A Phase II Clinical Trial of Pembrolizumab as Monotherapy and in Combination With Cisplatin+5-Fluorouracil in Subjects With Recurrent or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (KEYNOTE-059)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 318
- 主要终点
- Objective Response Rate (ORR) For All Participants in Cohorts 1 and 3
研究概览
简要总结
This is a study of pembrolizumab (MK-3475) for advanced gastric or gastroesophageal junction adenocarcinoma; pembrolizumab will be given as monotherapy to participants who have had previous treatment or who are treatment-naïve; pembrolizumab will also be evaluated as combination therapy with cisplatin and 5-Fluorouracil (5-FU) or (Japan only) capecitabine in treatment-naïve participants. The primary study hypothesis is that pembrolizumab will provide a clinically meaningful Overall Response Rate (ORR).
详细描述
This study will have 3 cohorts. In Cohort 1, participants who have received at least two prior therapies for their advanced disease will receive monotherapy with pembrolizumab. In Cohort 2, participants who have not received any previous therapy for their disease will receive pembrolizumab in combination with cisplatin and 5-FU or (Japan only) capecitabine. In Cohort 3, participants who have not received any previous therapy and who have programmed death ligand 1 (PD-L1)-positive tumors will receive pembrolizumab monotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Cohort 2: Pembrolizumab combination therapy, treatment naive
Participants receive pembrolizumab 200 mg IV each 3-week cycle (Q3W) + cisplatin 80 mg/m^2 IV Q3W for up to 6 cycles + 5-FU 800 mg/m^2 IV on Days 1-5 every 3 weeks or (Japan only) capecitabine 1000 mg/m^2 orally, twice per day (BID) on Days 1-14 of each 3-week cycle
干预措施: pembrolizumab (Biological)
Cohort 1: Pembrolizumab monotherapy, previously treated
Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W)
干预措施: pembrolizumab (Biological)
Cohort 2: Pembrolizumab combination therapy, treatment naive
Participants receive pembrolizumab 200 mg IV each 3-week cycle (Q3W) + cisplatin 80 mg/m^2 IV Q3W for up to 6 cycles + 5-FU 800 mg/m^2 IV on Days 1-5 every 3 weeks or (Japan only) capecitabine 1000 mg/m^2 orally, twice per day (BID) on Days 1-14 of each 3-week cycle
干预措施: cisplatin (Drug)
Cohort 2: Pembrolizumab combination therapy, treatment naive
Participants receive pembrolizumab 200 mg IV each 3-week cycle (Q3W) + cisplatin 80 mg/m^2 IV Q3W for up to 6 cycles + 5-FU 800 mg/m^2 IV on Days 1-5 every 3 weeks or (Japan only) capecitabine 1000 mg/m^2 orally, twice per day (BID) on Days 1-14 of each 3-week cycle
干预措施: 5-FU (Drug)
Cohort 2: Pembrolizumab combination therapy, treatment naive
Participants receive pembrolizumab 200 mg IV each 3-week cycle (Q3W) + cisplatin 80 mg/m^2 IV Q3W for up to 6 cycles + 5-FU 800 mg/m^2 IV on Days 1-5 every 3 weeks or (Japan only) capecitabine 1000 mg/m^2 orally, twice per day (BID) on Days 1-14 of each 3-week cycle
干预措施: capecitabine (Drug)
Cohort 3: Pembrolizumab monotherapy, treatment naive, PD-L1 positive
Programmed death-ligand 1 (PD-L1) positive participants receive pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W)
干预措施: pembrolizumab (Biological)
结局指标
主要结局
Objective Response Rate (ORR) For All Participants in Cohorts 1 and 3
时间窗: Up to approximately 75 months
The Objective Response Rate (ORR) was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by central radiology review. The percentage of all participants (regardless of programmed death-ligand 1 \[PD-L1\] tumor status) in Cohorts 1 and 3 who had a CR or PR during first course pembrolizumab treatment per protocol, is presented.
Number of Participants Discontinuing Study Drug Due to AEs
时间窗: Up to approximately 52 months
An AE was defined as any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with the study drug. The number of participants who discontinued study drug due to an AE is presented. Per protocol, the number of participants who discontinued drug during first course pembrolizumab treatment is presented.
Objective Response Rate For PD-L1 Positive Participants in Cohorts 1 and 3
时间窗: Up to approximately 75 months
The ORR was defined as the percentage of participants in the analysis population who had a CR or PR (CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, as assessed by central radiology review. The percentage of all participants in Cohorts 1 and 3 with PD-L1+ tumor status who experienced a CR or PR during first course pembrolizumab treatment per protocol, is presented. Note: All participants in Cohort 3 had a PD-L1-positive tumor status.
Number of Participants Experiencing Adverse Events (AEs)
时间窗: Up to approximately 65 months
An AE is defined as any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with the study drug. The number of participants who experienced at least one AE is presented. Per protocol, the number of participants who experienced at least one AE during first course pembrolizumab treatment is presented.
次要结局
- Duration of Response (DOR) For All Participants(Up to approximately 75 months)
- Overall Survival (OS) For All Participants(Up to approximately 75 months)
- Objective Response Rate For PD-L1 Positive Participants in Cohort 2(Up to approximately 75 months)
- Objective Response Rate (ORR) For All Participants in Cohort 2(Up to approximately 75 months)
- Overall Survival For PD-L1 Positive Participants(Up to approximately 75 months)
- Disease Control Rate (DCR) For All Participants(Up to approximately 75 months)
- Progression-Free Survival (PFS) For All Participants(Up to approximately 75 months)
- Duration of Response For PD-L1 Positive Participants(Up to approximately 75 months)
- Progression-Free Survival For PD-L1 Positive Participants(Up to approximately 75 months)
- Disease Control Rate For PD-L1 Positive Participants(Up to approximately 75 months)