A Single-Arm, Exploratory Study of 4 Additional Cycles of Trastuzumab Rezetecan (T-DXh) as Neoadjuvant Therapy in Patients With Early or Locally Advanced HER2-Positive Breast Cancer Who Have Non-pCR After TCbHP Neoadjuvant Therapy
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 59
- 主要终点
- Total Pathological Complete Response (tpCR)
研究概览
简要总结
This is a prospective, multi-center, single-arm, phase 2 exploratory study to evaluate the efficacy and safety of adding 4 cycles of Trastuzumab Rezetecan (T-DXh), an anti-HER2 antibody-drug conjugate, as continued neoadjuvant therapy in patients with early or locally advanced HER2-positive breast cancer who have residual invasive disease after standard 6-cycle TCbHP (taxane, carboplatin, trastuzumab, pertuzumab) neoadjuvant therapy. Patients will receive 4 cycles of T-DXh (4.8 mg/kg IV Q3W) followed by radical surgery. The primary endpoint is tpCR rate. Secondary endpoints include ORR, EFS, OS, 3-year iDFS, and safety. Simon's two-stage design (H0: pCR ≤10%, H1: pCR ≥25%, α=0.05, β=0.2) requires 43 evaluable patients; with 10% dropout, 48 patients will be enrolled.
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 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years.
- •For premenopausal and perimenopausal patients: negative pregnancy test and agreement to use reliable contraception during the treatment period.
- •Pathologically confirmed HER2-positive invasive breast cancer (IHC 3+ or IHC 2+ with FISH+).
- •Completed standard neoadjuvant TCbHP (taxane + carboplatin + trastuzumab + pertuzumab) with imaging assessment not achieving clinical complete remission (non-cCR).
- •Agree to undergo a core needle biopsy.
- •ECOG performance status 0 or
- •Adequate organ function meeting the following criteria: hemoglobin ≥ 90 g/L, white blood cell count ≥ 3.5 × 10^9/L, platelet count ≥ 100 × 10^9/L, absolute neutrophil count ≥ 1.5 × 10^9/L, AST/ALT ≤ 3 × ULN, total bilirubin ≤ 1.5 × ULN, serum creatinine ≤ 1.5 × ULN.
- •No myocardial ischemia on ECG; New York Heart Association (NYHA) functional class I; left ventricular ejection fraction (LVEF) ≥ 55% by echocardiography; cardiac troponin I (cTnI) and brain natriuretic peptide (BNP) within normal limits.
- •Signed informed consent.
排除标准
- •Male breast cancer or inflammatory breast cancer.
- •Metastatic breast cancer (Stage IV).
- •Concurrent other malignancy or history of other malignancy within the past 5 years, except adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.
- •Concurrent other anti-tumor therapy or participation in another clinical trial.
- •Severe non-malignant disease that would affect compliance or place the patient at risk.
- •Major surgery within 4 weeks prior to start of study treatment or anticipated need for major surgery during the study.
- •History of allergic reaction or contraindication to any component of the study drug.
- •Dementia, mental abnormality, or any psychiatric illness that interferes with understanding of the informed consent.
- •Any other condition assessed by the investigator as unsuitable for inclusion.
研究组 & 干预措施
Experimental: Trastuzumab Rezetecan (T-DXh) as Continued Neoadjuvant Therapy
Patients with residual invasive disease after standard 6 cycles of TCbHP neoadjuvant therapy receive 4 cycles of Trastuzumab Rezetecan (T-DXh) 4.8 mg/kg intravenously every 3 weeks (Q3W), followed by radical surgery. After surgery:
- Patients achieving pathological complete response (pCR) receive 7 additional cycles of T-DXh as adjuvant therapy.
- Patients not achieving pCR receive investigator-selected adjuvant therapy (optional: trastuzumab + pertuzumab followed by 1 year of pyrotinib).
干预措施: Trastuzumab Rezetecan (Drug)
结局指标
主要结局
Total Pathological Complete Response (tpCR)
时间窗: At the time of surgery, approximately 12 weeks after the start of the 4-cycle Trastuzumab Rezetecan treatment.
Absence of invasive residual cancer in both the breast primary tumor and axillary lymph nodes (ypT0/is, ypN0) after neoadjuvant therapy and surgery. Presence of ductal carcinoma in situ (DCIS) is allowed.
次要结局
- Event-Free Survival (EFS)(From first dose up to 5 years after last patient enrolled.)
- Overall Survival (OS)(From first dose up to 5 years after last patient enrolled.)
- 3-Year Invasive Disease-Free Survival (iDFS) Rate(3 years after surgery.)
- Incidence of Adverse Events (AEs)(From signing of informed consent until 28 days after the last dose of study treatment.)
研究者
Liu Xiaoan
Professor
The First Affiliated Hospital with Nanjing Medical University