HR+/HER2- Advanced/Metastatic Breast Cancer
Conditions
Brief summary
This study is a multicenter, open, non-randomized phase II clinical trial consisting of a safety introduction phase followed by a single-arm phase 2 phase. This phase II trial enrolled patients with HR+/HER2- advanced breast cancer who had failed aromatase inhibitor (AI)/fulvestrant ± CDK4/6i. Pts failing prior AI ± CDK4/6i received nab-Sirolimus + fulvestrant, while those failing fulvestrant ± CDK4/6i received nab-Sirolimus + AI.
Interventions
DRUGLetrozole
Oral administration at a dose of 2.5 mg once daily for a 4-week cycle
DRUGAnastrozole
Oral administration at a dose of 1 mg once daily for a 4-week cycle
DRUGExemestane
Oral administration at a dose of 25 mg once daily with a meal every 4 weeks
DRUGFulvestrant
Fulvestrant: 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
IV infusion, every 2 weeks, 4 weeks per treatment cycle
Sponsors
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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\. 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.
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. * 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 |
|---|---|
| Objective Response Rate (ORR) | Up to ~24 months |
Secondary
| Measure | Time frame |
|---|---|
| Duration of Response (DoR) | Up to ~24 months |
| Progression-Free Survival (PFS) | Up to ~24 months |
| Disease Control Rate (DCR） | Up to ~36 months |
| Safety and Tolerability :the incidence and severity of Treatment Emergent Adverse Events（TEAEs）and Treatment-Related Adverse Events（TRAEs） | Up to ~24 months |
| PK parameter: the concentration of sirolimus | Up to ~24 months |
| Overall Survivial (OS) | Up to ~24 months |
Countries
China
Outcome results
None listed