Jeffrey Weber, MD, PhD from the NYU Langone Medical Center, New York, NY discusses what he hopes to achieve with an upcoming Phase I, triple combination therapy trial in metastatic melanoma while at the 2016 World Congress on Cancers of the Skin (WCCS) and the Congress of the European Association of Dermato-Oncology (EADO) in Vienna, Austria. Prof. Weber begins by explaining how at the beginning of a treatment regimen with high response rate and outstanding survival, tolerability and toxicity are assessed in order to determine if a third drug, like a histone deacetylator (HDAC) inhibitor can be added to the backbone of ipilimumab and nivolumab. Correlative studies carried out alongside can help to understand which genes are altered in their expression when the HDAC inhibitor is given in combination with ipilimumab and nivolumab. In addition peripheral blood parameters will be monitored at baseline to see if they are predictive of patient outcome. Ultimately, Prof. Weber says that if the triple combinations are well tolerated, a randomised Phase II trial should be considered for the triple combination compared to the double combination of ipilimumab and nivolumab.