A Phase IB/II to Evaluate Efficacy and Safety of SHR6390 in Combination With Letrozole or Anastrozole or Fulvestrant in Patients With HR Positive and HER2 Negative Recurrent/Metastatic Breast Cancer

Date de début de l'étude : 22 mars 2018

Inclusion Criteria: 1. Has the pathologically-confirmed diagnosis of locally recurrent or metastatic, hormone-receptor positive, HER2 negative Breast Cancer. 2. Age: 18 - 75 years old, postmenopausal women.prepostmenopausal women, but should receive Ovary castration. Inclusion Criteria 3. Cohort 1 and Cohort 2 :No prior systemic anti-cancer therapy for advanced HR+ disease. Cohort 3 and Cohort 4 : Patients must satisfy the following criteria for prior therapy: 1. a) Progressed after 2 years during treatment of adjuvant therapy with an aromatase inhibitor if postmenopausal, or tamoxifen if pre- or perimenopausal. b)Progressed within 12 months of completion of adjuvant therapy with an aromatase inhibitor if postmenopausal, or tamoxifen if pre- or perimenopausal. c) Progressed while 6 month after the end of prior aromatase inhibitor therapy for advanced/metastatic breast cancer if postmenopausal, or prior endocrine treatment for advanced/metastatic breast cancer if pre- or perimenopausal. 2. One previous line of chemotherapy for advanced/metastatic disease is allowed in addition to endocrine therapy. 4\. Eastern Cooperative Oncology Group \[ECOG\] 0-1 Measurable disease as per Response Evaluation Criterion in Solid Tumors\[RECIST\] 1.1 5\. Adequate organ and marrow function Exclusion Criteria 1. Confirmed diagnosis of HER2 positive disease 2. Patients who received any endocrine therapy as neo/adjuvant therapy for breast cancer are eligible. If the neo/adjuvant therapy of any endocrine therapy , the disease-free interval must be greater than 12 months from the completion of treatment until study entry. 3. Patients who received prior treatment with any CDK4/6 inhibitor, everolimus,fulvestant. 4. Clinically significant cardiovascular and cerebrovascular diseases,including but not limited to severe acute myocardial infarction within 6 months before enrollment, unstable or severe angina, Congestive heart failure (New York heart association (NYHA) class \> 2), or ventricular arrhythmia which need medical intervention. 5. Has known active central nervous system metastases.