Phase 2 Study of KHK2375 in Subjects With Advanced or Recurrent Breast Cancer

Exclusion Criteria

• •1. Endocrine therapy (except for LH-RH agonist), treatment with everolimus, treatment with a cyclin-dependent kinase inhibitor, or radiation therapy within 14 days before enrollment
• •Subjects with prior treatment with exemestane may be enrolled if they meet either of the following criteria:
• •* Start of treatment with exemestane for advanced or recurrent breast cancer within 28 days before enrollment
• •* Recurrence-free period \>12 months after completion of treatment with exemestane as postoperative adjuvant therapy. For painful bone lesions or impending fractures, radiation therapy may be used concomitantly if there is a measurable or nonmeasurable lesion that is suitable for efficacy evaluation in a region other than the radiation field
• •2. Two or more prior chemotherapy regimens for advanced or recurrent breast cancer
• •3. Chemotherapy within 21 days before enrollment
• •4. Treatment with bisphosphonates or anti-RANKL antibody that is scheduled to be started within 7 days before the first dose of investigational product
• •5. History of or current central nervous system metastasis, or current leptomeningeal or periosteal disease
• •6. History of cancer other than breast cancer within 5 years, or concurrent cancer other than breast cancer (except for basal cell carcinoma of skin, squamous cell carcinoma of skin, and intraepithelial carcinoma of uterine cervix).Subjects continuing to receive treatment for cancer other than breast cancer are ineligible for enrollment
• •7. Ongoing treatment with any other anticancer therapy or investigational product (Except for treatment with exemestane or radiotherapy as described in exclusion criterion 1)
• •8. Prior treatment with histone deacetylase inhibitor (e.g. valproate, vorinostat)
• •9. Known allergy to imidazoles, exemestane, or entinostat
• •10. Any medical or psychiatric condition that could affect compliance with the protocol, ability to give consent, or assessment of anticipated toxicities
• •11. Uncontrolled complications (e.g., active infections)
• •12. Positive for either hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus antibody
• •13. Any other conditions unsuitable for the study in the opinion of the investigator or subinvestigator