sirolimus for injection (albumin-bound) combined with fulvestrant for hr+/her2- advanced/metastatic breast cancer patients previously treated with cdk4/6 inhibitors

Conditions: HR+/HER2- Advanced/Metastatic Breast Cancer

Summary: a randomized, double-blind, multicenter phase iii clinical study to evaluate the efficacy and safety of sirolimus for injection (albumin-bound) combined with fulvestrant in patients with hr+ and her2- advanced breast cancer.


Eligibility criteria:
inclusion criteria: * 1. aged 18 or above, regardless of gender; female patients must be postmenopausal, or premenopausal/perimenopausal. * 2. pathologically confirmed hr+, her2- breast cancer. * 3. locally advanced or metastatic breast cancer, not suitable for curative surgery or radiotherapy, and no current clinical indication for chemotherapy. * 4. previously received at least one, up to two lines of systemic therapy (including at least one line of endocrine therapy combined with cdk4/6 inhibitor therapy). * 5. at least one measurable lesion according to recist 1.1 criteria. * 6. willing to provide tumor and/or blood samples for biomarker testing; if unable to provide, subject to investigator and sponsor evaluation for eligibility. * 7. ecog performance status score of 0-1. * 8. investigator-assessed life expectancy ≥6 months. * 9. adequate organ and bone marrow function. * 10. 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 2 years after stopping study treatment; female patients of childbearing potential must have a negative pregnancy blood test before starting study treatment and must not be breastfeeding. * 11. male patients must agree to use barrier contraception (i.e., condoms) during the study and for 2 years after stopping study treatment; for men with future fertility plans, sperm freezing is recommended before starting study treatment. * 12. participants must provide informed consent before the trial and voluntarily sign the written icf. exclusion criteria: * 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, fulvestrant, or other er-targeted therapies (including oral serds, er protein degraders protac, etc.). * 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. * 11. diagnosed with other malignancies within 5 years before randomization. * 12. suffering from severe cardiovascular or cerebrovascular diseases. * 13. adverse reactions from previous anti-tumor treatments have not recovered to ctcae 5.0 grade ≤1. * 14. active leptomeningeal disease or poorly controlled central nervous system metastases. * 15. presence of pleural/abdominal effusion or pericardial effusion with clinical symptoms or requiring symptomatic treatment. * 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.