2023-505210-18-00进行中（未招募）3 期
A Phase 3 Open-label Trial of Neoadjuvant Trastuzumab Deruxtecan (TDXd) 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）
- 入组人数
- 280
- 试验地点
- 33
- 主要终点
- pCR (ypT0/Tis ypN0): Rate of pCR is defined as the proportion of participants who have no evidence by 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.
研究概览
简要总结
"This is a Phase 3, open-label, three-arm study to determine the safety and efficacy of T-DXd monotherapy or T-DXd followed by THP as neoadjuvant treatment compared to standard of care (ddAC-THP) in participants with locally advanced or inflammatory HER2-positive early breast cancer.
The target population of interest in this study is participants with high-risk HER2-positive early breast cancer. Participants will be randomized in a 1:1:1 ratio to one of the following intervention groups: T DXd monotherapy (Arm A), T-DXd followed by THP (Arm B), or ddAC-THP (Arm C).
The primary objective is to demonstrate the superiority of neoadjuvant T-DXd alone or in sequence with THP relative to ddAC-THP by assessment of pCR (pathological complete response, ypT0/Tis ypN0) using central evaluation in participants with HER2-positive early breast cancer."
研究设计
- 分配方式
- Randomized
- 主要目的
- N/a
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Patients must be at least 18 years of age.
- •Histologically documented HER2-positive EBC participants with: (a) Locally assessed HER2-positive (IHC 3+ or ISH+) according to ASCO-CAP guidelines and prospectively centrally confirmed as HER2 positive based on a tumour sample (b) Unifocal and multifocal tumours (> 1 tumour confined to the same quadrant as the primary tumour) must have 1 focus sampled and centrally confirmed as HER2 positive (c) Multi-centric tumours (multiple tumours involving > 1 quadrant of the breast) must have 1 lesion from each involved quadrant sampled and centrally confirmed as HER2 positive. All quadrants tested must be centrally confirmed as HER2 positive (d) Tumours documented as HR-positive (either ER and/or PgR positive [ER or PgR ≥ 1%]) or HR-negative (ER and PgR negative) by local assessment per ASCO-CAP guidelines (Allison et al 2020) (e) 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 (Hortobagyi et al 2017) (f) Pathologic confirmation of nodal involvement with malignancy as determined by fine-needle aspiration or core-needle biopsy, when applicable.
- •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
- •ECOG performance status of 0 or 1 at randomization
- •Adequate organ and bone marrow function
- •LVEF ≥ 50% within 28 days before randomization
排除标准
- •Prior history of invasive breast cancer
- •Lung-specific intercurrent clinically significant illnesses including, but not limited to, any pulmonary disorder
- •Investigator judgement of 1 or more of the following: (a) Mean resting corrected QTcF interval of >470 ms (females) or >450 ms (males) (b) History of QT prolongation associated with other medications that required discontinuation of that medication or any medication known to prolong QT interval and cause TdP. (c) Congenital long QT syndrome, family history of long QT syndrome or unexplained death under 40 years in first degree relatives
- •History of arrhythmia, symptomatic or uncontrolled atrial fibrillation or asymptomatic sustained ventricular tachycardia
- •Any primary malignancy within 3 years, except adequately resected non-melanoma skin cancer, or curatively treated in situ disease Note: This includes a second current breast primary malignancy (ie, bilateral breast cancer)
- •History of DCIS, except for participants treated with mastectomy only > 5 years prior to current diagnosis
- •Prior sentinel lymph node biopsy or axillary lymph node dissection before initiation of neoadjuvant treatment
- •Prior systemic therapy for the treatment of breast cancer
- •Previous treatment with anthracyclines, cyclophosphamide or taxanes for any malignancy; cyclophosphamide allowed for non-cancer treatment if last dose > 6 months
- •Ineligible for any medication in the control Arm C
- •Any concurrent anticancer treatment
- •History of non-infectious ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
结局指标
主要结局
pCR (ypT0/Tis ypN0): Rate of pCR is defined as the proportion of participants who have no evidence by 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.
pCR (ypT0/Tis ypN0): Rate of pCR is defined as the proportion of participants who have no evidence by 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
- PK of T-DXd: Serum concentration of T-DXd, anti-HER2 antibody, and DXd.
- pCR (ypT0 ypN0): Rate of pCR is defined as the proportion of participants who have no evidence by H&E staining of residual invasive disease and in situ cancer in the complete resected breast specimen and all sampled regional lymph nodes (ypT0 ypN0) following completion of neoadjuvant therapy.
- EFS
- IDFS
- OS
- HRQoL: Symptomatic AEs assessed by the PRO-CTCAE and items from the EORTC Item Library. Overall side-effect bother measured by PGI-TT at each time point in each treatment arm. Physical function assessed by the EORTC QLQ-C30 Physical Function Scale.
- Safety and Tolerability: Occurrence of AEs, SAEs and changes from baseline in vital signs, clinical laboratory results, ECGs, and ECHO/MUGA. Heart failure evaluated by the percentage of participants with NYHA Class III and IV heart failure. Decreases in LVEF (requires at least 2 consecutive readings of decline) by percentage of participants with decreases in LVEF of at least 10 points from baseline and to below 50%.
- Immunogenicity for T-DXd: Number and percentage of participants who develop ADAs for T-DXd.
研究者
Clinical Study Information Center
Scientific
AstraZeneca AB
研究点 (33)
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