A Phase 2, Multicenter, Open-Label Study of DS-8201a, an Anti-HER2-Antibody Drug Conjugate (ADC) for HER2-Positive, Unresectable and/or Metastatic Breast Cancer Subjects Previously Treated With T-DM1 (DESTINY-Breast01)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 253
- 试验地点
- 99
- 主要终点
- Objective Response Rate as Confirmed by Independent Central Review Following Intravenous Administration of 5.4 mg/kg DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)
研究概览
简要总结
Some human epidermal growth factor receptor 2 (HER-2) breast cancer patients do not respond or become resistant to current treatment. DS-8201a is a new experimental product that is a combination of an antibody and a drug. It has not yet been approved for use. DS-8201a may slow down tumor growth. This might improve outcomes for these patients.
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
盲法说明
In Part 1, about 60 trastuzumab emtansine (T-DM1) resistant/refractory patients initially will be randomized into three treatment groups (low, medium and high doses) for Pharmacokinetics (PK), then about another 60 will be randomized into low and high doses to determine recommended dose (RD). After that, about 100 will receive the recommended dose in an open-label continuation stage (Part 2). About 10 TDM-1 intolerant patients will join the continuation stage as an exploratory only arm.
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
- •Men or women the age of majority in their country
- •Has pathologically documented breast cancer that:
- •is unresectable or metastatic
- •has HER2 positive expression confirmed per protocol
- •Has an adequate tumor sample
- •Has at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- •Has protocol-defined adequate cardiac, renal and hepatic function
- •Agrees to follow protocol-defined method(s) of contraception
排除标准
- •Has a medical history of myocardial infarction, symptomatic congestive heart failure (CHF) (NYHA classes II-IV), unstable angina or serious cardiac arrhythmia
- •Has a corrected QT interval (QTc) prolongation to > 450 millisecond (ms) in males and > 470 ms in females
- •Has a medical history of clinically significant lung disease
- •Is suspected to have certain other protocol-defined diseases based on imaging at screening period
- •Has history of any disease, metastatic condition, drug/medication use or other condition that might, per protocol or in the opinion of the investigator, compromise:
- •safety or well-being of the participant or offspring
- •safety of study staff
- •analysis of results
研究组 & 干预措施
DS-8201a Low Dose
T-DM1 resistant/refractory (R/R) patients in the low dose treatment group
干预措施: DS-8201a (Drug)
DS-8201a Medium Dose
T-DM1 resistant/refractory (R/R) patients in the medium dose treatment group
干预措施: DS-8201a (Drug)
DS-8201a High Dose
T-DM1 resistant/refractory (R/R) patients in the high dose treatment group
干预措施: DS-8201a (Drug)
Exploratory Arm
In Part 2b- Continuation Stage, about 10 T-DM1 Intolerant patients will receive the DS-8201a recommended dose (RD) as an exploratory arm
干预措施: DS-8201a (Drug)
结局指标
主要结局
Objective Response Rate as Confirmed by Independent Central Review Following Intravenous Administration of 5.4 mg/kg DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)
时间窗: at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)
The number of participants with objective response was assessed every six weeks from Cycle 1 Day 1 through discontinuation of treatment, by independent central imaging facility review based on RECIST version 1.1.
次要结局
- Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)(at least 6 months after last participant enrolled received first dose up to 19 months (data cut off))
- Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)(Baseline up to Week 6, 12, 18, 24, 30, 36 post dose)
- Objective Response Rate as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)(at least 6 months after last participant enrolled received first dose up to 19 months (data cut off))
- Disease Control Rate and Clinical Benefit Rate as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)(at least 6 months after last participant enrolled received first dose up to 19 months (data cut off))
- Duration of Response (Complete Response or Partial Response) as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)(at least 6 months after last participant enrolled received first dose up to 19 months (data cut off))
- Progression-Free Survival Estimate As Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)(at least 6 months after last participant enrolled received first dose up to 19 months (data cut off))
- Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set)(Day 0 to Day 47 post last dose)