Syndax Pharmaceuticals, Inc., a late-stage oncology company focused on the clinical development of epigenetic therapies in solid tumors, announced that previously reported results from ENCORE 401, a randomized, placebo controlled Phase 2 study of erlotinib with or without entinostat in advanced non-small cell lung cancer patients were published in the Journal of Clinical Oncology (JCO). The article entitled, "Randomized Phase II Trial of Erlotinib With and Without Entinostat in Advanced Non-Small Cell Lung Cancer Patients Who Progressed on Prior Chemotherapy" was featured in the April 12th JCO online edition of the journal.
The study was based on preclinical observations that entinostat can reverse and/or delay the emergence of epigenetically driven resistance to epidermal growth factor receptor inhibitors such as erlotinib in NSCLC tumors. The results from ENCORE 401 confirmed the preclinical findings and demonstrated an improved overall survival in the subset of NSCLC patients with tumors expressing elevated levels of E-cadherin (a molecular marker of epithelial tumors and EGFRi sensitivity). In an accompanying JCO Understanding the Pathways article the authors note "The clinical data thus partially recapitulate the laboratory work, suggesting that HDAC inhibitors can preserve a pre-existing epithelial phenotype and that such patients will demonstrate sensitivity to erlotinib for a longer period of time."
Based on these findings Syndax recently partnered with Ventana Medical Systems to develop an E-cadherin companion diagnostic assay to select those NSCLC patients with elevated E-cadherin levels in their tumor cells for treatment with erlotinib and entinostat in the confirmatory study.