Merck and Syndax Pharmaceuticals have started dosing first patients in the Phase Ib / II clinical trial of entinostat in combination with Keytruda in patients with non-small cell lung cancer (NSCLC) or melanoma.
Entinostat is Syndax’s oral, small molecule that targets immune regulatory cells, while Keytruda (pembrolizumab) is Merck’s anti-programmed cell death protein 1 (anti-PD-1) antibody.
The trial, designated ENCORE 601 by Syndax and KEYNOTE 142 by Merck, is designed to evaluate the safety, tolerability and efficacy of the immuno-oncology combination in these patients.
Syndax chief development officer Michael Meyers said: "This is an important clinical milestone for Syndax and our collaboration with Merck that was achieved on schedule with our joint development plan.
"As entinostat has been shown in preclinical models to reduce the number and inhibit the function of host immune suppressor cells, we believe that entinostat combined with Keytruda could result in an improved response rate for the combination compared to either agent alone.
"The initiation of this trial advances our immuno-oncology program developing entinostat as a potential combination therapy in multiple cancer indications with an initial focus on tumours that have shown sensitivity to immunotherapy."
The trial is designed with dose escalation for entinostat, in which the Phase Ib portion will assess the safety and tolerability of the combination of entinostat and Keytruda in patients with NSCLC, and the second portion will evaluate the safety and preliminary efficacy of the combination in separate cohorts in patients with NSCLC or melanoma.
Up to 178 patients are expected to be enrolled in this open label Phase Ib / II trial, which will be conducted in the US.
Keytruda is a humanised monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2.
The drug is indicated to treat patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor.
Image: Micrograph of a squamous carcinoma, a type of non-small-cell lung carcinoma. Photo: courtesy of Nephron.