A Single-Arm, Prospective, Multicenter Phase II Study of Culmerciclib Plus Letrozole and Trastuzumab (TQB211)/Pertuzumab (TQB2440) as Neoadjuvant Therapy in Patients With HR-Positive/HER2-Positive Early or Locally Advanced Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 33
- 试验地点
- 1
- 主要终点
- Breast Pathological Complete Response Rate (bpCR)
研究概览
简要总结
This is a single-arm, prospective, multicenter, phase II clinical study evaluating the efficacy and safety of a chemotherapy-free neoadjuvant regimen in patients with HR-positive/HER2-positive (HR+/HER2+) early or locally advanced breast cancer.
Approximately 33 treatment-naive patients with stage II-III (AJCC 8th edition) HR+/HER2+ breast cancer will receive 5 cycles of neoadjuvant treatment with culmerciclib (a CDK4/6 inhibitor) plus letrozole, trastuzumab (TQB211) and pertuzumab (TQB2440), followed by definitive breast surgery.
The primary endpoint is breast pathological complete response rate (bpCR, ypT0/is ypN0). Secondary endpoints include objective response rate (ORR), residual cancer burden (RCB), Ki67 change rate, patient-reported outcomes, and safety assessed per CTCAE v5.0.
详细描述
HR-positive/HER2-positive breast cancer accounts for approximately 10% of all breast cancers and shows lower pathological complete response rates to neoadjuvant therapy compared with the HR-negative/HER2-positive subtype. Crosstalk between HER2 and ER signaling pathways contributes to resistance to endocrine and anti-HER2 therapy. Preclinical evidence suggests that CDK4/6 inhibitors synergize with anti-HER2 therapy and may restore tumor sensitivity to HER2 blockade.
Eligible patients receive:
- culmerciclib 180 mg orally once daily, in 28-day cycles, for 5 cycles;
- Letrozole 2.5 mg orally once daily, in 28-day cycles, for 5 cycles;
- Trastuzumab (TQB211) 8 mg/kg loading dose followed by 6 mg/kg intravenously every 3 weeks, for 6 doses;
- Pertuzumab (TQB2440) 840 mg loading dose followed by 420 mg intravenously every 3 weeks, for 6 doses.
Tumor response is assessed by imaging (ultrasound, mammography, and MRI) according to RECIST 1.1. After completion of 5 cycles of neoadjuvant treatment, patients undergo definitive breast cancer surgery, and postoperative pathology is evaluated for bpCR and RCB. Adverse events are assessed per CTCAE v5.0. Exploratory analyses will investigate correlations between biomarkers and treatment response.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed HR-positive (ER >=50%, PR >=10%) and HER2-positive (IHC 3+ or ISH+) breast cancer;
- •Clinical stage II-III (AJCC 8th edition);
- •Treatment-naive: no prior systemic anti-tumor therapy for breast cancer;
- •ECOG performance status 0-1;
- •Adequate organ function;
- •Signed informed consent.
排除标准
- •Distant metastasis (stage IV disease);
- •Prior chemotherapy, endocrine therapy, or anti-HER2 therapy for the current breast cancer;
- •Severe cardiac dysfunction or left ventricular ejection fraction (LVEF) below the institutional lower limit of normal;
- •Pregnancy or lactation;
- •Any other condition that, in the investigator's opinion, makes the patient unsuitable for the study.
研究组 & 干预措施
Culmerciclib + Letrozole + TQB211 + TQB2440
Patients receive Culmerciclib plus letrozole, trastuzumab (TQB211) and pertuzumab (TQB2440) as neoadjuvant therapy for 5 cycles, followed by definitive breast cancer surgery.
干预措施: Trastuzumab (TQB211) (Drug)
Culmerciclib + Letrozole + TQB211 + TQB2440
Patients receive Culmerciclib plus letrozole, trastuzumab (TQB211) and pertuzumab (TQB2440) as neoadjuvant therapy for 5 cycles, followed by definitive breast cancer surgery.
干预措施: Pertuzumab (TQB2440) (Drug)
Culmerciclib + Letrozole + TQB211 + TQB2440
Patients receive Culmerciclib plus letrozole, trastuzumab (TQB211) and pertuzumab (TQB2440) as neoadjuvant therapy for 5 cycles, followed by definitive breast cancer surgery.
干预措施: Culmerciclib (Drug)
Culmerciclib + Letrozole + TQB211 + TQB2440
Patients receive Culmerciclib plus letrozole, trastuzumab (TQB211) and pertuzumab (TQB2440) as neoadjuvant therapy for 5 cycles, followed by definitive breast cancer surgery.
干预措施: Letrozole (Drug)
结局指标
主要结局
Breast Pathological Complete Response Rate (bpCR)
时间窗: At time of surgery, after completion of 5 cycles of neoadjuvant therapy (approximately 5 months from treatment start)
Proportion of patients achieving ypT0/is ypN0 (no invasive cancer in the breast and no involved axillary lymph nodes), assessed by postoperative pathology.
次要结局
- Objective Response Rate (ORR)(At end of neoadjuvant treatment (approximately 5 months from treatment start))
- Residual Cancer Burden (RCB)(At time of surgery (approximately 5 months from treatment start))
- Ki67 Change Rate(From baseline to surgery (approximately 5 months))
- Patient-Reported Outcomes (PRO)(From baseline through end of treatment (approximately 5 months))
- Incidence and Severity of Adverse Events(From first dose through 30 days after surgery (approximately 6 months))
研究者
Jianyi Li
Chief Physician
Liaoning Cancer Hospital & Institute