NCT03867084已完成3 期
A Phase 3 Double-blinded, Two-arm Study to Evaluate the Safety and Efficacy of Pembrolizumab (MK-3475) Versus Placebo as Adjuvant Therapy in Participants With Hepatocellular Carcinoma and Complete Radiological Response After Surgical Resection or Local Ablation (KEYNOTE-937)
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
- 959
- 试验地点
- 249
- 主要终点
- Recurrence-Free Survival (RFS)
研究概览
简要总结
This study will evaluate the safety and efficacy of pembrolizumab (MK-3475) versus placebo as adjuvant therapy in participants with hepatocellular carcinoma (HCC) and complete radiological response after surgical resection or local ablation. The primary hypotheses of this study are that adjuvant pembrolizumab is superior to placebo with respect to: 1) recurrence-free survival (RFS) as assessed by blinded independent central review (BICR); and 2) overall survival (OS).
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 diagnosis of HCC by radiological criteria and/or pathological confirmation.
- •Has an eligibility scan (CT of the chest, triphasic CT scan or MRI of the abdomen, and CT or MRI of the pelvis) confirming complete radiological response ≥4 weeks after complete surgical resection or local ablation. Randomization needs to occur within 12 weeks of the date of surgical resection or local ablation.
- •Has no radiologic evidence of disease prior to enrollment.
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to Cycle 1, Day
- •Has a Child-Pugh class A liver score (5 to 6 points) within 7 days prior to Cycle 1, Day
- •Has alpha fetoprotein (AFP) concentration lower than 400 ng/mL within 28 days prior to Cycle 1, Day
- •Has controlled hepatitis B (Hep B).
- •Has recovered adequately from toxicity and/or complications from the local intervention (surgical resection or local ablation) prior to starting study treatment.
- •If female, is not pregnant or breastfeeding, and at least one of the following conditions applies: 1) Is not a woman of childbearing potential (WOCBP); or 2) Is a WOCBP and using a contraceptive method that is highly effective or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (a WOCBP must have a negative pregnancy test within 72 hours before the first dose of study treatment).
- •If undergoing surgical resection, has submitted a tumor tissue sample during Screening.
- •Has adequate organ function.
排除标准
- •Has a known additional malignancy that is progressing or has required active antineoplastic treatment (including hormonal) or surgery within the past 3 years.
- •Has had esophageal or gastric variceal bleeding within the last 6 months.
- •Has clinically apparent ascites on physical examination.
- •Has had clinically diagnosed hepatic encephalopathy in the last 6 months.
- •Has received local therapy to liver ablation other than with radiofrequency or microwave ablation.
- •Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- •Has an active infection requiring systemic therapy.
- •Has dual active Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infection at study entry.
- •Has a known history of human immunodeficiency virus (HIV) infection.
- •Has known active tuberculosis (TB; Bacillus tuberculosis).
- •Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
- •Has received prior systemic anti-cancer therapy for HCC including investigational agents.
- •Is receiving any of the following prohibited concomitant therapies:1) Antineoplastic systemic chemotherapy or biological therapy; 2) Immunotherapy not specified in this protocol; 3) Investigational agents other than pembrolizumab; 4) Radiation therapy; 5) Oncological surgical therapy; or systemic glucocorticoids for any purpose other than to modulate symptoms from an AE that is suspected to have an immunologic etiology.
- •Has received a live vaccine within 30 days prior to the first dose of study treatment.
- •Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to Cycle 1, Day
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to Cycle 1, Day
- •Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
- •Has an active autoimmune disease that has required systemic treatment in past 2 years.
- •Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
- •Has had an allogenic tissue/solid organ transplant.
研究组 & 干预措施
Placebo
Placebo Comparator
Participants receive IV placebo on Day 1 of each 21-day cycle for up to 17 cycles.
干预措施: Placebo (Drug)
Pembrolizumab
Experimental
Participants receive intravenous (IV) pembrolizumab at 200 mg on Day 1 of each 21-day cycle for up to 17 cycles.
干预措施: Pembrolizumab (Biological)
结局指标
主要结局
Recurrence-Free Survival (RFS)
时间窗: Up to ~6 years
RFS is defined as the time from randomization to first documentation of disease recurrence (local, regional, or distant) as assessed by BICR or by pathology consistent with HCC if required per the site's standard of care, or death due to any cause (both cancer and non-cancer causes of death), whichever occurs first.
Overall Survival (OS)
时间窗: Up to ~8 years
OS is defined as the time from randomization to death due to any cause.
Recurrence-Free Survival (RFS)
时间窗: Up to approximately 69 months
RFS was defined as the time from randomization to first documentation of disease recurrence (local, regional, or distant) as assessed by blinded independent central review (BICR) or by pathology consistent with HCC if required per the site's standard of care, or death due to any cause (both cancer and non-cancer causes of death), whichever occurred first. RFS was reported for each arm.
Overall Survival (OS)
时间窗: Up to approximately 69 months
OS was defined as the time from randomization to death due to any cause. OS was reported for each arm.
次要结局
- Percentage of Participants who Experience an Adverse Event (AE)(Up to ~8 years)
- Percentage of Participants who Discontinue Study Treatment Due to an AE(Up to ~1 year)
- Change from Baseline in European Quality of Life (EuroQoL)-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) Health Utility Score(Baseline and time of last PRO assessment (up to ~5 years))
- Number of Participants Who Experienced an Adverse Event (AE)(Up to approximately 26 months)
- Number of Participants Who Discontinued Study Treatment Due to an AE(Up to approximately 23 months)
- Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Combined Global Health Status (GHS) / Quality of Life (QoL) Scale Score(Baseline and up to approximately 120 weeks)
- Change From Baseline in EORTC QLQ-C30 Physical Functioning Scale Score(Baseline and up to approximately 120 weeks)
- Change From Baseline in EORTC QLQ-C30 Role Functioning Scale Score(Baseline and up to approximately 120 weeks)
- Change From Baseline in EORTC QLQ-Hepatocellular Carcinoma Module (EORTC QLQ-HCC18) Abdominal Swelling Scale Score(Baseline and up to approximately 120 weeks)
- Change From Baseline in EORTC QLQ-HCC18 Fatigue Scale Score(Baseline and up to approximately 120 weeks)
- Change From Baseline in EORTC QLQ-HCC18 Pain Scale Score(Baseline and up to approximately 120 weeks)
- Change From Baseline in Visual Analogue Scale (VAS) Score on the European Quality of Life (EuroQoL)-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) Health Utility Score(Baseline and up to approximately 120 weeks)
- Time to Deterioration (TTD) in the EORTC QLQ-C30 Combined GHS / QoL Scale Score(Baseline and up to approximately 120 weeks)
- TTD in the EORTC QLQ-C30 Physical Functioning Scale Score(Baseline and up to approximately 120 weeks)
- TTD in the EORTC QLQ-C30 Role Functioning Scale Score(Baseline and up to approximately 120 weeks)
- TTD in the EORTC QLQ-HCC18 Abdominal Swelling Scale Score(Baseline and up to approximately 120 weeks)
- TTD in the EORTC QLQ-HCC18 Fatigue Scale Score(Baseline and up to approximately 120 weeks)
- TTD in the EORTC QLQ-HCC18 Pain Scale Score(Baseline and up to approximately 120 weeks)
- Change from Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Combined Global Health Status (GHS) / Quality of Life (QoL) Scale Score(Baseline and time of last patient reported outcome (PRO) assessment (up to ~5 years))
- Change from Baseline in EORTC QLQ-C30 Physical Functioning Scale Score(Baseline and time of last PRO assessment (up to ~5 years))
- Change from Baseline in EORTC QLQ-C30 Role Functioning Scale Score(Baseline and time of last PRO assessment (up to ~5 years))
- Change from Baseline in EORTC QLQ-Hepatocellular Carcinoma Module (EORTC QLQ-HCC18) Abdominal Swelling Scale Score(Baseline and time of last PRO assessment (up to ~5 years))
- Change from Baseline in EORTC QLQ-HCC18 Fatigue Scale Score(Baseline and time of last PRO assessment (up to ~5 years))
- Change from Baseline in EORTC QLQ-HCC18 Pain Scale Score(Baseline and time of last PRO assessment (up to ~5 years))
- Time to Deterioration (TTD) in the EORTC QLQ-C30 Combined GHS / QoL Scale Score(Baseline and time of last PRO assessment (up to ~5 years))
- TTD in the EORTC QLQ-C30 Physical Functioning Scale Score(Baseline and time of last PRO assessment (up to ~5 years))
- TTD in the EORTC QLQ-C30 Role Functioning Scale Score(Baseline and time of last PRO assessment (up to ~5 years))
- TTD in the EORTC QLQ-HCC18 Abdominal Swelling Scale Score(Baseline and time of last PRO assessment (up to ~5 years))
- TTD in the EORTC QLQ-HCC18 Fatigue Scale Score(Baseline and time of last PRO assessment (up to ~5 years))
- TTD in the EORTC QLQ-HCC18 Pain Scale Score(Baseline and time of last PRO assessment (up to ~5 years))
研究者
研究点 (249)
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