NCT03062358已完成3 期
A Phase III Randomized Double-blind Study of Pembrolizumab Plus Best Supportive Care vs. Placebo Plus Best Supportive Care as Second-Line Therapy in Asian Subjects With Previously Systemically Treated Advanced Hepatocellular Carcinoma (KEYNOTE-394)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 453
- 试验地点
- 41
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
The purpose of this study is to determine the efficacy and safety of pembrolizumab or placebo given with best supportive care (BSC) in Asian participants with previously systemically treated advanced hepatocellular carcinoma (HCC). The primary hypothesis of this study is that overall survival is prolonged in participants who receive pembrolizumab compared to those who receive placebo.
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
- Double (Participant, Investigator)
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
- •Has a HCC diagnosis confirmed by radiology, histology, or cytology (fibrolamellar, and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible)
- •Has Barcelona Clinic Liver Cancer (BCLC) Stage C disease or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy and not amenable to a curative treatment approach.
- •Has a Child-Pugh A liver score within 7 days prior to first dose of study medication
- •Has a life expectancy of >3 months
- •Has at least one measurable lesion based on RECIST version 1.1 as determined by investigator.
- •Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 7 days prior to receiving the first dose of study medication.
- •Has documented objective radiographic progression during or after treatment with sorafenib or oxaliplatin-based chemotherapy, or else intolerance to sorafenib or oxaliplatin-based chemotherapy
- •Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study therapy
- •Female and male participants of reproductive potential must agree to use adequate contraception starting from the first dose of study medication, throughout the study period, and for up to 120 days after the last dose of study medication
排除标准
- •Is currently participating or has participated in a study with an investigational agent or using an investigational device within 4 weeks of the first dose of study medication
- •Has received sorafenib or oxaliplatin-based chemotherapy within 14 days of first dose of study medication
- •Has had esophageal or gastric variceal bleeding within the last 6 months
- •Has clinically apparent ascites on physical examination
- •Has portal vein invasion at the main portal branch (Vp4), inferior vena cava, or cardiac involvement of HCC based on imaging
- •Has had clinically diagnosed hepatic encephalopathy in the last 6 months
- •Has had a solid organ or hematologic transplant
- •Has had prior systemic therapy for HCC in the advanced (incurable) setting other than sorafenib or oxaliplatin-based chemotherapy, prior to start of study medication
- •Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment.
- •Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication
- •Has received locoregional therapy to liver (transcatheter chemoembolization [TACE], transcatheter embolization [TAE], hepatic arterial infusion [HAI], radiation, radioembolization, or ablation) within 4 weeks prior to the first dose of study medication
- •Has had major surgery to liver or other site within 4 weeks prior to the first dose of study medication
- •Has had a minor surgery ≤7 days prior to the first dose of study medication
- •Has not recovered adequately (i.e., Grade ≤1 or baseline) from the toxicity and/or complications from any intervention prior to study start
- •Has a diagnosed additional malignancy within 3 years prior to first dose of study medication with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or curatively resected in situ cancers
- •Has a known history of, or any evidence of, central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
- •Has an active infection requiring systemic therapy
- •Is pregnant or breast feeding or expecting to conceive or father starting from the first dose of study medication, throughout the study period, and for up to 120 days after the last dose of study medication
- •Has received prior immunotherapy with an anti-Programmed Cell Death Receptor 1 (PD-1), Programmed Cell Death Receptor Ligand 1 (anti-PD-L1), or anti-Programmed Cell Death Receptor Ligand 2 (PD-L2) or has previously participated in clinical studies with pembrolizumab
- •Has a known history of human immunodeficiency virus (HIV)
- •Has untreated active Hepatitis B
- •Has Hepatitis C in which participants received therapy for HCV <4 weeks prior to receiving pembrolizumab
- •Has received a live vaccine within 30 days prior to the first dose of study therapy
研究组 & 干预措施
pembrolizumab + BSC
Experimental
Participants receive pembrolizumab by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.
干预措施: pembrolizumab (Biological)
pembrolizumab + BSC
Experimental
Participants receive pembrolizumab by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.
干预措施: best supportive care (BSC) (Other)
placebo + BSC
Placebo Comparator
Participants receive placebo by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.
干预措施: placebo (Drug)
placebo + BSC
Placebo Comparator
Participants receive placebo by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.
干预措施: best supportive care (BSC) (Other)
结局指标
主要结局
Overall Survival (OS)
时间窗: Up to approximately 4 years
OS is the time from randomization to death due to any cause, based on the Kaplan-Meier method for censored data.
次要结局
- Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)(Up to approximately 4 years)
- Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)(Up to approximately 4 years)
- Duration Of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)(Up to approximately 4 years)
- Number of Participants Who Experienced At Least One Adverse Event (AE)(Up to approximately 30 months.)
- Disease Control Rate (DCR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)(Up to approximately 4 years)
- Number of Participants Who Discontinued Study Treatment Due to an AE(Up to approximately 27 months.)
- Time To Progression (TTP) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)(Up to approximately 4 years)
研究者
研究点 (41)
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