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

Recruitment Status
COMPLETED - HAS RESULTS
(See Contacts and Locations)Verified December 2024 by Bristol-Myers Squibb
Sponsor
Bristol-Myers Squibb
Information Provided by (Responsible Party)
Bristol-Myers Squibb
Clinicaltrials.gov Identifier
NCT02576509
Other Study ID Numbers:
CA209-459
First Submitted
October 12, 2015
First Posted
October 14, 2015
Results First Posted
May 28, 2020
Last Update Posted
February 16, 2025
Last Verified
December 2024

ClinicalTrials.gov processed this data on January 2025Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Hepatocellular Carcinoma
Drug: NivolumabDrug: Sorafenib

Study Design

Study TypeInterventional
Actual Enrollment743 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingNone (Open Label)
Primary PurposeTreatment
Official TitleA 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 Start DateDecember 6, 2015
Actual Primary Completion DateMay 29, 2019
Actual Study Completion DateFebruary 6, 2024

Groups and Cohorts

Group/CohortIntervention/Treatment
Nivolumab
Nivolumab specified dose on specified days
Drug: Nivolumab
Specified Dose on Specified Days
Sorafenib
Sorafenib specified dose on specified days
Drug: Sorafenib
Specified Dose on Specified Days

Outcome Measures

Primary Outcome Measures
  1. Overall Survival (OS)
    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.
Secondary Outcome Measures
  1. Objective Response Rate (ORR) Per BICR RECIST 1.1
    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
  2. Progression-Free Survival (PFS)
    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.
  3. Efficacy Based on PD-L1 Expression - OS and PFS
    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.
  4. Efficacy Based on PD-L1 Expression - ORR
    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.

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
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

Contacts and Locations

Sponsors and CollaboratorsBristol-Myers Squibb
Locations
Local Institution - 0066 | Birmingham Alabama, United States, 35294Local Institution - 0020 | Los Angeles California, United States, 90095Local Institution - 0015 | San Francisco California, United States, 94115Local Institution - 0084 | San Francisco California, United States, 94143Local Institution - 0061 | Chicago Illinois, United States, 60637Ochsner Clinic Foundation | New Orleans Louisiana, United States, 70121Local Institution - 0083 | New York New York, United States, 10029Local Institution - 0093 | New York New York, United States, 10065Local Institution - 0016 | Charlotte North Carolina, United States, 28204Local Institution - 0095 | Philadelphia Pennsylvania, United States, 19104Local Institution - 0019 | Philadelphia Pennsylvania, United States, 19107UT Southwestern Medical Center | Dallas Texas, United States, 75390Local Institution - 0017 | San Antonio Texas, United States, 78229Scott & White Memorial Hospital And Clinic | Temple Texas, United States, 76508Local Institution - 0026 | Seattle Washington, United States, 98101University of Washington - Seattle Cancer Care Alliance | Seattle Washington, United States, 98109Local Institution - 0050 | Madison Wisconsin, United States, 53792Local Institution - 0005 | Camperdown New South Wales, Australia, 2050Local Institution - 0007 | Adelaide South Australia, Australia, 5000Local Institution - 0001 | Clayton Victoria, Australia, 3168Local Institution - 0002 | Heidelberg Victoria, Australia, 3084Local Institution - 0003 | Prahran Victoria, Australia, 3181Local Institution - 0008 | Nedlands Western Australia, Australia, 6009Local Institution - 0039 | Graz , Austria, 8036Local Institution - 0038 | Vienna , Austria, 1090Local Institution - 0075 | Brussels , Belgium, 1000Local Institution - 0091 | Leuven , Belgium, 3000Local Institution - 0077 | Liège , Belgium, 4000Local Institution - 0043 | Calgary Alberta, Canada, T2N 4N2Local Institution - 0044 | Vancouver British Columbia, Canada, V5Z 4E6Local Institution - 0042 | Québec Quebec, Canada, G1R 2J6Local Institution - 0164 | Hefei Anhui, China, 230061Local Institution - 0139 | Beijing Beijing Municipality, China, 100050Local Institution - 0137 | Beijing Beijing Municipality, China, 100071Local Institution - 0140 | Beijing Beijing Municipality, China, 100142Local Institution - 0141 | Beijing Beijing Municipality, China, 100142Local Institution - 0152 | Fuzhou Fujian, China, 350025Local Institution - 0161 | Guangzhou Guangdong, China, 510060Local Institution - 0157 | Guangzhou Guangdong, China, 510080Local Institution - 0144 | Guangzhou Guangdong, China, 510515Local Institution - 0158 | Nanning Guangxi, China, 530021Local Institution - 0142 | Harbin Heilongjiang, China, 155040Local Institution - 0148 | Changsha Hunan, China, 410013Local Institution - 0162 | Changsha Hunan, China, 410013Local Institution - 0169 | Changzhou Jiangsu, China, 213003Local Institution - 0135 | Nanjing Jiangsu, China, 210002Local Institution - 0136 | Changchun Jilin, China, 130012Local Institution - 0163 | Changchun Jilin, China, 130021Local Institution - 0166 | Dalian Liaoning, China, 116000Local Institution - 0138 | Xi'an Shan3xi, China, 710038Local Institution - 0145 | Shanghai Shanghai Municipality, China, 200032Local Institution - 0151 | Shanghai Shanghai Municipality, China, 200032Local Institution - 0159 | Tianjin Tianjin Municipality, China, 300060Local Institution - 0173 | Hangzhou Zhejiang, China, 310003Local Institution - 0146 | Hangzhou Zhejiang, China, 310022Local Institution - 0029 | Brno , Czechia, 656 53Local Institution - 0027 | Hradec Králové , Czechia, 500 05Local Institution - 0028 | Olomouc , Czechia, 779 00Local Institution - 0071 | La Tronche , France, 38700Local Institution - 0072 | Lille , France, 59037Local Institution - 0069 | Lyon , France, 69004Local Institution - 0073 | Montpellier , France, 34295Local Institution - 0067 | Paris , France, 75651Local Institution - 0068 | Pessac , France, 33604Local Institution - 0070 | Rennes , France, 35042Local Institution - 0074 | Toulouse , France, 31059Local Institution - 0036 | Berlin , Germany, 13353Local Institution - 0037 | Essen , Germany, 45136Local Institution - 0167 | Frankfurt , Germany, 60590Local Institution - 0034 | Hamburg , Germany, 20246Local Institution - 0031 | Leipzig , Germany, 04103Local Institution - 0035 | Mainz , Germany, 55131Local Institution - 0033 | Munich , Germany, 81366Local Institution - 0032 | Regensburg , Germany, 93053Local Institution - 0030 | Tübingen , Germany, 72076Local Institution - 0011 | Hong Kong , Hong Kong, 0Local Institution - 0012 | Hong Kong , Hong Kong, Local Institution - 0082 | Haifa , Israel, 31096Local Institution - 0060 | Jerusalem , Israel, 91120Local Institution - 0058 | Petah Tikva , Israel, 49100Local Institution - 0059 | Tel Aviv , Israel, 64239Local Institution - 0054 | Benevento , Italy, 82100Local Institution - 0062 | Bergamo , Italy, 0Local Institution - 0055 | Milan , Italy, 20133Local Institution - 0063 | Orbassano , Italy, 10043Local Institution - 0064 | Siena , Italy, 53100Local Institution - 0100 | Chiba Chiba, Japan, 2608670Local Institution - 0103 | Matsuyama Ehime, Japan, 7900024Local Institution - 0107 | Kurume-shi Fukuoka, Japan, 8300011Local Institution - 0127 | Ogaki-shi Gifu, Japan, 5038502Local Institution - 0102 | Sapporo Hokkaido, Japan, 0600033Local Institution - 0130 | Sapporo Hokkaido, Japan, 0608648Local Institution - 0105 | Kanazawa Ishikawa-ken, Japan, 9208641Local Institution - 0110 | Kawasaki-shi Kanagawa, Japan, 2138587Local Institution - 0112 | Yokohama Kanagawa, Japan, 2320024Local Institution - 0104 | Yokohama Kanagawa, Japan, 2418515Local Institution - 0111 | Kyoto Kyoto, Japan, 6028566Local Institution - 0106 | Osaka-Sayama-Shi Osaka, Japan, 5898511Local Institution - 0113 | Suita Osaka, Japan, 5650871Local Institution - 0115 | Saga Saga-ken, Japan, 8408571Local Institution - 0131 | Chiyoda-ku Tokyo, Japan, 101-0062Local Institution - 0114 | Mitaka-shi Tokyo, Japan, 181-8611Local Institution - 0108 | Musashino-shi Tokyo, Japan, 180-8610Local Institution - 0126 | Shinjuku-ku Tokyo, Japan, 1628655Local Institution - 0101 | Hiroshima , Japan, 734-8551Local Institution - 0023 | Gdansk , Poland, 80952Local Institution - 0056 | Warsaw , Poland, 02-781Local Institution - 0045 | Wroclaw , Poland, 50-556Local Institution - 0096 | Moscow , Russia, 115478Local Institution - 0013 | Singapore , Singapore, 168583Local Institution - 0014 | Singapore , Singapore, 308433Local Institution - 0117 | Seoul Seocho-gu, South Korea, 06591Local Institution - 0125 | Daegu , South Korea, 41944Local Institution - 0116 | Goyang-si , South Korea, 10408Local Institution - 0118 | Jeollanam-do , South Korea, 58128Local Institution - 0123 | Seoul , South Korea, 03080Local Institution - 0119 | Seoul , South Korea, 03722Local Institution - 0122 | Seoul , South Korea, 05505Local Institution - 0124 | Seoul , South Korea, 06351Local Institution - 0065 | Alicante , Spain, 03010Local Institution - 0085 | Majadahonda - Madrid , Spain, 28222Local Institution - 0009 | Pamplona , Spain, 31008Local Institution - 0010 | Santiago Compostela , Spain, 15706Local Institution - 0088 | Gothenburg , Sweden, 413 45Local Institution - 0087 | Stockholm , Sweden, 141 86Local Institution - 0040 | Basel , Switzerland, 4031Local Institution - 0041 | Bern , Switzerland, 3010Local Institution - 0129 | Kaohsiung County , Taiwan, 83301Local Institution - 0133 | Taichung , Taiwan, 40447Local Institution - 0121 | Tainan , Taiwan, 704Local Institution - 0132 | Tainan , Taiwan, 736Local Institution - 0099 | Taipei , Taiwan, 10002Local Institution - 0120 | Taipei , Taiwan, 11217Local Institution - 0128 | Taoyuan County , Taiwan, 33305Local Institution - 0080 | London Greater London, United Kingdom, NW3 2QGLocal Institution - 0078 | London Greater London, United Kingdom, SE5 9RSLocal Institution - 0079 | Glasgow Lanarkshire, United Kingdom, G12 0YNLocal Institution - 0081 | Liverpool , United Kingdom, L7 8YA
Investigators
Study Director: Bristol Myers Squibb, Bristol-Myers Squibb
Study Documents (Full Text)
Documents provided by Bristol-Myers SquibbStudy Protocol  January 14, 2019Documents provided by Bristol-Myers SquibbStatistical Analysis Plan  May 17, 2020