A Phase III Randomized Open-Label Study of Single Agent Pembrolizumab vs Physicians' Choice of Single Agent Docetaxel, Paclitaxel, or Irinotecan in Subjects With Advanced/Metastatic Adenocarcinoma and Squamous Cell Carcinoma of the Esophagus That Have Progressed After First-Line Standard Therapy (KEYNOTE-181)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 628
- 主要终点
- Overall Survival (OS) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus
研究概览
简要总结
In this study, participants with advanced or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus or Siewert type I adenocarcinoma of the esophagogastric junction (EGJ) that had progressed after first-line standard therapy were randomized to receive either pembrolizumab (MK-3475) OR the Investigator's choice of standard chemotherapy with paclitaxel, docetaxel, or irinotecan.
The primary study hypothesis was that treatment with pembrolizumab would prolong overall survival (OS) as compared to treatment with standard chemotherapy.
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
- •Histologically- or cytologically-confirmed diagnosis of adenocarcinoma or squamous cell carcinoma of the esophagus or Siewert type I adenocarcinoma of the EGJ
- •Metastatic disease or locally advanced, unresectable disease
- •Life expectancy of greater than 3 months
- •Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
- •Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
- •Documented radiographic or clinical disease progression on no more or less than one previous line of standard therapy
- •Can provide either a newly obtained or archival tumor tissue sample for intra-tumoral immune-related testing and for anti-programmed cell death (PD)-1
- •Participants of reproductive potential must be willing to use adequate contraception for the course of the study through 120 days after the last dose of pembrolizumab or through 180 days after the last dose of paclitaxel, docetaxel or irinotecan
- •Adequate organ function
排除标准
- •Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study treatment
- •Active autoimmune disease that has required systemic treatment in past 2 years
- •Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
- •Known central nervous system (CNS) metastases and/or carcinomatous meningitis (includes past history or current metastasis)
- •Has received prior anti-cancer monoclonal antibody (mAb), chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or not recovered from adverse events due to a previously administered agent
- •Has had a severe hypersensitivity reaction to treatment with another mAb
- •Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1), or anti-PD-L2 agent, or previously participated in Merck pembrolizumab (MK-3475) study
- •Has a known additional malignancy that has progressed or required active treatment within the last 5 years with the exception of curatively treated basal cell and squamous cell carcinoma of the skin and/or curatively resected in-situ cervical and/or breast cancers, and in-situ or intra-mucosal pharyngeal cancer
- •Received a live vaccine within 30 days of the first dose of study treatment
- •Known history of human immunodeficiency virus (HIV) infection
- •Known history of or is positive for hepatitis B or known active hepatitis C
- •History of non-infectious pneumonitis that required steroids or current pneumonitis
- •Active infection requiring systemic therapy
- •Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
- •Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study starting with the screening visit through 120 days after the last dose of pembrolizumab or through 180 days after the last dose of paclitaxel, docetaxel or irinotecan
- •Known allergy, hypersensitivity, or contraindication to paclitaxel, docetaxel, or irinotecan or any components used in their preparation
- •Experienced weight loss >10% over approximately 2 months prior to first dose of study treatment
- •Has ascites or pleural effusion by physical exam
- •Has experienced documented objective radiographic or clinical disease progression during or after receiving >1 line of therapy
研究组 & 干预措施
Pembrolizumab
Participants received pembrolizumab 200 mg, intravenously (IV) on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to approximately 25 months).
干预措施: pembrolizumab (Biological)
Chemotherapy
Participants received Investigator's choice of paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle (up to approximately 19 months).
干预措施: paclitaxel (Drug)
Chemotherapy
Participants received Investigator's choice of paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle (up to approximately 19 months).
干预措施: docetaxel (Drug)
Chemotherapy
Participants received Investigator's choice of paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle (up to approximately 19 months).
干预措施: irinotecan (Drug)
结局指标
主要结局
Overall Survival (OS) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus
时间窗: Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)
OS was defined as the time from randomization to death due to any cause. Median OS in participants with SCC of the esophagus is presented.
Overall Survival (OS) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10)
时间窗: Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)
OS was defined as the time from randomization to death due to any cause. Median OS in participants with a PD-L1 CPS ≥10 is presented.
Overall Survival (OS) in All Participants
时间窗: Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)
OS was defined as the time from randomization to death due to any cause. Median OS in all participants is presented.
次要结局
- Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants(Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months))
- Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants(Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months))
- Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus(Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months))
- Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10)(Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months))
- Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus(Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months))
- Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10)(Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months))
- Number of Participants Experiencing an Adverse Event (AE)(Through End-of-Trial Analysis data cutoff date of 14-Mar-2022 (up to approximately 6 years))
- Number of Participants Discontinuing Study Treatment Due an Adverse Event (AE)(Through End-of-Trial Analysis data cutoff date of 14-Mar-2022 (up to approximately 6 years))