Clinical trial NCT02576509: An Investigational Immuno-therapy Study of Nivolumab Compared to Sorafenib as a First Treatment in Patients With Advanced Hepatocellular Carcinoma
Official title: A Randomized, Multi-center Phase III Study of Nivolumab Versus Sorafenib as First-Line Treatment in Patients With Advanced Hepatocellular Carcinoma (CheckMate 459: CHECKpoint Pathway and nivoluMAb Clinical Trial Evaluation 459)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatocellular Carcinoma
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Ono Pharmaceutical Co. Ltd
First posted: 2015-10-15
Enrollment: 743
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if nivolumab or sorafenib is more effective in the treatment of Advanced Hepatocellular Carcinoma.


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed advanced hepatocellular carcinoma, not eligible for surgical and/or locoregional therapies; or progressive disease after surgical and /or locoregional therapies
* Locoregional therapy for hepatocellular carcinoma (HCC) must be completed at least 4 weeks prior to the baseline scan
* Child-Pugh Class A
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

Exclusion Criteria:

* Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
* Prior liver transplant
* Active, known, or suspected autoimmune disease

Other protocol-defined inclusion/exclusion criteria apply

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: time from the date of randomization to the date of death due to any cause, assessed up to June 2019 (approximately 41 months)
Secondary outcomes:
measure: Objective Response Rate (ORR) Per BICR RECIST 1.1
timeFrame: the date of randomization and the date of first objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first, assessed up to May 2019 (approximately 40 months)
measure: Progression-Free Survival (PFS)
timeFrame: time from the date of randomization to the date of the first objectively documented tumor progression or death, assessed up to May 2019 (approximately 40 months)
measure: Efficacy Based on PD-L1 Expression - OS and PFS
timeFrame: the date of randomization and the date of first objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first, assessed up to May 2019 (approximately 40 months)
measure: Efficacy Based on PD-L1 Expression - ORR
timeFrame: the date of randomization and the date of first objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first, assessed up to May 2019 (approximately 40 months)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Local Institution - 0066
state: Alabama
city: Los Angeles
country: United States
facility: Local Institution - 0020
state: California
city: San Francisco
country: United States
facility: Local Institution - 0015
state: California
city: San Francisco
country: United States
facility: Local Institution - 0084
state: California
city: Chicago
country: United States
facility: Local Institution - 0061
state: Illinois
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: New York
country: United States
facility: Local Institution - 0083
state: New York
city: New York
country: United States
facility: Local Institution - 0093
state: New York
city: Charlotte
country: United States
facility: Local Institution - 0016
state: North Carolina
city: Philadelphia
country: United States
facility: Local Institution - 0095
state: Pennsylvania
city: Philadelphia
country: United States
facility: Local Institution - 0019
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: San Antonio
country: United States
facility: Local Institution - 0017
state: Texas
city: Temple
country: United States
facility: Scott & White Memorial Hospital And Clinic
state: Texas
city: Seattle
country: United States
facility: Local Institution - 0026
state: Washington
city: Seattle
country: United States
facility: University of Washington - Seattle Cancer Care Alliance
state: Washington
city: Madison
country: United States
facility: Local Institution - 0050
state: Wisconsin
city: Camperdown
country: Australia
facility: Local Institution - 0005
state: New South Wales
city: Adelaide
country: Australia
facility: Local Institution - 0007
state: South Australia
city: Clayton
country: Australia
facility: Local Institution - 0001
state: Victoria
city: Heidelberg
country: Australia
facility: Local Institution - 0002
state: Victoria
city: Prahran
country: Australia
facility: Local Institution - 0003
state: Victoria
city: Nedlands
country: Australia
facility: Local Institution - 0008
state: Western Australia
city: Graz
country: Austria
facility: Local Institution - 0039
city: Wien
country: Austria
facility: Local Institution - 0038
city: Bruxelles
country: Belgium
facility: Local Institution - 0075
city: Leuven
country: Belgium
facility: Local Institution - 0091
city: Liege
country: Belgium
facility: Local Institution - 0077
city: Calgary
country: Canada
facility: Local Institution - 0043
state: Alberta
city: Vancouver
country: Canada
facility: Local Institution - 0044
state: British Columbia
city: Quebec
country: Canada
facility: Local Institution - 0042
city: Hefei
country: China
facility: Local Institution - 0164
state: Anhui
city: Beijing
country: China
facility: Local Institution - 0139
state: Beijing
city: Beijing
country: China
facility: Local Institution - 0137
state: Beijing
city: Beijing
country: China
facility: Local Institution - 0140
state: Beijing
city: Beijing
country: China
facility: Local Institution - 0141
state: Beijing
city: Fuzhou
country: China
facility: Local Institution - 0152
state: Fujian
city: Guangzhou
country: China
facility: Local Institution - 0161
state: Guangdong
city: Guangzhou
country: China
facility: Local Institution - 0157
state: Guangdong
city: Guangzhou
country: China
facility: Local Institution - 0144
state: Guangdong
city: Nanning
country: China
facility: Local Institution - 0158
state: Guangxi
city: Harbin
country: China
facility: Local Institution - 0142
state: Heilongjiang
city: Changsha
country: China
facility: Local Institution - 0148
state: Hunan
city: Changsha
country: China
facility: Local Institution - 0162
state: Hunan
city: Changzhou
country: China
facility: Local Institution - 0169
state: Jiangsu
city: Nanjing
country: China
facility: Local Institution - 0135
state: Jiangsu
city: Changchun
country: China
facility: Local Institution - 0136
state: Jilin
city: Changchun
country: China
facility: Local Institution - 0163
state: Jilin
city: Dalian
country: China
facility: Local Institution - 0166
state: Liaoning
city: Xi'an
country: China
facility: Local Institution - 0138
state: Shan3xi
city: Shanghai
country: China
facility: Local Institution - 0145
state: Shanghai
city: Shanghai
country: China
facility: Local Institution - 0151
state: Shanghai
city: Tianjin
country: China
facility: Local Institution - 0159
state: Tianjin
city: Hangzhou
country: China
facility: Local Institution - 0173
state: Zhejiang
city: Hangzhou
country: China
facility: Local Institution - 0146
state: Zhejiang
city: Brno
country: Czechia
facility: Local Institution - 0029
city: Hradec Kralove
country: Czechia
facility: Local Institution - 0027
city: Olomouc
country: Czechia
facility: Local Institution - 0028
city: La Tronche
country: France
facility: Local Institution - 0071
city: Lille Cedex
country: France
facility: Local Institution - 0072
city: Lyon
country: France
facility: Local Institution - 0069
city: Montpellier Cedex
country: France
facility: Local Institution - 0073
city: Paris Cedex 13
country: France
facility: Local Institution - 0067
city: Pessac
country: France
facility: Local Institution - 0068
city: Rennes Cedex
country: France
facility: Local Institution - 0070
city: Toulouse Cedex 9
country: France
facility: Local Institution - 0074
city: Berlin
country: Germany
facility: Local Institution - 0036
city: Essen
country: Germany
facility: Local Institution - 0037
city: Frankfurt
country: Germany
facility: Local Institution - 0167
city: Hamburg
country: Germany
facility: Local Institution - 0034
city: Leipzig
country: Germany
facility: Local Institution - 0031
city: Mainz
country: Germany
facility: Local Institution - 0035
city: Munich
country: Germany
facility: Local Institution - 0033
city: Regensburg
country: Germany
facility: Local Institution - 0032
city: Tuebingen
country: Germany
facility: Local Institution - 0030
city: Hong Kong
country: Hong Kong
facility: Local Institution - 0011
city: Hong Kong
country: Hong Kong
facility: Local Institution - 0012
city: Haifa
country: Israel
facility: Local Institution - 0082
city: Jerusalem
country: Israel
facility: Local Institution - 0060
city: Petah-tikva
country: Israel
facility: Local Institution - 0058
city: Tel Aviv
country: Israel
facility: Local Institution - 0059
city: Benevento
country: Italy
facility: Local Institution - 0054
city: Bergamo
country: Italy
facility: Local Institution - 0062
city: Milan
country: Italy
facility: Local Institution - 0055
city: Orbassano
country: Italy
facility: Local Institution - 0063
city: Siena
country: Italy
facility: Local Institution - 0064
city: Chiba City
country: Japan
facility: Local Institution - 0100
state: Chiba
city: Matsuyama-shi
country: Japan
facility: Local Institution - 0103
state: Ehime
city: Kurume-shi
country: Japan
facility: Local Institution - 0107
state: Fukuoka
city: Ogaki-shi
country: Japan
facility: Local Institution - 0127
state: Gifu
city: Sapporo-shi
country: Japan
facility: Local Institution - 0102
state: Hokkaido
city: Sapporo-shi
country: Japan
facility: Local Institution - 0130
state: Hokkaido
city: Kanazawa-shi
country: Japan
facility: Local Institution - 0105
state: Ishikawa
city: Kawasaki-shi
country: Japan
facility: Local Institution - 0110
state: Kanagawa
city: Yokohama-shi
country: Japan
facility: Local Institution - 0112
state: Kanagawa
city: Yokohama-shi
country: Japan
facility: Local Institution - 0104
state: Kanagawa
city: Kyoto-shi
country: Japan
facility: Local Institution - 0111
state: Kyoto
city: Osaka-Sayama-Shi
country: Japan
facility: Local Institution - 0106
state: Osaka
city: Suita
country: Japan
facility: Local Institution - 0113
state: Osaka
city: Saga-shi
country: Japan
facility: Local Institution - 0115
state: Saga
city: Chiyoda-ku
country: Japan
facility: Local Institution - 0131
state: Tokyo
city: Mitaka-shi
country: Japan
facility: Local Institution - 0114
state: Tokyo
city: Musashino-shi
country: Japan
facility: Local Institution - 0108
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Local Institution - 0126
state: Tokyo
city: Hiroshima
country: Japan
facility: Local Institution - 0101
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0117
state: Seocho-gu
city: Daegu
country: Korea, Republic of
facility: Local Institution - 0125
city: Goyang-si
country: Korea, Republic of
facility: Local Institution - 0116
city: Jeollanam-do
country: Korea, Republic of
facility: Local Institution - 0118
city: Seoul-si
country: Korea, Republic of
facility: Local Institution - 0119
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0123
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0122
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0124
city: Gdansk
country: Poland
facility: Local Institution - 0023
city: Warszawa
country: Poland
facility: Local Institution - 0056
city: Wroclaw
country: Poland
facility: Local Institution - 0045
city: Moscow
country: Russian Federation
facility: Local Institution - 0096
city: Singapore
country: Singapore
facility: Local Institution - 0013
city: Singapore
country: Singapore
facility: Local Institution - 0014
city: Alicante
country: Spain
facility: Local Institution - 0065
city: Majadahonda - Madrid
country: Spain
facility: Local Institution - 0085
city: Pamplona
country: Spain
facility: Local Institution - 0009
city: Santiago Compostela
country: Spain
facility: Local Institution - 0010
city: Goteborg
country: Sweden
facility: Local Institution - 0088
city: Stockholm
country: Sweden
facility: Local Institution - 0087
city: Basel
country: Switzerland
facility: Local Institution - 0040
city: Bern
country: Switzerland
facility: Local Institution - 0041
city: Kaohsiung County
country: Taiwan
facility: Local Institution - 0129
city: Taichung
country: Taiwan
facility: Local Institution - 0133
city: Tainan
country: Taiwan
facility: Local Institution - 0121
city: Tainan
country: Taiwan
facility: Local Institution - 0132
city: Taipei
country: Taiwan
facility: Local Institution - 0099
city: Taipei
country: Taiwan
facility: Local Institution - 0120
city: Taoyuan County
country: Taiwan
facility: Local Institution - 0128
city: London
country: United Kingdom
facility: Local Institution - 0080
state: Greater London
city: London
country: United Kingdom
facility: Local Institution - 0078
state: Greater London
city: Glasgow
country: United Kingdom
facility: Local Institution - 0079
state: Lanarkshire
city: Liverpool
country: United Kingdom
facility: Local Institution - 0081
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Li Y, Liang X, Li H, Chen X. Atezolizumab plus bevacizumab versus nivolumab as first-line treatment for advanced or unresectable hepatocellular carcinoma: A cost-effectiveness analysis. Cancer. 2022 Nov 15;128(22):3995-4003. doi: 10.1002/cncr.34457. Epub 2022 Sep 16.
citation: Shi J, Liu J, Tu X, Li B, Tong Z, Wang T, Zheng Y, Shi H, Zeng X, Chen W, Yin W, Fang W. Single-cell immune signature for detecting early-stage HCC and early assessing anti-PD-1 immunotherapy efficacy. J Immunother Cancer. 2022 Jan;10(1):e003133. doi: 10.1136/jitc-2021-003133.
citation: Yau T, Park JW, Finn RS, Cheng AL, Mathurin P, Edeline J, Kudo M, Harding JJ, Merle P, Rosmorduc O, Wyrwicz L, Schott E, Choo SP, Kelley RK, Sieghart W, Assenat E, Zaucha R, Furuse J, Abou-Alfa GK, El-Khoueiry AB, Melero I, Begic D, Chen G, Neely J, Wisniewski T, Tschaika M, Sangro B. Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol. 2022 Jan;23(1):77-90. doi: 10.1016/S1470-2045(21)00604-5. Epub 2021 Dec 13.