a study of shr-a1811 and fulvestrant, with or without hs-10352, in locally advanced or metastatic breast cancer patients

Conditions: Breast Cancer; Locally Advanced or Metastatic Breast Cancer

Summary: this study is being conducted to evaluate the efficacy and safety of shr-a1811 and fulvestrant in combination with or without hs-10352 in locally advanced or metastatic breast cancer patients. subjects will receive shr-a1811 and fulvestrant in combination with or without hs-10352.

this study plans to enroll breast cancer patients whose disease progressed during treatment or within 12 months of completing adjuvant therapy and who have not received prior systemic therapy. shr-a1811 + fulvestrant group will receive treatment with shr-a1811 and fulvestrant. hs-10352 group will receive treatment with shr-a1811, fulvestrant, and hs-10352. treatment will continue until disease progression or the occurrence of intolerable toxicity.

Eligibility criteria:
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 adjuvant therapy ; 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 surgical sterilization: during the treatment period and for at least 7 months after the final dose of study medication, agree to abstain from sexual activity or utilize effective contraceptive 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 judged by 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 antitumor biologics within 4 weeks; or received endocrine therapy, chemotherapy, small molecule targeted drug therapy, or traditional chinese medicine treatment with antitumor indications within 2 weeks; 9. received radical radiotherapy within 4 weeks, or received palliative radiotherapy within 2 weeks; 10. previously received antitumor treatment or radiotherapy for any malignancy, excluding malignancies such as cured cervical carcinoma in situ, basal cell carcinoma, or squamous cell carcinoma; 11. a history of other malignancies within the past 5 years, excluding cured cases of skin 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 or congenital immunodeficiency diseases, or a history of organ transplantation; 14. interstitial pneumonia/interstitial lung disease, or presence of moderate to severe pulmonary disease that may interfere with the detection or management of drug-related pulmonary toxicity within 3 months prior to the first administration of the study drug, as well as any autoimmune, connective tissue, or inflammatory diseases involving the lungs, or a history of total pulmonary resection surgery 15. presence of active hepatitis b, hepatitis c, liver cirrhosis, or severe infections requiring control with antibiotics, antiviral drugs, or antifungal medications; 16. history of hereditary or acquired bleeding and thrombotic tendencies (such as haemophilia, coagulation disorders, etc.); 17. inability to swallow, intestinal obstruction, or the presence of other factors affecting drug intake and absorption; 18. patients with known allergies or contraindications to the study drug and its excipient components; 19. female patients who are pregnant or lactating, those of reproductive potential with a positive baseline pregnancy test, or those of reproductive age who are unwilling to use effective contraceptive measures throughout the entire study period; 20. according to the investigator's judgment, patients with severe concomitant diseases that pose a risk to their safety or prevent them from completing the study, a history of definite neurological or psychiatric disorders, including epilepsy or dementia, or any other condition deemed by the investigator to make the patient unsuitable for participation in this study.

Keywords: breast cancer shr-a1811 hs-10352