A Phase III Randomized Clinical Trial of Pembrolizumab (MK-3475) Versus Paclitaxel, Docetaxel or Vinflunine in Subjects With Recurrent or Progressive Metastatic Urothelial Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 542
- 主要终点
- OS - Participants With PD-L1 Positive Tumors
研究概览
简要总结
Participants with metastatic or locally advanced/unresectable urothelial cancer that has recurred or progressed following platinum-based chemotherapy will be randomly assigned to receive Investigator's choice of paclitaxel, docetaxel, or vinflunine (Control), or pembrolizumab. The primary study hypotheses are that pembrolizumab will prolong Overall Survival (OS) and Progression-free Survival (PFS) compared to paclitaxel, docetaxel, or vinflunine.
详细描述
For the purposes of this study, participants with a programmed cell death-ligand 1 (PD-L1) combined positive score (CPS) ≥10% were considered to have a strongly PD-L1 positive tumor status and participants with PD-L1 CPS ≥1% were considered to have a PD-L1 positive tumor status.
Effective with Amendment 15, eligible participants who are allocated to the Control arm (Investigator's Choice) and experience disease progression will be provided with the opportunity to switch over to receive pembrolizumab 200 mg one time every three weeks (Q3W) for up to two years of 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Control
Participants receive paclitaxel 175 mg/m^2 intravenously (IV) or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV, on Day 1 of each 3-week cycle (Q3W). Eligible participants who experience disease progression may be able to switch over to receive pembrolizumab 200 mg Q3W for up to 35 treatment administrations (up to approximately 2 years).
干预措施: paclitaxel (Drug)
Control
Participants receive paclitaxel 175 mg/m^2 intravenously (IV) or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV, on Day 1 of each 3-week cycle (Q3W). Eligible participants who experience disease progression may be able to switch over to receive pembrolizumab 200 mg Q3W for up to 35 treatment administrations (up to approximately 2 years).
干预措施: vinflunine (Drug)
Control
Participants receive paclitaxel 175 mg/m^2 intravenously (IV) or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV, on Day 1 of each 3-week cycle (Q3W). Eligible participants who experience disease progression may be able to switch over to receive pembrolizumab 200 mg Q3W for up to 35 treatment administrations (up to approximately 2 years).
干预措施: docetaxel (Drug)
Pembrolizumab
Participants receive pembrolizumab 200 mg IV on Day 1 Q3W. Eligible participants who stop pembrolizumab with Stable Disease (SD) or better but progress after discontinuation may be able to initiate a second course of pembrolizumab 200 mg for up to 17 cycles (up to approximately 1 additional year).
干预措施: pembrolizumab (Biological)
结局指标
主要结局
OS - Participants With PD-L1 Positive Tumors
时间窗: Through primary analysis database cut-off date of 07-Sep-2016 (Up to approximately 20 months)
OS was defined as the time from randomization to death due to any cause. For the purposes of this study, participants with PD-L1 CPS ≥1% were considered to have a PD-L1 positive tumor status. OS was assessed in all participants who had PD-L1 positive tumors (CPS ≥1%) up through the primary analysis database cut-off date of 07-Sep-2016.
PFS Per RECIST 1.1 - Participants With Programmed Cell Death-Ligand (PD-L1) Positive Tumors
时间窗: Through primary analysis database cut-off date of 07-Sep-2016 (Up to approximately 20 months)
PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as at least a 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 at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. PFS per RECIST 1.1 was assessed by BICR in all participants who had PD-L1 positive tumors (combined positive score \[CPS\] ≥1%) up through the primary analysis database cut-off date of 07-Sep-2016.
PFS Per RECIST 1.1 - Participants With Strongly PD-L1 Positive Tumors
时间窗: Through primary analysis database cut-off date of 07-Sep-2016 (Up to approximately 20 months)
PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as at least a 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 at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. PFS per RECIST 1.1 was assessed by BICR in all participants who had strongly PD-L1 positive tumors (CPS ≥10%) up through the primary analysis database cut-off date of 07-Sep-2016.
OS - Participants With Strongly PD-L1 Positive Tumors
时间窗: Through primary analysis database cut-off date of 07-Sep-2016 (Up to approximately 20 months)
OS was defined as the time from randomization to death due to any cause. For the purposes of this study, participants with a PD-L1 CPS ≥10% were considered to have a strongly PD-L1 positive tumor status. The OS was assessed in all participants who had strongly PD-L1 positive tumors (CPS ≥10%) up through the primary analysis database cut-off date of 07-Sep-2016.
Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - All Participants
时间窗: Through primary analysis database cut-off date of 07-Sep-2016 (Up to approximately 20 months)
PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease (PD) was defined as at least a 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 at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was assessed by blinded independent central review (BICR) in all participants up through the primary analysis database cut-off date of 07-Sep-2016.
Overall Survival (OS) - All Participants
时间窗: Through primary analysis database cut-off date of 07-Sep-2016 (Up to approximately 20 months)
OS was defined as the time from randomization to death due to any cause. The OS was assessed in all participants up through the primary analysis database cut-off date of 07-Sep-2016.
次要结局
- Number of Participants Who Discontinued Study Treatment Due to an AE(Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months))
- Number of Participants Who Experienced an Adverse Event (AE)(Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months))
- ORR Per RECIST 1.1 - All Participants(Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months))
- PFS Per mRECIST - All Participants(Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months))
- ORR Per mRECIST - Participants With Strongly PD-L1 Positive Tumors(Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months))
- Objective Response Rate (ORR) Per RECIST 1.1 - Participants With Strongly PD-L1 Positive Tumors(Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months))
- ORR Per RECIST 1.1 - Participants With PD-L1 Positive Tumors(Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months))
- PFS Per Modified RECIST (mRECIST) - Participants With Strongly PD-L1 Positive Tumors(Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months))
- PFS Per mRECIST - Participants With PD-L1 Positive Tumors(Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months))
- ORR Per mRECIST - Participants With PD-L1 Positive Tumors(Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months))
- ORR Per mRECIST - All Participants(Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months))
- Duration of Response (DOR) Per RECIST 1.1 - Participants With Strongly PD-L1 Positive Tumors(Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months))
- DOR Per RECIST 1.1 - Participants With PD-L1 Positive Tumors(Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months))
- DOR Per RECIST 1.1 - All Participants(Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months))