Our primary strategy with entinostat is aimed at treating hormone receptor positive (HR-positive) breast cancer patients in combination with hormone therapy. HR-positive breast cancer refers to cases in which the estrogen receptor or progesterone receptor is expressed alone or in combination with each other. This type of breast cancer represents approximately 70% of all breast cancer cases. We are initially focused on the treatment of men and postmenopausal women with advanced breast cancer 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 may 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: HR-positive 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 HR-positive men and postmenopausal women with hormone refractory, advanced breast cancer. We and the ECOG-ACRIN Cancer Research Group have designed the trial to have two primary endpoints of progression-free survival (PFS) and overall survival. We expect that either endpoint may serve as the basis for submitting a New Drug Application (NDA), if data are positive. The trial will be conducted by the ECOG-ACRIN Cancer Research Group under sponsorship and funding support from the National Cancer Institute (NCI). We are supporting the Phase 3 clinical trial under a Cooperative Research and Development Agreement with the NCI and a separate agreement with the ECOG-ACRIN Cancer Research Group. The protocol for the Phase 3 clinical trial was reviewed and agreed upon by the FDA under a Special Protocol Assessment agreement with the NCI in January 2014. A Special Protocol Assessment agreement is a written agreement on the design and size of clinical trials intended to form the primary basis of a claim of effectiveness in an NDA from the FDA. The ECOG-ACRIN Cancer Research Group activated the trial in March 2014 and we expect patient enrollment to begin in the second quarter of 2014 with PFS data expected in mid-2017.
- ENCORE 305: HR-positive 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 postmenopausal women with HR-positive locally advanced breast cancer. The trial is intended to further study 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 early 2016.
In addition, clinical investigators are further evaluating entinostat combinations in two additional breast cancer patient populations: human epidermal growth factor receptor 2 positive patients; and triple-negative breast cancer patients.