A Trial of HRS-6209 in Combination With Fulvestrant, Letrozole, HRS-8080, or HRS-1358 in Breast Cancer Patients

Inclusion Criteria: 1. Females aged 18-75 years (inclusive); 2. ECOG performance status (PS) score of 0-1; 3. Patients with histopathologically confirmed metastatic or unresectable locally advanced breast cancer; 4. Patients with advanced malignant solid tumors confirmed by histopathology or cytopathology, who have failed standard treatment, or for whom no effective standard treatment regimen is available, or who are unable to receive further standard treatment. 5. Menopausal status: 1. Having had bilateral oophorectomy, or aged ≥ 60 years old; or 2. Aged \< 60, natural menopause (defined as spontaneous cessation of regular menses for at least 12 consecutive months in the absence of other pathological or physiological causes) with E2 and FSH at postmenopausal levels; or 3. Premenopausal or perimenopausal patients, agree to start or continue receive LHRH agonists during the study (exclude from the QT/QTc group). 6. Disease progression evidenced by imaging during or after the last systemic anti-tumor treatment prior to the first dose (limited to the efficacy expansion stage); 7. With at least one extracranial measurable target lesion at baseline per RECIST v1.1; 8. Life expectancy of \> 3 months; 9. Adequate organ and marrow function as defined by the protocol;Female subjects of childbearing potential should agree to adopt effective contraceptive measures during the study period and within 7months after the end of the study treatment; female subjects of childbearing potential must have a negative serum HCG test result within 7 days before enrollment in the study and must not be in the lactation; 10. Voluntarily participate in this clinical study, be willing and able to comply with procedures related to clinical visits and study, and understand and have signed written informed consent. Exclusion Criteria: 1. With symptomatic visceral metastases deemed unfit for endocrine therapy by the investigator; 2. With active brain metastases, carcinomatous meningitis, spinal cord compression, or a history of primary tumors of the central nervous system; 3. History of clinically significant cardiovascular disease, including; 4. Abnormal ECG findings, which are judged by the investigator to be clinically significant and and need to intervene; 5. Previous use of fulvestrant for cohort of HRS-6209 in combination with fulvestrant (efficacy expansion stage). 6. With factors that affect oral medication, active gastrointestinal diseases, or other diseases that may obviously affect drug absorption, distribution, metabolism, or excretion; 7. With clinically significant endometrial abnormalities, including but not limited to endometrial hyperplasia and dysfunctional uterine bleeding; 8. Active infection or unexplained fever \> 38.5 °C during the screening period or on the day of first dose; 9. With uncontrollable chronic systemic complications as judged by the investigator. 10. With active autoimmune diseases, history of immunodeficiency and history of autoimmune diseases, history of diseases or syndromes that require systemic corticosteroids or immunosuppressive drugs, other acquired (HIV infection) or congenital immunodeficiency, or history of organ transplantation (including allogeneic bone marrow transplantation); 11. With acute infection or active tuberculosis requiring medication. 12. With a known history of clinically significant liver disease, untreated active hepatitis; 13. Had other concurrent malignant tumors in the past 5 years, except: 1. Cervical carcinoma in situ that has been cured, 2. Second primary cancer that has been cured without recurrence within five years; 14. Use of moderate and strong CYP3A4 inhibitors within 1 week or moderate and strong CYP3A4 inducers within 2 weeks prior to the first dose; 15. Use of any drugs with the risk of prolonging QT/QTc interval or causing torsade de pointes (TdP) within 4 weeks prior to the first dose, and with previous congenital QT interval prolongation syndrome or a family history of QT interval prolongation, implanted pacemakers or automatic implantable cardioverter defibrillators, uncorrectable electrolyte disorders, and other factors that may affect the QT/QTc study; 16. Surgical treatment (except for needle biopsy or PICC catheterization or PORT catheterization), chemotherapy (except for 5-Fu drugs), immunotherapy, macromolecular targeted therapy, etc. within 4 weeks before the first dose; Received endocrine therapy, 5-FU chemotherapy or radiotherapy within 2 weeks before the first dose; Small molecule targeted drugs need to be washed out for 2 weeks or 5 half-lives (whichever is longer); 17. Pregnant or lactating women, or females planning to become pregnant during the study period; 18. With clear history of neural or mental disorders or with history of psychotropic abuse or drug abuse; 20\) Subjects who are expected to receive other anti-tumor therapies or drugs during this study.