Pharmacokinetics analyses showed similar OTX015 levels in plasma and tumor samples 4 h after the last treatment when administrated as a single agent, with values of ~750 ng/ml in plasma, which is equivalent to the 1.5 μM concentration that has strong in vitro activity , and ~750 ng/g of tissue for tumor samples (Figure 2A–2B). Terminal levels of the bromodomain inhibitor in all experimental groups treated with OTX015 in combination, differed from the group exposed to OTX015 as single agent. Co-treatment with ibrutinib or everolimus induced an increase in OTX015 concentrations both in plasma (Figure 2A) and tumor samples (Figure 2B). On the other hand, treatment with rituximab decreased OTX015 accumulation in the tumor tissue and OTX015 was not detected in plasma samples in mice concomitantly receiving vorinostat. These results are based on a limited number of mice but suggest that extended pharmacokinetic/pharmacodynamic studies should be mandatory in phase I combination studies to explore the behavior of OTX015 when administered with other agents.