A Study of SHR-A1811 and Fulvestrant, With or Without HS-10352, in Locally Advanced or Metastatic Breast Cancer Patients

Inclusion Criteria:

1. Female patients aged ≥18 years and ≤75 years;

2. ECOG Performance Status of 0 -2;

3. Locally advanced/metastatic breast cancer not amenable to curative therapy

4. Disease progression during treatment or within 12 months of completing adjuvanttherapy ;

5. No prior anti-cancer systemic therapy has been administered;

6. Fasting blood glucose < 126 mg/dL, and HbA1C < 6.0%;

7. Life expectancy of ≥3 months;

8. Patients have at least one target lesion according to RECEST 1.1;

9. Adequate function of major organs;

10. Female patients who are either premenopausal or have not undergone surgicalsterilization: during the treatment period and for at least 7 months after the finaldose of study medication, agree to abstain from sexual activity or utilize effectivecontraceptive methods.

11. Sign Informed Consent Form.

Exclusion Criteria:

1. Breast cancer that has not been histologically confirmed;

2. Inflammatory breast cancer;

3. Participants ineligible for endocrine therapy due to any disease burden, as judgedby the investigator;

4. Meningeal metastasis or active parenchymal brain metastasis;

5. Presence of diabetes symptoms, history of primary diabetes, gestational diabetes,steroid-induced diabetes, or other secondary diabetes;

6. Prior anti-cancer systemic therapy has been administered;

7. Use of investigational drugs within 4 weeks；

8. Received immunotherapy, macromolecular targeted therapy, or other antitumorbiologics within 4 weeks; or received endocrine therapy, chemotherapy, smallmolecule targeted drug therapy, or traditional Chinese medicine treatment withantitumor indications within 2 weeks;

9. Received radical radiotherapy within 4 weeks, or received palliative radiotherapywithin 2 weeks;

10. Previously received antitumor treatment or radiotherapy for any malignancy,excluding malignancies such as cured cervical carcinoma in situ, basal cellcarcinoma, or squamous cell carcinoma;

11. A history of other malignancies within the past 5 years, excluding cured cases ofskin basal cell carcinoma and cervical carcinoma in situ;

12. Prior anti-tumor treatment toxicities have not yet recovered to NCI CTCAE V5.0 grade ≤1 or baseline levels;

13. A history of immunodeficiency, including HIV positivity, other acquired orcongenital immunodeficiency diseases, or a history of organ transplantation;

14. Interstitial pneumonia/interstitial lung disease, or presence of moderate to severepulmonary disease that may interfere with the detection or management ofdrug-related pulmonary toxicity within 3 months prior to the first administration ofthe study drug, as well as any autoimmune, connective tissue, or inflammatorydiseases involving the lungs, or a history of total pulmonary resection surgery

15. Presence of active hepatitis B, hepatitis C, liver cirrhosis, or severe infectionsrequiring control with antibiotics, antiviral drugs, or antifungal medications;

16. History of hereditary or acquired bleeding and thrombotic tendencies (such ashaemophilia, coagulation disorders, etc.);

17. Inability to swallow, intestinal obstruction, or the presence of other factorsaffecting drug intake and absorption;

18. Patients with known allergies or contraindications to the study drug and itsexcipient components;

19. Female patients who are pregnant or lactating, those of reproductive potential witha positive baseline pregnancy test, or those of reproductive age who are unwillingto use effective contraceptive measures throughout the entire study period;

20. According to the investigator's judgment, patients with severe concomitant diseasesthat pose a risk to their safety or prevent them from completing the study, ahistory of definite neurological or psychiatric disorders, including epilepsy ordementia, or any other condition deemed by the investigator to make the patientunsuitable for participation in this study.