Syndax Pharmaceuticals, based in Waltham, Mass., and Merck have entered into a clinical trial collaboration to evaluate the safety and efficacy of combining Syndax’s entinostat, an investigational epigenetic therapy, with Merck’s Keytruda (pembrolizumab), the first anti-PD-1 therapy approved in the U.S. The phase Ib/II study will evaluate this novel combination regimen in patients with either advanced non-small cell lung cancer (NSCLC) or melanoma. The study is expected to begin enrolling patients in the second half of 2015.
Entinostat is an oral, highly selective histone deacetylase (HDAC) inhibitor granted Breakthrough Therapy designation in combination with hormone therapy in advanced hormone receptor positive (HR+) breast cancer and currently in phase III testing in this indication. Entinostat has been shown in preclinical models to reduce the number and function of host immune suppressor cells thereby enhancing the anti-tumor activity of immune checkpoint blockade. Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 (programmed death receptor-1) and its ligands, PD-L1 and PD-L2.
The financial terms and additional details of the agreement between Syndax and Merck, through a subsidiary, have not been disclosed. The agreement includes a provision where the parties may extend the collaboration to include a potential phase III clinical trial. The planned phase Ib/II multicenter, open-label clinical trial will be conducted in two parts. The phase Ib portion is designed to determine the safety and tolerability of entinostat in combination with Keytruda. The phase II portion is designed to evaluate the efficacy of entinostat combined with Keytruda in patients with advanced NSCLC and melanoma.