A Clinical Study Evaluating the Efficacy and Safety of BAT8001 Injection for the Treatment of HER2-positive Advanced Breast Cancer - A Multicenter, Randomized, Open-label, Positive-controlled, Superiority Phase III Clinical Trial in China
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 410
- 试验地点
- 51
- 主要终点
- Progression-free survival (PFS)
研究概览
简要总结
To evaluate the safety and efficacy of BAT8001 for the treatment of HER2-positive advanced breast cancer, using lapatinib in combination with capecitabine as the positive control drug.
详细描述
This is a multicenter, randomized, open-label, positive-controlled, superiority phase III clinical study. The object is to evaluate the safety and efficacy of BAT8001 for the treatment of HER2-positive advanced breast cancer, using lapatinib in combination with capecitabine as the positive control drug.
Eligible subjects will be randomized to the experimental or control group in a 1:1 ratio and stratified by the number of HER2-positive advanced/metastatic breast cancer treatment regimens (0, 1 VS > 1) and lesion site (organ VS non-organ).
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients are required to provide at least 10 unstained sections.
- •HER2-positive (defined as: IHC 3+ or FISH+) confirmed by the central laboratory of this study.
- •Histologically and/or cytologically confirmed invasive breast cancer, including unresectable locally advanced breast cancer (LABC) or metastatic breast cancer (MBC).
- •LABC or MBC that has progressed during or after treatment, or during or within 12 month following adjuvant therapy as confirmed by imaging.
- •Previously received adjuvant therapy, or locally advanced/metastatic breast cancer treatment regimen that included taxanes and trastuzumab (including approved biosimilars) as monotherapy or combination therapy。
- •At least one measurable lesion or a single metastatic tumor in the bone as per the Response Evaluation Criteria in Solid Tumor (RECIST) 1.
- •A score of 0-1 for performance status as per the Eastern Cooperative Oncology Group (ECOG) scale.
- •Expected survival ≥ 3 months.
- •Left ventricular ejection fraction (LVEF) ≥ 50%.
- •If anthracyclines are used, the cumulative dose must meet the following criteria: the cumulative dose must not exceed the equivalent dose of doxorubicin 500 mg/m
- •Women of childbearing age or fertile male subjects must agree to use oral, implanted, or injectable hormone contraceptives as well as one or two forms of non-hormonal contraceptive measures during the study period and until 6 months after the end of the study.
- •Blood pregnancy test must indicate non-pregnant for all women of childbearing potential and those who do not meet the definition of postmenopause.
排除标准
- •Current presence of grade ≥ 2 peripheral neuropathy.
- •History of other malignant tumors within the past 5 years, but does not include properly treated cervical carcinoma in situ, non-melanoma skin cancer, stage 1 uterine cancer, or other tumors with good prognosis.
- •Received treatment with a cancer drug or investigational drug within 21 days from the first dose of the study drug, except for hormone therapy..
- •Received radiation therapy within 14 days prior to the first test drug administration of this study; or subject has not recovered from the acute toxicity of radiation therapy prior to the first test drug administration of this study.
- •Brain metastasis that is symptomatic or requires treatment to control symptoms within 30 days before randomization.
- •Subjects who must receive the first test drug administration within less than 14 days following the completion of radiation therapy for symptomatic brain metastasis.
- •Currently experiences moderate or severe dyspnea at rest caused by advanced malignancy or other complications or severe primary lung diseases, or currently requires continuous oxygen therapy, or subject currently suffers from interstitial lung disease (ILD) or pneumonia/pneumonitis.
- •History of myocardial infarction or unstable angina within 6 months prior to first test drug administration.
- •Previous history of LVEF falling below 40%; or presence of symptomatic congestive heart failure (CHF) during trastuzumab (including other analogues) treatment.
- •Symptomatic congestive heart failure (CHF; New York Heart Association [NYHA] Class II-IV); Severe arrhythmias requiring treatment.
- •Presence of severe and uncontrollable systemic diseases (e.g. clinically significant cardiovascular, lung or metabolic diseases).
- •Patients who currently require coumarin derivative-based anticoagulation therapy such as warfarin and phenprocoumon.
- •Presence of diseases that may affect intestinal absorption, including malabsorption syndrome, stomach and small bowel resection, and ulcerative colitis.
- •Intolerance (grade 3-4 infusion reactions) or allergy to trastuzumab (and other analogues) or mouse proteins or any ingredient of the medication.
研究组 & 干预措施
BAT8001 for injection
Participants with HER2-positive, unresectable LABC or MBC who have experienced disease progression after treatment with trastuzumab and a taxane will be treated with trastuzumab emtansine. Participants may continue to receive study treatment until disease progression (as assessed by the investigator), unmanageable toxicity, or study termination by the Sponsor.
干预措施: BAT8001 for injection (Biological)
Control (lapatinib + capecitabine)
Participants with HER2-positive, unresectable LABC or MBC who have experienced disease progression after treatment with trastuzumab and a taxane will be treated with lapatinib plus capecitabine. Participants may continue to receive study treatment until disease progression (as assessed by the investigator), unmanageable toxicity, or study termination by the Sponsor.
干预措施: Lapatinib (Drug)
Control (lapatinib + capecitabine)
Participants with HER2-positive, unresectable LABC or MBC who have experienced disease progression after treatment with trastuzumab and a taxane will be treated with lapatinib plus capecitabine. Participants may continue to receive study treatment until disease progression (as assessed by the investigator), unmanageable toxicity, or study termination by the Sponsor.
干预措施: Capecitabine (Drug)
结局指标
主要结局
Progression-free survival (PFS)
时间窗: Up to approximately 18 months
PFS is defined as the time from randomization to the first occurrence of disease progression as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) Version (v1.1), or death from any cause during the study, whichever occurs first.
次要结局
- Overall Survival (OS)(Up to approximately 30 months)
- Objective Response Rate (ORR)(Up to approximately 30 months)
- Duration of Response (DOR)(Up to approximately 30 months)
- Clinical Benefit Rate (CBR)(Up to approximately 30 months)
- Serum Concentration of BAT8001(Pre-dose and 15-30 minutes after dose on Day 1, Day 8, Day 15 of each 21-day cycle during Cycles 1-4 and at completion/early termination visit (up to approximately 30 months))
- Serum Concentration of total antibody of BAT8001 for injection(Pre-dose and 15-30 minutes after dose on Day 1, Day 8, Day 15 of each 21-day cycle during Cycles 1-4 and at completion/early termination visit (up to approximately 30 months))
- Plasma Concentration of batansine (a maytansine derivative, which is the 3AA-MDC complex)(Pre-dose and 15-30 minutes after dose on Day 1, Day 8, Day 15 of each 21-day cycle during Cycles 1-4 and at completion/early termination visit (up to approximately 30 months))
- Percentage of Participants with Anti-therapeutic Antibodies (ATA) to BAT8001(Pre-dose on Day 1 of each 21-day cycle during Cycles 1-4 and at completion/early termination visit (up to approximately 30 months))