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

NCT02576509 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: CA209-459
• Study Type: interventional
• Target: 743
• Locations: 21 countries
• Sites: 136

Brief Summary

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

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (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.

  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 (4)

• Objective Response Rate (ORR) Per BICR RECIST 1.1

  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 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

  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

  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)

Study Arms (2)

Nivolumab

EXPERIMENTAL

Nivolumab specified dose on specified days

Drug: Nivolumab

Sorafenib

ACTIVE COMPARATOR

Sorafenib specified dose on specified days

Drug: Sorafenib

Interventions

Nivolumab DRUG

Specified Dose on Specified Days

Nivolumab

Sorafenib DRUG

Specified Dose on Specified Days

Sorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead
• Ono Pharmaceutical Co. Ltd: collaborator

Study Sites (138)

Local Institution - 0066

Birmingham, Alabama, 35294, United States

Location

Local Institution - 0020

Los Angeles, California, 90095, United States

Location

Local Institution - 0015

San Francisco, California, 94115, United States

Location

Local Institution - 0084

San Francisco, California, 94143, United States

Location

Local Institution - 0061

Chicago, Illinois, 60637, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Local Institution - 0083

New York, New York, 10029, United States

Location

Local Institution - 0093

New York, New York, 10065, United States

Location

Local Institution - 0016

Charlotte, North Carolina, 28204, United States

Location

Local Institution - 0095

Philadelphia, Pennsylvania, 19104, United States

Location

Local Institution - 0019

Philadelphia, Pennsylvania, 19107, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Local Institution - 0017

San Antonio, Texas, 78229, United States

Location

Scott & White Memorial Hospital And Clinic

Temple, Texas, 76508, United States

Location

Local Institution - 0026

Seattle, Washington, 98101, United States

Location

University of Washington - Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Local Institution - 0050

Madison, Wisconsin, 53792, United States

Location

Local Institution - 0005

Camperdown, New South Wales, 2050, Australia

Location

Local Institution - 0007

Adelaide, South Australia, 5000, Australia

Location

Local Institution - 0001

Clayton, Victoria, 3168, Australia

Location

Local Institution - 0002

Heidelberg, Victoria, 3084, Australia

Location

Local Institution - 0003

Prahran, Victoria, 3181, Australia

Location

Local Institution - 0008

Nedlands, Western Australia, 6009, Australia

Location

Local Institution - 0039

Graz, 8036, Austria

Location

Local Institution - 0038

Vienna, 1090, Austria

Location

Local Institution - 0075

Brussels, 1000, Belgium

Location

Local Institution - 0091

Leuven, 3000, Belgium

Location

Local Institution - 0077

Liège, 4000, Belgium

Location

Local Institution - 0043

Calgary, Alberta, T2N 4N2, Canada

Location

Local Institution - 0044

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Local Institution - 0042

Québec, Quebec, G1R 2J6, Canada

Location

Local Institution - 0164

Hefei, Anhui, 230061, China

Location

Local Institution - 0139

Beijing, Beijing Municipality, 100050, China

Location

Local Institution - 0137

Beijing, Beijing Municipality, 100071, China

Location

Local Institution - 0140

Beijing, Beijing Municipality, 100142, China

Location

Local Institution - 0141

Beijing, Beijing Municipality, 100142, China

Location

Local Institution - 0152

Fuzhou, Fujian, 350025, China

Location

Local Institution - 0161

Guangzhou, Guangdong, 510060, China

Location

Local Institution - 0157

Guangzhou, Guangdong, 510080, China

Location

Local Institution - 0144

Guangzhou, Guangdong, 510515, China

Location

Local Institution - 0158

Nanning, Guangxi, 530021, China

Location

Local Institution - 0142

Harbin, Heilongjiang, 155040, China

Location

Local Institution - 0148

Changsha, Hunan, 410013, China

Location

Local Institution - 0162

Changsha, Hunan, 410013, China

Location

Local Institution - 0169

Changzhou, Jiangsu, 213003, China

Location

Local Institution - 0135

Nanjing, Jiangsu, 210002, China

Location

Local Institution - 0136

Changchun, Jilin, 130012, China

Location

Local Institution - 0163

Changchun, Jilin, 130021, China

Location

Local Institution - 0166

Dalian, Liaoning, 116000, China

Location

Local Institution - 0138

Xi'an, Shan3xi, 710038, China

Location

Local Institution - 0145

Shanghai, Shanghai Municipality, 200032, China

Location

Local Institution - 0151

Shanghai, Shanghai Municipality, 200032, China

Location

Local Institution - 0159

Tianjin, Tianjin Municipality, 300060, China

Location

Local Institution - 0173

Hangzhou, Zhejiang, 310003, China

Location

Local Institution - 0146

Hangzhou, Zhejiang, 310022, China

Location

Local Institution - 0029

Brno, 656 53, Czechia

Location

Local Institution - 0027

Hradec Králové, 500 05, Czechia

Location

Local Institution - 0028

Olomouc, 779 00, Czechia

Location

Local Institution - 0071

La Tronche, 38700, France

Location

Local Institution - 0072

Lille, 59037, France

Location

Local Institution - 0069

Lyon, 69004, France

Location

Local Institution - 0073

Montpellier, 34295, France

Location

Local Institution - 0067

Paris, 75651, France

Location

Local Institution - 0068

Pessac, 33604, France

Location

Local Institution - 0070

Rennes, 35042, France

Location

Local Institution - 0074

Toulouse, 31059, France

Location

Local Institution - 0036

Berlin, 13353, Germany

Location

Local Institution - 0037

Essen, 45136, Germany

Location

Local Institution - 0167

Frankfurt, 60590, Germany

Location

Local Institution - 0034

Hamburg, 20246, Germany

Location

Local Institution - 0031

Leipzig, 04103, Germany

Location

Local Institution - 0035

Mainz, 55131, Germany

Location

Local Institution - 0033

Munich, 81366, Germany

Location

Local Institution - 0032

Regensburg, 93053, Germany

Location

Local Institution - 0030

Tübingen, 72076, Germany

Location

Local Institution - 0011

Hong Kong, 0, Hong Kong

Location

Local Institution - 0012

Hong Kong, Hong Kong

Location

Local Institution - 0082

Haifa, 31096, Israel

Location

Local Institution - 0060

Jerusalem, 91120, Israel

Location

Local Institution - 0058

Petah Tikva, 49100, Israel

Location

Local Institution - 0059

Tel Aviv, 64239, Israel

Location

Local Institution - 0054

Benevento, 82100, Italy

Location

Local Institution - 0062

Bergamo, 0, Italy

Location

Local Institution - 0055

Milan, 20133, Italy

Location

Local Institution - 0063

Orbassano, 10043, Italy

Location

Local Institution - 0064

Siena, 53100, Italy

Location

Local Institution - 0100

Chiba, Chiba, 2608670, Japan

Location

Local Institution - 0103

Matsuyama, Ehime, 7900024, Japan

Location

Local Institution - 0107

Kurume-shi, Fukuoka, 8300011, Japan

Location

Local Institution - 0127

Ogaki-shi, Gifu, 5038502, Japan

Location

Local Institution - 0102

Sapporo, Hokkaido, 0600033, Japan

Location

Local Institution - 0130

Sapporo, Hokkaido, 0608648, Japan

Location

Local Institution - 0105

Kanazawa, Ishikawa-ken, 9208641, Japan

Location

Local Institution - 0110

Kawasaki-shi, Kanagawa, 2138587, Japan

Location

Local Institution - 0112

Yokohama, Kanagawa, 2320024, Japan

Location

Local Institution - 0104

Yokohama, Kanagawa, 2418515, Japan

Location

Local Institution - 0111

Kyoto, Kyoto, 6028566, Japan

Location

Local Institution - 0106

Osaka-Sayama-Shi, Osaka, 5898511, Japan

Location

Local Institution - 0113

Suita, Osaka, 5650871, Japan

Location

Local Institution - 0115

Saga, Saga-ken, 8408571, Japan

Location

Local Institution - 0131

Chiyoda-ku, Tokyo, 101-0062, Japan

Location

Local Institution - 0114

Mitaka-shi, Tokyo, 181-8611, Japan

Location

Local Institution - 0108

Musashino-shi, Tokyo, 180-8610, Japan

Location

Local Institution - 0126

Shinjuku-ku, Tokyo, 1628655, Japan

Location

Local Institution - 0101

Hiroshima, 734-8551, Japan

Location

Local Institution - 0023

Gdansk, 80952, Poland

Location

Local Institution - 0056

Warsaw, 02-781, Poland

Location

Local Institution - 0045

Wroclaw, 50-556, Poland

Location

Local Institution - 0096

Moscow, 115478, Russia

Location

Local Institution - 0013

Singapore, 168583, Singapore

Location

Local Institution - 0014

Singapore, 308433, Singapore

Location

Local Institution - 0117

Seoul, Seocho-gu, 06591, South Korea

Location

Local Institution - 0125

Daegu, 41944, South Korea

Location

Local Institution - 0116

Goyang-si, 10408, South Korea

Location

Local Institution - 0118

Jeollanam-do, 58128, South Korea

Location

Local Institution - 0123

Seoul, 03080, South Korea

Location

Local Institution - 0119

Seoul, 03722, South Korea

Location

Local Institution - 0122

Seoul, 05505, South Korea

Location

Local Institution - 0124

Seoul, 06351, South Korea

Location

Local Institution - 0065

Alicante, 03010, Spain

Location

Local Institution - 0085

Majadahonda - Madrid, 28222, Spain

Location

Local Institution - 0009

Pamplona, 31008, Spain

Location

Local Institution - 0010

Santiago Compostela, 15706, Spain

Location

Local Institution - 0088

Gothenburg, 413 45, Sweden

Location

Local Institution - 0087

Stockholm, 141 86, Sweden

Location

Local Institution - 0040

Basel, 4031, Switzerland

Location

Local Institution - 0041

Bern, 3010, Switzerland

Location

Local Institution - 0129

Kaohsiung County, 83301, Taiwan

Location

Local Institution - 0133

Taichung, 40447, Taiwan

Location

Local Institution - 0121

Tainan, 704, Taiwan

Location

Local Institution - 0132

Tainan, 736, Taiwan

Location

Local Institution - 0099

Taipei, 10002, Taiwan

Location

Local Institution - 0120

Taipei, 11217, Taiwan

Location

Local Institution - 0128

Taoyuan, 33305, Taiwan

Location

Local Institution - 0080

London, Greater London, NW3 2QG, United Kingdom

Location

Local Institution - 0078

London, Greater London, SE5 9RS, United Kingdom

Location

Local Institution - 0079

Glasgow, Lanarkshire, G12 0YN, United Kingdom

Location

Local Institution - 0081

Liverpool, L7 8YA, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 36852452 DERIVED

• 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.

  PMID: 36111952 DERIVED

• 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.

  PMID: 35101942 DERIVED

• 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.

  PMID: 34914889 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Nivolumab; Sorafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email:

Study Officials

• Bristol Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2015
• First Posted: October 15, 2015
• Study Start: December 7, 2015
• Primary Completion: May 30, 2019
• Study Completion: February 7, 2024
• Last Updated: February 17, 2025
• Results First Posted: June 26, 2020

Record last verified: 2025-01

Locations

RU (1); CZ (3); CH (2); ES (4); BE (3); FR (8); DE (9); IT (5); CN (24); KR (8); GB (4); PL (3); SE (2); CA (3); HK (2); SG (2); JP (19); AU (6); TW (7); US (17); IL (4)