Syndax Pharmaceuticals, Inc., a clinical stage biopharmaceutical company, and Merck, a global health care leader, announced the dosing of the first patient in the phase 1b/2 clinical trial of Syndax’s entinostat in combination with Merck’s anti-PD-1 therapy Keytruda (pembrolizumab) in patients with non-small cell lung cancer (NSCLC) or melanoma.

The clinical trial, designated ENCORE 601 by Syndax and KEYNOTE 142 by Merck, is evaluating the safety, tolerability and efficacy of entinostat, an oral, small molecule that targets immune regulatory cells, combined with Keytruda, an anti-programmed cell death protein 1 (anti-PD-1) antibody.

“This is an important clinical milestone for Syndax and our collaboration with Merck that was achieved on schedule with our joint development plan,” said Michael L. Meyers, M.D., Ph.D., Syndax’s chief development officer.

“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 tumors that have shown sensitivity to immunotherapy.”

“Our collaboration with Syndax exemplifies our interest in exploring innovative therapeutic combinations with Keytruda,” said Eric Rubin, M.D., vice president and therapeutic area head, early-stage oncology development, Merck Research Laboratories.

“We are pleased with the rapid initiation and progress being made by Syndax towards gaining a better understanding of the potential of Keytruda and entinostat in these difficult-to-treat patient populations.”

The ENCORE 601/KEYNOTE 142 trial is designed as a phase 1b/2 open label clinical trial with dose escalation for entinostat, in which the Phase 1b portion will evaluate the safety and tolerability of the combination of entinostat and Keytruda in patients with NSCLC, and the phase 2 portion will assess the safety and preliminary efficacy of the combination in separate cohorts in patients with NSCLC or melanoma. The trial will be conducted in the United States and is expected to enroll up to 178 patients.

Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. By binding to the PD-1 receptor and blocking the interaction with the receptor ligands, Keytruda releases the PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. Keytruda is indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. This indication is approved under accelerated approval based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

The most common adverse reactions (reported in at least 20 per cent of patients) were fatigue (47 per cent), cough (30 per cent), nausea (30 per cent), pruritus (30 per cent), rash (29 per cent), decreased appetite (26 per cent), constipation (21 per cent), arthralgia (20 per cent), and diarrhea (20 per cent).

The recommended dose of Keytruda is 2 mg/kg administered as an intravenous infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity. No formal pharmacokinetic drug interaction studies have been conducted with Keytruda.