A Study of SHR6390 in Combination With Letrozole or Anastrozole or Fulvestrant in Patients With HR Positive and HER2 Negative Advanced Breast Cancer

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

This is a phase IB/II clinical trial to evaluate the efficacy and safety of SHR6390 in combination with Letrozole or Anastrozole or Fulvestrant. Patients who have HR positive and HER2 negative recurrent/metastatic breast cancer and have not received systemic anticancer therapy are eligible for study.

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.