The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02702414




Registration number
NCT02702414
Ethics application status
Date submitted
3/03/2016
Date registered
3/03/2016
Date last updated
30/01/2019

Titles & IDs
Public title
Study of Pembrolizumab (MK-3475) as Monotherapy in Participants With Advanced Hepatocellular Carcinoma (MK-3475-224/KEYNOTE-224)
Scientific title
A Phase 2 Study of Pembrolizumab (MK-3475) as Monotherapy in Subjects With Advanced Hepatocellular Carcinoma (KEYNOTE-224)
Secondary ID [1] 0 0
2015-004566-28
Secondary ID [2] 0 0
3475-224
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatocellular Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Liver

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Pembrolizumab

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.

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.


Other interventions: Pembrolizumab


Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR)
Timepoint [1] 0 0
Up to approximately 3 years
Secondary outcome [1] 0 0
Duration of Response (DOR)
Timepoint [1] 0 0
Up to approximately 3 years
Secondary outcome [2] 0 0
Disease Control Rate (DCR)
Timepoint [2] 0 0
Up to approximately 3 years
Secondary outcome [3] 0 0
Time To Progression (TTP)
Timepoint [3] 0 0
Up to approximately 3 years
Secondary outcome [4] 0 0
Progression-Free Survival (PFS)
Timepoint [4] 0 0
Up to approximately 3 years
Secondary outcome [5] 0 0
Overall Survival (OS)
Timepoint [5] 0 0
Up to approximately 3 years

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Alfred Health ( Site 0151) - Melbourne
Recruitment hospital [2] 0 0
Monash Health-Monash Medical Centre ( Site 0153) - Melbourne
Recruitment hospital [3] 0 0
Royal Prince Alfred Hospital ( Site 0152) - Camperdown
Recruitment postcode(s) [1] 0 0
3004 - Melbourne
Recruitment postcode(s) [2] 0 0
3168 - Melbourne
Recruitment postcode(s) [3] 0 0
2050 - Camperdown
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Iowa
Country [4] 0 0
United States of America
State/province [4] 0 0
Louisiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Minnesota
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Oregon
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
South Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Virginia
Country [13] 0 0
United States of America
State/province [13] 0 0
Washington
Country [14] 0 0
United States of America
State/province [14] 0 0
Wisconsin
Country [15] 0 0
Belgium
State/province [15] 0 0
Brussels
Country [16] 0 0
Belgium
State/province [16] 0 0
Gent
Country [17] 0 0
Belgium
State/province [17] 0 0
Leuven
Country [18] 0 0
Canada
State/province [18] 0 0
British Columbia
Country [19] 0 0
Canada
State/province [19] 0 0
Quebec
Country [20] 0 0
France
State/province [20] 0 0
Lille
Country [21] 0 0
France
State/province [21] 0 0
Paris
Country [22] 0 0
France
State/province [22] 0 0
Pessac
Country [23] 0 0
France
State/province [23] 0 0
Rennes
Country [24] 0 0
Germany
State/province [24] 0 0
Frankfurt
Country [25] 0 0
Germany
State/province [25] 0 0
Hannover
Country [26] 0 0
Germany
State/province [26] 0 0
Heidelberg
Country [27] 0 0
Italy
State/province [27] 0 0
Padova
Country [28] 0 0
Italy
State/province [28] 0 0
Reggio Emilia
Country [29] 0 0
Japan
State/province [29] 0 0
Hokkaido
Country [30] 0 0
Japan
State/province [30] 0 0
Ishikawa
Country [31] 0 0
Japan
State/province [31] 0 0
Kanagawa
Country [32] 0 0
Japan
State/province [32] 0 0
Osaka
Country [33] 0 0
Japan
State/province [33] 0 0
Chiba
Country [34] 0 0
Japan
State/province [34] 0 0
Kumamoto
Country [35] 0 0
Sweden
State/province [35] 0 0
Goteborg
Country [36] 0 0
Sweden
State/province [36] 0 0
Stockholm
Country [37] 0 0
United Kingdom
State/province [37] 0 0
London
Country [38] 0 0
United Kingdom
State/province [38] 0 0
Wirral

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme Corp.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02702414
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme Corp.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
Trialsites@merck.com
Contact person for scientific queries

No data has been provided for results reporting
Summary results
Not applicable