A Phase 3, Multicenter, Randomized, Open-label, Active Controlled Trial of DS-8201a, an Anti-HER2-antibody Drug Conjugate (ADC), Versus Treatment of Physician's Choice for HER2-low, Unresectable and/or Metastatic Breast Cancer Subjects
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 557
- 试验地点
- 208
- 主要终点
- Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer
研究概览
简要总结
This study will compare DS-8201a to physician choice standard treatment.
Participants must have HER2-low breast cancer that has been treated before.
Participants' cancer:
- Cannot be removed by an operation
- Has spread to other parts of the body
详细描述
This is a randomized, 2-arm, Phase 3, open-label, multicenter study to compare the safety and efficacy of trastuzumab deruxtecan versus the physician's choice (2:1) in HER2-low, unresectable and/or metastatic breast cancer participants.
The Sponsor proposes to define a new HER2-low population in this trial including tumors with IHC 1+ and IHC 2+/ISH- HER2 expression.
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
- •Is the age of majority in their country
- •Has pathologically documented breast cancer that:
- •Is unresectable or metastatic
- •Has low-HER2 expression defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested)
- •Is HR-positive or HR-negative
- •Has progressed on, and would no longer benefit from, endocrine therapy
- •Has been treated with 1 to 2 prior lines of chemotherapy/adjuvant in the recurrent or metastatic setting
- •Was never previously HER2-positive (ICH 3+ or ISH+) on prior pathology testing (per American Society of Clinical Oncology-College of American Pathologists [ASCO-CAP] guidelines)
- •Has documented radiologic progression (during or after most recent treatment)
- •Has adequate archival tumor samples available or is wiling to provide fresh biopsies prior to randomization for:
- •assessment of HER2 status
- •assessment of post-treatment status
- •Has at least 1 measurable lesion per Response Evaluation Criteria In Solid Tumors 1.1
- •Has protocol-defined adequate cardiac, bone marrow, renal, hepatic and blood clotting functions
- •Male and female participants of reproductive/childbearing potential, agrees to follow instructions for method(s) of contraception and agrees to avoid preserving ova or sperm for at least 4.5 months after treatment (or longer, per locally approved labels)
排除标准
- •Is ineligible for all options in the physician's choice arm
- •Has breast cancer ever assessed with high-HER2 expression
- •Has previously been treated with any anti-HER2 therapy, including an antibody drug conjugate
- •Has uncontrolled or significant cardiovascular disease
- •Has spinal cord compression or clinically active central nervous system metastases
- •Has history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
- •Has any medical history or condition that per protocol or in the opinion of the investigator is inappropriate for the study
研究组 & 干预措施
Physician's Choice
HER2-low, unresectable, and/or metastatic breast cancer participants previously treated with chemotherapy randomized to Physician's choice from the following options:
- Capecitabine
- Eribulin
- Gemcitabine
- Paclitaxel
- Nab-paclitaxel
干预措施: Gemcitabine (Drug)
Trastuzumab deruxtecan
HER2-low, unresectable, and/or metastatic breast cancer participants previously treated with chemotherapy randomized to DS8201a
干预措施: Trastuzumab deruxtecan (DS-8201a) (Drug)
Physician's Choice
HER2-low, unresectable, and/or metastatic breast cancer participants previously treated with chemotherapy randomized to Physician's choice from the following options:
- Capecitabine
- Eribulin
- Gemcitabine
- Paclitaxel
- Nab-paclitaxel
干预措施: Capecitabine (Drug)
Physician's Choice
HER2-low, unresectable, and/or metastatic breast cancer participants previously treated with chemotherapy randomized to Physician's choice from the following options:
- Capecitabine
- Eribulin
- Gemcitabine
- Paclitaxel
- Nab-paclitaxel
干预措施: Eribulin (Drug)
Physician's Choice
HER2-low, unresectable, and/or metastatic breast cancer participants previously treated with chemotherapy randomized to Physician's choice from the following options:
- Capecitabine
- Eribulin
- Gemcitabine
- Paclitaxel
- Nab-paclitaxel
干预措施: Paclitaxel (Drug)
Physician's Choice
HER2-low, unresectable, and/or metastatic breast cancer participants previously treated with chemotherapy randomized to Physician's choice from the following options:
- Capecitabine
- Eribulin
- Gemcitabine
- Paclitaxel
- Nab-paclitaxel
干预措施: Nab-paclitaxel (Drug)
结局指标
主要结局
Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer
时间窗: From the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, up to approximately 3 years
Progression-free survival (PFS), defined as at least a 20% increase in the sum of diameters of target lesions, was assessed from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever came first. PFS was based on blinded independent central review (BICR) in the hormone receptor-positive cohort according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. Median PFS was from Kaplan-Meier analysis. Confidence interval for median was computed using the Brookmeyer-Crowley method.
次要结局
- Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer(From screening and every 6 weeks up to withdrawal of subject consent, progressive disease (PD), or unacceptable toxicity, up to approximately 3 years)
- Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients)(From screening and every 6 weeks up to withdrawal of subject consent, progressive disease (PD), or unacceptable toxicity, up to approximately 3 years)
- Duration of Response in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer(From the date of the first documented objective response (CR or PR) to the first documented disease progression or death, whichever occurs first, up to approximately 3 years)
- Duration of Response in Participants With HER2-low Breast Cancer (All Patients)(From the date of the first documented objective response (CR or PR) to the first documented disease progression or death, whichever occurs first, up to approximately 3 years)
- Overall Survival (OS) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer(From the date of randomization up to the date of death due to any cause, up to approximately 3 years)
- Overall Survival (OS) in All Patients(From the date of randomization up to the date of death due to any cause, up to approximately 3 years)
- Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR) in Participants With HER2-low Breast Cancer (All Patients) Regardless of Hormone Receptor Status(From the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, up to approximately 3 years)
- Progression-free Survival Based on Investigator Assessment in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer(From the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, up to approximately 3 years)
- Progression-free Survival Based on Investigator Assessment in Participants With HER2-low Breast Cancer (All Patients)(From the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, up to approximately 3 years)
- Number of Overall Survival Events (Deaths)(From the date of randomization up to the date of death due to any cause, up to approximately 3 years)