JCO publishes Syndax erlotinib-entinostat Phase 2 study for advanced non-small cell lung cancer

Apr 30 2012

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.

"The positive results from this trial, while preliminary, offer exciting possibilities for the future," said Paul A. Bunn, Jr, MD, professor, James Dudley Chair in cancer research, School of Medicine, division of medical oncology, University of Colorado.  "The use of E-cadherin appears to be an excellent predictive biomarker to select patients, especially those with wild type EGFR for this combination therapy.  For these patients, the combination may provide an important improvement in the small benefit of erlotinib therapy.  Patients with EGFR mutations usually have high E-cadherin levels and may also have great benefit from this combination with a higher response and longer duration of remission. Of course, further studies in both of these groups of patients will be necessary to confirm these observations."

"The data published in JCO adds to the growing body of clinical data supporting the promise for entinostat and our continued development of epigenetic strategies to overcome resistance to standard of care agents in solid tumors," said Joanna Horobin, MD, president of Syndax.  "Given this NSCLC data plus our recently reported positive data with entinostat in advanced breast cancer patients, we are eager to initiate our pivotal programs and ultimately provide new treatment options based on a backbone of epigenetic therapy to cancer patients."

SOURCE Syndax Pharmaceuticals, Inc.