Sirolimus for Injection (Albumin-bound) in Combination With Endocrine Therapy for HR+/HER2- Advanced/Metastatic Breast Cancer Patients Who Have Failed Standard Therapy

Prior treatment

• 1\. Previous pathological diagnosis of HER2-positive breast cancer.
• 2\. Patients judged by the investigator to be unsuitable for endocrine therapy.
• 3\. Patients who have previously received PI3K/AKT/mTOR inhibitors.
• 4\. Received chemotherapy, radiotherapy, biological therapy, targeted therapy, immunotherapy, or other anti-tumor treatments within 4 weeks before randomization.
• 5\. Received other unapproved investigational drugs within 4 weeks before randomization.
• 6\. Underwent major surgery within 4 weeks before randomization or has not fully recovered from any previous invasive procedures.
• 7\. Received systemic glucocorticoids (prednisone \>10 mg/day or equivalent) or other immunosuppressive treatments within 2 weeks before randomization.
• 8\. Had an infection within 2 weeks before randomization requiring systemic (oral or IV) anti-infective treatment (uncomplicated urinary tract infections or upper respiratory tract infections excluded).
• 9\. Received inactivated or live attenuated vaccines or COVID-19 vaccines within 4 weeks before randomization.
• 10\. Used strong inhibitors or inducers of CYP3A4 hepatic metabolic enzymes within 2 weeks before randomization or still need to continue using such drugs.
• 13\. Adverse reactions from previous anti-tumor treatments have not recovered to CTCAE 5.0 grade ≤1.

Other illness

• 11\. Diagnosed with other malignancies within 5 years before randomization.
• 12\. Suffering from severe cardiovascular or cerebrovascular diseases.
• 14\. Active leptomeningeal disease or poorly controlled central nervous system metastases.
• 16\. Known bleeding tendency (constitution) or coagulation disorders.
• 17\. History of severe lung diseases such as interstitial lung disease and/or pneumonia, pulmonary hypertension, or radiation pneumonitis requiring glucocorticoid treatment.
• 18\. Known hypersensitivity or intolerance to any component of the study drug or its excipients, or LHRH agonists (if applicable).
• 19\. History of autoimmune diseases (except tuberous sclerosis), immunodeficiency diseases, including HIV-positive, or other acquired or congenital immunodeficiency diseases, or organ transplant history.
• 20\. Active HBV, HCV, syphilis, or tuberculosis infection.
• 21\. Other conditions judged by the investigator to be unsuitable for participation in this study.

Other

• 15\. Presence of pleural/abdominal effusion or pericardial effusion with clinical symptoms or requiring symptomatic treatment.

• 1\. Aged 18 or above, regardless of gender; female patients must be postmenopausal, or premenopausal/perimenopausal.
• 2\. Pathologically confirmed HR+, HER2- breast cancer.
• 3\. Patients who have failed prior treatment with AI or fulvestrant with or without CDK4/6 inhibitors.
• 4\. No more than 3 lines of chemotherapy for inoperable locally advanced or metastatic disease.
• 5\. At least one measurable lesion according to RECIST 1.1 criteria. Patients with bone lesions only may be eligible.
• 6\. ECOG performance status score of 0-1.
• 7\. Investigator-assessed life expectancy ≥3 months.
• 8\. Adequate organ and bone marrow function.
• 9\. Baseline fasting serum triglyceride \<300mg/dL or 3.42mmol/L, fasting serum cholesterol \<350mg/dL or 9.07mmol/L
• 10\. The baseline fasting plasma glucose (FPG) ˂ 7.8 mmol/L and glycosylated hemoglobin (HbA1c) ˂ 8%
• 11\. Premenopausal female patients using LHRH agonists to suppress ovarian function must agree to use two acceptable forms of highly effective contraception during the study and for 6 months after stopping study treatment; female patients of childbearing potential must have a negative pregnancy test before starting study treatment and must not be breastfeeding.
• 12\. Male patients must agree to use barrier contraception (i.e., condoms) during the study and for 6 months after stopping study treatment; for men with future fertility plans, sperm freezing is recommended before starting study treatment.
• 13\. Participants must provide informed consent before the trial and voluntarily sign the written ICF.