A Phase 3 Open-label Trial of Neoadjuvant Trastuzumab Deruxtecan (T-DXd) Monotherapy or T-DXd Followed by THP Compared to ddAC-THP in Participants With High-risk HER2-positive Early-stage Breast Cancer (DESTINY-Breast11)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 927
- 试验地点
- 145
- 主要终点
- Rate of Pathologic Complete Response (pCR).
研究概览
简要总结
This study will look at the efficacy and safety of trastuzumab deruxtecan (T-DXd) in a neoadjuvant setting, in high-risk, HER2-positive early non-metastatic breast cancer.
详细描述
The target population of interest in this study is participants with high-risk HER2-positive early-stage breast cancer. The purpose of this study is to determine the efficacy and safety of T-DXd neoadjuvant therapy.
Participants will be randomised to one of 3 arms: T-DXd monotherapy (Arm A), T-DXd followed by THP (Arm B), or ddAC-THP (Arm C).
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
- •Patients must be at least 18 years of age.
- •Histologically documented HER2-positive early breast cancer (EBC) participants, including clinical stage at presentation (based on mammogram or breast MRI assessment): T0-4 (inclusive of inflammatory breast cancer), N1-3, M0 or ≥ T3, N0, M0 as determined by the AJCC staging system, 8th edition
- •ECOG performance status of 0 or 1 at randomization
- •Adequate organ and bone marrow function
- •LVEF ≥ 50% within 28 days before randomization
- •FFPE tissue block (2 cores) or 20 freshly-cut, serial tumor slides for HER2 assessment by central lab. If blocks are incomplete or fewer than 20 slides are available, participants may be eligible following discussion with the AstraZeneca Study Physician
排除标准
- •prior history of invasive breast cancer
- •stage IV breast cancer (determined by AJCC staging system)
- •any primary malignancy within 3 years (except resected non-melanoma skin cancer, curatively treated in situ disease) Note: This includes a second current breast primary malignancy (ie, bilateral breast cancer)
- •history of DCIS (except those treated with mastectomy >5 years prior to current diagnosis)
- •History of, or current, ILD/pneumonitis
- •Prior systemic therapy for the treatment of breast cancer
- •Previous treatment with anthracyclines, cyclophosphamide or taxanes for any malignancy
研究组 & 干预措施
Arm B
T-DXd, followed by THP
干预措施: Trastuzumab Deruxtecan (Drug)
Arm B
T-DXd, followed by THP
干预措施: Paclitaxel (Drug)
Arm B
T-DXd, followed by THP
干预措施: Pertuzumab (Drug)
Arm B
T-DXd, followed by THP
干预措施: Trastuzumab (Drug)
Arm A
Trastuzumab deruxtecan
干预措施: Trastuzumab Deruxtecan (Drug)
Arm C
doxorubicin and cyclophosphamide, followed by THP
干预措施: Paclitaxel (Drug)
Arm C
doxorubicin and cyclophosphamide, followed by THP
干预措施: Trastuzumab (Drug)
Arm C
doxorubicin and cyclophosphamide, followed by THP
干预措施: Pertuzumab (Drug)
Arm C
doxorubicin and cyclophosphamide, followed by THP
干预措施: cyclophosphamide (Drug)
Arm C
doxorubicin and cyclophosphamide, followed by THP
干预措施: Doxorubicin (Drug)
结局指标
主要结局
Rate of Pathologic Complete Response (pCR).
时间窗: Through to definitive surgery or discontinuation/withdrawal from study, up to a maximum of approximately 40 months from randomization to primary pCR DCO (12MAR2025)
Proportion of participants who have no evidence by Hematoxylin \& Eosin (H\&E) staining of residual invasive disease in the complete resected breast specimen and all sampled regional lymph nodes (ypT0/Tis ypN0) by central evaluation following completion of neoadjuvant therapy.
次要结局
- Event-Free Survival (Duration)(Up to a maximum of approximately 65 months from randomization to EFS final analysis DCO (Apr 2027))
- Event-Free Survival (Count)(Up to a maximum of approximately 65 months from randomization to EFS final analysis DCO (Apr 2027))