A Randomized, Open-label, Phase 3 Study of Sacituzumab Govitecan and Pembrolizumab Versus Treatment of Physician's Choice and Pembrolizumab in Patients With Previously Untreated, Locally Advanced Inoperable or Metastatic Triple-Negative Breast Cancer, Whose Tumors Express PD-L1
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 440
- 试验地点
- 504
- 主要终点
- Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
研究概览
简要总结
The primary objective of this study is to compare the progression-free survival (PFS) between sacituzumab govitecan-hziy (SG) and pembrolizumab versus treatment of physician's choice (TPC) and pembrolizumab in participants with previously untreated, locally advanced inoperable or metastatic triple-negative breast cancer, whose tumors express programmed cell death ligand 1 (PD-L1).
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
- •Individuals with locally advanced, inoperable, or metastatic triple-negative breast cancer (TNBC) who have not received previous systemic therapy for advanced disease and whose tumors are programmed cell death ligand 1 (PD-L1) positive at screening.
- •Individuals must have completed treatment for Stage I to III breast cancer, if indicated, and ≥ 6 months must have elapsed between completion of treatment with curative intent and first documented local or distant disease recurrence.
- •Individuals presenting with de novo metastatic TNBC are eligible for this study.
- •TNBC status and tumor PD-L1 combined positive score (CPS) will be confirmed centrally on a recent or archival tumor specimen.
- •Individuals must have measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria as evaluated locally.
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or
- •Demonstrates adequate organ function
- •Male and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception.
- •Individuals with HIV must be on antiretroviral therapy (ART) and have a well-controlled HIV infection/disease.
排除标准
- •Positive serum pregnancy test or women who are lactating.
- •Received prior therapy with an agent directed to another stimulatory or coinhibitory T-cell receptor.
- •Individuals may not have received systemic anticancer treatment (with the exception of endocrine therapy) within the previous 6 months or radiation therapy within 2 weeks prior to enrollment.
- •Individuals may not be participating in a study with an investigational agent or investigational device within 4 weeks prior to randomization. Individuals participating in observational studies are eligible.
- •Have previously received topoisomerase 1 inhibitors or antibody drug conjugates containing a topoisomerase inhibitor.
- •Have an active second malignancy.
- •Have active serious infection requiring antibiotics.
- •Individuals positive for HIV-1 or 2 with a history of Kaposi sarcoma and/or Multicentric Castleman Disease.
- •Have active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
- •Has an active autoimmune disease that has required systemic treatment in the past 2 years.
- •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 on Days 1 and 8 of 21-day cycles and pembrolizumab 200 mg on Day 1 of 21-day cycles
Pembrolizumab will be administered for a maximum of 35 cycles.
干预措施: Sacituzumab Govitecan-hziy (Drug)
Sacituzumab Govitecan-hziy (SG) + Pembrolizumab
Participants will receive SG 10 mg/kg on Days 1 and 8 of 21-day cycles and pembrolizumab 200 mg on Day 1 of 21-day cycles
Pembrolizumab will be administered for a maximum of 35 cycles.
干预措施: Pembrolizumab (Drug)
Pembrolizumab + Treatment of Physician's Choice (TPC)
Participants will receive pembrolizumab 200 mg on Day 1 of each 21-day cycle (maximum 35 cycles) plus TPC determined prior to randomization from 1 of the 3 allowed regimens:
- Paclitaxel 90 mg/m^2 on Days 1, 8, and 15 of 28-day cycles
- nab-Paclitaxel 100 mg/m^2 on Days 1, 8, and 15 of 28-day cycles
- Gemcitabine 1000 mg/m^2 + carboplatin area under the curve (AUC) 2 on Days 1 and 8 of 21-day cycles
干预措施: Pembrolizumab (Drug)
Pembrolizumab + Treatment of Physician's Choice (TPC)
Participants will receive pembrolizumab 200 mg on Day 1 of each 21-day cycle (maximum 35 cycles) plus TPC determined prior to randomization from 1 of the 3 allowed regimens:
- Paclitaxel 90 mg/m^2 on Days 1, 8, and 15 of 28-day cycles
- nab-Paclitaxel 100 mg/m^2 on Days 1, 8, and 15 of 28-day cycles
- Gemcitabine 1000 mg/m^2 + carboplatin area under the curve (AUC) 2 on Days 1 and 8 of 21-day cycles
干预措施: Paclitaxel (Drug)
Pembrolizumab + Treatment of Physician's Choice (TPC)
Participants will receive pembrolizumab 200 mg on Day 1 of each 21-day cycle (maximum 35 cycles) plus TPC determined prior to randomization from 1 of the 3 allowed regimens:
- Paclitaxel 90 mg/m^2 on Days 1, 8, and 15 of 28-day cycles
- nab-Paclitaxel 100 mg/m^2 on Days 1, 8, and 15 of 28-day cycles
- Gemcitabine 1000 mg/m^2 + carboplatin area under the curve (AUC) 2 on Days 1 and 8 of 21-day cycles
干预措施: nab-Paclitaxel (Drug)
Pembrolizumab + Treatment of Physician's Choice (TPC)
Participants will receive pembrolizumab 200 mg on Day 1 of each 21-day cycle (maximum 35 cycles) plus TPC determined prior to randomization from 1 of the 3 allowed regimens:
- Paclitaxel 90 mg/m^2 on Days 1, 8, and 15 of 28-day cycles
- nab-Paclitaxel 100 mg/m^2 on Days 1, 8, and 15 of 28-day cycles
- Gemcitabine 1000 mg/m^2 + carboplatin area under the curve (AUC) 2 on Days 1 and 8 of 21-day cycles
干预措施: Gemcitabine (Drug)
Pembrolizumab + Treatment of Physician's Choice (TPC)
Participants will receive pembrolizumab 200 mg on Day 1 of each 21-day cycle (maximum 35 cycles) plus TPC determined prior to randomization from 1 of the 3 allowed regimens:
- Paclitaxel 90 mg/m^2 on Days 1, 8, and 15 of 28-day cycles
- nab-Paclitaxel 100 mg/m^2 on Days 1, 8, and 15 of 28-day cycles
- Gemcitabine 1000 mg/m^2 + carboplatin area under the curve (AUC) 2 on Days 1 and 8 of 21-day cycles
干预措施: Carboplatin (Drug)
结局指标
主要结局
Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
时间窗: Randomization up to approximately 33 months
PFS is defined as the time from the date of randomization until the date of objective progressive disease (PD) or death (whichever comes first).
次要结局
- Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)(First dose date up to 53 months plus 30 days)
- Percentage of Participants Experiencing Clinical Laboratory Abnormalities(First dose date up to 53 months plus 30 days)
- Overall Survival (OS)(Randomization up to approximately 53 months)
- Objective Response Rate (ORR) as Assessed by BICR per RECIST Version 1.1(Randomization up to approximately 53 months)
- Time to Response (TTR) as Assessed by BICR per RECIST Version 1.1(Randomization up to approximately 53 months)
- Time to Deterioration (TTD) in Global Health Status/Quality of Life (QoL) Scale as Measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core Questionnaire, Version 3.0 (EORTC QLQ-C30)(Randomization up to approximately 53 months)
- TTD of Pain Score as Measured by EORTC QLQ-C30(Randomization up to approximately 53 months)
- TTD of Role Functioning Score as Measured by EORTC QLQ-C30(Randomization up to approximately 53 months)
- Duration of Response (DOR) as Assessed by BICR per RECIST Version 1.1(Randomization up to approximately 53 months)
- TTD of Fatigue Score as Measured by EORTC QLQ-C30(Randomization up to approximately 53 months)
- TTD of Physical Functioning Domain Score as Measured by EORTC QLQ-C30(Randomization up to approximately 53 months)