Phase III Study of Trastuzumab Deruxtecan (T-DXd) With or Without Pertuzumab Versus Taxane, Trastuzumab and Pertuzumab in HER2-positive, First-line Metastatic Breast Cancer (DESTINY-Breast09)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 1,157
- 试验地点
- 284
- 主要终点
- Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) assessment
研究概览
简要总结
The study will evaluate the efficacy and safety of trastuzumab deruxtecan (also known as T-DXd, DS-8201a), either alone or in combination with pertuzumab, in treating patients with Human epidermal growth factor receptor 2 (HER2)-positive breast cancer as a first line of treatment in the metastatic setting.
详细描述
Eligible participants will be those diagnosed with HER2-positive (IHC 3+ or ISH+), metastatic breast cancer, who have received no prior chemotherapy or HER2-targeted therapy for advanced or metastatic breast cancer.
The study aims to evaluate the efficacy, and safety of trastuzumab deruxtecan, alone or with pertuzumab, compared with the standard of care treatment (taxane [docetaxel or paclitaxel], trastuzumab and pertuzumab). This study aims to see if trastuzumab deruxtecan allows patients to live longer without the cancer getting worse, or simply to live longer, compared to patients receiving standard of care chemotherapy. This study is also looking to see how the treatment and the cancer affects patients' quality of life.
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
This study is open-label with respect to the control arm. Pertuzumab/placebo in the experimental arms will be blinded to the investigator and patients.
The study will be "Sponsor-blind". To maintain the integrity of the study, Sponsor personnel directly involved in study conduct will not undertake or have access to efficacy data aggregated by treatment group prior to final data readout for the primary endpoint.
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be ≥18 years of age
- •Pathologically documented breast cancer that:
- •is advanced or metastatic
- •is locally assessed and prospectively centrally confirmed as HER2-positive (IHC3+ or ISH+)
- •is documented by local testing as hormone receptor (HR)-positive or HR-negative disease in the metastatic setting
- •No prior chemotherapy or HER2-targeted therapy for advanced or metastatic breast cancer or only 1 previous line of endocrine therapy in the metastatic setting. Participants who have received chemotherapy or HER2-targeted therapy in the neo-adjuvant or adjuvant setting are eligible if > 6 months from treatment to metastatic diagnosis.
- •Has protocol-defined adequate organ and bone marrow function
- •ECOG performance status 0 or 1
排除标准
- •Ineligible for any of the agents on the study.
- •Any substance abuse or other medical conditions that, in the investigator's opinion, may interfere with subject's participation or study results
- •Patients with spinal cord compression or clinically active central nervous system metastases. Participants with clinically inactive brain metastases or treated brain metastases that are no longer symptomatic may be included in the study.
- •Active or prior documented interstitial lung disease (ILD)/pneumonitis or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
- •Prior randomization or treatment in a previous trastuzumab deruxtecan study regardless of treatment arm assignment
研究组 & 干预措施
Arm B
Trastuzumab deruxtecan (T-DXd) plus pertuzumab
干预措施: Pertuzumab (Drug)
Arm C
Standard of care (Taxane (paclitaxel or docetaxel), trastuzumab, and pertuzumab)
干预措施: Taxane (Drug)
Arm A
Trastuzumab deruxtecan (T-DXd) plus pertuzumab-matching placebo
干预措施: Placebo (Drug)
Arm A
Trastuzumab deruxtecan (T-DXd) plus pertuzumab-matching placebo
干预措施: Trastuzumab deruxtecan (Drug)
Arm B
Trastuzumab deruxtecan (T-DXd) plus pertuzumab
干预措施: Trastuzumab deruxtecan (Drug)
Arm C
Standard of care (Taxane (paclitaxel or docetaxel), trastuzumab, and pertuzumab)
干预措施: Pertuzumab (Drug)
Arm C
Standard of care (Taxane (paclitaxel or docetaxel), trastuzumab, and pertuzumab)
干预措施: Trastuzumab (Drug)
结局指标
主要结局
Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) assessment
时间窗: Until progression or death, assessed up to approximately 60 months
Defined as time from date of randomisation until the date of objective radiological disease progression according to Blinded Independent Central Review (BICR) using RECIST 1.1 or death by any cause.
次要结局
- Progression Free Survival (PFS) by Investigator assessment(Until progression or death, assessed up to approximately 60 months)
- Overall Survival (OS)(Until death, assessed up to approximately 104 months)
- Objective Response Rate (ORR) by BICR and Investigator assessment(Until progression or death (in the absence of progression), assessed up to approximately 60 months)
- Duration of Response (DoR) by BICR and Investigator Assessment(Until progression or death (in the absence of progression), assessed up to approximately 60 months)
- Time to second progression or death (PFS2) by Investigator assessment(Assessed up to approximately 104 months)
- To assess the effect of T-DXd ± pertuzumab relative to THP in terms of patient-reported pain in participants with HER2 positive, first-line mBC'.(Assessed up to approximately 60 months)
- Safety and tolerability of trastuzumab deruxtecan, alone or with pertuzumab(Assessed up to approximately 60 months)
- Serum concentration of trastuzumab deruxtecan and pertuzumab(Up to Cycle 6, approximately Week 18; each cycle is 21 days)
- Immunogenicity of trastuzumab deruxtecan.(Up to follow-up period, approximately 60 months)
- To assess patient-reported treatment tolerability(Assessed up to approximately 60 months)