Overview

The purpose of this clinical trial is to evaluate the efficacy and safety of Fluzoparib combined with docetaxel in sequential paclitaxel combined with cyclophosphamide for HRD-positive, HR+/HER2- early breast cancer. The main question it aims to answer is:

Does the proportion of patients with residual tumor burden (RCB) 0/I increase when Fluzoparib combined with docetaxel is sequentially followed by paclitaxel combined with cyclophosphamide for patients with HRD-positive, HR+/HER2- early breast cancer? What medical problems will participants encounter when using Fluzoparib combined with docetaxel in sequential paclitaxel combined with cyclophosphamide?

Participants will:

After confirming their enrollment, they need to receive the trial drug treatment within 72 hours, with each 3-week period as a treatment cycle, for a total of 8 cycles. The first to fourth cycles will receive Fluzoparib combined with docetaxel treatment, and the fifth to eighth cycles will receive paclitaxel and cyclophosphamide treatment. The treatment will continue until the end of the treatment course or disease progression, occurrence of intolerable toxicity, or the subject withdrawing the informed consent form.

Eligibility

Inclusion Criteria

Subjects must meet all of the following inclusion criteria to be enrolled in this trial:

1. Female patients with newly diagnosed breast cancer, aged ≥18 years and ≤70 years;
2. Histopathologically confirmed early or locally advanced HR+/HER2- invasive breast cancer, as defined by the latest ASCO/CAP guidelines, meeting the following

   conditions

   • HER2-negative: IHC 0/1+ or IHC 2+ with negative ISH;
   • ER-positive: IHC >1%; PR-positive: IHC >1%;
   • cT1c or above with positive lymph nodes; cT2 or above with negative lymph nodes must meet at least one of the following: age ≤40 years; Ki67 >50%; lymphovascular invasion; histological grade III;
   • HRD-positive: defined as HRD score ≥42 points and/or germline BRCA1/2 mutation (pathogenic or likely pathogenic);
   • ECOG performance status 0-1;

3. Presence of at least one measurable lesion according to RECIST 1.1 criteria;
4. Organ function must meet the following requirements:
   1. Hematology
      • Absolute neutrophil count (ANC) ≥1.5×109/L (no use of hematopoietic stimulating factors within 14 days before the first administration of the study drug);
      • Platelet count (PLT) ≥100×109/L (no blood transfusion within 14 days before the first administration of the study drug);
      • Hemoglobin (Hb) ≥90 g/L; 2) Blood biochemistry
      • Total bilirubin (TBIL) ≤1.5×ULN;
      • Aspartate transaminase and alanine transaminase (ALT and AST) ≤2.5×ULN;
      • Blood urea nitrogen (BUN) and creatinine (Cr) ≤1.5×ULN; 3) Cardiac function
      • Echocardiogram: LVEF ≥50%;
      • 12-lead electrocardiogram: QTc interval <470 ms in females. 5. Subjects voluntarily participate in the study and sign the informed consent form.

Exclusion Criteria

Subjects with any of the following conditions are excluded:

1. Tumor-related symptoms and treatment 1) Patients with metastatic breast cancer or bilateral breast cancer; 2) Patients with inflammatory breast cancer; 3) Participation in other drug trials or receipt of any anti-tumor therapy (including endocrine therapy, bisphosphonate therapy, immunotherapy, biological therapy, or tumor embolization) within 4 weeks before enrollment; 4) Previous treatment with PARP inhibitors;
2. Comorbidities/medical history 1) Previous history of other malignant tumors that have received any systemic anti-tumor therapy or local treatment (including surgery and radiotherapy), excluding cured malignant tumors such as carcinoma in situ of the cervix, basal cell carcinoma, or squamous cell carcinoma; 2) Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome; active hepatitis (hepatitis B, defined as HBV-DNA ≥500 IU/ml; hepatitis C, positive anti-HCV and HCV-RNA above the lower limit of detection by the analytical method) or combined hepatitis B and C co-infection; autoimmune hepatitis; 3) Severe infection within 4 weeks before the first administration, including but not limited to bacteremia requiring hospitalization, severe pneumonia, etc.; or active infection of CTCAE ≥Grade 2 requiring systemic antibiotic treatment within 2 weeks before the first administration, or unexplained fever >38.5°C during screening/first administration (fever caused by tumors, as judged by the investigator, is allowed); 4) Subjects with a history of or planned allogeneic bone marrow transplantation or solid organ transplantation; 5) Severe heart disease or disorders, including but not limited to:
   • Confirmed history of heart failure or systolic dysfunction (LVEF <50%);
   • High-risk uncontrolled arrhythmias, such as atrial tachycardia with resting heart rate >100 bpm, significant ventricular arrhythmias (e.g., ventricular tachycardia), or high-grade atrioventricular block (i.e., Mobitz II second-degree or third-degree atrioventricular block);
   • Angina pectoris requiring anti-anginal medication;
   • Clinically significant valvular heart disease;
   • ECG showing transmural myocardial infarction;
   • Poorly controlled hypertension (systolic blood pressure >180 mmHg and/or diastolic blood pressure >100 mmHg);
3. Pregnant or lactating women, women of childbearing potential with positive baseline

   pregnancy test, or women of childbearing potential unwilling to use effective contraception throughout the trial period;

4. Previous clear history of neurological or psychiatric disorders, including epilepsy or dementia; known history of psychiatric drug abuse, alcoholism, or drug addiction;
5. Any other conditions deemed inappropriate for the study by the investigator.