Neoadjuvant Therapy With Trastuzumab Deruxtecan (SHR-A1811) + Pertuzumab or Trastuzumab Deruxtecan (SHR-A1811) + Pertuzumab Sequenced With Paclitaxel-based Regimens + Trastuzumab + Pyrotinib in HER2+ Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- pCR
研究概览
简要总结
Patients with Stage II-III HER2-positive breast cancer will receive three cycles of treatment with Trastuzumab Deruxtecan (SHR-A1811) + Pertuzumab, followed by imaging assessment. If clinical complete response (cCR) or radiological complete response/near radiological complete response (rCR/near rCR) is achieved, they will continue to receive an additional three cycles of treatment with Trastuzumab Deruxtecan (SHR-A1811) + Pertuzumab, followed by surgery.
If cCR/rCR or near rCR is not achieved, the treatment will be switched to the THPy regimen (paclitaxel-based regimen + Trastuzumab + Pyrotinib) for three cycles.
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
- •Age and Gender: Female patients aged ≥18 years and ≤70 years. Histological Confirmation: Patients must have histologically confirmed invasive breast cancer and must not have received any prior systemic anti-tumor therapy for breast cancer.
- •HER2 Positivity: Histologically confirmed HER2 receptor positivity, following the 2018 ASCO-CAP HER2 positivity judgment guidelines.
- •Confirmed by pathology laboratory with immunohistochemistry (IHC) score of 3+, or 2+ with positive in situ hybridization (ISH) test (ISH amplification rate ≥2.0).
- •Tumor Stage: Patients must have tumor staging conforming to the Stage II-III breast cancer criteria according to the eighth edition of the AJCC breast cancer TNM staging system (T1~T4, N1~N3, M0).
- •Measurable Target Lesion: At least one measurable target lesion according to RECIST V1.
- •ECOG Performance Status: ECOG functional status score of 0~
- •Organ Function: Adequate organ function levels, with the following requirements (no blood transfusion or use of leukocyte or platelet elevation drugs within 2 weeks prior to screening):
- •Hematology: Absolute neutrophil count (ANC) > 1.5 × 109/L; Platelet count (PLT) > 75 × 109/L; Hemoglobin (Hb) > 90 g/L.
- •Blood Chemistry: Total bilirubin (TBIL) < 1.5 × ULN; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 1.5 × ULN; Alkaline phosphatase < 2.5 × ULN; Blood urea nitrogen/urea (BUN/UREA) and creatinine (Cr) < 1.5 × ULN.
- •Cardiac Ultrasound: Left ventricular ejection fraction (LVEF) ≥ 55%.
- •12-Lead ECG: Fridericia's method corrected QT interval (QTcF) < 470 msec.
- •Reproductive Status: For premenopausal women with potential fertility, a pregnancy test must be performed within 7 days before treatment initiation, with negative serum/urine pregnancy results.
- •Patients must not be lactating and must use adequate barrier contraception throughout the treatment cycle and for 6 months after treatment completion.
- •Voluntary Participation: Voluntary participation in the study with signed informed consent, good compliance, and willingness to cooperate with visit schedules and research-related procedures.
排除标准
- •Stage IV Breast Cancer: Patients with Stage IV breast cancer. Inflammatory Breast Cancer: Patients with inflammatory breast cancer. Prior Malignancy Treatment: Patients who have received prior anti-tumor therapy or radiotherapy for any malignancy, or have concurrent other malignancies, excluding cured cervical intraepithelial neoplasia, basal cell carcinoma, or squamous cell carcinoma.
- •Concurrent Anti-Tumor Therapy: Patients currently participating in other clinical trials involving anti-tumor therapy, including but not limited to chemotherapy, endocrine therapy, biological therapy, bone modification therapy, or immune checkpoint inhibitor therapy.
- •Recent Surgery: Patients who have undergone major surgery unrelated to breast cancer within 4 weeks prior to the first dose of the study drug, or have not fully recovered from such surgery.
- •Serious Cardiac Disease: Patients with serious cardiac conditions, including but not limited to:
- •History of heart failure or systolic dysfunction (LVEF < 50%). Uncontrolled high-risk arrhythmia, such as atrial tachycardia, resting heart rate > 100 bpm, significant ventricular arrhythmia, or advanced atrioventricular block (i.e., Mobitz II second-degree or third-degree atrioventricular block).
- •Angina pectoris requiring medication.
- •Clinically significant heart valve disease.
- •ECG showing transmural myocardial infarction.
- •Uncontrolled hypertension (after medication, systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg).
- •Uncontrolled Active Infection: Patients with uncontrolled active infection requiring treatment, or with a history of immunodeficiency, including HIV positivity, other acquired or congenital immunodeficiency diseases, or a history of organ transplantation.
- •Allergy to Study Drugs: Patients with a known history of allergy to any component of the study drugs.
- •Pregnant or Lactating Women: Pregnant or lactating women, women of childbearing potential with positive baseline pregnancy test, or those unwilling to use effective contraception during the trial period and for 6 months after the last dose of the study drug.
- •Interstitial Lung Disease: Patients with known or suspected interstitial lung disease; those with other severe pulmonary diseases that may interfere with drug-related pulmonary toxicity detection or management within 3 months prior to the first dose, including but not limited to idiopathic pulmonary fibrosis, organizing pneumonia/obliterative bronchiolitis, pulmonary embolism, severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive/obstructive lung disease, or any pulmonary autoimmune or inflammatory disease such as rheumatoid arthritis, Sjögren's syndrome, or sarcoidosis; or those with a history of total pneumonectomy.
- •Severe Concomitant Diseases: Patients with severe concomitant diseases or other conditions that may interfere with the planned treatment, or those deemed unsuitable for the study by the investigator for any other reason.
研究组 & 干预措施
Study Arm
Patients will receive three cycles of treatment with Trastuzumab Deruxtecan (SHR-A1811) + Pertuzumab, followed by imaging assessment. If clinical complete response (cCR) or radiological complete response/near radiological complete response (rCR/near rCR) is achieved, they will continue to receive an additional three cycles of treatment with Trastuzumab Deruxtecan (SHR-A1811) + Pertuzumab, followed by surgery.Patients who did not achieve cCR/rCR or near rCR at the end of cycle 3 will change to the THPy regimen (paclitaxel-based regimen + Trastuzumab + Pyrotinib) for three cycles.
干预措施: Trastuzumab Deruxtecan (Drug)
Study Arm
Patients will receive three cycles of treatment with Trastuzumab Deruxtecan (SHR-A1811) + Pertuzumab, followed by imaging assessment. If clinical complete response (cCR) or radiological complete response/near radiological complete response (rCR/near rCR) is achieved, they will continue to receive an additional three cycles of treatment with Trastuzumab Deruxtecan (SHR-A1811) + Pertuzumab, followed by surgery.Patients who did not achieve cCR/rCR or near rCR at the end of cycle 3 will change to the THPy regimen (paclitaxel-based regimen + Trastuzumab + Pyrotinib) for three cycles.
干预措施: Pertuzumab (Drug)
Study Arm
Patients will receive three cycles of treatment with Trastuzumab Deruxtecan (SHR-A1811) + Pertuzumab, followed by imaging assessment. If clinical complete response (cCR) or radiological complete response/near radiological complete response (rCR/near rCR) is achieved, they will continue to receive an additional three cycles of treatment with Trastuzumab Deruxtecan (SHR-A1811) + Pertuzumab, followed by surgery.Patients who did not achieve cCR/rCR or near rCR at the end of cycle 3 will change to the THPy regimen (paclitaxel-based regimen + Trastuzumab + Pyrotinib) for three cycles.
干预措施: Taxane Chemotherapy (Drug)
Study Arm
Patients will receive three cycles of treatment with Trastuzumab Deruxtecan (SHR-A1811) + Pertuzumab, followed by imaging assessment. If clinical complete response (cCR) or radiological complete response/near radiological complete response (rCR/near rCR) is achieved, they will continue to receive an additional three cycles of treatment with Trastuzumab Deruxtecan (SHR-A1811) + Pertuzumab, followed by surgery.Patients who did not achieve cCR/rCR or near rCR at the end of cycle 3 will change to the THPy regimen (paclitaxel-based regimen + Trastuzumab + Pyrotinib) for three cycles.
干预措施: Trastuzumab (or biosimilar) (Drug)
Study Arm
Patients will receive three cycles of treatment with Trastuzumab Deruxtecan (SHR-A1811) + Pertuzumab, followed by imaging assessment. If clinical complete response (cCR) or radiological complete response/near radiological complete response (rCR/near rCR) is achieved, they will continue to receive an additional three cycles of treatment with Trastuzumab Deruxtecan (SHR-A1811) + Pertuzumab, followed by surgery.Patients who did not achieve cCR/rCR or near rCR at the end of cycle 3 will change to the THPy regimen (paclitaxel-based regimen + Trastuzumab + Pyrotinib) for three cycles.
干预措施: Pyrotinib 320mg (Drug)
结局指标
主要结局
pCR
时间窗: after neoadjuvant treatment, at surgery
ypT0/Tis ypN0
次要结局
- ORR(after neoadjuvant treatment, at surgery)
- EFS(From enrollment to 5 years after surgery)
- OS(From enrollment to 5 years after surgery)
- bpCR(after neoadjuvant treatment, at surgery)
研究者
Kunwei Shen
Head of Comprehensive Breast Health Center
Ruijin Hospital