HR+/HER2- Advanced/Metastatic Breast Cancer
Conditions
Brief 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.
Interventions
IV infusion, every 2 weeks, 4 weeks per treatment cycle
IM injection, 500 mg, on day 1 and day 15 of Cycle 1, and then on day 1 of each cycle thereafter, 4 weeks per treatment cycle
DRUGPlacebo for Sirolimus for Injection (Albumin-bound)
IV infusion, every 2 weeks, 4 weeks per treatment cycle
Sponsors
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free Survival（PFS） | Up to ~24 months |
Secondary
| Measure | Time frame |
|---|---|
| Overall response rate（ORR） | Up to ~24 months |
| Clinical benefit rate（CBR） | Up to ~24 months |
| Disease control rate（DCR） | Up to ~24 months |
| Overall Survival（OS） | Up to ~36 months |
| Safety and Tolerability：the incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) | Up to ~24 months |
| PK metrics：plasma concentration of sirolimus | Up to ~24 months |
| Duration of Response（DOR） | Up to ~24 months |
Countries
China
Contacts
Primary ContactClinical Trials Information Group officer
Outcome results
None listed