Serplulimab Combined With Trastuzumab Rezetecan as Neoadjuvant Therapy for Triple-Negative Breast Cancer: A Phase II Single-Arm Clinical Study
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 84
- 试验地点
- 1
- 主要终点
- Pathological Complete Response (pCR) Rate
研究概览
简要总结
To evaluate the efficacy and safety of Serplulimab in combination with Trastuzumab Restuzumab for the neoadjuvant treatment of triple-negative breast cancer, aiming to provide evidence for optimizing the strategy of combining immunotherapy with ADC drugs in the neoadjuvant setting.
详细描述
This is a prospective, single-arm, open-label, Phase II clinical trial investigating the efficacy and safety of a non-chemotherapy regimen comprising Serplulimab (an anti-PD-1 monoclonal antibody) and Trastuzumab Restuzumab (SHR-A1811, an antibody-drug conjugate) as neoadjuvant therapy for early-stage triple-negative breast cancer.
Primary Objective:To assess the pathological complete response rate, defined as the absence of invasive carcinoma in both the breast and sampled regional lymph nodes (ypT0/Tis ypN0), following neoadjuvant treatment with serplulimab plus SHR-A1811.
Secondary Objectives:
To evaluate invasive disease-free survival, event-free survival, and the objective response rate according to RECIST 1.1 criteria.
To determine the rate of breast-conserving surgery. To characterize the safety and tolerability profile of the combination regimen, including the incidence and severity of adverse events.
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
- •Female patients aged 18 to 70 years, inclusive.
- •Histologically confirmed, treatment-naïve, early-stage triple-negative breast cancer (TNBC), defined as estrogen receptor (ER) and progesterone receptor (PR) expression <1% by immunohistochemistry (IHC), and human epidermal growth factor receptor 2 (HER2)-negative (IHC 0/1+ or IHC 2+ with negative in situ hybridization confirmation) per current American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines.
- •Clinical stage T1cN1-2 or T2-4N0-2 according to the American Joint Committee on Cancer (AJCC) staging system, 8th edition.
- •At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Adequate hematologic, hepatic, renal, and cardiac function within 14 days prior to enrollment:
- •Hematologic: Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L; platelet count ≥100 × 10⁹/L; hemoglobin ≥90 g/L (without transfusion or growth factor support within 14 days).
- •Hepatic: Total bilirubin ≤1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN.
- •Renal: Serum creatinine and blood urea nitrogen (BUN) ≤1.5 × ULN.
- •Cardiac: Left ventricular ejection fraction (LVEF) ≥50% measured by echocardiogram; corrected QT interval (QTc) <470 ms on 12-lead electrocardiogram (ECG).
- •Willingness to provide archival or fresh tumor tissue sample for programmed death-ligand 1 (PD-L1) biomarker analysis using the 22C3 pharmDx assay.
- •Ability to understand and willingness to sign a written informed consent document.
排除标准
- •Evidence of metastatic (Stage IV) disease or bilateral breast cancer at diagnosis.
- •Prior systemic anticancer therapy (including chemotherapy, endocrine therapy, immunotherapy, or biological therapy) for any malignancy within 4 weeks before the first dose of study treatment.
- •Diagnosis of any other malignancy within the past 5 years, except for adequately treated non-melanoma skin cancer, basal cell carcinoma, or carcinoma in situ of the cervix.
- •Known active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV-DNA ≥500 IU/mL), or hepatitis C virus (detectable HCV-RNA).
- •Active autoimmune disease requiring systemic immunosuppressive therapy within the past 2 years.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring systemic antibiotic therapy within 2 weeks, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness that would limit compliance with study requirements.
- •History of allogeneic hematopoietic stem cell or solid organ transplantation.
- •Pregnant or lactating women, or women of childbearing potential who are unwilling to use a highly effective method of contraception during the treatment period and for at least 7 months after the last dose.
- •Known hypersensitivity to any component of serplulimab or SHR-A
- •Any condition that, in the opinion of the investigator, would compromise patient safety or interfere with the completion of the study procedures.
研究组 & 干预措施
Neoadjuvant Serplulimab + SHR-A1811
All enrolled participants will receive the investigational combination therapy as neoadjuvant treatment. This regimen consists of Serplulimab (an anti-PD-1 monoclonal antibody) and SHR-A1811 (Trastuzumab Restuzumab , an antibody-drug conjugate). Both agents are administered intravenously every 3 weeks (Q3W) for 6 cycles prior to definitive surgery. The primary objective is to evaluate the efficacy and safety of this chemotherapy-free combination in patients with early-stage triple-negative breast cancer (TNBC).
干预措施: Serplulimab (Drug)
Neoadjuvant Serplulimab + SHR-A1811
All enrolled participants will receive the investigational combination therapy as neoadjuvant treatment. This regimen consists of Serplulimab (an anti-PD-1 monoclonal antibody) and SHR-A1811 (Trastuzumab Restuzumab , an antibody-drug conjugate). Both agents are administered intravenously every 3 weeks (Q3W) for 6 cycles prior to definitive surgery. The primary objective is to evaluate the efficacy and safety of this chemotherapy-free combination in patients with early-stage triple-negative breast cancer (TNBC).
干预措施: SHR-A1811 (Drug)
结局指标
主要结局
Pathological Complete Response (pCR) Rate
时间窗: At the time of definitive surgery (after 6 cycles of neoadjuvant therapy; each cycle is 21 days).
Proportion of participants achieving a pathological complete response, defined as the absence of residual invasive cancer in the breast and sampled ipsilateral lymph nodes (ypT0/Tis, ypN0) upon pathological review of the surgical resection specimen following completion of neoadjuvant therapy.
次要结局
- Objective Response Rate (ORR)(From baseline until the end of neoadjuvant therapy (up to 6 cycles), with tumor assessments performed at the end of Cycles 2, 4, and 6（each cycle is 21days).)
- Invasive Disease-Free Survival (iDFS)(From surgery until first documented iDFS event or death, assessed up to 5 years (60 months).)
- Event-Free Survival (EFS)(From enrollment until first documented EFS event or death, assessed up to 5 years (60 months).)
- Breast-Conserving Surgery Rate(During surgery)
- Incidence and Severity of Adverse Events(From first study treatment administration until 30 days after the last dose (approximately 25 weeks).)