An Immuno-therapy Study to Evaluate the Effectiveness, Safety and Tolerability of Nivolumab or Nivolumab in Combination With Other Agents in Patients With Advanced Liver Cancer
NCT ID: NCT01658878
Last Updated: 2025-12-24
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE1/PHASE2
657 participants
INTERVENTIONAL
2012-10-30
2024-11-12
Brief Summary
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The second part of the study is the Expansion Phase designed to generate additional clinical data at specified doses for each of the 3 cohorts. A third cohort has been added in this study to compare the efficacy of nivolumab and sorafenib in the treatment of Advanced HCC. A fourth cohort will generate data on the safety and efficacy of the combination nivolumab plus ipilimumab in the treatment of Advanced HCC. In the fifth cohort, additional clinical data will be generated for Child-Pugh B subjects. A Cabozantinib Combination Cohort has been added to evaluate the safety and tolerability of nivolumab in combination with cabozantinib and nivolumab with ipilimumab in combination with cabozantinib.
Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Non-infected: Nivolumab
Nivolumab intravenous solution on specific days
Nivolumab
HCV-infected: Nivolumab
Nivolumab intravenous solution on specific days
Nivolumab
HBV-infected: Nivolumab
Nivolumab intravenous solution on specific days
Nivolumab
Nivolumab
Nivolumab intravenous solution on specific days
Nivolumab
Sorafenib
Sorafenib tablets on specific days
Sorafenib
Nivolumab plus Ipilimumab Combination
Nivolumab intravenous solution + Ipilimumab intravenous solution on specific days
Nivolumab
Ipilimumab
Child-Pugh B
Nivolumab intravenous solution on specific days
Nivolumab
Nivolumab plus Cabozantinib Combination
Nivolumab intravenous solution + cabozantinib oral tablets on specific days
Cabozantinib
Nivolumab plus Ipilimumab plus Cabozantinib
Nivolumab intravenous solution + Ipilimumab intravenous solution + cabozantinib oral tablets on specific days
Cabozantinib
Interventions
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Nivolumab
Sorafenib
Ipilimumab
Cabozantinib
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
* Dose Escalation Phase: Child-Pugh score of 7 points or less. Cohort 5: Child-Pugh Class B (B7-B8). For all other cohorts Child-Pugh score of 6 points or less
Exclusion Criteria
* Any prior or current clinically significant ascites
* Any history of hepatic encephalopathy
18 Years
ALL
No
Sponsors
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Ono Pharmaceutical Co. Ltd
INDUSTRY
Bristol-Myers Squibb
INDUSTRY
Responsible Party
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Principal Investigators
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Bristol-Myers Squibb
Role: STUDY_DIRECTOR
Bristol-Myers Squibb
Locations
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Local Institution - 0008
Los Angeles, California, United States
Local Institution - 0048
Washington D.C., District of Columbia, United States
Local Institution - 0053
Pensacola, Florida, United States
Local Institution - 0047
Atlanta, Georgia, United States
Local Institution - 0025
Boston, Massachusetts, United States
Local Institution - 0002
Ann Arbor, Michigan, United States
Local Institution - 0054
Hackensack, New Jersey, United States
Local Institution - 0067
Paterson, New Jersey, United States
Local Institution - 0001
Portland, Oregon, United States
The University Of Texas MD Anderson Cancer Center
Houston, Texas, United States
Local Institution - 0065
Halifax, Nova Scotia, Canada
Local Institution - 0039
Toronto, Ontario, Canada
Local Institution - 0022
Montreal, Quebec, Canada
Local Institution - 0061
Angers, , France
Local Institution - 0064
Créteil, , France
Local Institution - 0062
Marseille, , France
Local Institution - 0059
Marseille, , France
Local Institution - 0042
Paris, , France
Local Institution - 0060
Reims, , France
Local Institution - 0058
Vandœuvre-lès-Nancy, , France
Local Institution - 0030
Essen, , Germany
Local Institution - 0028
Frankfurt, , Germany
Local Institution - 0029
Hanover, , Germany
Local Institution - 0031
Heidelberg, , Germany
Local Institution - 0005
Hong Kong, , Hong Kong
Local Institution - 0006
Hong Kong, , Hong Kong
Local Institution - 0032
Bologna, , Italy
Local Institution - 0056
Florence, , Italy
Local Institution - 0063
Meldola (FC), , Italy
Local Institution - 0055
Milan, , Italy
Local Institution - 0034
Napoli, , Italy
Local Institution - 0035
Padua, , Italy
Local Institution - 0040
Rozzano, , Italy
Local Institution - 0036
Kashiwa-shi, Chiba, Japan
Local Institution - 0038
Kurume-shi, Fukuoka, Japan
Local Institution - 0049
Yokohama, Kanagawa, Japan
Local Institution - 0050
Kyoto, Kyoto, Japan
Local Institution - 0037
Ōsaka-sayama, Osaka, Japan
Local Institution - 0051
Saga, , Japan
Local Institution - 0070
San Juan, , Puerto Rico
Local Institution - 0017
Singapore, , Singapore
Local Institution - 0009
Singapore, , Singapore
Local Institution - 0007
Singapore, , Singapore
Local Institution - 0066
Seoul, , South Korea
Local Institution - 0021
Seoul, , South Korea
Local Institution - 0026
Seoul, , South Korea
Local Institution - 0016
Seoul, , South Korea
Local Institution - 0019
Barcelona, , Spain
Local Institution - 0020
Madrid, , Spain
Local Institution - 0018
Madrid, , Spain
Local Institution - 0003
Pamplona, , Spain
Local Institution - 0027
Taipei, , Taiwan
Local Institution - 0024
Taipei, , Taiwan
Local Institution - 0023
Taoyuan District, , Taiwan
Local Institution - 0011
London, Greater London, United Kingdom
Local Institution - 0014
Manchester, Greater Manchester, United Kingdom
Local Institution - 0012
Glasgow, Lanarkshire, United Kingdom
Local Institution - 0015
Metropolitan Borough of Wirral, Merseyside, United Kingdom
Local Institution - 0013
Birmingham, West Midlands, United Kingdom
Local Institution - 0010
London, , United Kingdom
Countries
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References
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Zhou X, Cao J, Topatana W, Xie T, Chen T, Hu J, Li S, Juengpanic S, Lu Z, Zhang B, Wang K, Feng X, Shen J, Chen M. Evaluation of PD-L1 as a biomarker for immunotherapy for hepatocellular carcinoma: systematic review and meta-analysis. Immunotherapy. 2023 Apr;15(5):353-365. doi: 10.2217/imt-2022-0168. Epub 2023 Feb 27.
Yau T, Zagonel V, Santoro A, Acosta-Rivera M, Choo SP, Matilla A, He AR, Cubillo Gracian A, El-Khoueiry AB, Sangro B, Eldawy TE, Bruix J, Frassineti GL, Vaccaro GM, Tschaika M, Scheffold C, Koopmans P, Neely J, Piscaglia F. Nivolumab Plus Cabozantinib With or Without Ipilimumab for Advanced Hepatocellular Carcinoma: Results From Cohort 6 of the CheckMate 040 Trial. J Clin Oncol. 2023 Mar 20;41(9):1747-1757. doi: 10.1200/JCO.22.00972. Epub 2022 Dec 13.
Sove RJ, Verma BK, Wang H, Ho WJ, Yarchoan M, Popel AS. Virtual clinical trials of anti-PD-1 and anti-CTLA-4 immunotherapy in advanced hepatocellular carcinoma using a quantitative systems pharmacology model. J Immunother Cancer. 2022 Nov;10(11):e005414. doi: 10.1136/jitc-2022-005414.
Kudo M, Matilla A, Santoro A, Melero I, Gracian AC, Acosta-Rivera M, Choo SP, El-Khoueiry AB, Kuromatsu R, El-Rayes B, Numata K, Itoh Y, Di Costanzo F, Crysler O, Reig M, Shen Y, Neely J, Tschaika M, Wisniewski T, Sangro B. CheckMate 040 cohort 5: A phase I/II study of nivolumab in patients with advanced hepatocellular carcinoma and Child-Pugh B cirrhosis. J Hepatol. 2021 Sep;75(3):600-609. doi: 10.1016/j.jhep.2021.04.047. Epub 2021 May 26.
Yau T, Kang YK, Kim TY, El-Khoueiry AB, Santoro A, Sangro B, Melero I, Kudo M, Hou MM, Matilla A, Tovoli F, Knox JJ, Ruth He A, El-Rayes BF, Acosta-Rivera M, Lim HY, Neely J, Shen Y, Wisniewski T, Anderson J, Hsu C. Efficacy and Safety of Nivolumab Plus Ipilimumab in Patients With Advanced Hepatocellular Carcinoma Previously Treated With Sorafenib: The CheckMate 040 Randomized Clinical Trial. JAMA Oncol. 2020 Nov 1;6(11):e204564. doi: 10.1001/jamaoncol.2020.4564. Epub 2020 Nov 12.
Sangro B, Melero I, Wadhawan S, Finn RS, Abou-Alfa GK, Cheng AL, Yau T, Furuse J, Park JW, Boyd Z, Tang HT, Shen Y, Tschaika M, Neely J, El-Khoueiry A. Association of inflammatory biomarkers with clinical outcomes in nivolumab-treated patients with advanced hepatocellular carcinoma. J Hepatol. 2020 Dec;73(6):1460-1469. doi: 10.1016/j.jhep.2020.07.026. Epub 2020 Jul 22.
Yau T, Hsu C, Kim TY, Choo SP, Kang YK, Hou MM, Numata K, Yeo W, Chopra A, Ikeda M, Kuromatsu R, Moriguchi M, Chao Y, Zhao H, Anderson J, Cruz CD, Kudo M. Nivolumab in advanced hepatocellular carcinoma: Sorafenib-experienced Asian cohort analysis. J Hepatol. 2019 Sep;71(3):543-552. doi: 10.1016/j.jhep.2019.05.014. Epub 2019 Jun 7.
El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, Kim TY, Choo SP, Trojan J, Welling TH Rd, Meyer T, Kang YK, Yeo W, Chopra A, Anderson J, Dela Cruz C, Lang L, Neely J, Tang H, Dastani HB, Melero I. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017 Jun 24;389(10088):2492-2502. doi: 10.1016/S0140-6736(17)31046-2. Epub 2017 Apr 20.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Related Links
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BMS Clinical Trial Information
BMS Clinical Trial Patient Recruiting
Other Identifiers
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2012-001514-42
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
CA209-040
Identifier Type: -
Identifier Source: org_study_id