A Multicenter, Prospective, Randomized Phase II Trial Evaluating Trastuzumab, Pertuzumab, Docetaxel Combined With QL1706 Versus Combined With Carboplatin as Neoadjuvant Therapy for Early or Locally Advanced HER2+ Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 188
- 试验地点
- 8
- 主要终点
- Pathological complete response (pCR) rate using the definition of ypT0/Tis ypN0 (i.e., no invasive residual in breast or nodes; noninvasive breast residuals allowed) at the time of definitive surgery
研究概览
简要总结
This study is a multicenter, prospective, randomized phase II trial designed to observe and evaluate the efficacy and safety of trastuzumab, pertuzumab, docetaxel combined with QL1706 versus combined with carboplatin as neoadjuvant therapy in patients with operable or locally advanced HER2-positive breast cancer.
详细描述
This multicenter, randomized phase II trial evaluates the efficacy and safety of neoadjuvant therapy with trastuzumab, pertuzumab, and docetaxel plus QL1706 versus the same regimen plus carboplatin in patients with operable or locally advanced HER2-positive breast cancer.
The study will enroll 188 subjects, randomly assigned 1:1 to either the QL1706 combination arm or the carboplatin combination arm, stratified by nodal status and hormone receptor status (<10% vs ≥10%). Both treatment groups will receive four 3-week cycles of assigned therapy followed by surgical resection and response assessment. Postoperative adjuvant treatment will be administered according to investigator discretion and guideline recommendations.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Signed informed consent and compliant.
- •Age 18-70 years.
- •ECOG PS 0-1; life expectancy >6 months.
- •Histologically/cytologically confirmed primary breast cancer.
- •Primary tumor >2cm (by local standard assessment) or node-positive disease.
- •AJCC 8th edition Stage II-IIIC (T2-T4 any N, or any T N1-3 M0) unilateral invasive breast cancer.
- •Confirmed HER2-positive (IHC 3+ or ISH positive). Note: Patients with HER2-negative primary tumor but HER2-positive nodes are eligible.
- •At least one measurable lesion per RECIST 1.
- •Agreement to undergo surgery if indicated after neoadjuvant therapy.
- •Willing to provide tumor tissue for biomarker analysis.
- •Adequate organ function:
- •ANC ≥1.5×10⁹/L; PLT ≥100×10⁹/L; HGB ≥90 g/L
- •Albumin ≥30 g/L
- •. TBIL ≤1.5×ULN; ALT/AST ≤2.5×ULN (≤5×ULN if liver metastases); AKP ≤2.5×ULN
- •Creatinine ≤1.5×ULN
- •PT/APTT/INR ≤1.5×ULN (or within therapeutic range if on anticoagulants)
- •For women of childbearing potential: negative pregnancy test within 7 days prior to treatment; must not be breastfeeding.
- •Use of highly effective contraception during and for 3 months after treatment.
排除标准
- •Stage IV metastatic breast cancer or patients deemed ineligible for curative surgery after neoadjuvant therapy.
- •Inflammatory breast cancer.
- •Other malignancies within 3 years, except: those treated with surgery alone and disease-free for 5 years; cured cervical carcinoma in situ, non-melanoma skin cancer, or superficial bladder cancer [Ta, Tis, T1].
- •Prior anti-tumor therapy (chemotherapy, endocrine, anti-HER2) or breast surgery for breast cancer within 3 years (excluding diagnostic biopsy).
- •Major surgery or significant traumatic injury within 28 days before treatment (excluding diagnostic biopsy).
- •Active or history of autoimmune diseases (e.g., autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism). Exceptions: vitiligo, childhood asthma in complete remission without intervention in adulthood.
- •Current use of immunosuppressants or systemic corticosteroids (>10mg/day prednisone equivalent) within 2 weeks prior to enrollment.
- •History of severe hypersensitivity to monoclonal antibodies.
- •Known central nervous system metastases.
- •Poorly controlled concurrent illnesses, including:
- •Uncontrolled hypertension (SBP>150 or DBP>100 mmHg on medication) or history of hypertensive crisis/encephalopathy.
- •History of heart failure or systolic dysfunction (LVEF <55%).
- •Myocardial ischemia/infarction (≥Grade 2), arrhythmias (QTc≥450ms M, ≥470ms F), or CHF (≥NYHA Class II).
- •Angina requiring medication; clinically significant valvular disease.
- •Active HCV (RNA+), HIV+, syphilis (unless cured), or HBV (HBsAg+ with HBV DNA≥2000 IU/ml or positive qualitative test).
- •Use of Chinese patent medicines with approved anti-tumor indications within 2 weeks prior to treatment.
- •Significant bleeding tendency or clinical bleeding within 3 months; positive fecal occult blood requiring gastroscopy if persistently positive.
- •Tumor invasion or high risk of invasion into major vessels, potentially causing fatal hemorrhage.
- •Pleural, peritoneal, or pericardial effusion requiring drainage (eligible if stable after drainage).
- •Arterial/venous thromboembolic events within 6 months (e.g., CVA, TIA, DVT, PE).
- •Known hereditary or acquired bleeding/thrombotic tendencies (e.g., hemophilia).
- •Severe, non-healing wounds, active ulcers, or untreated fractures.
- •Urinary protein ≥++ confirmed by 24-hour urine protein >1.0g.
- •Active infection, unexplained fever ≥38.5°C within 7 days, or baseline WBC >15×10⁹/L.
- •History of drug abuse or psychiatric disorders.
- •Participation in other anti-tumor drug trials within 4 weeks.
- •Allergy to any study drug or its components.
- •Any condition deemed by the investigator to pose a safety risk or affect study completion.
研究组 & 干预措施
QL1706 arm
Trastuzumab, pertuzumab, docetaxel combined with QL1706, q3w, for a total of 4 cycles
干预措施: QL1706 injection (Drug)
QL1706 arm
Trastuzumab, pertuzumab, docetaxel combined with QL1706, q3w, for a total of 4 cycles
干预措施: Trastuzumab (or biosimilar) (Drug)
QL1706 arm
Trastuzumab, pertuzumab, docetaxel combined with QL1706, q3w, for a total of 4 cycles
干预措施: Pertuzumab (or biosimilar) (Drug)
QL1706 arm
Trastuzumab, pertuzumab, docetaxel combined with QL1706, q3w, for a total of 4 cycles
干预措施: Docetaxel (Drug)
Standard therapy arm
Trastuzumab, pertuzumab, docetaxel combined with carboplatin, q3w, for a total of 4 cycles
干预措施: Trastuzumab (or biosimilar) (Drug)
Standard therapy arm
Trastuzumab, pertuzumab, docetaxel combined with carboplatin, q3w, for a total of 4 cycles
干预措施: Pertuzumab (or biosimilar) (Drug)
Standard therapy arm
Trastuzumab, pertuzumab, docetaxel combined with carboplatin, q3w, for a total of 4 cycles
干预措施: Docetaxel (Drug)
Standard therapy arm
Trastuzumab, pertuzumab, docetaxel combined with carboplatin, q3w, for a total of 4 cycles
干预措施: Carboplatin (Drug)
结局指标
主要结局
Pathological complete response (pCR) rate using the definition of ypT0/Tis ypN0 (i.e., no invasive residual in breast or nodes; noninvasive breast residuals allowed) at the time of definitive surgery
时间窗: Up to approximately 16-18weeks
pCR rate (ypT0/Tis ypN0) is defined as the percentage of participants without residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by current American Joint Committee on Cancer (AJCC) staging criteria assessed by the local pathologist at the time of definitive surgery.
次要结局
- pCR rate using the definition of ypT0/Tis (i.e., no invasive residual in breast or nodes; noninvasive breast residuals allowed) at the time of definitive surgery(Up to approximately 16-18 weeks)
- Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)(Up to approximately 12 weeks)
- Event Free Survival(Up to approximately 5 years)
- Disease-free Survival(Up to approximately 5 years)
- Overall survival (OS)(Up to approximately 5 years)
- Breast-conserving surgery rate(Up to approximately 16-18 weeks)
- Radical resection rate(Up to approximately 16-18 weeks)