Clinical Trials List
Protocol NumberMK-3475-937
NCT Number(ClinicalTrials.gov Identfier)NCT03867084
Completed
2019-05-01 - 2029-12-31
Phase III
Recruiting3
Terminated3
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)
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Trial Applicant
Merck Sharp & Dohme (I.A.) LLC
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Sponsor
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Trial scale
Multi-Regional Multi-Center
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Update
2026/07/08
Investigators and Locations
Co-Principal Investigator
- 楊宏仁 Division of General Surgery
- Hsueh-Chou Lai Digestive System Department
- 陳德鴻 Division of General Surgery
- 許士超 Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Ann-Lii Cheng Division of Hematology & Oncology
- Chih-Hung Hsu Division of Hematology & Oncology
- 林宗哲 Division of Hematology & Oncology
- 何承懋 Division of General Surgery
- Ying-Chun Shen Division of Hematology & Oncology
- - - Division of Radiology
- JA-DER LIANG Division of General Internal Medicine
- Chien-Hung Chen Division of General Internal Medicine
- Ming-Chih Ho Division of General Surgery
- 吳志宏 Division of Radiology
- Yao-Ming Wu Division of General Surgery
- Shih-Jer Hsu Division of General Internal Medicine
- YU-YUN SHAO Division of Hematology & Oncology
- 呂理駿 Division of Hematology & Oncology
- TSUNG-HAO LIU Division of Hematology & Oncology
- REY-HENG HU Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Gar-Yang Chau Division of General Surgery
- I-Cheng Lee Digestive System Department
- 周書正 Division of General Surgery
- Pei-Chang Lee Digestive System Department
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 周宏學 Division of Gastroenterological Surgery
- Shi-Ming Lin Digestive System Department
- 呂嘉偉 Division of Radiology
- Kun-Ming Chan Division of Gastroenterological Surgery
- 潘廣澤 Division of Radiology
- 洪建福 Division of Radiology
- 吳宗翰 Division of General Surgery
- Chia-Hsun Hsieh Division of Hematology & Oncology
- 李兆偉 Division of General Surgery
- Cheng-Yu Lin Digestive System Department
- 陳俊瑋 Digestive System Department
- 黃書偉 Digestive System Department
- 周宏學 Division of Gastroenterological Surgery
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Tai-Jan Chiu Division of Hematology & Oncology
- 劉建廷 Division of Hematology & Oncology
- Shau-Hsuan Li Division of Hematology & Oncology
- Yu-Li Su Division of Hematology & Oncology
- 陳彥豪 Division of Hematology & Oncology
- 吳佳哲 Division of Hematology & Oncology
- 賴香蘭 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Principal Investigator
Ting-Tsung Chang
Co-Principal Investigator
- 吳毅晉 Digestive System Department
- Liu Yi-Sheng Division of Radiology
- Nai-Jung Chiang 未分科
- 邱彥程 Digestive System Department
- Chiu Hung Chiu Digestive System Department
- 簡世杰 Digestive System Department
- Hsin-Yu Kuo Digestive System Department
- Yih-Jyh Lin Division of Others -
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Hepatocellular Carcinoma
Objectives
1. To test the safety of the investigational drug pembrolizumab in liver cancer patients after surgery or ablation (a procedure that uses radiation to destroy cancer cells in the liver).
2. To understand whether pembrolizumab used after surgery or ablation is more effective in delaying recurrence than a placebo (a product that looks similar but does not contain the active ingredient) used after surgery or ablation.
3. To understand how well subjects' bodies process pembrolizumab compared to a placebo used after surgery or ablation.
4. To understand how well pembrolizumab is compared to a placebo after surgery or ablation.
5. To understand whether pembrolizumab helps patients live longer or improves their quality of life.
Test Drug
Injectable
Active Ingredient
MK-3475
Dosage Form
270
Dosage
ML
Endpoints
Primary Assessment Indicators:
- Relapse-free survival (RFS)
- Overall survival (OS)
Secondary Assessment Indicators:
- Adverse events (AEs)
- Trial intervention discontinuation due to AEs
- Overall health status score measured on the EORTC QLQ-C30 and EORTC QLQ-HCC18, as measured by the Overall Health Status/Quality of Life (QoL) scale
- Time to first decline of 10 points or more since baseline. Time to Treatment (TTD) for overall health status/QOL assessment using the EORTC QLQ-C30 and EORTC QLQ-HCC18
- EQ-5D-5L health status utility score
- Relapse-free survival (RFS)
- Overall survival (OS)
Secondary Assessment Indicators:
- Adverse events (AEs)
- Trial intervention discontinuation due to AEs
- Overall health status score measured on the EORTC QLQ-C30 and EORTC QLQ-HCC18, as measured by the Overall Health Status/Quality of Life (QoL) scale
- Time to first decline of 10 points or more since baseline. Time to Treatment (TTD) for overall health status/QOL assessment using the EORTC QLQ-C30 and EORTC QLQ-HCC18
- EQ-5D-5L health status utility score
Inclution Criteria
Inclusion Criteria:
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 1.
Has a Child-Pugh class A liver score (5 to 6 points) within 7 days prior to Cycle 1, Day 1.
Has alpha fetoprotein (AFP) concentration lower than 400 ng/mL within 28 days prior to Cycle 1, Day 1.
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.
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 1.
Has a Child-Pugh class A liver score (5 to 6 points) within 7 days prior to Cycle 1, Day 1.
Has alpha fetoprotein (AFP) concentration lower than 400 ng/mL within 28 days prior to Cycle 1, Day 1.
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.
Exclusion Criteria
Exclusion Criteria:
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 1.
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 1.
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.
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 1.
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 1.
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.
The Estimated Number of Participants
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Taiwan
30 participants
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Global
950 participants
