An Open-label, Multicenter, Phase 3 Randomized, Active-Comparator-Controlled Clinical Study of Pembrolizumab (MK-3475) in Combination With Sacituzumab Govitecan Versus MK-3475 Monotherapy as First-line Treatment in Participants With PD L1 TPS Greater Than or Equal to 50% Metastatic Non-small Cell Lung Cancer (KEYNOTE D46/EVOKE-03)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 614
- 试验地点
- 180
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
The purpose of this study is to compare pembrolizumab (MK-3475) in combination with sacituzumab govitecan with pembrolizumab alone with respect to progression-free survival (PFS) and overall survival (OS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR) among adults with metastatic non-small cell lung cancer (NSCLC) with programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥50%).
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
- •The main inclusion criteria include but are not limited to the following:
- •Has a histologically or cytologically confirmed diagnosis of metastatic non-small cell lung cancer (NSCLC)
- •Has confirmation that epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase 1 (ALK-1), or ROS proto-oncogene 1 (ROS-1)-directed therapy is not indicated as primary therapy
- •Has provided tumor tissue that demonstrates PD-L1 tumor proportion score (TPS) ≥50% of tumor cells as assessed by immunohistochemistry (IHC) at a central laboratory
- •Has a life expectancy of at least 3 months
排除标准
- •The main exclusion criteria include but are not limited to the following:
- •Has history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years
- •Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their metastatic NSCLC
- •Has previously received treatment with Topoisomerase 1 inhibitors or Trop-2 targeted therapy
- •Has received prior therapy with an anti-programmed cell death 1 protein (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti anti- programmed cell death ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
- •Has received prior radiotherapy within 2 weeks of start of study intervention or has radiation-related toxicities requiring corticosteroids
- •Has received radiation therapy to the lung that is >30 Gray (Gy) within 6 months of the first dose of study intervention
- •Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
- •Has received an investigational agent or has used an investigational device within 4 weeks before study intervention administration
- •Has cardiac disease
- •Myocardial infarction or unstable angina pectoris within 6 months of enrollment
- •History of serious ventricular arrhythmia, high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications; history of QT interval prolongation
- •New York Heart Association (NYHA) Class III or greater congestive heart failure or left ventricular ejection fraction of <40%
- •Has active chronic inflammatory bowel disease
- •Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Has severe hypersensitivity (≥Grade 3) to pembrolizumab or sacituzumab govitecan and/or any of their excipients
- •Has active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy
- •History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- •Has active infection requiring systemic therapy
- •Has history of human immunodeficiency virus (HIV) infection
- •History of hepatitis B or known active hepatitis C virus infection
- •Has history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator
- •Have not adequately recovered from major surgery or have ongoing surgical complications
研究组 & 干预措施
Pembrolizumab
Participants receive pembrolizumab 200mg IV infusion on Day 1 Q3W for up to 35 cycles (each cycle length = 21 days).
干预措施: Pembrolizumab (Biological)
Pembrolizumab + Sacituzumab Govitecan
Participants receive sacituzumab govitecan 10mg/kg intravenous (IV) infusion once weekly on Day 1 and Day 8 of a continuous 21-day cycle until progressive disease (PD) requiring discontinuation, unacceptable toxicity, withdrawal of consent, or death. Participants receive pembrolizumab 200mg IV infusion on Day 1 every 3 weeks (Q3W) for up to 35 cycles (each cycle length = 21 days).
干预措施: Sacituzumab Govitecan (Biological)
Pembrolizumab + Sacituzumab Govitecan
Participants receive sacituzumab govitecan 10mg/kg intravenous (IV) infusion once weekly on Day 1 and Day 8 of a continuous 21-day cycle until progressive disease (PD) requiring discontinuation, unacceptable toxicity, withdrawal of consent, or death. Participants receive pembrolizumab 200mg IV infusion on Day 1 every 3 weeks (Q3W) for up to 35 cycles (each cycle length = 21 days).
干预措施: Pembrolizumab (Biological)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: Up to approximately 38 months
PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as per the Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1). PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. RECIST 1.1 is modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. PFS as assessed by blinded independent central review (BICR) will be presented.
Overall Survival (OS)
时间窗: Up to approximately 48 months
OS is defined as the time from randomization to death due to any cause.
次要结局
- Objective Response (OR)(Up to approximately 38 months)
- Duration of Response (DOR)(Up to approximately 48 months)
- Change from Baseline in the Global Health Status/Quality of Life (Items 29 and 30) Combined Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30)(Baseline and up to approximately 48 months)
- Change from Baseline in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30(Baseline and up to approximately 48 months)
- Change from Baseline in Role Functioning (Items 6-7) Combined Score on the EORTC QLQ-C30(Baseline and up to approximately 48 months)
- Change from Baseline in Dyspnea Score (Item 8) on the EORTC QLQ-C30(Baseline and up to approximately 48 months)
- Change from Baseline in Cough Score (Item 31) on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 (EORTC QLQ-LC13)(Baseline and up to approximately 48 months)
- Change from Baseline in Chest Pain Score (Item 40) on the EORTC QLQ-LC13(Baseline and up to approximately 48 months)
- Time to Deterioration (TTD) in the Global Health Status/Quality of Life (Items 29 and 30) Combined Score on the EORTC QLQ-C30(Up to approximately 48 months)
- TTD in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30(Up to approximately 48 months)
- TTD in Role Functioning (Items 6-7) Combined Score on the EORTC QLQ-C30(Up to approximately 48 months)
- TTD in Dyspnea Score (Item 8) on the EORTC QLQ-C30 11(Up to approximately 48 months)
- TTD in Cough Score (Item 31) on the EORTC QLQ-LC13(Up to approximately 48 months)
- TTD in Chest Pain Score (Item 40) on the EORTC QLQ-LC13(Up to approximately 48 months)
- Number of Participants Who Experience an Adverse Event (AE)(Up to approximately 48 months)
- Number of Participants Who Discontinue Study Treatment Due To an AE(Up to approximately 48 months)