NCT03529110进行中（未招募）3 期
A Phase 3, Multicenter, Randomized, Open-Label, Active-Controlled Study of DS-8201a (Trastuzumab Deruxtecan), an Anti-HER2 Antibody Drug Conjugate (ADC), Versus Ado Trastuzumab Emtansine (T-DM1) for HER2-Positive, Unresectable and/or Metastatic Breast Cancer Subjects Previously Treated With Trastuzumab and Taxane
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 524
- 试验地点
- 164
- 主要终点
- Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR) in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane
研究概览
简要总结
This study is designed to compare the anti-tumor activity as well as the safety and efficacy of DS-8201a versus T-DM1 in HER2-positive, unresectable and/or metastatic breast cancer subjects previously treated with trastuzumab and taxane.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must be competent and able to comprehend, sign, and date an Institutional Review Board (IRB) or Ethics Committee (EC) approved ICF before performance of any study-specific procedures or tests.
- •Adults ≥18 y old. (Please follow local regulatory requirements if the legal age of consent for study participation is >18 y old.)
- •Pathologically documented breast cancer that:
- •is unresectable or metastatic.
- •has confirmed HER2-positive expression as determined according to American Society of Clinical Oncology - College of American Pathologists guidelines evaluated at a central laboratory.23
- •was previously treated with trastuzumab and taxane in the advanced/ metastatic setting or progressed within 6 mo after neoadjuvant or adjuvant treatment involving a regimen including trastuzumab and taxane.
- •Documented radiologic progression (during or after most recent treatment or within 6 mo after completing adjuvant therapy).
- •Subjects must be HER2-positive as confirmed by central laboratory assessment of most recent tumor tissue sample available. If archived tissue is not available, a fresh biopsy is required.
- •Presence of at least 1 measurable lesion per modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1
排除标准
- •Prior treatment with an anti-HER2 ADC (such as T-DM1) in the metastatic setting. Prior treatment in the adjuvant/neoadjuvant setting would be allowed if progression of disease did not occur within 12 mo of end of adjuvant therapy.
- •Uncontrolled or significant cardiovascular disease, including any of the following:
- •History of myocardial infarction within 6 mo before randomization;
- •History of symptomatic congestive heart failure (New York Heart Association Class II to IV);
- •Troponin levels consistent with myocardial infarction as defined according to the manufacturer within 28 d prior to randomization;
- •Corrected QT interval (QTc) prolongation to > 470 ms (females) or >450 ms (male) based on average of Screening triplicate 12-lead ECG;
- •LVEF < 50% within 28 d prior to randomization
- •Has a history of (noninfectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
- •Spinal cord compression or clinically active central nervous system (CNS) metastases, defined as untreated or symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.
- •Subjects with clinically inactive brain metastases may be included in the study.
- •Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 wk must have elapsed between the end of whole brain radiotherapy and study enrollment.
- •Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product.
- •History of severe hypersensitivity reactions to other mAbs.
研究组 & 干预措施
Trastuzumab deruxtecan (T-DXd)
Experimental
Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DXd as a sterile intravenous (IV) solution at a dose of 5.4 mg/kg every 3 weeks (Q3W).
干预措施: Trastuzumab deruxtecan (T-DXd) (Drug)
Ado-trastuzumab emtansine (T-DM1)
Active Comparator
Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DM1 in accordance with the approved label.
干预措施: Ado-trastuzumab emtansine (T-DM1) (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR) in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane
时间窗: Up to 33 months (data cut-off)
Progression-free survival (PFS) by BICR was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.
次要结局
- Overall Survival (OS) in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane(Up to 33 months (data cut-off))
- Progression-Free Survival (PFS) Based on Investigator Assessment in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane(Up to 33 months (data cut-off))
- Percentage of Participants With Objective Response Rate (ORR) Based on BICR and Investigator Assessment in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane(Up to 33 months (data cut-off))
- Duration of Response (DoR) Based on BICR and Investigator Assessment in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane(Up to 33 months (data cut-off))
研究者
研究点 (164)
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