A Phase II Single-arm Clinical Trial of the Efficacy and Tolerability of Inetetamab Combined With Cyclophosphamide Metronomic Chemotherapy and Aromatase Inhibitor in Metastatic HER2+/HR+ Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 78
- 试验地点
- 1
- 主要终点
- Objective response rate (ORR)
研究概览
简要总结
Antibody-dependent cell-mediated cytotoxicity (ADCC) is one of the important mechanisms for suppressing tumors of Trastuzumab. Pre-clinical data suggest that the ADCC effect of Inetetamab, an anti-HER2 monoclonal antibody with a modified Fc segment, is 1.11 times that of trastuzumab. Previous studies indicated that enhanced ADCC effects can be transformed into clinical benefits. Immune induction through cyclophosphamide metronomic chemotherapy may further enhance the ADCC effect of anti-HER2 monoclonal antibodies. Therefore, we conducted this study to explore the efficacy and the safety of Inetetamab combined with cyclophosphamide metronomic chemotherapy and aromatase inhibitors(AI) in the treatment of metastatic HER2-positive and HR-positive breast cancer patients and to explore the possible mechanisms.
详细描述
Trastuzumab is a humanized monoclonal antibody, and antibody-dependent cell-mediated cytotoxicity (ADCC) is one of its important mechanisms for suppressing tumors. Pre-clinical data suggest that the ADCC effect of Inetetamab, an anti-HER2 monoclonal antibody with a modified Fc segment, is 1.11 times that of trastuzumab. Previous studies indicated that enhanced ADCC effects can be transformed into clinical benefits, but the absolute benefits are still unsatisfactory. Further improvement of ADCC effects and monoclonal antibody-induced immune responses may improve the clinical benefits. Immune induction through cyclophosphamide metronomic chemotherapy may further enhance the ADCC effect of anti-HER2 monoclonal antibodies. According to previous clinical studies, for HR-positive and HER2-positive metastatic breast cancer patients, metronomic chemotherapy combined with endocrine therapy and anti-HER2 targeted therapy may be one of the treatment options. Therefore, we conducted this study to explore the efficacy and the safety of Inetetamab combined with cyclophosphamide metronomic chemotherapy and aromatase inhibitors(AI) in the treatment of metastatic HER2-positive and HR-positive breast cancer patients, and we further exploring the possible mechanisms.
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 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Voluntarily sign the informed consent form;
- •18-75 years old;
- •The expected survival period is ≥12 weeks;
- •Eastern Cooperative Oncology Group (ECOG) score [0-2] points;
- •The diagnosis of invasive carcinoma by histology or cytology; Estrogen receptor (ER) positive (defined as >1% nuclear ER staining); HER2 negative (defined as IHC 0 or 1+, or HER2(2+) with HER2 FISH detection no amplification);
- •Inoperable or recurrent/metastatic breast cancer patients with aromatase inhibitor treatment failure;
- •In the state of disease progression before enrollment;
- •Measurable disease according to RECIST version 1.1 or only bone metastasis;
- •Adequate hematological, hepatic and renal function;
- •NYHA class I or II and Left ventricular ejection fraction (LVEF) ≥50%.
- •The diagnosis of invasive carcinoma by histology or cytology: Hormone receptor (HR) positive (defined as >1% nuclear estrogen receptor staining); HER2 positive (defined as IHC 3+, or HER2 FISH detection amplification);
- •In the state of disease progression before enrollment;
- •Have lesions able to and agree to perform tissue biopsy at the time requested in the study;
- •Treatment ≥1 line after recurrence/metastasis, or relapse within 12 months after completing trastuzumab-based adjuvant therapy or during trastuzumab adjuvant therapy;
- •Previously received trastuzumab for anti-HER2 therapy;
- •Measurable disease according to RECIST version 1.1.
排除标准
- •Allergic to the ingredients of Inetetamab, cyclophosphamide or similar drugs;
- •Concomitant diseases/conditions that is not controllable, and any other major illness that, in the investigator's judgment, will substantially increase the risk associated with the patient's participation in this study;
- •Patients who cannot accept drugs orally;
- •Women who are pregnant or breastfeeding or planning to give birth;
- •Patients with currently symptomatic brain or meningeal metastasis;
- •History of other primary malignancy;
- •Resistant to steroidal or nonsteroidal aromatase Inhibitor;
- •Have used Inetetamab;
- •Patients with life-threatening, symptomatic, metastatic visceral disease.
研究组 & 干预措施
Inetetamab Plus Cyclophosphamide Metronomic Chemotherapy Plus AI
Each participant receives Inetetamab(8mg/kg iv day 1 followed by 6mg/kg iv day 1, cycled every 21 days) plus cyclophosphamide metronomic chemotherapy(50mg once a day orally) plus aromatase(once a day orally).
干预措施: Inetetamab Plus Cyclophosphamide Metronomic Chemotherapy Plus AI (Drug)
结局指标
主要结局
Objective response rate (ORR)
时间窗: 1 year
The proportion of best overall response of either complete or partial response.
次要结局
- Clinical benefit rate (CBR)(1 year)
- Overall survival (OS)(3 years)
- Progression free survival (PFS)(1 year)
- Duration of response (DOR)(1 year)
- Number of Participants with Adverse Events(1 year)
- The quality of life(1 year)
研究者
wang shusen
Chief Physician
Sun Yat-sen University