Syndax Pharmaceuticals, a clinical-stage epigenetics oncology company based in Waltham, Mass., has initiated a phase I/II study combining its lead product entinostat with lapatinib ditosylate (Tykerb) in patients with locally recurrent or distant relapsed metastatic breast cancer previously treated with trastuzumab (Herceptin).

The study, which is being conducted at the University of Texas MD Anderson Cancer Center's department of breast medical oncology, is in collaboration with the National Cancer Institute's (NCI) division of cancer treatment and diagnosis and GlaxoSmithKline (GSK). Preclinical data has demonstrated that entinostat, a novel, selective histone deacetylase inhibitor can overcome acquired resistance to HER2 targeted therapies when combined with lapatinib.

"Based on preclinical work conducted by Syndax's collaborators, GSK scientists and our own laboratory, we believe entinostat may be effective in tackling the resistance pathways that contribute to the reduced efficacy of HER2-targeted agents in breast cancer patients progressing on such therapies," said Naoto T. Ueno, MD, PhD, FACP, principle investigator of the study and executive director, Morgan Welch inflammatory breast cancer program and clinic, MD Anderson Cancer Center. "With the data we have generated, we are particularly excited to test this combination in patients with inflammatory breast cancer, a subset of breast cancer often expressing HER2 for whom there are few effective treatment options.

The phase I portion of the study will characterize the safety profile of the combination and identify the appropriate dosing regimen to be used in the phase II portion. Translational studies will provide valuable insight into the mechanism of action for the combination in tumor cells while potentially identifying biomarkers for patient selection in subsequent studies.

"This study represents our continued commitment to work with the NCI and our industry and academic collaborators to expand the ENCORE (ENtinostat Combinations Overcoming REsistance) platform aimed at overcoming resistance to targeted therapies in breast cancer and other solid tumors," said Joanna Horobin, MD, president and CEO of Syndax. "With our recently reported positive data in ENCORE 301 targeting ER+ breast cancer and the NCI sponsored study NCT01234532 combining entinostat with Arimidex in ER-, PR-, HER2- triple negative breast cancer, we are pleased to be in a position to provide proof-of-concept clinical data across all segments of breast cancer."