Efficacy Study of Nivolumab Plus Ipilimumab or Nivolumab Plus Chemotherapy Against Chemotherapy in Stomach Cancer or Stomach/Esophagus Junction Cancer

NCT ID: NCT02872116

Last Updated: 2025-08-07

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

2031 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-10-12

Study Completion Date

2024-06-06

Brief Summary

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The main purpose of this study is to compare how long patients with gastric or gastroesophageal junction cancer live after receiving nivolumab and ipilimumab or nivolumab and chemotherapy compared with patients receiving chemotherapy alone.

Detailed Description

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Conditions

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Gastric Cancer Gastroesophageal Junction Cancer Esophageal Adenocarcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Nivolumab + Ipilimumab

Nivolumab + Ipilimumab for 4 doses, followed by Nivolumab monotherapy

Enrollment is closed for this arm

Group Type EXPERIMENTAL

Nivolumab

Intervention Type DRUG

Specified dose on specified days

Ipilimumab

Intervention Type DRUG

Specified dose on specified days

XELOX (Oxaliplatin + Capecitabine)

Group Type ACTIVE_COMPARATOR

Oxaliplatin

Intervention Type DRUG

Specified dose on specified days

Capecitabine

Intervention Type DRUG

Specified dose on specified days

FOLFOX (Oxaliplatin + Leucovorin + Fluorouracil)

Group Type ACTIVE_COMPARATOR

Oxaliplatin

Intervention Type DRUG

Specified dose on specified days

Leucovorin

Intervention Type DRUG

Specified dose on specified days

Fluorouracil

Intervention Type DRUG

Specified dose on specified days

Nivolumab + XELOX

Group Type EXPERIMENTAL

Nivolumab

Intervention Type DRUG

Specified dose on specified days

Oxaliplatin

Intervention Type DRUG

Specified dose on specified days

Capecitabine

Intervention Type DRUG

Specified dose on specified days

Nivolumab + FOLFOX

Group Type EXPERIMENTAL

Nivolumab

Intervention Type DRUG

Specified dose on specified days

Oxaliplatin

Intervention Type DRUG

Specified dose on specified days

Leucovorin

Intervention Type DRUG

Specified dose on specified days

Fluorouracil

Intervention Type DRUG

Specified dose on specified days

Interventions

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Nivolumab

Specified dose on specified days

Intervention Type DRUG

Ipilimumab

Specified dose on specified days

Intervention Type DRUG

Oxaliplatin

Specified dose on specified days

Intervention Type DRUG

Capecitabine

Specified dose on specified days

Intervention Type DRUG

Leucovorin

Specified dose on specified days

Intervention Type DRUG

Fluorouracil

Specified dose on specified days

Intervention Type DRUG

Other Intervention Names

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Opdivo BMS-936558 Yervoy BMS-734016

Eligibility Criteria

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Inclusion Criteria

* Male or Female at least 18 years of age
* Must have gastric cancer or gastroesophageal junction cancer that cannot be operated on and that is advanced or has spread out
* Did not receive neoadjuvant or adjuvant treatment (chemotherapy, radiotherapy, or both) for their disease within the last 6 months
* Must have full activity or, if limited, must be able to walk and carry out light activities such as light house work or office work
* Must agree to provide tumor tissue sample, either from a previous surgery or biopsy within 6 months or fresh, prior to the start of treatment in this study

Exclusion Criteria

* Presence of tumor cells in the brain or spinal cord that have not been treated
* Active known or suspected autoimmune disease
* Any serious or uncontrolled medical disorder or active infection
* Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
* Any positive test result for hepatitis B or C indicating acute or chronic infection
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ono Pharmaceutical Co. Ltd

INDUSTRY

Sponsor Role collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

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Local Institution - 0005

Los Angeles, California, United States

Site Status

Local Institution - 0001

San Francisco, California, United States

Site Status

Local Institution - 0066

Aurora, Colorado, United States

Site Status

Local Institution - 0151

Denver, Colorado, United States

Site Status

Local Institution - 0136

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

Site Status

Florida Cancer Specialists S.

Fort Myers, Florida, United States

Site Status

Local Institution - 0147

Miami, Florida, United States

Site Status

Florida Cancer Specialists

St. Petersburg, Florida, United States

Site Status

Local Institution - 0179

Marietta, Georgia, United States

Site Status

Local Institution - 0219

Arlington Heights, Illinois, United States

Site Status

Local Institution - 0120

Chicago, Illinois, United States

Site Status

Local Institution - 0021

Baltimore, Maryland, United States

Site Status

Local Institution - 0002

Boston, Massachusetts, United States

Site Status

Local Institution - 0135

Boston, Massachusetts, United States

Site Status

Local Institution - 0003

New York, New York, United States

Site Status

Local Institution - 0138

Cleveland, Ohio, United States

Site Status

Local Institution - 0186

Cleveland, Ohio, United States

Site Status

Local Institution - 0146

Eugene, Oregon, United States

Site Status

Lehigh Valley Health Network

Allentown, Pennsylvania, United States

Site Status

Local Institution - 0065

Pittsburgh, Pennsylvania, United States

Site Status

Local Institution - 0104

Nashville, Tennessee, United States

Site Status

Local Institution - 0140

Bedford, Texas, United States

Site Status

Local Institution - 0143

Dallas, Texas, United States

Site Status

Local Institution - 0213

Dallas, Texas, United States

Site Status

Local Institution - 0004

Houston, Texas, United States

Site Status

Texas Oncology-Plano East

Plano, Texas, United States

Site Status

Local Institution - 0150

Newport News, Virginia, United States

Site Status

Local Institution - 0030

Caba, Buenos Aires, Argentina

Site Status

Local Institution - 0028

Capital Federal, Buenos Aires, Argentina

Site Status

Local Institution - 0029

Capital Federal, Buenos Aires, Argentina

Site Status

Local Institution - 0026

San Miguel de Tucumán, Tucumán Province, Argentina

Site Status

Local Institution - 0027

Córdoba, , Argentina

Site Status

Local Institution - 0184

La Rioja, , Argentina

Site Status

Local Institution - 0183

Viedma, , Argentina

Site Status

Local Institution - 0202

Blacktown, New South Wales, Australia

Site Status

Local Institution - 0100

Gosford, New South Wales, Australia

Site Status

Local Institution - 0190

Southport, Queensland, Australia

Site Status

Local Institution - 0101

Adelaide, South Australia, Australia

Site Status

Local Institution - 0103

Ballarat, Victoria, Australia

Site Status

Local Institution - 0102

Shepparton, Victoria, Australia

Site Status

Local Institution - 0214

St Albans, Victoria, Australia

Site Status

Local Institution - 0099

Perth, Western Australia, Australia

Site Status

Local Institution - 0053

Salvador, Estado de Bahia, Brazil

Site Status

Local Institution - 0046

Ijuí, Rio Grande do Sul, Brazil

Site Status

Local Institution - 0047

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Local Institution - 0048

Barretos, São Paulo, Brazil

Site Status

Local Institution - 0054

São Paulo, , Brazil

Site Status

Local Institution - 0035

Edmonton, Alberta, Canada

Site Status

Local Institution - 0036

London, Ontario, Canada

Site Status

Local Institution - 0067

Toronto, Ontario, Canada

Site Status

Local Institution - 0052

Montreal, Quebec, Canada

Site Status

Local Institution - 0196

Montreal, Quebec, Canada

Site Status

Local Institution - 0051

Québec, Quebec, Canada

Site Status

Local Institution - 0068

Sherbrooke, Quebec, Canada

Site Status

Local Institution - 0034

Trois-Rivières, Quebec, Canada

Site Status

Local Institution - 0032

Temuco, Región de la Araucanía, Chile

Site Status

Local Institution - 0033

Viña del Mar, Región de Valparaíso, Chile

Site Status

Local Institution - 0058

Independencia, Santiago Metropolitan, Chile

Site Status

Local Institution - 0057

Santiago, Santiago Metropolitan, Chile

Site Status

Local Institution - 0031

Santiago, Santiago Metropolitan, Chile

Site Status

Local Institution - 0176

Beijing, Beijing Municipality, China

Site Status

Local Institution - 0178

Beijing, Beijing Municipality, China

Site Status

Local Institution - 0171

Beijing, Beijing Municipality, China

Site Status

Local Institution - 0185

Fuzhou, Fujian, China

Site Status

Local Institution - 0166

Guangzhou, Guangdong, China

Site Status

Local Institution - 0160

Harbin, Heilongjiang, China

Site Status

Local Institution - 0159

Zhengzhou, Henan, China

Site Status

Local Institution - 0173

Changsha, Hunan, China

Site Status

Local Institution - 0158

Changzhou, Jiangsu, China

Site Status

Local Institution - 0154

Nanjing, Jiangsu, China

Site Status

Local Institution - 0187

Nanjing, Jiangsu, China

Site Status

Local Institution - 0156

Changchun, Jilin, China

Site Status

Local Institution - 0155

Changchun, Jilin, China

Site Status

Local Institution - 0181

Shenyang, Liaoning, China

Site Status

Local Institution - 0182

Qingdao, Shandong, China

Site Status

Local Institution - 0165

Shanghai, Shanghai Municipality, China

Site Status

Local Institution - 0175

Shanghai, Shanghai Municipality, China

Site Status

Local Institution - 0167

Ürümqi, Xinjiang, China

Site Status

Local Institution - 0161

Hangzhou, Zhejiang, China

Site Status

Local Institution - 0168

Hangzhou, Zhejiang, China

Site Status

Local Institution - 0174

Hangzhou, , China

Site Status

Local Institution - 0172

Tianjin, , China

Site Status

Local Institution - 0025

Bogota, Cundinamarca, Colombia

Site Status

Local Institution - 0022

Bogotá, , Colombia

Site Status

Local Institution - 0024

Pasto, , Colombia

Site Status

Local Institution - 0200

Brno, , Czechia

Site Status

Local Institution - 0197

Brno, , Czechia

Site Status

Local Institution - 0077

Lille, Nord, France

Site Status

Local Institution - 0080

Caen, , France

Site Status

Local Institution - 0081

Dijon, , France

Site Status

Local Institution - 0083

Montpellier, , France

Site Status

Local Institution - 0113

Nantes, , France

Site Status

Local Institution - 0079

Nice, , France

Site Status

Local Institution - 0078

Paris, , France

Site Status

Local Institution - 0119

Plérin, , France

Site Status

Local Institution - 0092

Mainz, Rhineland-Palatinate, Germany

Site Status

Local Institution - 0094

Berlin, , Germany

Site Status

Local Institution - 0095

Cologne, , Germany

Site Status

Local Institution - 0089

Dresden, , Germany

Site Status

Local Institution - 0188

Düsseldorf, , Germany

Site Status

Local Institution - 0091

Essen, , Germany

Site Status

Local Institution - 0096

Freiburg im Breisgau, , Germany

Site Status

Local Institution - 0093

Hamburg, , Germany

Site Status

Local Institution - 0149

München, , Germany

Site Status

Local Institution - 0017

Nea Kifissia, Attikí, Greece

Site Status

Local Institution - 0056

Athens, , Greece

Site Status

Local Institution - 0019

Ioannina, , Greece

Site Status

Local Institution - 0018

Pátrai, , Greece

Site Status

Local Institution - 0191

Hong Kong, , Hong Kong

Site Status

Local Institution - 0195

Hong Kong, , Hong Kong

Site Status

Local Institution - 0008

Budapest, , Hungary

Site Status

Local Institution - 0007

Budapest, , Hungary

Site Status

Local Institution - 0108

Debrecen, , Hungary

Site Status

Local Institution - 0118

Haifa, , Israel

Site Status

Local Institution - 0116

Jerusalem, , Israel

Site Status

Local Institution - 0115

Petah Tikva, , Israel

Site Status

Local Institution - 0117

Ramat Gan, , Israel

Site Status

Local Institution - 0114

Tel Aviv, , Israel

Site Status

Local Institution - 0063

Pisa, Tuscany, Italy

Site Status

Local Institution - 0062

Bergamo, , Italy

Site Status

Local Institution - 0205

Modena, , Italy

Site Status

Local Institution - 0061

Napoli, , Italy

Site Status

Local Institution - 0059

Roma, , Italy

Site Status

Local Institution - 0064

San Giovanni Rotondo, , Italy

Site Status

Local Institution - 0130

Nagoya, Aichi-ken, Japan

Site Status

Local Institution - 0128

Chiba, Chiba, Japan

Site Status

Local Institution - 0125

Kashiwa, Chiba, Japan

Site Status

Local Institution - 0137

Sapporo, Hokkaido, Japan

Site Status

Local Institution - 0127

Kita-Gun, Kagawa-ken, Japan

Site Status

Local Institution - 0124

Suita-shi, Osaka, Japan

Site Status

Local Institution - 0123

Kitaadachi-gun, Saitama, Japan

Site Status

Local Institution - 0126

Chuo-ku, Tokyo, Japan

Site Status

Local Institution - 0122

Minato-ku, Tokyo, Japan

Site Status

Local Institution - 0129

Tokyo, , Japan

Site Status

Local Institution - 0215

Mexico City, Mexico City, Mexico

Site Status

Local Institution - 0217

Toluca, State of Mexico, Mexico

Site Status

Local Institution - 0216

Querétaro, , Mexico

Site Status

Local Institution - 0189

Lima, , Peru

Site Status

Local Institution - 0039

Lima, , Peru

Site Status

Local Institution - 0037

Lima, , Peru

Site Status

Local Institution - 0139

Lima, , Peru

Site Status

Local Institution - 0016

Lublin, , Poland

Site Status

Local Institution - 0013

Tarnobrzeg, , Poland

Site Status

Local Institution - 0014

Warsaw, , Poland

Site Status

Local Institution - 0043

Lisbon, , Portugal

Site Status

Local Institution - 0210

Porto, , Portugal

Site Status

Local Institution - 0041

Craiova, Dolj, Romania

Site Status

Local Institution - 0012

Baia Mare, Jud Maramures, Romania

Site Status

Local Institution - 0040

Bucharest, , Romania

Site Status

Local Institution - 0042

Cluj-Napoca, , Romania

Site Status

Local Institution - 0055

Suceava, , Romania

Site Status

Local Institution - 0071

Chelyabinsk, , Russia

Site Status

Local Institution - 0086

Moscow, , Russia

Site Status

Local Institution - 0069

Moscow, , Russia

Site Status

Local Institution - 0105

Moscow, , Russia

Site Status

Local Institution - 0085

Saint Petersburg, , Russia

Site Status

Local Institution - 0193

Singapore, Central Singapore, Singapore

Site Status

Local Institution - 0194

Singapore, , Singapore

Site Status

Local Institution - 0132

Seoul, , South Korea

Site Status

Local Institution - 0131

Seoul, , South Korea

Site Status

Local Institution - 0050

Badajoz, , Spain

Site Status

Local Institution - 0209

Badalona-barcelona, , Spain

Site Status

Local Institution - 0044

Barcelona, , Spain

Site Status

Local Institution - 0049

Pozuelo de Alarcon, Madrid, , Spain

Site Status

Local Institution - 0045

Valencia, , Spain

Site Status

Local Institution - 0212

Zaragoza, , Spain

Site Status

Local Institution - 0148

Tainan City, , Taiwan

Site Status

Local Institution - 0133

Taipei, , Taiwan

Site Status

Local Institution - 0134

Taoyuan, , Taiwan

Site Status

Local Institution - 0203

Ankara, , Turkey (Türkiye)

Site Status

Local Institution - 0211

Ankara, , Turkey (Türkiye)

Site Status

Local Institution - 0201

Antalya, , Turkey (Türkiye)

Site Status

Local Institution - 0208

Diyarbakır, , Turkey (Türkiye)

Site Status

Local Institution - 0207

Edrine, , Turkey (Türkiye)

Site Status

Local Institution - 0074

London, Greater London, United Kingdom

Site Status

Local Institution - 0073

Manchester, Greater Manchester, United Kingdom

Site Status

Local Institution - 0076

Nottingham, Nottinghamshire, United Kingdom

Site Status

Local Institution - 0075

Sutton, Surrey, United Kingdom

Site Status

Local Institution - 0072

Southampton, , United Kingdom

Site Status

Countries

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United States Argentina Australia Brazil Canada Chile China Colombia Czechia France Germany Greece Hong Kong Hungary Israel Italy Japan Mexico Peru Poland Portugal Romania Russia Singapore South Korea Spain Taiwan Turkey (Türkiye) United Kingdom

References

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Lin D, Quan W, Garretson M, Chirikov V, Chen C, Singh P, Davis C, Sugarman R. Q-TWiST analysis of first-line nivolumab plus chemotherapy versus chemotherapy in patients with advanced gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma from CheckMate 649: 4-year follow-up results. Gastric Cancer. 2025 Sep;28(5):935-944. doi: 10.1007/s10120-025-01634-6. Epub 2025 Jul 9.

Reference Type DERIVED
PMID: 40632415 (View on PubMed)

Janjigian YY, Ajani JA, Moehler M, Shen L, Garrido M, Gallardo C, Wyrwicz L, Yamaguchi K, Cleary JM, Elimova E, Karamouzis M, Bruges R, Skoczylas T, Bragagnoli A, Liu T, Tehfe M, Zander T, Kowalyszyn R, Pazo-Cid R, Schenker M, Feeny K, Wang R, Lei M, Chen C, Nathani R, Shitara K. First-Line Nivolumab Plus Chemotherapy for Advanced Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma: 3-Year Follow-Up of the Phase III CheckMate 649 Trial. J Clin Oncol. 2024 Jun 10;42(17):2012-2020. doi: 10.1200/JCO.23.01601. Epub 2024 Feb 21.

Reference Type DERIVED
PMID: 38382001 (View on PubMed)

Moehler M, Xiao H, Blum SI, Elimova E, Cella D, Shitara K, Ajani JA, Janjigian YY, Garrido M, Shen L, Yamaguchi K, Liu T, Schenker M, Kowalyszyn R, Bragagnoli AC, Bruges R, Montesarchio V, Pazo-Cid R, Hunter S, Davenport E, Wang J, Kondo K, Li M, Wyrwicz L. Health-Related Quality of Life With Nivolumab Plus Chemotherapy Versus Chemotherapy in Patients With Advanced Gastric/Gastroesophageal Junction Cancer or Esophageal Adenocarcinoma From CheckMate 649. J Clin Oncol. 2023 Dec 10;41(35):5388-5399. doi: 10.1200/JCO.23.00170. Epub 2023 Sep 15.

Reference Type DERIVED
PMID: 37713657 (View on PubMed)

Janjigian YY, Shitara K, Moehler M, Garrido M, Salman P, Wyrwicz L, Yamaguchi K, Skoczylas T, Bragagnoli AC, Liu T, Schenker M, Yanez P, Tehfe M, Kowalyszyn R, Karamouzis MV, Bruges R, Zander T, Pazo-Cid R, Hitre E, Feeney K, Cleary JM, Poulart V, Cullen D, Lei M, Xiao H, Kondo K, Li M, Ajani JA. A plain language summary of the CheckMate 649 study: nivolumab in combination with chemotherapy compared to chemotherapy alone for untreated advanced or metastatic cancer of the stomach or esophagus. Future Oncol. 2023 Apr;19(11):739-752. doi: 10.2217/fon-2022-1149. Epub 2023 Mar 15.

Reference Type DERIVED
PMID: 36919706 (View on PubMed)

Liu T, Bai Y, Lin X, Li W, Wang J, Zhang X, Pan H, Bai C, Bai L, Cheng Y, Zhang J, Zhong H, Ba Y, Hu W, Xu R, Guo W, Qin S, Yang N, Lu J, Shitara K, Lei M, Li M, Bao N, Chen T, Shen L. First-line nivolumab plus chemotherapy vs chemotherapy in patients with advanced gastric, gastroesophageal junction and esophageal adenocarcinoma: CheckMate 649 Chinese subgroup analysis. Int J Cancer. 2023 Feb 15;152(4):749-760. doi: 10.1002/ijc.34296. Epub 2022 Oct 31.

Reference Type DERIVED
PMID: 36121651 (View on PubMed)

Janjigian YY, Shitara K, Moehler M, Garrido M, Salman P, Shen L, Wyrwicz L, Yamaguchi K, Skoczylas T, Campos Bragagnoli A, Liu T, Schenker M, Yanez P, Tehfe M, Kowalyszyn R, Karamouzis MV, Bruges R, Zander T, Pazo-Cid R, Hitre E, Feeney K, Cleary JM, Poulart V, Cullen D, Lei M, Xiao H, Kondo K, Li M, Ajani JA. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021 Jul 3;398(10294):27-40. doi: 10.1016/S0140-6736(21)00797-2. Epub 2021 Jun 5.

Reference Type DERIVED
PMID: 34102137 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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2016-001018-76

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CA209-649

Identifier Type: -

Identifier Source: org_study_id

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