Optimizing Neoadjuvant Therapy for HER2-Positive Breast Cancer Based on Dynamic Efficacy Monitoring: A Trial of Trastuzumab Plus Pyrotinib and Albumin-Bound Paclitaxel Followed by SHR-A1811 Plus Pertuzumab（OnThePath Trial）
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 30
- 主要终点
- tpCR
研究概览
简要总结
This study aims to optimize neoadjuvant therapy for HER2-positive breast cancer by implementing a dynamic monitoring-guided treatment strategy. Patients will initially receive trastuzumab, pyrotinib, and albumin-bound paclitaxel. Those who do not achieve a radiological response after Cycle 2 will switch to SHR-A1811 (a HER2-targeted antibody-drug conjugate) combined with pertuzumab. The primary objective is to evaluate whether this sequential treatment strategy improves the pathological complete response (pCR) rate while maintaining safety. The study will also explore the value of dynamic efficacy monitoring in guiding treatment adjustments and assess the safety and tolerability of the regimens.
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 invasive cancer of the breast and meet the clinical stage II（T2N0-1M0/T3N0M0）or III（T2N2M0/T3N1-2M0) criteria;
- •Age between18-70 years;
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
- •Histologically confirmed to be HER2-positive invasive breast cancer;
- •At least one measurable lesion according to RECIST version 1.1
- •Normal organ and marrow function: Hemoglobin (HB) ≥90 g/L (No blood was transfused within 14 days), Absolute neutrophil count ≥ 1500/μL, Platelets ≥ 75,000/μL, Total bilirubin ≤ 1.5 x ULN), aspartate aminotransferase (AST) (SGOT) and alanine aminotransferase (ALT) (SGPT) ≤ 3 x ULN, creatinine < 1 x ULN, endogenous creatinine clearance > 50 ml/min (Cockcroft-Gault formula);
- •Non-pregnant and non-lactating, fertile female subjects were required to use a medically approved contraceptive method for the duration of the study treatment and at least 3 months after the last use of the study drug; Ability to understand and willingness to sign a written informed consent
排除标准
- •Stage IV (metastatic) breast cancer.
- •The patient has a second primary malignant tumor, except for fully treated skin cancer.
- •The patient had undergone major surgical procedures unrelated to breast cancer within 4 weeks before enrollment, or the patient has not fully recovered from such surgical procedures.
- •The presence of uncontrolled cardiovascular and cerebrovascular disease, including (but not limited to) any of the following within the 6 months prior to the first dose: congestive heart failure (NYHA III or IV), myocardial infarction or cerebral infarction, pulmonary embolism, unstable angina, or arrhythmia requiring treatment at the time of screening; 5.Primary cardiomyopathy (e.g., dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restricted cardiomyopathy, undefined cardiomyopathy); A clinically significant history of prolonged QTc, grade II type II atrioventricular block or grade III atrioventricular block or QTc interphase (F method) > 470 msec (female); Atrial fibrillation (EHRA grade ≥2b); Unmanageable hypertension, which the investigators judged unsuitable for study participation.
- •6.Individuals with a known history of allergies to the drug components of this protocol; 7.Having a history of immunodeficiency, including HIV testing positive, or suffering from other acquired or congenital immunodeficiency diseases, or having a history of organ transplantation.
研究组 & 干预措施
SHR-A1811+Pertuzumab
Patients will initially receive trastuzumab, pyrotinib, and albumin-bound paclitaxel. Those who do not achieve a radiological response after Cycle 2 will switch to SHR-A1811 (a HER2-targeted antibody-drug conjugate) combined with pertuzumab.
干预措施: Patients will initially receive trastuzumab, pyrotinib, and albumin-bound paclitaxel. Those who do not achieve a radiological response after Cycle 2 will switch to SHR-A1811 (a HER2-targeted antibody (Drug)
trastuzumab, pyrotinib, and nab-paclitaxe
Patients will initially receive trastuzumab, pyrotinib, and nab-paclitaxel. Those who achieve a partial response (PR) or complete response (CR) after cycle 2 will continue on the same regimen.
干预措施: Patients will initially receive trastuzumab, pyrotinib, and nab-paclitaxel. Those who achieve a partial response (PR) or complete response (CR) after cycle 2 will continue on the same regimen. (Drug)
结局指标
主要结局
tpCR
时间窗: At the time of surgery
Total pathological complete response (tpCR: ypT0-is/ypN0)
次要结局
- EFS(5 years)