Gastric CancerPhase 3CheckMate649NCT02872116

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

A Phase 3 study testing Nivolumab, Ipilimumab and Oxaliplatin in people with Gastric Cancer and Gastroesophageal Junction Cancer, run by Bristol-Myers Squibb at 179 sites in 29 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Gastric Cancer, Gastroesophageal Junction Cancer, Esophageal Adenocarcinoma
What is being tested?: Nivolumab, Ipilimumab and Oxaliplatin
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 2,031 participants
Where: 179 sitesin 29 countries
Study dates: 12 Oct 2016to 6 Jun 2024
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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
Other protocol-defined inclusion/exclusion criteria apply

Trial locations and contacts

179 sites in 29 countries.

Country

City, postcode or hospital

179 sites in 29 countries

United States27 sites

Lehigh Valley Health Network
Allentown, Pennsylvania, 18105
Local Institution - 0219
Arlington Heights, Illinois, 60005
Local Institution - 0066
Aurora, Colorado, 80045
Local Institution - 0021
Baltimore, Maryland, 21224
Local Institution - 0140
Bedford, Texas, 76022
Local Institution - 0002
Boston, Massachusetts, 02215
Local Institution - 0135
Boston, Massachusetts, 02215
Local Institution - 0120
Chicago, Illinois, 60611
Local Institution - 0138
Cleveland, Ohio, 44106
Local Institution - 0186
Cleveland, Ohio, 44195
Local Institution - 0143
Dallas, Texas, 75230
Local Institution - 0213
Dallas, Texas, 75246
Local Institution - 0151
Denver, Colorado, 80218
Local Institution - 0146
Eugene, Oregon, 97401
Florida Cancer Specialists S.
Fort Myers, Florida, 33901
Local Institution - 0004
Houston, Texas, 77030
Local Institution - 0005
Los Angeles, California, 90033
Local Institution - 0179
Marietta, Georgia, 30060
Local Institution - 0147
Miami, Florida, 33176
Local Institution - 0104
Nashville, Tennessee, 37203
Local Institution - 0003
New York, New York, 10065
Local Institution - 0150
Newport News, Virginia, 23606
Local Institution - 0065
Pittsburgh, Pennsylvania, 15212
Texas Oncology-Plano East
Plano, Texas, 75075-7787
Local Institution - 0001
San Francisco, California, 94115-1932
Florida Cancer Specialists
St. Petersburg, Florida, 33705
Local Institution - 0136
Washington D.C., District of Columbia, 20007

Other trials in United States

China22 sites

Local Institution - 0176
Beijing, Beijing Municipality, 100001
Local Institution - 0178
Beijing, Beijing Municipality, 100032
Local Institution - 0171
Beijing, Beijing Municipality, 100142
Local Institution - 0156
Changchun, Jilin, 130012
Local Institution - 0155
Changchun, Jilin, 130021
Local Institution - 0173
Changsha, Hunan, 410013
Local Institution - 0158
Changzhou, Jiangsu, 213003
Local Institution - 0185
Fuzhou, Fujian, 350000
Local Institution - 0166
Guangzhou, Guangdong, 510060
Local Institution - 0161
Hangzhou, Zhejiang, 310009
Local Institution - 0168
Hangzhou, Zhejiang, 310022
Local Institution - 0174
Hangzhou, 310016
Local Institution - 0160
Harbin, Heilongjiang, 150081
Local Institution - 0154
Nanjing, Jiangsu, 210002
Local Institution - 0187
Nanjing, Jiangsu, 210008
Local Institution - 0182
Qingdao, Shandong, 266061
Local Institution - 0165
Shanghai, Shanghai Municipality, 200032
Local Institution - 0175
Shanghai, Shanghai Municipality, 200032
Local Institution - 0181
Shenyang, Liaoning, 110046
Local Institution - 0172
Tianjin, 300060
Local Institution - 0167
Ürümqi, Xinjiang, 830011
Local Institution - 0159
Zhengzhou, Henan, 450008

Other trials in China

Japan10 sites

Local Institution - 0128
Chiba, Chiba, 260-8717
Local Institution - 0126
Chuo-ku, Tokyo, 1040045
Local Institution - 0125
Kashiwa, Chiba, 277-8577
Local Institution - 0127
Kita-Gun, Kagawa-ken, 7610793
Local Institution - 0123
Kitaadachi-gun, Saitama, 3620806
Local Institution - 0122
Minato-ku, Tokyo, 1058470
Local Institution - 0130
Nagoya, Aichi-ken, 4648681
Local Institution - 0137
Sapporo, Hokkaido, 0608648
Local Institution - 0124
Suita-shi, Osaka, 565-0871
Local Institution - 0129
Tokyo, 1358550

Other trials in Japan

Germany9 sites

Local Institution - 0094
Berlin, 13353
Local Institution - 0095
Cologne, 50937
Local Institution - 0089
Dresden, 01307
Local Institution - 0188
Düsseldorf, 40225
Local Institution - 0091
Essen, 45122
Local Institution - 0096
Freiburg im Breisgau, 79106
Local Institution - 0093
Hamburg, 20251
Local Institution - 0092
Mainz, Rhineland-Palatinate, 55131
Local Institution - 0149
München, 81675

Other trials in Germany

Australia8 sites

Local Institution - 0101
Adelaide, South Australia, 5000
Local Institution - 0103
Ballarat, Victoria, 3350
Local Institution - 0202
Blacktown, New South Wales, 2148
Local Institution - 0100
Gosford, New South Wales, 2250
Local Institution - 0099
Perth, Western Australia, 6150
Local Institution - 0102
Shepparton, Victoria, 3630
Local Institution - 0190
Southport, Queensland, 4215
Local Institution - 0214
St Albans, Victoria, 3021

Other trials in Australia

Canada8 sites

Local Institution - 0035
Edmonton, Alberta, T6G 1Z2
Local Institution - 0036
London, Ontario, N6A 4L6
Local Institution - 0052
Montreal, Quebec, H2X 3E4
Local Institution - 0196
Montreal, Quebec, H3T 1E2
Local Institution - 0051
Québec, Quebec, G1J 1Z4
Local Institution - 0068
Sherbrooke, Quebec, J1H 5N4
Local Institution - 0067
Toronto, Ontario, M5G 2M9
Local Institution - 0034
Trois-Rivières, Quebec, G8Z 3R9

Other trials in Canada

France8 sites

Local Institution - 0080
Caen, 14000
Local Institution - 0081
Dijon, 21000
Local Institution - 0077
Lille, Nord, 59000
Local Institution - 0083
Montpellier, 34090
Local Institution - 0113
Nantes, 44000
Local Institution - 0079
Nice, 06189
Local Institution - 0078
Paris, 75012
Local Institution - 0119
Plérin, 22190

Other trials in France

Argentina7 sites

Local Institution - 0030
Caba, Buenos Aires, 1426
Local Institution - 0028
Capital Federal, Buenos Aires, 1264
Local Institution - 0029
Capital Federal, Buenos Aires, 1280
Local Institution - 0027
Córdoba, 5000
Local Institution - 0184
La Rioja, 5300
Local Institution - 0026
San Miguel de Tucumán, Tucumán Province, 4000
Local Institution - 0183
Viedma, 8500

Other trials in Argentina

Italy6 sites

Local Institution - 0062
Bergamo, 24127
Local Institution - 0205
Modena, 41124
Local Institution - 0061
Naples, 80131
Local Institution - 0063
Pisa, Tuscany, 56126
Local Institution - 0059
Roma, 00168
Local Institution - 0064
San Giovanni Rotondo, 71013

Other trials in Italy

Spain6 sites

Local Institution - 0050
Badajoz, 06006
Local Institution - 0209
Badalona-barcelona, 08916
Local Institution - 0044
Barcelona, 08035
Local Institution - 0049
Pozuelo de Alarcon, Madrid, 28223
Local Institution - 0045
Valencia, 46010
Local Institution - 0212
Zaragoza, 50009

Other trials in Spain

Brazil5 sites

Local Institution - 0048
Barretos, São Paulo, 14784-400
Local Institution - 0046
Ijuí, Rio Grande do Sul, 98700-000
Local Institution - 0047
Porto Alegre, Rio Grande do Sul, 90035-903
Local Institution - 0053
Salvador, Estado de Bahia, 41950-610
Local Institution - 0054
São Paulo, 01246-000

Other trials in Brazil

Chile5 sites

Local Institution - 0058
Independencia, Santiago Metropolitan
Local Institution - 0057
Santiago, Santiago Metropolitan, 8320000
Local Institution - 0031
Santiago, Santiago Metropolitan
Local Institution - 0032
Temuco, Araucania, 4800827
Local Institution - 0033
Viña del Mar, Valparaiso, 2540364

Other trials in Chile

Israel5 sites

Local Institution - 0118
Haifa, 31096
Local Institution - 0116
Jerusalem, 91120
Local Institution - 0115
Petah Tikva, 49100
Local Institution - 0117
Ramat Gan, 52621
Local Institution - 0114
Tel Aviv, 64239

Other trials in Israel

Romania5 sites

Local Institution - 0012
Baia Mare, Jud Maramures, 430291
Local Institution - 0040
Bucharest, 022328
Local Institution - 0042
Cluj-Napoca, 400015
Local Institution - 0041
Craiova, Dolj, 200542
Local Institution - 0055
Suceava, 720237

Other trials in Romania

Russia5 sites

Local Institution - 0071
Chelyabinsk, 454048
Local Institution - 0086
Moscow, 115478
Local Institution - 0069
Moscow, 121309
Local Institution - 0105
Moscow, 125284
Local Institution - 0085
Saint Petersburg, 198255

Other trials in Russia

Turkey (Türkiye)5 sites

Local Institution - 0203
Ankara, 06800
Local Institution - 0211
Ankara, 06800
Local Institution - 0201
Antalya, 07070
Local Institution - 0208
Diyarbakır, 21280
Local Institution - 0207
Edrine, 22010

Other trials in Turkey (Türkiye)

United Kingdom5 sites

Local Institution - 0074
London, Greater London, SW3 6JJ
Local Institution - 0073
Manchester, Greater Manchester, M20 4BX
Local Institution - 0076
Nottingham, Nottinghamshire, NG5 1PB
Local Institution - 0072
Southampton, SO16 6YD
Local Institution - 0075
Sutton, Surrey, SM2 5PT

Other trials in United Kingdom

Greece4 sites

Local Institution - 0056
Athens, 11526
Local Institution - 0019
Ioannina, 45500
Local Institution - 0017
Nea Kifissia, Attikí, 14564
Local Institution - 0018
Pátrai, 26504

Other trials in Greece

Peru4 sites

Local Institution - 0189
Lima, 27
Local Institution - 0039
Lima, 34
Local Institution - 0037
Lima, LIMA 31
Local Institution - 0139
Lima, Lima 41

Other trials in Peru

Colombia3 sites

Local Institution - 0025
Bogota, Cundinamarca, 0
Local Institution - 0022
Bogotá, 0
Local Institution - 0024
Pasto, 0

Other trials in Colombia

Hungary3 sites

Local Institution - 0008
Budapest, 1083
Local Institution - 0007
Budapest, 1122
Local Institution - 0108
Debrecen, 0

Other trials in Hungary

Mexico3 sites

Local Institution - 0215
Mexico City, Mexico City, 03100
Local Institution - 0216
Querétaro, 76090
Local Institution - 0217
Toluca, State of Mexico, 50120

Other trials in Mexico

Poland3 sites

Local Institution - 0016
Lublin, 20-081
Local Institution - 0013
Tarnobrzeg, 39-400
Local Institution - 0014
Warsaw, 02-034

Other trials in Poland

Taiwan3 sites

Local Institution - 0148
Tainan, 70403
Local Institution - 0133
Taipei, 11217
Local Institution - 0134
Taoyuan County, 333

Other trials in Taiwan

Czechia2 sites

Local Institution - 0200
Brno, 625 00
Local Institution - 0197
Brno, 656 53

Other trials in Czechia

Hong Kong2 sites

Local Institution - 0191
Hong Kong, 0
Local Institution - 0195
Hong Kong, 0

Other trials in Hong Kong

Portugal2 sites

Local Institution - 0043
Lisbon, 1649-035
Local Institution - 0210
Porto, 4200-072

Other trials in Portugal

Singapore2 sites

Local Institution - 0193
Singapore, Central Singapore, 168583
Local Institution - 0194
Singapore, 119228

Other trials in Singapore

South Korea2 sites

Local Institution - 0132
Seoul, 03722
Local Institution - 0131
Seoul, 05505

Other trials in South Korea

About this study

Official title: A Randomized, Multicenter, Open-Label, Phase 3 Study of Nivolumab Plus Ipilimumab or Nivolumab in Combination With Oxaliplatin Plus Fluoropyrimidine Versus Oxaliplatin Plus Fluoropyrimidine in Subjects With Previously Untreated Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer

Conditions: Gastric Cancer, Gastroesophageal Junction Cancer, Esophageal Adenocarcinoma
Being tested: Nivolumab, Ipilimumab, Oxaliplatin, Capecitabine, Leucovorin
Medical subject headings: Stomach Neoplasms, Adenocarcinoma Of Esophagus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

NivolumabDrug
Also called Opdivo, BMS-936558
Specified dose on specified days
IpilimumabDrug
Also called Yervoy, BMS-734016
Specified dose on specified days
OxaliplatinDrug
Specified dose on specified days
CapecitabineDrug
Specified dose on specified days
LeucovorinDrug
Specified dose on specified days
FluorouracilDrug
Specified dose on specified days

Study groups in NCT02872116
Study group	Role	What they receive
Nivolumab + Ipilimumab	Experimental	Nivolumab + Ipilimumab for 4 doses, followed by Nivolumab monotherapy Enrollment is closed for this arm Receives: Drug: Nivolumab; Drug: Ipilimumab
XELOX (Oxaliplatin + Capecitabine)	Active comparator	Not described Receives: Drug: Oxaliplatin; Drug: Capecitabine
FOLFOX (Oxaliplatin + Leucovorin + Fluorouracil)	Active comparator	Not described Receives: Drug: Oxaliplatin; Drug: Leucovorin; Drug: Fluorouracil
Nivolumab + XELOX	Experimental	Not described Receives: Drug: Nivolumab; Drug: Oxaliplatin; Drug: Capecitabine
Nivolumab + FOLFOX	Experimental	Not described Receives: Drug: Nivolumab; Drug: Oxaliplatin; Drug: Leucovorin; Drug: Fluorouracil

What is being measured

The primary outcome is the main question the study is designed to answer.

Overall Survival (OS) in Participants Treated With Nivolumab Plus Chemotherapy vs Chemotherapy With PD-L1 CPS ≥ 5
Overall survival (OS), defined as the time from randomization to the time of death, in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy with PD-L1 CPS (combined positive score) ≥ 5. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.
Measured: From the date of randomization up to the date of death, up to approximately 17 months
Progression Free Survival (PFS) in Participants Treated With Nivolumab Plus Chemotherapy vs Chemotherapy With PD-L1 CPS ≥ 5
Progression Free Survival (PFS) is defined as the time from randomization to the date of the first documented PD or death due to any cause. PD is determined by blinded independent committee review (BICR) per RECIST1.1 criteria in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy with PD-L1 CPS ≥ 5. Progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking in reference the smallest sum on study that also demonstrated an absolute increase of at least 5 mm. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.
Measured: From randomization to the date of the first documented progressive disease (PD) per BICR or death due to any cause (up to approximately 10 months)

Secondary outcomes (7)

OS in Participants Treated With Nivolumab Plus Chemotherapy vs Chemotherapy
Overall survival (OS), defined as the time from randomization to the time of death, in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy with PD-L1 CPS ≥ 1, 10, and all randomized participants. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.
Measured: From the date of randomization up to the date of death, up to approximately 17 months
PFS in Participants Treated With Nivolumab Plus Chemotherapy vs Chemotherapy
Progression free survival (PFS), defined as the time from randomization to the date of the first documented progressive disease (PD) or death due to any cause, in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy by BICR per RECIST1.1 in participants with PD-L1 CPS ≥ 10, 1, or all randomized subjects. Progreessive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking in reference the smallest sum on study that also demonstrated an absolute increase of at least 5 mm. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.
Measured: From randomization to the date of the first documented progressive disease (PD) per BICR or death due to any cause (up to approximately 10 months)
Objective Response Rate in Participants Treated With Nivolumab Plus Chemotherapy vs Chemotherapy
Objective response rate (ORR) as assessed by BICR in participants with PD-L1 CPS ≥ 10, 5, 1, or all randomized participants. ORR is a percentage of participants determined by the number of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of measurable participants with target lesion at baseline. BOR is defined as the best response designation as determined by the BICR, recorded between the date of randomization and the date of objectively documented progression (per RECIST 1.1 as determined by the BICR) or the date of subsequent anti-cancer therapy, whichever occurs first. CR is defined as the disappearance of all target lesions. PR is define as at 30% decrease in the sum of diameters of target lesions. The 806 chemotherapy treated participants are split into two separate arms (Arm 2a and Arm 2b) to act as comparison groups to the other treatment arms.
Measured: From randomization to the date of objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first (up to approximately 43 months)
Time to Symptom Deterioration (TTSD) in Participants Treated With Nivolumab Plus Chemotherapy vs Chemotherapy
TTSD is defined as the the time from randomization until a clinically meaningful decline from baseline in Gastric Cancer Subscale (GaCS) score. A clinically meaningful deterioration is defined as a reduction of 8.2 points in the GaCS score. Subjects who do not deteriorate will be censored at the time of their last GACS assessment. Subjects without baseline GaCS assessment will be censored on the randomization date. Those with baseline GaCS, who do not have any GaCS assessments after randomization will be censored on the day after randomization.
Measured: From randomization until a clinically meaningful decline from baseline in GaCS score (approximately 10 months)
OS in Participants Treated With Nivolumab Plus Ipilimumab vs Chemotherapy
Overall survival (OS), defined as the time from randomization to the time of death, in participants treated with Nivolumab plus Ipilimumab vs Chemotherapy with PD-L1 CPS (combined positive score) ≥ 1, 5, 10, and all randomized participants. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.
Measured: From the date of randomization up to the date of death, up to approximately 14 months
PFS in Participants Treated With Nivolumab Plus Ipilimumab vs Chemotherapy
Progression Free Survival (PFS) is defined as the time from randomization to the date of the first documented PD or death due to any cause. PD is determined by blinded independent committee review (BICR) per RECIST1.1 criteria in participants treated with Nivolumab plus Ipilumab vs Chemotherapy with PD-L1 CPS ≥ 10, 5, 1 or all randomized participants. Progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking in reference the smallest sum on study that also demonstrated an absolute increase of at least 5 mm. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.
Measured: From randomization to the date of the first documented progressive disease (PD) per BICR or death due to any cause (up to approximately 9 months)
Objective Response Rate in Participants Treated With Nivolumab Plus Ipilimumab vs Chemotherapy
Objective response rate (ORR) as assessed by BICR in participants with PD-L1 CPS ≥ 10, 5, 1, or all randomized participants. ORR is a percentage of participants determined by the number of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of measurable participants with target lesion at baseline. BOR is defined as the best response designation as determined by the BICR, recorded between the date of randomization and the date of objectively documented progression (per RECIST 1.1 as determined by the BICR) or the date of subsequent anti-cancer therapy, whichever occurs first. CR is defined as the disappearance of all target lesions. PR is define as at 30% decrease in the sum of diameters of target lesions. The 806 chemotherapy treated participants are split into two separate arms (Arm 2a and Arm 2b) to act as comparison groups to the other treatment arms.
Measured: From randomization to the date of objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first (up to approximately 43 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

12 Oct 20166 Jun 2024

First posted19 Aug 2016 (estimated)
Study start12 Oct 2016
Primary completion27 May 2020
Study completion6 Jun 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (6)Papers the sponsor has linked to this study.
Other trials for Gastric CancerStudies of the same condition, open and under way.
More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 2,031 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02872116
Sponsor's protocol ID: CA209-649
Other IDs: 2016-001018-76, 2016
Acronym: CheckMate649
Status last verified: Jul 2025
First submitted: 16 Aug 2016
Last updated: 7 Aug 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

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.
PubMed 40632415
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.
PubMed 38382001
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.
PubMed 37713657
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.
PubMed 36919706
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.
PubMed 36121651
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.
PubMed 34102137

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RecruitingPhase 1/2
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Study at a glance

From the registry record, last updated by the sponsor on 7 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Multicenter, Open-Label, Phase 3 Study of Nivolumab Plus Ipilimumab or Nivolumab in Combination With Oxaliplatin Plus Fluoropyrimidine Versus Oxaliplatin Plus Fluoropyrimidine in Subjects With Previously Untreated Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer
ClinicalTrials.gov ID: NCT02872116
Acronym / sponsor ID: CheckMate649 / CA209-649
Conditions: Gastric Cancer, Gastroesophageal Junction Cancer, Esophageal Adenocarcinoma
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 2,031 participants (actual)
Lead sponsor: Bristol-Myers SquibbIndustry (pharma, biotech, devices)
Collaborators: Ono Pharmaceutical Co., Ltd.
Study start: 12 Oct 2016 (actual)
Primary completion: 27 May 2020 (actual)
Study completion: 6 Jun 2024 (actual)
First posted: 19 Aug 2016 (estimated)
Results: Posted 28 Jun 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 5

Arm	Type	Receives
Nivolumab + Ipilimumab	Experimental	Drug: Nivolumab, Drug: IpilimumabNivolumab + Ipilimumab for 4 doses, followed by Nivolumab monotherapy Enrollment is closed for this arm
XELOX (Oxaliplatin + Capecitabine)	Active comparator	Drug: Oxaliplatin, Drug: Capecitabine
FOLFOX (Oxaliplatin + Leucovorin + Fluorouracil)	Active comparator	Drug: Oxaliplatin, Drug: Leucovorin, Drug: Fluorouracil
Nivolumab + XELOX	Experimental	Drug: Nivolumab, Drug: Oxaliplatin, Drug: Capecitabine
Nivolumab + FOLFOX	Experimental	Drug: Nivolumab, Drug: Oxaliplatin, Drug: Leucovorin, Drug: Fluorouracil

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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

Key exclusion criteria (6 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
NivolumabAlso: Opdivo, BMS-936558Specified dose on specified days	Drug	Nivolumab + FOLFOX, Nivolumab + Ipilimumab, Nivolumab + XELOX
IpilimumabAlso: Yervoy, BMS-734016Specified dose on specified days	Drug	Nivolumab + Ipilimumab
OxaliplatinSpecified dose on specified days	Drug	FOLFOX (Oxaliplatin + Leucovorin + Fluorouracil), Nivolumab + FOLFOX, Nivolumab + XELOX, XELOX (Oxaliplatin + Capecitabine)
CapecitabineSpecified dose on specified days	Drug	Nivolumab + XELOX, XELOX (Oxaliplatin + Capecitabine)
LeucovorinSpecified dose on specified days	Drug	FOLFOX (Oxaliplatin + Leucovorin + Fluorouracil), Nivolumab + FOLFOX
FluorouracilSpecified dose on specified days	Drug	FOLFOX (Oxaliplatin + Leucovorin + Fluorouracil), Nivolumab + FOLFOX

Primary outcome

Overall Survival (OS) in Participants Treated With Nivolumab Plus Chemotherapy vs Chemotherapy With PD-L1 CPS ≥ 5
Time frame: From the date of randomization up to the date of death, up to approximately 17 months
Overall survival (OS), defined as the time from randomization to the time of death, in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy with PD-L1 CPS (combined positive score) ≥ 5. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.
Progression Free Survival (PFS) in Participants Treated With Nivolumab Plus Chemotherapy vs Chemotherapy With PD-L1 CPS ≥ 5
Time frame: From randomization to the date of the first documented progressive disease (PD) per BICR or death due to any cause (up to approximately 10 months)
Progression Free Survival (PFS) is defined as the time from randomization to the date of the first documented PD or death due to any cause. PD is determined by blinded independent committee review (BICR) per RECIST1.1 criteria in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy with PD-L1 CPS ≥ 5. Progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking in reference the smallest sum on study that also demonstrated an absolute increase of at least 5 mm. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.

7 secondary outcomes

OS in Participants Treated With Nivolumab Plus Chemotherapy vs Chemotherapy
Time frame: From the date of randomization up to the date of death, up to approximately 17 months
PFS in Participants Treated With Nivolumab Plus Chemotherapy vs Chemotherapy
Time frame: From randomization to the date of the first documented progressive disease (PD) per BICR or death due to any cause (up to approximately 10 months)
Objective Response Rate in Participants Treated With Nivolumab Plus Chemotherapy vs Chemotherapy
Time frame: From randomization to the date of objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first (up to approximately 43 months)
Time to Symptom Deterioration (TTSD) in Participants Treated With Nivolumab Plus Chemotherapy vs Chemotherapy
Time frame: From randomization until a clinically meaningful decline from baseline in GaCS score (approximately 10 months)
OS in Participants Treated With Nivolumab Plus Ipilimumab vs Chemotherapy
Time frame: From the date of randomization up to the date of death, up to approximately 14 months
PFS in Participants Treated With Nivolumab Plus Ipilimumab vs Chemotherapy
Time frame: From randomization to the date of the first documented progressive disease (PD) per BICR or death due to any cause (up to approximately 9 months)
Objective Response Rate in Participants Treated With Nivolumab Plus Ipilimumab vs Chemotherapy
Time frame: From randomization to the date of objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first (up to approximately 43 months)

Results and safety

Results posted to the registry on 28 Jun 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Arm 1: Nivolumab + Chemotherapy (XELOX or FOLFOX)	789	782
Arm 2: Chemotherapy (XELOX or FOLFOX)	833	806
Arm 3: Nivolumab + Ipilimumab	409	403

Primary outcome: Overall Survival (OS) in Participants Treated With Nivolumab Plus Chemotherapy vs Chemotherapy With PD-L1 CPS ≥ 5

Time frame: From the date of randomization up to the date of death, up to approximately 17 months. Median (95% Confidence Interval). Unit: Months

Measure	Arm 1: Nivolumab + Chemotherapy (XELOX or FOLFOX) n = 473	Arm 2a: Chemotherapy (XELOX or FOLFOX) n = 482
Value	14.39 (13.11 to 16.23)	11.10 (10.02 to 12.09)

Arm 1: Nivolumab + Chemotherapy (XELOX or FOLFOX) vs Arm 2a: Chemotherapy (XELOX or FOLFOX): Hazard Ratio (HR): 0.71 (98.4% CI 0.59 to 0.86), p <0.0001, Log Rank

Population analysed: All randomized participants with PD-L1 CPS ≥ 5

Primary outcome: Progression Free Survival (PFS) in Participants Treated With Nivolumab Plus Chemotherapy vs Chemotherapy With PD-L1 CPS ≥ 5

Time frame: From randomization to the date of the first documented progressive disease (PD) per BICR or death due to any cause (up to approximately 10 months). Median (95% Confidence Interval). Unit: Months

Measure	Arm 1: Nivolumab + Chemotherapy (XELOX or FOLFOX) n = 473	Arm 2a: Chemotherapy (XELOX or FOLFOX) n = 482
Value	7.69 (7.03 to 9.17)	6.05 (5.55 to 6.90)

Arm 1: Nivolumab + Chemotherapy (XELOX or FOLFOX) vs Arm 2a: Chemotherapy (XELOX or FOLFOX): Hazard Ratio (HR): 0.68 (98% CI 0.56 to 0.81), p <0.0001, Log Rank

Population analysed: All randomized participants with PD-L1 CPS ≥ 5

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: All-cause mortality was assessed from date of randomization to study completion (up to approximately 5 years). Serious Adverse events and other adverse events were assessed from date of first dose to 100 days following date of last dose (up to approximately 5 years).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Nivo + Chemo	529 of 782 (67.6%)	763 of 782 (97.6%)	691 of 782
Chemo	474 of 806 (58.8%)	756 of 806 (93.8%)	741 of 806
Nivo + Ipi	307 of 403 (76.2%)	369 of 403 (91.6%)	361 of 403

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 40632415Lin 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.
Derived from this study: PubMed 38382001Janjigian 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.
Derived from this study: PubMed 37713657Moehler 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.
Derived from this study: PubMed 36919706Janjigian 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.
Derived from this study: PubMed 36121651Liu 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.
Derived from this study: PubMed 34102137Janjigian 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.
BMS Clinical Trial InformationLink provided by the sponsor.
BMS Clinical Trial Patient RecruitingLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Bristol-Myers Squibb study director

Bristol-Myers Squibb

179 sites in 29 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Nivolumab, Ipilimumab and Oxaliplatin in people with Gastric Cancer and Gastroesophageal Junction Cancer, run by Bristol-Myers Squibb at 179 sites in 29 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 179 sites in United States, China, Japan, Germany, Australia and 24 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (OS) in Participants Treated With Nivolumab Plus Chemotherapy vs Chemotherapy With PD-L1 CPS ≥ 5 (time frame: From the date of randomization up to the date of death, up to approximately 17 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02872116, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2025.