A Study of Nivolumab in Combination With Ipilimumab in Participants With Advanced Hepatocellular Carcinoma

NCT04039607 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: CA209-9DW
• Study Type: interventional
• Target: 732
• Locations: 25 countries
• Sites: 200

Brief Summary

The main purpose of this study is to compare the overall survival (OS) of nivolumab plus ipilimumab versus standard of care (SOC) (sorafenib or lenvatinib) in all randomized participants with advanced hepatocellular carcinoma (HCC) who have not received prior systemic therapy.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  Up to 4 years

Secondary Outcomes (3)

• Objective Response Rate (ORR)

  Up to 4 years

• Duration of Response (DOR)

  Up to 4 years

• Time to Symptom Deterioration (TTSD)

  Up to 4 years

Study Arms (2)

Nivolumab + Ipilimumab

EXPERIMENTAL

Drug: Nivolumab; Drug: Ipilimumab

Sorafenib/lenvatinib

ACTIVE COMPARATOR

Drug: Sorafenib; Drug: lenvatinib

Interventions

Nivolumab DRUG

Participants will receive nivolumab as intravenous (IV) infusion.

Nivolumab + Ipilimumab

Ipilimumab DRUG

Participants will receive ipilimumab as IV infusion.

Nivolumab + Ipilimumab

Sorafenib DRUG

Participants will receive sorafenib as oral tablets.

Sorafenib/lenvatinib

lenvatinib DRUG

Participants will receive lenvatinib as oral capsules.

Sorafenib/lenvatinib

Eligibility Criteria

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

You may qualify if:

• Participants must have a diagnosis of HCC based on histological confirmation
• Participants must have an advanced HCC
• Participants must have at least one Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 measurable previously untreated lesion
• Child-Pugh score 5 or 6
• 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
• Episodes of hepatic encephalopathy (greater than or equal to \[\>=\] Grade 2) within 12 months prior to randomization
• Active brain metastases or leptomeningeal metastases

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (210)

Local Institution - 0292

Tucson, Arizona, 85719, United States

Location

Local Institution - 0288

Coronado, California, 92118, United States

Location

Local Institution - 0157

Duarte, California, 91010-3012, United States

Location

Local Institution - 0077

Washington D.C., District of Columbia, 20007, United States

Location

Local Institution - 0027

Louisville, Kentucky, 40217, United States

Location

Local Institution - 0190

Baltimore, Maryland, 21287, United States

Location

Local Institution

Ann Arbor, Michigan, 48105, United States

Location

Local Institution - 0018

Detroit, Michigan, 48202, United States

Location

Local Institution - 0295

Newark, New Jersey, 07103, United States

Location

Local Institution - 0043

Toledo, Ohio, 43623, United States

Location

Local Institution - 0284

Pittsburgh, Pennsylvania, 15212, United States

Location

Local Institution - 0304

Dallas, Texas, 75203, United States

Location

Local Institution - 0202

Houston, Texas, 77030, United States

Location

Local Institution - 0046

Lubbock, Texas, 79410, United States

Location

Local Institution - 0172

Salt Lake City, Utah, 84106, United States

Location

Local Institution - 0037

Caba, Buenos Aires, C1090AAS, Argentina

Location

Local Institution - 0194

Pilar, Buenos Aires, B1629ODT, Argentina

Location

Local Institution - 0282

Rosario, Santa Fe Province, 2000, Argentina

Location

Local Institution - 0136

Buenos Aires, C1426ANZ, Argentina

Location

Local Institution - 0058

San Miguel de Tucumán, 4000, Argentina

Location

Local Institution - 0003

Kogarah, New South Wales, 2217, Australia

Location

Local Institution - 0038

Liverpool, New South Wales, 1871, Australia

Location

Local Institution - 0002

Westmead, New South Wales, 2145, Australia

Location

Local Institution - 0004

Birtinya, Queensland, 4560, Australia

Location

Local Institution - 0013

Herston, Queensland, 4029, Australia

Location

Local Institution - 0009

Adelaide, South Australia, 5000, Australia

Location

Local Institution - 0019

Clayton, Victoria, 3168, Australia

Location

Local Institution - 0026

Fitzroy, Victoria, 3065, Australia

Location

Local Institution - 0001

Melbourne, Victoria, 3004, Australia

Location

Local Institution - 0020

St Albans, Victoria, 3021, Australia

Location

Local Institution - 0114

Sankt Pölten, Lower Austria, 3100, Austria

Location

Local Institution - 0057

Wiener Neustadt, Lower Austria, 2700, Austria

Location

Local Institution - 0188

Graz, 8036, Austria

Location

Local Institution - 0065

Klagenfurt, 9020, Austria

Location

Local Institution - 0186

Vienna, 1090, Austria

Location

Local Institution - 0034

Brussels, 1070, Belgium

Location

Local Institution - 0008

Federal District, 72115700, Belgium

Location

Local Institution - 0124

Ghent, 9000, Belgium

Location

Local Institution - 0298

Ghent, 9000, Belgium

Location

Local Institution - 0099

Haine-Saint-Paul, 7100, Belgium

Location

Local Institution - 0064

Leuven, 3000, Belgium

Location

Local Institution - 0104

Liège, 4000, Belgium

Location

Local Institution - 0278

Vitória, Espírito Santo, 29055-450, Brazil

Location

Local Institution

Salvador, Estado de Bahia, 41253190, Brazil

Location

Local Institution - 0061

Salvador, Estado de Bahia, 41950-640, Brazil

Location

Local Institution - 0181

Brasília, Federal District, 70200-730, Brazil

Location

Local Institution - 0279

Ijuí, Rio Grande do Sul, 98700-000, Brazil

Location

Local Institution - 0060

Pelotas, Rio Grande do Sul, 96020-360, Brazil

Location

Local Institution - 0054

Jaú, São Paulo, 17210-120, Brazil

Location

Hospital de Base de Sao Jose do Rio Preto

São José do Rio Preto, São Paulo, 15090-000, Brazil

Location

Local Institution - 0016

Paranã, 81520-060, Brazil

Location

Local Institution - 0015

Rio de Janeiro, 22793-080, Brazil

Location

Local Institution - 0023

São Paulo, 01246-000, Brazil

Location

Local Institution - 0022

São Paulo, 01323-900, Brazil

Location

Local Institution - 0050

São Paulo, 04038-034, Brazil

Location

Local Institution - 0192

Edmonton, Alberta, T6G 1Z2, Canada

Location

Local Institution - 0094

La Serena, Coquimbo Region, 1720430, Chile

Location

Local Institution - 0296

Temuco, Región de la Araucanía, 4780000, Chile

Location

Local Institution - 0012

Viña del Mar, Región de Valparaíso, 2520598, Chile

Location

Local Institution - 0216

Viña del Mar, Región de Valparaíso, 2540402, Chile

Location

Local Institution - 0283

Santiago, RM, 7630372, Chile

Location

Local Institution - 0095

Santiago, Santiago Metropolitan, 0, Chile

Location

Local Institution - 0024

Santiago, Santiago Metropolitan, 7710007, Chile

Location

Local Institution - 0156

Santiago, Santiago Metropolitan, 8380456, Chile

Location

Local Institution - 0120

Hefei, Anhui, 230022, China

Location

Local Institution - 0146

Hefei, Anhui, 230601, China

Location

Local Institution - 0175

Beijing, Beijing Municipality, 100000, China

Location

Local Institution - 0152

Beijing, Beijing Municipality, 100142, China

Location

Local Institution - 0151

Fuzhou, Fujian, 350002, China

Location

Local Institution - 0121

Fuzhou, Fujian, 350014, China

Location

Local Institution - 0125

Guangzhou, Guangdong, 510000, China

Location

Local Institution - 0150

Guangzhou, Guangdong, 510515, China

Location

Local Institution - 0135

Harbin, Heilongjiang, 150081, China

Location

Local Institution - 0109

Changsha, Hunan, 410006, China

Location

Local Institution - 0059

Changsha, Hunan, 410011, China

Location

Local Institution - 0130

Nanjing, Jiangsu, 210002, China

Location

Local Institution - 0145

Nanchang, Jiangxi, 330006, China

Location

Local Institution - 0149

Nanchang, Jiangxi, 330019, China

Location

Local Institution - 0162

Changchun, Jilin, 130021, China

Location

Local Institution - 0166

Changchun, Jilin, 130102, China

Location

Local Institution - 0131

Dalian, Liaoning, 116023, China

Location

Local Institution - 0123

Shenyang, Liaoning, 110004, China

Location

Local Institution - 0132

Shenyang, Liaoning, 110117, China

Location

Local Institution - 0133

Xi'an, Shaanxi, 710038, China

Location

Local Institution - 0147

Xi'an, Shan3xi, 710061, China

Location

Local Institution - 0307

Xi'an, Shan3xi, 710100, China

Location

Local Institution - 0153

Qingdao, Shandong, 266000, China

Location

Local Institution - 0134

Shanghai, Shanghai Municipality, 200032, China

Location

Local Institution - 0179

Chongqing, Sichuan, 400030, China

Location

Local Institution - 0108

Hangzhou, Zhejiang, 310000, China

Location

Local Institution - 0107

Hangzhou, Zhejiang, 310022, China

Location

Local Institution - 0274

Prague, Prague, 14059, Czechia

Location

Local Institution

Brno, 60200, Czechia

Location

Local Institution - 0068

Amiens, 80054, France

Location

Local Institution - 0116

Caen, 14033, France

Location

Local Institution - 0069

Clichy, 92110, France

Location

Local Institution - 0138

Dijon, 21000, France

Location

Local Institution - 0081

Grenoble, 38043, France

Location

Local Institution - 0070

Lyon, 69004, France

Location

Local Institution

Marseille, 13009, France

Location

Local Institution - 0082

Montpellier, 34295, France

Location

Local Institution - 0067

Nice, 6202, France

Location

Local Institution - 0025

Pessac, 33604, France

Location

Local Institution - 0137

Poitiers, 86021, France

Location

Local Institution - 0042

Toulouse, 31059, France

Location

Local Institution - 0071

Vandœuvre-lès-Nancy, 54500, France

Location

Local Institution - 0051

Villejuif, 94800, France

Location

Local Institution - 0005

Frankfurt am Main, Hesse, 60590, Germany

Location

Local Institution - 0231

Bonn, 53127, Germany

Location

Local Institution - 0028

Cologne, 50937, Germany

Location

Local Institution - 0052

Essen, 45147, Germany

Location

Local Institution - 0185

Freiburg im Breisgau, 79106, Germany

Location

Local Institution - 0006

Hamburg, 20246, Germany

Location

Local Institution - 0102

Hanover, 30625, Germany

Location

Local Institution - 0118

Leipzig, 04103, Germany

Location

Local Institution - 0031

Mainz, 55131, Germany

Location

Local Institution - 0056

Mannheim, 68167, Germany

Location

Local Institution

München, 81675, Germany

Location

Local Institution - 0053

North Rhine-Westphalia, 45136, Germany

Location

Local Institution - 0036

Hong Kong, 999077, Hong Kong

Location

Local Institution - 0032

Hong Kong, Hong Kong

Location

Local Institution - 0110

Meldola, Forli-Cesena, 47014, Italy

Location

Local Institution - 0101

Rozzano, Milano, 20089, Italy

Location

Local Institution - 0084

Candiolo, 10060, Italy

Location

Local Institution - 0039

Milan, 20122, Italy

Location

Local Institution - 0100

Novara, 28100, Italy

Location

Local Institution - 0219

Padua, 35128, Italy

Location

Local Institution - 0033

Parma, 43126, Italy

Location

Local Institution - 0112

Roma, 00128, Italy

Location

Local Institution - 0079

Rome, 00168, Italy

Location

Local Institution - 0111

Siena, 53100, Italy

Location

Local Institution - 0044

Vicenza, 36100, Italy

Location

Local Institution - 0193

Kashiwa-shi, Chiba, 2778577, Japan

Location

Local Institution - 0203

Matsuyama, Ehime, 790-0024, Japan

Location

Local Institution - 0176

Kanazawa, Ishikawa-ken, 920-8641, Japan

Location

Local Institution - 0200

Yokohama, Kanagawa, 2320024, Japan

Location

Local Institution - 0262

Yokohama, Kanagawa, 241-8515, Japan

Location

Local Institution - 0189

Kyoto, Kyoto, 602-8566, Japan

Location

Local Institution - 0261

Kashihara, Nara, 634-8522, Japan

Location

Local Institution - 0263

Abeno-ku, Osaka, 5458586, Japan

Location

Local Institution - 0127

Sayama, Osaka, 5898511, Japan

Location

Local Institution - 0281

Saga, Saga-ken, 8408571, Japan

Location

Local Institution - 0258

Iruma-gun, Saitama, 3500495, Japan

Location

Local Institution - 0259

Izunokuni-shi, Shizuoka, 410-2295, Japan

Location

Local Institution - 0128

Minato, Tokyo, 105-8470, Japan

Location

Local Institution - 0122

Minato-ku, Tokyo, 105-8470, Japan

Location

Local Institution - 0201

Mitaka, Tokyo, 181-8611, Japan

Location

Local Institution - 0199

Musashino-shi, Tokyo, 180-8610, Japan

Location

Local Institution - 0204

Chiba, 260-8677, Japan

Location

Local Institution - 0178

Fukuoka, 830-0011, Japan

Location

Local Institution - 0177

Hiroshima, 7348551, Japan

Location

Local Institution - 0155

Sapporo, 0600033, Japan

Location

Local Institution - 0286

Christchurch, Canterbury, 8011, New Zealand

Location

Local Institution - 0047

Auckland, 1023, New Zealand

Location

Local Institution - 0148

Gdansk, 80219, Poland

Location

Local Institution - 0049

Otwock, 05-400, Poland

Location

Local Institution - 0092

Warsaw, 02-034, Poland

Location

Local Institution - 0289

Rio Piedras, 00935, Puerto Rico

Location

Local Institution - 0035

San Juan, 00927-4308, Puerto Rico

Location

Local Institution - 0103

Craiova, Dolj, 200542, Romania

Location

Local Institution - 0164

Bucharest, 022328, Romania

Location

Local Institution - 0165

Cluj-Napoca, 400015, Romania

Location

Local Institution

Craiova, 200385, Romania

Location

Local Institution - 0163

Timișoara, 300166, Romania

Location

Local Institution - 0029

Arkhangelsk, 163045, Russia

Location

Local Institution - 0066

Barnaul, 656045, Russia

Location

Local Institution - 0074

Chelyabinsk, 454087, Russia

Location

Local Institution - 0007

Moscow, 115478, Russia

Location

Local Institution - 0072

Pyatigorsk, 357502, Russia

Location

Local Institution - 0075

Saint Petersburg, 197758, Russia

Location

Local Institution - 0091

Saint Petersburg, 198255, Russia

Location

Local Institution - 0073

Sochi, 354057, Russia

Location

Local Institution - 0048

Singapore, 168583, Singapore

Location

Local Institution - 0017

Singapore, 258499, Singapore

Location

Local Institution - 0174

Singapore, 308442, Singapore

Location

Local Institution - 0143

Seongnam-si, Gyeonggi-do, 13496, South Korea

Location

Local Institution - 0167

Guro-gu, Seoul, 8308, South Korea

Location

Local Institution - 0062

Jongno-gu, Seoul, 03080, South Korea

Location

Local Institution - 0142

Busan, 49241, South Korea

Location

Local Institution - 0097

Gyeonggi-do, 010408, South Korea

Location

Local Institution - 0098

Gyeongsangnam-do, 050612, South Korea

Location

Local Institution - 0141

Seoul, 03722, South Korea

Location

Local Institution - 0140

Seoul, 05505, South Korea

Location

Local Institution - 0139

Seoul, 06351, South Korea

Location

Local Institution - 0297

Barcelona, 08035, Spain

Location

Local Institution - 0055

Barcelona, 08036, Spain

Location

Local Institution - 0089

Barcelona, 08908, Spain

Location

Local Institution - 0090

Córdoba, 14004, Spain

Location

Local Institution - 0087

El Palmar, 30120, Spain

Location

Local Institution - 0041

Madrid, 28007, Spain

Location

Local Institution - 0093

Madrid, 28028, Spain

Location

Local Institution - 0290

Madrid, 28035, Spain

Location

Local Institution - 0045

Majadahonda, 28222, Spain

Location

Local Institution - 0085

Pamplona, 31008, Spain

Location

Local Institution - 0088

Santander, 39008, Spain

Location

Local Institution - 0040

Zaragoza, 50009, Spain

Location

Local Institution - 0063

Bern, 3010, Switzerland

Location

Local Institution - 0272

Kaohsiung City, 807, Taiwan

Location

Local Institution - 0096

Kaohsiung City, 83301, Taiwan

Location

Local Institution - 0105

Taichung, 40447, Taiwan

Location

Local Institution - 0271

Taichung, 40705, Taiwan

Location

Local Institution - 0168

Tainan, 704, Taiwan

Location

Local Institution - 0270

Tainan, 736, Taiwan

Location

Local Institution - 0144

Taipei, 10002, Taiwan

Location

Local Institution - 0078

Taipei, 11266, Taiwan

Location

Local Institution - 0173

Taoyuan District, 333, Taiwan

Location

Local Institution - 0171

London, Greater London, W12 OHS, United Kingdom

Location

Local Institution - 0154

Guildford, Surrey, GU2 7XX, United Kingdom

Location

Local Institution - 0160

Edinburgh, EH4 2XU, United Kingdom

Location

Local Institution - 0129

London, SE5 9RS, United Kingdom

Location

Related Publications (1)

• Yau T, Galle PR, Decaens T, Sangro B, Qin S, da Fonseca LG, Karachiwala H, Blanc JF, Park JW, Gane E, Pinter M, Pena AM, Ikeda M, Tai D, Santoro A, Pizarro G, Chiu CF, Schenker M, He A, Chon HJ, Wojcik-Tomaszewska J, Verset G, Wang QQ, Stromko C, Neely J, Singh P, Jimenez Exposito MJ, Kudo M; CheckMate 9DW investigators. Nivolumab plus ipilimumab versus lenvatinib or sorafenib as first-line treatment for unresectable hepatocellular carcinoma (CheckMate 9DW): an open-label, randomised, phase 3 trial. Lancet. 2025 May 24;405(10492):1851-1864. doi: 10.1016/S0140-6736(25)00403-9. Epub 2025 May 8.

  PMID: 40349714 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Nivolumab; Ipilimumab; Sorafenib; lenvatinib

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

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: July 30, 2019
• First Posted: July 31, 2019
• Study Start: September 30, 2019
• Primary Completion (Estimated): November 9, 2026
• Study Completion (Estimated): November 9, 2026
• Last Updated: February 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: See Plan Description
• Access Criteria: See Plan Description

Locations

TW (9); CN (27); BR (13); RU (8); FR (14); CH (1); GB (4); BE (7); PR (2); KR (9); HK (2); RO (5); CA (1); IT (11); AU (5); PL (3); SG (3); AR (5); CZ (2); DE (12); US (15); JP (20); NZ (2); CL (8); ES (12)