• Patients must understand and voluntarily sign the Informed Consent Form (ICF).

• Patients ≥ 18 years, female.

• Provision of blood sample to test ESR1 mutation status and for other biomarker assessment. In part A/B, the ESR1 mutation status will be tested retrospectively; In part C, only the patients with ESR1 mutation positive is eligible.

• Documented positive oestrogen receptor status of primary or metastatic tumour tissue, according to the local laboratory parameters. HER-2 negative. These laboratory parameters are consistent with accepted diagnostic guidelines such as the American Society of Clinical Oncology (ASCO) / College of American Pathologists (CAP) Clinical Practice Guideline for Pathologists estrogen (ER) and progesterone receptor (PgR) testing in breast cancer (Allison et al., 2020). HER2- defined as an Immunohistochemistry (IHC) status of 0, 1+ or negative by in situ hybridization test.

• Menopausal women according to one of the following criteria:

∙ Prior bilateral ovariectomy;

‣ Patients ≥ 60 years of age;

‣ Patients \< 60 years of age presenting an amenorrhea of more than 12 months and follicle stimulating hormone (FSH) and plasma estradiol levels within the postmenopausal range as assessed by the local laboratory in the absence of chemotherapy, tamoxifen, tolimifene, or ovarian castration in the past 1 year, and no oral contraceptives, hormone replacement therapy, or gonadotropin-releasing hormone agonist or antagonist;

‣ Patients \< 60 years of age who are taking either tamoxifen or tolomifene with two consecutive FSH and estradiol levels in the postmenopausal range.

‣ Or premenopausal or perimenopausal female subjects but must be willing to receive and maintain an approved luteinizing hormone-releasing hormone(LHRH) agonist during the study treatment period (LHRH agonist treatment initiated 28 days prior to the first study drug treatment);

• Previous therapy failed or intolerable, or standard therapy not available:

• Part A：Previous therapy failed or intolerable, or standard therapy not available； Prat B/C：Patients should have received at least 1 line endocrinotherapy, or received no more than 1-line systematic chemotherapy for advanced/metastatic disease, no more than 1 target therapy.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

• At least one measurable lesion according to RECISTv1.1 criteria.

• Life expectancy ≥ 12 weeks.

⁃ Adequate organ and bone marrow function (no use of hematopoietic stimulating factor, no blood transfusion or human albumin within 7 days prior to screening):

• Blood routine: Absolute neutrophil count (ANC) ≥ 1.5×109/L; Platelet count (PLT) ≥100×109/L; Hemoglobin (HGB) ≥ 90 g/L;

∙ Liver function: Serum Total bilirubin (TBIL) ≤ 1.5 Upper limit of normal value (ULN); Alanine aminotransferase (ALT) and Aspartate transferase (AST) ≤ 3×ULN in subjects without liver metastasis; ALT or AST≤ 5×ULN with liver metastasis;

∙ Renal function: Serum creatinine ≤ 1.5×ULN or estimated creatinine clearance (CLcr) ≥ 60 mL/min as calculated using Cockcroft-Gault formula;

∙ Coagulation function: Activated Partial thromboplastin Time (APTT) and international normalized ratio (INR) ≤ 1.5×ULN (or within target range if on anticoagulation therapy);

∙ Cardiac function: Echocardiography (ECHO) shows left ventricular ejection fraction (LVEF) \> 50%.

⁃ Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose. Female patients of childbearing potential must agree to use effective methods of contraception from the time of signature of informed consent, throughout the study and for 6 months after the last dose of the investigational product, like double barrier methods, condoms, oral or injectable contraceptives, intrauterine devices, etc. All female subjects will be considered to be of childbearing potential unless they are postmenopausal, postmenopausal, or sterilized (hysterectomy, tubal resection).