(ChemotherapyAdvisor) – Syndax Pharmaceuticals have announced that investigators at the University of Texas M.D. Anderson Cancer Center Department of Breast Medical Oncology have initiated a Phase 1/2 study to assess the safety of combining Syndax’s 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 sponsored by M.D. Anderson, is being conducted in collaboration with the National Cancer Institute (NCI) Division of Cancer Treatment and Diagnosis and GlaxoSmithKline (GSK).
The Phase 1/2 trial is premised on preclinical data that demonstrated entinostat’s ability to overcome acquired resistance to HER2 targeted therapies when combined with lapatinib. The Phase 1 portion of this trial will assess the safety profile of the combination and identify the appropriate dosing regimen to be used in the Phase 2 portion. Translational studies will be conducted to determine the mechanism of action for this combination in tumor cells; such studies which will also help to identify potential biomarkers for patient selection in subsequent studies.
Entinostat is a novel, oral, small-molecule inhibitor of class I histone deacetylases that has been studied in several clinical trials. There are promising results from randomized, placebo-controlled Phase 2 studies with entinostat in combination with aromatase inhibitors in breast cancer (ENCORE 301) and with the EGFR-TKI erlotinib (ENCORE 401) in non-small cell lung cancer.
“With our recently reported positive data in ENCORE 301 targeting ER-positive 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,” commented Joanna Horobin, MD, president and chief executive officer of Syndax.