Our primary strategy with entinostat is aimed at treating estrogen receptor positive (ER+) breast cancer patients in combination with hormone therapy. ER+ breast cancer refers to cases in which the estrogen receptor with or without the progesterone receptor is expressed. This type of breast cancer represents approximately 70% of all breast cancer cases. We are initially focused on the treatment of postmenopausal patients with advanced disease who have progressed after standard of care hormonal agents. Despite advances in the diagnosis and treatment of these patients, most will progress with an expected survival of approximately 18 to 24 months. We believe that our strategy to overcome resistance to hormonal agents with entinostat can improve outcomes for breast cancer patients.
Building on the statistically significant results shown in the Phase 2b clinical trial, ENCORE 301, we have the following two trials planned, which combine entinostat with approved therapies in our target patient populations in advanced breast cancer:
- E2112: ER+ Advanced Breast Cancer—Pivotal Registration Trial. This pivotal Phase 3 clinical trial is designed to be a double-blind, placebo-controlled, trial of exemestane with or without entinostat in 600 patients with ER+ postmenopausal, hormone refractory, advanced breast cancer. The trial has co-primary endpoints of progression-free survival (PFS) and overall survival, and either endpoint could be the basis for submitting a New Drug Application (NDA), if positive. The trial will be conducted by the Eastern Cooperative Oncology Group – American College of Radiology Imaging Network and the National Cancer Institute (NCI), and with substantial funding provided through our existing Clinical Research and Development Agreement with the NCI. The protocol for the Phase 3 clinical trial was reviewed and agreed upon by the FDA under a Special Protocol Assessment (SPA) agreement with the NCI in January 2014. Enrollment in this trial is expected to begin in the first half of 2014 with PFS data expected in mid-2017.
- ENCORE 305: ER+ Advanced Breast Cancer—Biomarker and Efficacy Trial. This Phase 2 clinical trial is designed as a randomized, double-blind, placebo-controlled, trial of fulvestrant with or without entinostat in 180 patients with ER+ postmenopausal, locally advanced breast cancer. The trial is intended to confirm the association between a potential biomarker of entinostat activity and clinical outcome identified in ENCORE 301. In addition, we expect the trial to inform us as to whether the clinical benefit observed in combination with exemestane in ENCORE 301 can be extended to a second hormone therapy, fulvestrant. The primary endpoint of the trial is PFS. We anticipate initiating this trial in mid-2014 with interim PFS data expected in late 2015.
In addition, we are currently collaborating with the NCI and investigators on combination trials of entinostat with other therapies for human epidermal growth factor receptor 2 positive breast cancer and triple-negative breast cancer.