A Randomized, Open-label, Phase 3 Study of Adjuvant Sacituzumab Govitecan and Pembrolizumab Versus Treatment of Physician's Choice in Patients With Triple Negative Breast Cancer Who Have Residual Invasive Disease After Surgery and Neoadjuvant Therapy
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 1,514
- 试验地点
- 657
- 主要终点
- Invasive Disease-free Survival (iDFS)
研究概览
简要总结
The goal of this study is to find out if the experimental product, sacituzumab govitecan-hziy (SG) in combination with pembrolizumab given after surgery, is effective and safe compared to the treatment of physician's choice (TPC) which includes either pembrolizumab or pembrolizumab plus capecitabine in participants with triple negative breast cancer that still remains after surgery and pre-surgical treatment.
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
- •Age > 18 years, with residual invasive triple negative breast cancer (TNBC) in the breast or lymph nodes after neoadjuvant therapy and surgery:
- •TNBC criteria for the study is defined as estrogen receptor (ER) and progesterone receptor (PR) ≤ 10%, human epidermal growth factor receptor 2 (HER2)-negative per American Society of Clinical Oncology and College of American Pathologists (ASCO/CAP) guidelines (immunohistochemistry (IHC) and/or in situ hybridization (ISH)).
- •Adequate excision and surgical removal of all clinically evident of disease in the breast and/or lymph nodes and have adequately recovered from surgery.
- •Submission of both pre-neoadjuvant treatment diagnostic biopsy and resected residual invasive disease tissue.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •Individuals must have received appropriate radiotherapy aligned with local/institutional practice and have recovered prior to starting study treatment.
- •Adequate organ function.
排除标准
- •Stage IV (metastatic) breast cancer as well as history of any prior (ipsi- or contralateral) invasive breast cancer.
- •Prior treatment with another stimulatory or coinhibitory T-cell receptor agent (eg, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), OX-40, cluster of differentiation 137 (CD137), prior treatment with any HER2-directed agent, prior endocrine therapy for > 4 weeks or planned concurrent endocrine therapy while receiving on-study treatment.
- •Evidence of recurrent disease following preoperative therapy and surgery.
- •Prior treatment with topoisomerase 1 inhibitors or antibody-drug conjugates (ADCs) containing a topoisomerase inhibitor.
- •Individuals with germline breast cancer gene (BRCA) mutations.
- •Myocardial infarction or unstable angina pectoris within 6 months of enrollment or history of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias or Left ventricular ejection fraction (LVEF) of < 50%
- •Active serious infections requiring anti-microbial therapy.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Sacituzumab govitecan-hziy (SG) + Pembrolizumab
Participants will receive SG 10 mg/kg intravenously on Days 1 and 8 of 21-day cycles and pembrolizumab 200 mg intravenously on Day 1 of 21-day cycles for 8 cycles.
Treatment will be administered until a maximum of 8 cycles, local or distant disease recurrence, unacceptable toxicity, physician decision, consent withdrawal, or death.
干预措施: Pembrolizumab (Drug)
Treatment of Physician's Choice (TPC): Pembrolizumab or Pembrolizumab + Capecitabine
Participants will receive one of the following TPC regimens determined prior to randomization:
- Pembrolizumab 200 mg intravenously on Day 1 of 21-day cycles for 8 cycles OR
- Pembrolizumab 200 mg intravenously on Day 1 of 21-day cycles and capecitabine 1000 mg/m^2 orally twice daily on Days 1 through 14 of 21-day cycles for 8 cycles.
Treatment will be administered until a maximum of 8 cycles, local or distant disease recurrence, unacceptable toxicity, physician decision, consent withdrawal, or death.
干预措施: Pembrolizumab (Drug)
Treatment of Physician's Choice (TPC): Pembrolizumab or Pembrolizumab + Capecitabine
Participants will receive one of the following TPC regimens determined prior to randomization:
- Pembrolizumab 200 mg intravenously on Day 1 of 21-day cycles for 8 cycles OR
- Pembrolizumab 200 mg intravenously on Day 1 of 21-day cycles and capecitabine 1000 mg/m^2 orally twice daily on Days 1 through 14 of 21-day cycles for 8 cycles.
Treatment will be administered until a maximum of 8 cycles, local or distant disease recurrence, unacceptable toxicity, physician decision, consent withdrawal, or death.
干预措施: Capecitabine (Drug)
Sacituzumab govitecan-hziy (SG) + Pembrolizumab
Participants will receive SG 10 mg/kg intravenously on Days 1 and 8 of 21-day cycles and pembrolizumab 200 mg intravenously on Day 1 of 21-day cycles for 8 cycles.
Treatment will be administered until a maximum of 8 cycles, local or distant disease recurrence, unacceptable toxicity, physician decision, consent withdrawal, or death.
干预措施: Sacituzumab govitecan-hziy (SG) (Drug)
结局指标
主要结局
Invasive Disease-free Survival (iDFS)
时间窗: Up to 60 months
iDFS is defined as the time from the date of randomization to death from any cause or one of the following events (whichever occurs first): invasive local, regional, or distant recurrence, invasive contralateral breast cancer.
iDFS is defined as the time from the date of randomization to death from any cause or one of the following events (whichever occurs first): invasive local, regional, or distant recurrence, or invasive contralateral breast cancer.
iDFS is defined as the time from the date of randomization to death from any cause or one of the following events (whichever occurs first): invasive local, regional, or distant recurrence, or invasive contralateral breast cancer.
次要结局
- Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)(First dose date up to 38 months plus 30 days)
- Overall Survival (OS)(Up to 96 months)
- Distant Disease-free Survival (dDFS)(Up to 60 months)
- Recurrence-free Survival (RFS)(Up to 60 months)
- Percentage of Participants Experiencing Laboratory Abnormalities(First dose date up to 38 months plus 30 days)
- Time to Worsening (TTW) of Quality of Life (QoL) Based on Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B) Trial Outcome Index (TOI) Scores(Up to 60 months)
- OS is defined as the time from the date of randomization until death due to any cause.
- dDFS is defined as the time from the date of randomization to death from any cause or one of the following events (whichever occurs first): distant recurrence, or second primary invasive cancer.
- RFS is defined as the time from the date of randomization to death from any cause or one of the following events (whichever occurs first): invasive local, regional, or distant recurrence
- Incidence of TEAEs and clinical laboratory abnormalities
- TTW of QoL based on FACT-B Trial Outcome Index (TOI) score