HR+/HER2- Locally Advanced, Metastatic Breast Cancer
Conditions
Keywords
BEBT-209, Efficacy, Safety
Brief summary
This study is a randomized, double-blind, multicenter, placebo-controlled Phase III clinical trial designed to evaluate the efficacy and safety of BEBT-209 in combination with fulvestrant in patients with HR+/HER2- locally advanced or metastatic breast cancer.
Detailed description
This study plans to enroll 330 eligible female patients with locally advanced or metastatic breast cancer. All eligible patients will be randomly assigned to the treatment group or the control group in a 2:1 ratio. The following two factors will be used for stratification: 1) visceral metastasis (yes or no); 2) menopausal status (postmenopausal; premenopausal or perimenopausal). The study consists of a screening period, a treatment period, and a follow-up period. It aims to evaluate the efficacy and safety of BEBT-209 in combination with fulvestrant versus placebo in combination with fulvestrant in patients with HR+/HER2- locally advanced or metastatic breast cancer who have experienced disease progression after prior endocrine therapy.
Interventions
Oral, 75 mg per dose, twice daily, in a 28-day cycle. Continuous dosing from day 1 to day 21, followed by a rest period from day 22 to day 28.
DRUGBEBT-209 Placebo capluses
Oral, 75 mg per dose, twice daily, in a 28-day cycle. Continuous dosing from day 1 to day 21, followed by a rest period from day 22 to day 28.
500 mg intramuscular injection, with a 28-day treatment cycle. Administration on day 1 and day 15 of the first cycle, and then on day 1 of each subsequent cycle.
Sponsors
Chinese Academy of Medical Sciences
BeBetter Med Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Women aged 18 years or older who are postmenopausal or premenopausal/perimenopausal, and meet one of the following criteria: previous bilateral oophorectomy, or age ≥60 years; or age \<60 years with natural menopause (defined as spontaneous cessation of regular menstruation for at least 12 consecutive months without other pathological or physiological causes), and estradiol (E2) and follicle-stimulating hormone (FSH) levels in the postmenopausal range; or premenopausal or perimenopausal women willing to receive luteinizing hormone-releasing hormone (LHRH) agonist therapy during the study period. 2. Patients with histologically confirmed HR+/HER2- breast cancer (based on the most recent test results from either recurrent/metastatic lesion tissue samples or prior primary lesion tissue samples): a) ER+ and/or PR+ is defined as ≥10% of tumor cells showing positive staining for ER/PR; b) HER2- is defined as an immunohistochemistry(IHC) score of 0 or 1+, or a fluorescence in situ hybridization(FISH) ratio of HER2/CEP17 less than 2.0, or HER2 gene copy number less than 4. 3. Evidence of focal recurrence or metastasis, not suitable for curative surgery or radiotherapy, and without clinical indications necessitating chemotherapy. 4. Previous endocrine therapy must meet one of the following criteria: a) progression during or within 12 months after discontinuation of adjuvant endocrine therapy (with an aromatase inhibitor \[aromatase inhibitor or selective estrogen receptor modulator such as tamoxifen, toremifene, etc.); b) progression during or within 1 month after discontinuation of endocrine therapy for first recurrence or metastasis. 5. Patients are allowed to have received no more than one line of chemotherapy during the recurrence or metastatic phase. 6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1. 7. Presence of measurable lesions according to response evaluation criteria in solid tumors (RECIST) 1.1 criteria or bone metastases only (including lytic or mixed lesions). 8. Adequate organ and marrow function, defined as follows: absolute neutrophil count (ANC) ≥1.5×10⁹/L (without use of growth factors within 14 days); platelets ≥100×10⁹/L (without corrective treatment within 7 days); hemoglobin ≥90 g/L (without corrective treatment within 7 days); serum creatinine ≤1.5 times the upper limit of normal (ULN) or estimated creatinine clearance ≥60 mL/min; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 times the ULN (≤5 times the ULN for patients with liver metastases); total serum bilirubin (TBIL) ≤2.5 times the ULN; 12-lead electrocardiogram: Fridericia-corrected QT interval (QTcF) \< 470 msec (for females). 9. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose of study drug and must be willing to use a medically accepted and highly effective method of contraception from the time of signing the informed consent form, throughout the study period, and for 1 year after the last administration of the study drug. 10. All acute toxicities from prior anti-tumor therapy must have resolved to grade 0-1 (according to national cancer institute(NCI) common terminology criteria for adverse events(CTCAE) version 5.0) or to the levels specified in the inclusion/
Exclusion criteria
. Exceptions include alopecia and other toxicities deemed by the investigator to pose no safety risk to the patient. 11. The patient has provided written informed consent and is willing and able to comply with the planned visits, study treatment schedule, laboratory tests, and other study procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PFS assessed by the Independent Imaging Review Committee | Up to 56 weeks | Progression free survival (PFS) assessed by the Independent Imaging Review Committee |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| OS | Up to 56 weeks | Overall Survival |
| ORR | Up to 56 weeks | Overall Objective Response |
| PFS assessed by investigators | Up to 56 weeks | Progression free survival assessed by investigators |
| DOR | Up to 56 weeks | Duration of Response |
| Occurrence of Adverse Events (AEs) | Up to 36 months | Occurrence of AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE V5.0). |
| CBR | Up to 56 weeks | Clinical Benefit Rate |
Countries
China
Contacts
Primary ContactKegang Jiang, Master
Outcome results
None listed