PD-L1 > 1% NSCLC in the preliminary results of a phase II trial in 47 patients, with patients in the combination arm experiencing more fatigue, anorexia, and nausea, but with grade 3 or higher adverse events in only one out of 23 patients (51), while Etinostat, another HDAC inhibitor, associated with pembrolizumab, produced a 19% ORR in patients with metastatic melanoma pretreated with anti-PD-1/PD-L1 drugs (52).