An Investigational Immuno-therapy Study of Nivolumab Compared to Sorafenib as a First Treatment in Patients With Advanced Hepatocellular Carcinoma

March 15, 2024 updated by: Bristol-Myers Squibb

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)

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

743

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Local Institution - 0005
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Local Institution - 0007
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Local Institution - 0001
      • Heidelberg, Victoria, Australia, 3084
        • Local Institution - 0002
      • Prahran, Victoria, Australia, 3181
        • Local Institution - 0003
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Local Institution - 0008
  • Austria
      • Graz, Austria, 8036
        • Local Institution - 0039
      • Wien, Austria, 1090
        • Local Institution - 0038
  • Belgium
      • Bruxelles, Belgium, 1000
        • Local Institution - 0075
      • Leuven, Belgium, 3000
        • Local Institution - 0091
      • Liege, Belgium, 4000
        • Local Institution - 0077
  • Canada
      • Quebec, Canada, G1R 2J6
        • Local Institution - 0042
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N2
        • Local Institution - 0043
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • Local Institution - 0044
  • China
    • Anhui
      • Hefei, Anhui, China, 230061
        • Local Institution - 0164
    • Beijing
      • Beijing, Beijing, China, 100050
        • Local Institution - 0139
      • Beijing, Beijing, China, 100071
        • Local Institution - 0137
      • Beijing, Beijing, China, 100142
        • Local Institution - 0140
      • Beijing, Beijing, China, 100142
        • Local Institution - 0141
    • Fujian
      • Fuzhou, Fujian, China, 350025
        • Local Institution - 0152
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Local Institution - 0161
      • Guangzhou, Guangdong, China, 510080
        • Local Institution - 0157
      • Guangzhou, Guangdong, China, 510515
        • Local Institution - 0144
    • Guangxi
      • Nanning, Guangxi, China, 530021
        • Local Institution - 0158
    • Heilongjiang
      • Harbin, Heilongjiang, China, 155040
        • Local Institution - 0142
    • Hunan
      • Changsha, Hunan, China, 410013
        • Local Institution - 0148
      • Changsha, Hunan, China, 410013
        • Local Institution - 0162
    • Jiangsu
      • Changzhou, Jiangsu, China, 213003
        • Local Institution - 0169
      • Nanjing, Jiangsu, China, 210002
        • Local Institution - 0135
    • Jilin
      • Changchun, Jilin, China, 130012
        • Local Institution - 0136
      • Changchun, Jilin, China, 130021
        • Local Institution - 0163
    • Liaoning
      • Dalian, Liaoning, China, 116000
        • Local Institution - 0166
    • Shan3xi
      • Xi'an, Shan3xi, China, 710038
        • Local Institution - 0138
    • Shanghai
      • Shanghai, Shanghai, China, 200032
        • Local Institution - 0145
      • Shanghai, Shanghai, China, 200032
        • Local Institution - 0151
    • Tianjin
      • Tianjin, Tianjin, China, 300060
        • Local Institution - 0159
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310003
        • Local Institution - 0173
      • Hangzhou, Zhejiang, China, 310022
        • Local Institution - 0146
  • Czechia
      • Brno, Czechia, 656 53
        • Local Institution - 0029
      • Hradec Kralove, Czechia, 500 05
        • Local Institution - 0027
      • Olomouc, Czechia, 779 00
        • Local Institution - 0028
  • France
      • La Tronche, France, 38700
        • Local Institution - 0071
      • Lille Cedex, France, 59037
        • Local Institution - 0072
      • Lyon, France, 69004
        • Local Institution - 0069
      • Montpellier Cedex, France, 34295
        • Local Institution - 0073
      • Paris Cedex 13, France, 75651
        • Local Institution - 0067
      • Pessac, France, 33604
        • Local Institution - 0068
      • Rennes Cedex, France, 35042
        • Local Institution - 0070
      • Toulouse Cedex 9, France, 31059
        • Local Institution - 0074
  • Germany
      • Berlin, Germany, 13353
        • Local Institution - 0036
      • Essen, Germany, 45136
        • Local Institution - 0037
      • Frankfurt, Germany, 60590
        • Local Institution - 0167
      • Hamburg, Germany, 20246
        • Local Institution - 0034
      • Leipzig, Germany, 04103
        • Local Institution - 0031
      • Mainz, Germany, 55131
        • Local Institution - 0035
      • Munich, Germany, 81366
        • Local Institution - 0033
      • Regensburg, Germany, 93053
        • Local Institution - 0032
      • Tuebingen, Germany, 72076
        • Local Institution - 0030
  • Hong Kong
      • Hong Kong, Hong Kong
        • Local Institution - 0011
      • Hong Kong, Hong Kong
        • Local Institution - 0012
  • Israel
      • Haifa, Israel, 31096
        • Local Institution - 0082
      • Jerusalem, Israel, 91120
        • Local Institution - 0060
      • Petah-tikva, Israel, 49100
        • Local Institution - 0058
      • Tel Aviv, Israel, 64239
        • Local Institution - 0059
  • Italy
      • Benevento, Italy, 82100
        • Local Institution - 0054
      • Bergamo, Italy
        • Local Institution - 0062
      • Milan, Italy, 20133
        • Local Institution - 0055
      • Orbassano, Italy, 10043
        • Local Institution - 0063
      • Siena, Italy, 53100
        • Local Institution - 0064
  • Japan
      • Hiroshima, Japan, 734-8551
        • Local Institution - 0101
    • Chiba
      • Chiba City, Chiba, Japan, 2608670
        • Local Institution - 0100
    • Ehime
      • Matsuyama-shi, Ehime, Japan, 7900024
        • Local Institution - 0103
    • Fukuoka
      • Kurume-shi, Fukuoka, Japan, 8300011
        • Local Institution - 0107
    • Gifu
      • Ogaki-shi, Gifu, Japan, 5038502
        • Local Institution - 0127
    • Hokkaido
      • Sapporo-shi, Hokkaido, Japan, 0600033
        • Local Institution - 0102
      • Sapporo-shi, Hokkaido, Japan, 0608648
        • Local Institution - 0130
    • Ishikawa
      • Kanazawa-shi, Ishikawa, Japan, 9208641
        • Local Institution - 0105
    • Kanagawa
      • Kawasaki-shi, Kanagawa, Japan, 2138587
        • Local Institution - 0110
      • Yokohama-shi, Kanagawa, Japan, 2320024
        • Local Institution - 0112
      • Yokohama-shi, Kanagawa, Japan, 2418515
        • Local Institution - 0104
    • Kyoto
      • Kyoto-shi, Kyoto, Japan, 6028566
        • Local Institution - 0111
    • Osaka
      • Osaka-Sayama-Shi, Osaka, Japan, 5898511
        • Local Institution - 0106
      • Suita, Osaka, Japan, 5650871
        • Local Institution - 0113
    • Saga
      • Saga-shi, Saga, Japan, 8408571
        • Local Institution - 0115
    • Tokyo
      • Chiyoda-ku, Tokyo, Japan, 101-0062
        • Local Institution - 0131
      • Mitaka-shi, Tokyo, Japan, 181-8611
        • Local Institution - 0114
      • Musashino-shi, Tokyo, Japan, 180-8610
        • Local Institution - 0108
      • Shinjuku-ku, Tokyo, Japan, 1628655
        • Local Institution - 0126
  • Korea, Republic of
      • Daegu, Korea, Republic of, 41944
        • Local Institution - 0125
      • Goyang-si, Korea, Republic of, 10408
        • Local Institution - 0116
      • Jeollanam-do, Korea, Republic of, 58128
        • Local Institution - 0118
      • Seoul, Korea, Republic of, 03080
        • Local Institution - 0123
      • Seoul, Korea, Republic of, 05505
        • Local Institution - 0122
      • Seoul, Korea, Republic of, 06351
        • Local Institution - 0124
      • Seoul-si, Korea, Republic of, 03722
        • Local Institution - 0119
    • Seocho-gu
      • Seoul, Seocho-gu, Korea, Republic of, 06591
        • Local Institution - 0117
  • Poland
      • Gdansk, Poland, 80952
        • Local Institution - 0023
      • Warszawa, Poland, 02-781
        • Local Institution - 0056
      • Wroclaw, Poland, 50-556
        • Local Institution - 0045
  • Russian Federation
      • Moscow, Russian Federation, 115478
        • Local Institution - 0096
  • Singapore
      • Singapore, Singapore, 308433
        • Local Institution - 0014
      • Singapore, Singapore, 168583
        • Local Institution - 0013
  • Spain
      • Alicante, Spain, 03010
        • Local Institution - 0065
      • Majadahonda - Madrid, Spain, 28222
        • Local Institution - 0085
      • Pamplona, Spain, 31008
        • Local Institution - 0009
      • Santiago Compostela, Spain, 15706
        • Local Institution - 0010
  • Sweden
      • Goteborg, Sweden, 413 45
        • Local Institution - 0088
      • Stockholm, Sweden, 141 86
        • Local Institution - 0087
  • Switzerland
      • Basel, Switzerland, 4031
        • Local Institution - 0040
      • Bern, Switzerland, 3010
        • Local Institution - 0041
  • Taiwan
      • Kaohsiung County, Taiwan, 83301
        • Local Institution - 0129
      • Taichung, Taiwan, 40447
        • Local Institution - 0133
      • Tainan, Taiwan, 704
        • Local Institution - 0121
      • Tainan, Taiwan, 736
        • Local Institution - 0132
      • Taipei, Taiwan, 10002
        • Local Institution - 0099
      • Taipei, Taiwan, 11217
        • Local Institution - 0120
      • Taoyuan County, Taiwan, 33305
        • Local Institution - 0128
  • United Kingdom
      • Liverpool, United Kingdom, L7 8YA
        • Local Institution - 0081
    • Greater London
      • London, Greater London, United Kingdom, NW3 2QG
        • Local Institution - 0080
      • London, Greater London, United Kingdom, SE5 9RS
        • Local Institution - 0078
    • Lanarkshire
      • Glasgow, Lanarkshire, United Kingdom, G12 0YN
        • Local Institution - 0079
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Local Institution - 0066
    • California
      • Los Angeles, California, United States, 90095
        • Local Institution - 0020
      • San Francisco, California, United States, 94115
        • Local Institution - 0015
      • San Francisco, California, United States, 94143
        • Local Institution - 0084
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Local Institution - 0061
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Clinic Foundation
    • New York
      • New York, New York, United States, 10029
        • Local Institution - 0083
      • New York, New York, United States, 10065
        • Local Institution - 0093
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Local Institution - 0016
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Local Institution - 0095
      • Philadelphia, Pennsylvania, United States, 19107
        • Local Institution - 0019
    • Texas
      • Dallas, Texas, United States, 75390
        • UT Southwestern Medical Center
      • San Antonio, Texas, United States, 78229
        • Local Institution - 0017
      • Temple, Texas, United States, 76508
        • Scott & White Memorial Hospital And Clinic
    • Washington
      • Seattle, Washington, United States, 98101
        • Local Institution - 0026
      • Seattle, Washington, United States, 98109
        • University of Washington - Seattle Cancer Care Alliance
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • Local Institution - 0050

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Nivolumab
Nivolumab specified dose on specified days
Drug: Nivolumab
Specified Dose on Specified Days
Active Comparator: Sorafenib
Sorafenib specified dose on specified days
Drug: Sorafenib
Specified Dose on Specified Days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: time from the date of randomization to the date of death due to any cause, assessed up to June 2019 (approximately 41 months)

OS is defined as the time from the date of randomization to the date of death due to any cause in all randomized participants. Participants who are alive will be censored at the last known alive dates.

Based on Kaplan-Meier Estimates.
time from the date of randomization to the date of death due to any cause, assessed up to June 2019 (approximately 41 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR) Per BICR RECIST 1.1
Time Frame: 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)

ORR is defined as the proportion of participants whose best overall response (BOR) is either a complete response (CR) or partial response (PR). BOR is defined as the best response designation, as determined based on BICR-assessed tumor response according to RECIST 1.1, recorded between the date of randomization and the date of first objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first. For participants without documented progression or subsequent anti-cancer therapy, all available response designations will contribute to the BOR determination. For a BOR of CR or PR, the initial response assessment must be confirmed by a consecutive assessment no less than 4 weeks (28 days) later.

Estimate of (Nivolumab - Sorafenib) is based on CMH method of weighting, stratified by stratification factors
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)
Progression-Free Survival (PFS)
Time Frame: 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)
PFS is defined as the time from the date of randomization to the date of the first objectively documented tumor progression as assessed by BICR according to RECIST 1.1 or death due to any cause in all randomized participants. Participants who die without a reported prior progression and without initiation of subsequent anti-cancer therapy will be considered to have progressed on the date of their death. Participants who did not progress or die will be censored on the date of their last tumor assessment. Participants who did not have baseline tumor assessment will be censored on the date they were randomized. Participants who did not have any on study tumor assessments and did not die will be censored on the date they were randomized. Participants who started any subsequent anti-cancer therapy without a prior reported progression will be censored at the last tumor assessment prior to subsequent anti-cancer therapy.
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)
Efficacy Based on PD-L1 Expression - OS and PFS
Time Frame: 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)

PD-L1 expression is defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per Dako PD-L1 IHC assay unless otherwise specified. This is referred as quantifiable PD-L1 expression. If the PD-L1 staining could not be quantified, it is further classifies as:

Indeterminate: Tumor cell membrane staining hampered for reasons attributed to the biology of the tumor biopsy specimen and not because of improper sample preparation or handling.

Not evaluable: Tumor biopsy specimen was not optimally collected or prepared (e.g. PD-L1 expression is neither quantifiable nor indeterminate).

PD-L1 status is a dichotomized variable using an X% cut-off for quantifiable PD-L1 expression:

  • PD-L1 > X %: ≥ X % PD-L1 expression
  • PD-L1 < X %: < X % PD-L1 expression where X% denotes the PD-L1 expression cut-off of 1%. Additional cut off values may also be explored.

Confidence interval based on the Clopper and Pearson method.
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)
Efficacy Based on PD-L1 Expression - ORR
Time Frame: 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)

PD-L1 expression is defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per Dako PD-L1 IHC assay unless otherwise specified. This is referred as quantifiable PD-L1 expression. If the PD-L1 staining could not be quantified, it is further classifies as:

Indeterminate: Tumor cell membrane staining hampered for reasons attributed to the biology of the tumor biopsy specimen and not because of improper sample preparation or handling.

Not evaluable: Tumor biopsy specimen was not optimally collected or prepared (e.g. PD-L1 expression is neither quantifiable nor indeterminate).

PD-L1 status is a dichotomized variable using an X% cut-off for quantifiable PD-L1 expression:

  • PD-L1 > X %: ≥ X % PD-L1 expression
  • PD-L1 < X %: < X % PD-L1 expression where X% denotes the PD-L1 expression cut-off of 1%. Additional cut off values may also be explored.

Confidence interval based on the Clopper and Pearson method.
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bristol-Myers Squibb

Collaborators

Ono Pharmaceutical Co. Ltd

Investigators

  • Study Director: Bristol Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 7, 2015

Primary Completion (Actual)

May 30, 2019

Study Completion (Actual)

February 7, 2024

Study Registration Dates

First Submitted

October 13, 2015

First Submitted That Met QC Criteria

October 14, 2015

First Posted (Estimated)

October 15, 2015

Study Record Updates

Last Update Posted (Actual)

March 19, 2024

Last Update Submitted That Met QC Criteria

March 15, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CA209-459

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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