HRD-Positive/HER2-Negative Advanced Breast Cancer, Metastatic Breast Cancer
Conditions
Brief summary
This is a Phase III clinical trial for patients with a specific type of advanced breast cancer that is HER2-negative and has a biomarker called "Homologous Recombination Deficiency (HRD)-positive." The study aims to compare the effectiveness and safety of two treatment strategies: Experimental Group: Patients will first receive 6 cycles of standard chemotherapy or antibody-drug conjugate (ADC) therapy chosen by their doctor. After completing these 6 cycles, they will switch to a combination of two oral targeted drugs: Fluorizoparib and Apatinib, as long-term maintenance therapy. Control Group: Patients will continue to receive their doctor's choice of standard chemotherapy or ADC therapy without switching to the targeted drug combination. Patients will be randomly assigned (like flipping a coin) to one of the two groups.
Interventions
DRUGChemotherapy/ADC Regimen
This is the initial induction phase of the experimental arm. Participants will receive 6 cycles of a standard intravenous or oral chemotherapy regimen or an Antibody-Drug Conjugate (ADC), selected by the investigator from protocol-specified options (e.g., eribulin, vinorelbine, gemcitabine, capecitabine, sacituzumab govitecan, or trastuzumab deruxtecan). Administration follows the standard schedule of the chosen agent. The purpose is to achieve disease control before switching to long-term maintenance therapy.
DRUGFluorizoparib
This oral PARP inhibitor is administered as part of the maintenance phase. Participants who complete the 6-cycle induction phase without disease progression switch to Fluorizoparib twice daily in continuous 21-day cycles, in combination with Apatinib, until disease progression or unacceptable toxicity.
DRUGApatinib
This oral anti-angiogenic TKI is administered as part of the maintenance phase. Participants who complete the 6-cycle induction phase without disease progression switch to Apatinib once daily in continuous 21-day cycles, in combination with Fluorizoparib, until disease progression or unacceptable toxicity.
DRUGPhysician's Choice Chemotherapy/ADC Regimen
Participants receive continuous treatment with a standard chemotherapy regimen or an Antibody-Drug Conjugate (ADC) selected by the investigator from protocol-specified options (e.g., eribulin, vinorelbine, gemcitabine, capecitabine, sacituzumab govitecan, or trastuzumab deruxtecan). Treatment is administered intravenously or orally according to the standard schedule of the chosen agent and continues without a planned switch to the oral targeted combination therapy, until disease progression, unacceptable toxicity, withdrawal of consent, or death.
Sponsors
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Female patients aged 18-70 years. Histologically confirmed HER2-negative metastatic breast cancer. Documented HRD-positive status (defined as BRCA1/2 mutation and/or HRD positive). HR+/HER2- patients must have received prior endocrine therapy for metastatic disease. Have received no more than 2 prior lines of chemotherapy or ADC therapy for metastatic disease. At least one measurable lesion per RECIST 1.1. ECOG performance status 0-2 and life expectancy ≥3 months. Adequate organ function (bone marrow, liver, renal, cardiac).
Exclusion criteria
* HR+/HER2- patients who have not received prior endocrine therapy for metastatic disease. Have not received any prior systemic therapy for metastatic breast cancer. Have received \>2 prior lines of chemotherapy or ADC therapy for metastatic disease. Known severe hypersensitivity to any component of the study drugs. Pregnant, lactating, or women of childbearing potential unwilling to use effective contraception. Uncontrolled or significant cardiovascular disease. Any other condition deemed inappropriate for the study by the investigato
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-Free Survival (PFS) assessed by Blinded Independent Central Review (BICR) | From randomization until disease progression or death (assessed up to approximately 4 years). |
Secondary
| Measure | Time frame |
|---|---|
| Objective Response Rate (ORR) | From randomization until first documented response or progression (assessed every 6-8 weeks during treatment, up to approximately 2 years) |
| Overall Survival (OS) | From randomization until death from any cause (assessed up to approximately 7 years, which is the total study duration) |
| Clinical Benefit Rate (CBR) | From randomization until progression or 24 weeks of stable disease (assessed up to approximately 2 years). |
| Disease Control Rate (DCR) | From randomization until the end of treatment or progression (assessed up to approximately 2 years) |
Countries
China
Outcome results
None listed