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Study of Pembrolizumab (MK-3475) as Monotherapy in Participants With Advanced Hepatocellular Carcinoma (MK-3475-224/KEYNOTE-224)

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ClinicalTrials.gov Identifier: NCT02702414
Recruitment Status : Recruiting
First Posted : March 8, 2016
Last Update Posted : August 14, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:

This is a efficacy and safety study of pembrolizumab (MK-3475, KEYTRUDA®) as monotherapy in participants with hepatocellular carcinoma (HCC) in two cohorts: participants with advanced HCC and with no curative option after disease progression on sorafenib or intolerance of sorafenib (Cohort 1) or who had not received treatment for systemic disease (Cohort 2). Study participants may receive pembrolizumab once every 3 weeks for up to 35 initial cycles (up to approximately 2 years) and a potential additional 17 cycles in a re-treatment phase (approximately an additional 1 year of treatment) .

The primary objective of this study is to determine the Objective Response Rate (ORR) of pembrolizumab given as monotherapy in participants with HCC.


Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Biological: Pembrolizumab Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Pembrolizumab (MK-3475) as Monotherapy in Subjects With Advanced Hepatocellular Carcinoma (KEYNOTE-224)
Actual Study Start Date : May 31, 2016
Estimated Primary Completion Date : May 30, 2021
Estimated Study Completion Date : May 30, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Prior Systemic Therapy
Participants with previously systemically treated HCC receive a pembrolizumab 200 mg intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stop pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stop after receiving 35 trial treatments may be eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they meet the criteria for re-treatment.
Biological: Pembrolizumab
Other Names:
  • MK-3475
  • KEYTRUDA®

Experimental: Systemic Therapy Naive
Participants with HCC who had not received treatment for systemic disease receive a pembrolizumab 200 mg intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stop pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stop after receiving 35 trial treatments may be eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they meet the criteria for re-treatment.
Biological: Pembrolizumab
Other Names:
  • MK-3475
  • KEYTRUDA®




Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Up to approximately 3 years ]

Secondary Outcome Measures :
  1. Duration of Response (DOR) [ Time Frame: Up to approximately 3 years ]
  2. Disease Control Rate (DCR) [ Time Frame: Up to approximately 3 years ]
  3. Time To Progression (TTP) [ Time Frame: Up to approximately 3 years ]
  4. Progression-Free Survival (PFS) [ Time Frame: Up to approximately 3 years ]
  5. Overall Survival (OS) [ Time Frame: Up to approximately 3 years ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • For Cohort 1: has histologically or cytologically confirmed diagnosis of HCC (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible) based on pathology report
  • For Cohort 2: has an 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 Class A liver score within 7 days of first dose of study drug
  • Has a predicted life expectancy >3 months
  • Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as confirmed by the blinded central imaging vendor
  • Has a performance status of 0 or 1 using the Eastern Cooperative Oncology Group (ECOG) Performance Scale within 7 days of first dose of study drug
  • For Cohort 1: has documented objective radiographic progression after stopping treatment with sorafenib or else intolerance to sorafenib
  • Is willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug (male and female participants of childbearing potential)
  • Demonstrates adequate organ function

Exclusion Criteria:

  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy, herbal/complementary oral or IV medicine, or used an investigational device within 4 weeks of the first dose of study drug. Participant must also have recovered from associated therapy (i.e., to Grade ≤1 or baseline) and from adverse events due to any prior therapy
  • For Cohort 1: has received sorafenib within 14 days of first dose of study drug
  • 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 (Vp4), inferior vena cava, or cardiac involvement of HCC based on imaging
  • Has had encephalopathy in the last 6 months. Participants on rifaximin or lactulose to control their encephalopathy are not allowed
  • Had a solid organ or hematologic transplant
  • For Cohort 1: had prior systemic therapy for HCC other than sorafenib, or intercurrent local therapy to the liver tumor between sorafenib and study drug
  • For Cohort 2: had prior systemic therapy in the advanced disease setting
  • Has active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs)
  • 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 drug
  • Has a diagnosed additional malignancy within 5 years for Cohort 1 and 3 years for Cohort 2 prior to first dose of study treatment with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or curatively resected in situ cervical and/or breast cancers
  • Has radiographically detectable central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has evidence or history of interstitial lung disease or active noninfectious pneumonitis
  • Has an active infection requiring systemic therapy
  • Has a known severe hypersensitivity to pembrolizumab, its active substance and/or any of its excipients
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment
  • Has received prior immunotherapy including anti-programmed death-1 (anti-PD-1), anti-PD-ligand-1 (anti-PD-L1), or anti-PD-L2 agents, or if the participant has previously participated in clinical studies with pembrolizumab (MK-3475)
  • Has a known history of human immunodeficiency virus (HIV)
  • Has untreated active Hepatitis B virus (HBV)
  • For Cohort 1: has dual infection with HBV/Hepatitis C virus (HCV) or other hepatitis combinations at study entry
  • For Cohort 2: has dual active HBV infection (Hepatitis B surface antigen positive and/or detectable HBV deoxyribonucleic acid [DNA]) and HCV infection (detectable HCV ribonucleic acid [RNA]) at study entry
  • Has received a live vaccine within 30 days of planned start of study drug (Cycle 1, Day 1)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02702414


Contacts
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

  Show 49 Study Locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02702414     History of Changes
Other Study ID Numbers: 3475-224
2015-004566-28 ( EudraCT Number )
163434 ( Registry Identifier: JAPIC-CTI )
MK-3475-224 ( Other Identifier: Merck Protocol Number )
KEYNOTE-224 ( Other Identifier: Merck Secondary Study Name )
First Posted: March 8, 2016    Key Record Dates
Last Update Posted: August 14, 2018
Last Verified: August 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Merck Sharp & Dohme Corp.:
PD1
PD-1
PDL1
PD-L1

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Pembrolizumab
Antineoplastic Agents