临床试验/NCT03867084

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)

Merck Sharp & Dohme LLC250 个研究点分布在 6 个国家目标入组 959 人2019年5月28日

适应症Hepatocellular Carcinoma

干预措施Placebo Pembrolizumab

概览

阶段: 3 期
干预措施: Placebo
疾病 / 适应症: Hepatocellular Carcinoma
发起方: Merck Sharp & Dohme LLC
入组人数: 959
试验地点: 250
主要终点: Recurrence-Free Survival (RFS)
状态: 已完成
最后更新: 8天前

概览研究者入排标准研究组 & 干预措施结局指标研究点相似试验

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).

注册库

clinicaltrials.gov

开始日期

2019年5月28日

结束日期

2025年9月30日

最后更新

8天前

研究类型

Interventional

研究设计

Parallel

性别

All

研究者

发起方

Merck Sharp & Dohme LLC

责任方

Sponsor

入排标准

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.

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).

研究组 & 干预措施

Placebo

Participants receive IV placebo on Day 1 of each 21-day cycle for up to 17 cycles.

干预措施: Placebo

Pembrolizumab

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

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))