Non-Small Cell Lung CancerPhase 3CheckMate 227NCT02477826
An Investigational Immuno-therapy Trial of Nivolumab, or Nivolumab Plus Ipilimumab, or Nivolumab Plus Platinum-doublet Chemotherapy, Compared to Platinum Doublet Chemotherapy in Patients With Stage IV Non-Small Cell Lung Cancer (NSCLC)
A Phase 3 study testing Nivolumab, Ipilimumab and Carboplatin in people with Non-Small Cell Lung Cancer, run by Bristol-Myers Squibb at 290 sites in 33 countries.
Trial summary
The purpose of this study is to show that Nivolumab, or Nivolumab plus Ipilimumab, or Nivolumab plus Platinum-Doublet Chemotherapy improves progression free survival and/or overall survival compared with chemotherapy in patients with advanced lung cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Small Cell Lung Cancer
- What is being tested?
- Nivolumab, Ipilimumab and Carboplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,747 participants
- Where
- 290 sitesin 33 countries
- Study dates
- 5 Aug 2015to 25 Oct 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
- Subjects with histologically confirmed Stage IV or recurrent NSCLC squamous or non-squamous histology, with no prior systemic anticancer therapy
- Subjects must have programmed death-ligand 1 (PD -L1) immunohistochemical (IHC) testing, with results, performed by the central lab during the Screening period
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1
- Measurable disease by CT or MRI per response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) criteria
Who cannot join
- Subjects with untreated Central nervous system (CNS) metastases are excluded
- Subjects with an active, known or suspected autoimmune disease are excluded
- Any positive test for hepatitis B virus or hepatitis C virus or human immunodeficiency virus (HIV) indicating acute or chronic infection
- Other protocol defined inclusion/exclusion criteria apply
Trial locations and contacts
290 sites in 33 countries.
290 sites in 33 countries
China37 sites
Local Institution - 0313
Beijing, Beijing Municipality, 100001
Local Institution - 0315
Beijing, Beijing Municipality, 100021
Local Institution - 0316
Beijing, Beijing Municipality, 100021
Local Institution - 0314
Beijing, Beijing Municipality, 100032
Local Institution - 0329
Changchun, Jilin, 130012
Local Institution - 0361
Changchun, Jilin, 130021
Local Institution - 0362
Changsha, Hunan, 410013
Local Institution - 0328
Changsha, 0
Local Institution - 0376
Chengdu, Sichuan, 610041
Local Institution - 0365
Chongqing, Chongqing Municipality, 400037
Local Institution - 0364
Chongqing, Chongqing Municipality, 400038
Local Institution - 0378
Chongqing, Chongqing Municipality, 400042
Local Institution - 0322
Guangzhou, Guangdong, 510060
Local Institution - 0372
Guangzhou, Guangdong, 510095
Local Institution - 0319
Guanzhou, Guangdong, 510080
Local Institution - 0325
Haerbin, Heilongjiang, 150081
Local Institution - 0323
Haikou, Hainan, 570311
Local Institution - 0343
Hangzhou, Zhejiang, 310003
Local Institution - 0370
Hangzhou, Zhejiang, 310009
Local Institution - 0342
Hangzhou, Zhejiang, 310022
Local Institution - 0341
Hangzhou, 310016
Local Institution - 0380
Hefei, Anhui, 230001
Local Institution - 0345
Kunming, 0
Local Institution - 0347
Nanchang, Jiangxi, 0
Local Institution - 0360
Qingdao, Shandong, 266061
Local Institution - 0336
Shanghai, Shanghai Municipality, 200030
Local Institution - 0334
Shanghai, Shanghai Municipality, 200032
Local Institution - 0337
Shanghai, 200030
Local Institution - 0374
Shantou, 0
Local Institution - 0359
Shenyang, Liaoning, 110000
Local Institution - 0373
Tianjin, Tianjin Municipality, 300060
Local Institution - 0340
Ürümqi, Xinjiang, 830011
Local Institution - 0375
Wuhan, Hubei, 430024
Local Institution - 0371
Xi'an, Shaanxi, 710061
Local Institution - 0333
Xi'an, Shan3xi, 710038
Local Institution - 0324
Zhengzhou, Henan, 0
Local Institution - 0379
Zhengzhou, Henan, 450052
Japan35 sites
Local Institution - 0252
Akashi-shi, Hyōgo, 6738558
Local Institution - 0260
Chiba, Chiba, 260-8677
Local Institution - 0147
Chuo-ku, Tokyo, 1040045
Local Institution - 0160
Fukuoka, Fukuoka, 8120054
Local Institution - 0353
Hidaka-shi, Saitama, 3501298
Local Institution - 0155
Hirakata-shi, Osaka, 5731191
Local Institution - 0258
Hiroshima, Hiroshima, 7308518
Local Institution - 0146
Kanazawa, Ishikawa-ken, 9208641
Local Institution - 0148
Kashiwa-shi, Chiba, 2778577
Local Institution - 0256
Kitaadachi-gun, Saitama, 3620806
Local Institution - 0156
Kobe, Hyōgo, 6500047
Local Institution - 0149
Koto-ku, Tokyo, 1358550
Local Institution - 0158
Kurashiki-shi, Okayama-ken, 7100052
Local Institution - 0259
Kurume-shi, Fukuoka, 8300011
Local Institution - 0159
Matsuyama, Ehime, 791-0280
Local Institution - 0153
Nagoya, Aichi-ken, 4600001
Local Institution - 0152
Nagoya, Aichi-ken, 4648681
Local Institution - 0275
Natori-shi, Miyagi, 9811293
Local Institution - 0164
Niigata, Niigata, 9518566
Local Institution - 0165
Okayama, 700-8558
Local Institution - 0154
Osaka, Osaka, 5340021
Local Institution - 0251
Osakasayama-shi, Osaka, 5890014
Local Institution - 0255
Ota-shi, Gunma, 3730828
Local Institution - 0163
Sapporo, Hokkaido, 0030804
Local Institution - 0253
Sapporo, Hokkaido, 0608648
Local Institution - 0254
Sendai, Miyagi, 9800873
Local Institution - 0145
Sendai, Miyagi, 9808574
Local Institution - 0278
Shinjuku-ku, Tokyo, 1600023
Local Institution - 0151
Sunto-gun, Shizuoka, 4118777
Local Institution - 0257
Takatsuki-shi, Osaka, 5698686
Local Institution - 0162
Tokyo, 113-8603
Local Institution - 0354
Ube-shi, Yamaguchi, 7550241
Local Institution - 0157
Wakayama, Wakayama, 641-8510
Local Institution - 0161
Yokohama, Kanagawa, 2210855
Local Institution - 0150
Yokohama, Kanagawa, 2360051
United States25 sites
Local Institution - 0007
Allentown, Pennsylvania, 18103
Local Institution - 0001
Atlanta, Georgia, 30322
Local Institution - 0005
Buffalo, New York, 14263
Local Institution - 0008
Charleston, South Carolina, 29425
Local Institution - 0014
Cleveland, Ohio, 44106
Local Institution - 0009
Columbus, Ohio, 43210
Local Institution - 0306
Dallas, Texas, 75390-8852
Local Institution - 0003
Dallas, Texas, 75390
Local Institution - 0080
Greenville, South Carolina, 29605
Local Institution - 0010
Greenville, South Carolina, 29607
Local Institution - 0102
Houston, Texas, 77030
Local Institution - 0074
Kennewick, Washington, 99336
Local Institution - 0075
Langhorne, Pennsylvania, 19047
Local Institution - 0004
Lexington, Kentucky, 40503
Local Institution - 0013
Marietta, Georgia, 30060
Southern Cancer Center, Inc.
Mobile, Alabama, 36608
Local Institution - 0020
Nashville, Tennessee, 37232
Local Institution - 0021
New Haven, Connecticut, 06520
Local Institution - 0019
New York, New York, 10065
Local Institution - 0299
Philadelphia, Pennsylvania, 19107
Local Institution - 0012
Philadelphia, Pennsylvania, 19111-2412
Local Institution - 0011
Salt Lake City, Utah, 84108
Local Institution - 0017
San Francisco, California, 94115
Local Institution - 0015
Sayre, Pennsylvania, 18840
Local Institution - 0115
St Louis, Missouri, 63110
France15 sites
Local Institution - 0216
Angers, 49055
Local Institution - 0229
Besançon, 0
Local Institution - 0222
Bron, Rhône, 69677
Local Institution - 0283
Caen, 14076
Local Institution - 0218
Créteil, 94010
Local Institution - 0228
Limoges, 87042
Local Institution - 0215
Marseille, 13915
Local Institution - 0230
Paris, 75018
Local Institution - 0227
Pessac, 33604
Local Institution - 0223
Rennes, 350330
Local Institution - 0225
Rouen, 76000
Local Institution - 0217
Saint-Herblain, 44805
Local Institution - 0221
Saint-Priest-en-Jarez, 42271
Local Institution - 0224
Strasbourg, 67000
Local Institution - 0226
Toulon, 83056
Germany14 sites
Local Institution - 0213
Bad Berka, 99437
Local Institution - 0208
Berlin, 13125
Local Institution - 0205
Essen, 45147
Local Institution - 0210
Frankfurt, 60590
Local Institution - 0211
Gera, 07548
Local Institution - 0203
Großhansdorf, 22927
Local Institution - 0209
Halle, 06120
Local Institution - 0202
Heidelberg, 69126
Local Institution - 0214
Hemer, 58675
Local Institution - 0206
Immenstadt im Allgäu, 87509
Local Institution - 0231
Magdeburg, Saxony-Anhalt, 39120
Local Institution - 0204
München, 81925
Local Institution - 0201
Stuttgart, 70376
Local Institution - 0212
Wiesbaden, 65199
Italy13 sites
Azienda Ospedaliera Moscati
Avellino, 83024
Local Institution - 0179
Bergamo, 24127
IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola
Bologna, 40138
Local Institution - 0084
Livorno, 57124
Policlinico G. Martino
Messina, 98125
Local Institution - 0083
Milan, Lombardy, 20141
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, 20133
Istituto Nazionale Tumori Fondazione Pascale
Naples, 80131
Local Institution - 0087
Perugia, 06132
Ospedale Santa Maria delle Croci
Ravenna, 48121
Ifo-Istituto Regina Elena
Roma, 00144
Local Institution - 0089
Roma, 00161
Local Institution - 0085
Terni, 05100
Mexico12 sites
Local Institution - 0192
Chihuahua City, 31217
Local Institution - 0198
Cuautitlán, State of Mexico, 54769
Local Institution - 0196
Df, Mexico City, 06720
Local Institution - 0197
Guadalajara, Jalisco, 44270
Local Institution - 0303
Mérida, Yucatán, 97070
Local Institution - 0193
Mexico City, Mexico City, 14080
Local Institution - 0277
Monterrey, Nuevo León, 64060
Local Institution - 0267
Morelia, Michoacán, 58000
Local Institution - 0195
San Luis Potosí City, 78200
Local Institution - 0236
San Luis Potosí City, 78213
Local Institution - 0194
Toluca, 50180
Local Institution - 0191
Zapopan, Jalisco, 44280
Argentina10 sites
Local Institution - 0170
Berazategui, Buenos Aires, 1880
Local Institution - 0171
Capital Federal, Buenos Aires, 1426
Local Institution - 0172
Ciudad Autonoma de Buenos Aire, Buenos Aires, 1181
Local Institution - 0176
Ciudad de Buenos Aires, Buenos Aires, 1025
Local Institution - 0268
Córdoba, 5000
Local Institution - 0272
Córdoba, 5016
Local Institution - 0297
Córdoba, X50004FHP
Local Institution - 0296
Mar del Plata, Buenos Aires, 7600
Local Institution - 0130
San Miguel de Tucumán, Tucumán Province, 4000
Local Institution - 0177
Viedma, 8500
Australia10 sites
Local Institution - 0301
Blacktown, New South Wales, 2148
Local Institution - 0045
Brisbane, Queensland, 4102
Local Institution - 0043
Clayton, Victoria, 3168
Local Institution - 0046
Elizabeth Vale, South Australia, 5112
Local Institution - 0042
Fitzroy, Victoria, 3065
Local Institution - 0182
Garran, Australian Capital Territory, 2605
Local Institution - 0300
Gosford, New South Wales, 2250
Local Institution - 0040
Murdoch, 6150
Local Institution - 0183
North Tamworth, 2340
Local Institution - 0180
Perth, Western Australia, 6150
United Kingdom10 sites
Local Institution - 0265
Birmingham, B4 6DHH
Local Institution - 0051
Cambridgeshire, CB2 2QQ
Local Institution - 0109
Edinburgh, EH4 2XU
Local Institution - 0118
Leicester, Leicestershire, LE1 5WW
Local Institution - 0098
London, Greater London, SW3 6JJ
Local Institution - 0097
London, N18 1QX
Local Institution - 0050
London, SE1 9RT
Local Institution - 0266
Middlesbrough, Cleveland, TS4 3BW
Local Institution - 0099
Southampton, Hampshire, SO16 0YD
Local Institution - 0119
Surrey, SM2 5PT
Canada9 sites
Local Institution - 0103
Edmonton, Alberta, T6G 1Z2
Local Institution - 0104
London, Ontario, N6A 5W9
Local Institution - 0122
Montreal, Quebec, H3T 1E2
Local Institution - 0106
Québec, Quebec, G1J 1Z4
Local Institution - 0302
Québec, Quebec, G1V 4G5
Local Institution - 0107
Rimouski, Quebec, G5L 5T1
Local Institution - 0291
Sherbrooke, Quebec, J1H 5N4
Local Institution - 0290
St. John's, Newfoundland and Labrador, A1B 3V6
Local Institution - 0292
Trois-Rivières, Quebec, G8Z 3R9
Brazil8 sites
Local Institution - 0127
Barretos, São Paulo, 14784-400
Local Institution - 0124
Ijuí, Rio Grande do Sul, 98700-000
Local Institution - 0123
Porto Alegre, Rio Grande do Sul, 90610-000
Local Institution - 0129
Rio de Janeiro, 20231-050
Local Institution - 0125
Salvador, Estado de Bahia, 40170-110
Local Institution - 0144
São Paulo, 01321-001
Local Institution - 0126
São Paulo, 01509-010
Local Institution - 0128
São Paulo, 05403-010
Poland7 sites
Local Institution - 0060
Bydgoszcz, 85-796
Local Institution - 0058
Gdansk, 80-19
Local Institution - 0063
Gdynia, 81-519
Local Institution - 0072
Gliwice, 44-101
Local Institution - 0057
Lodz, 93-513
Local Institution - 0059
Warsaw, 02-781
Local Institution - 0070
Wroclaw, 52-229
Russia7 sites
Local Institution - 0137
Chelyabinsk, 454048
Local Institution - 0142
Kazan', 420029
Local Institution - 0022
Moscow, 115478
Local Institution - 0028
Saint Petersburg, 194291
Local Institution - 0049
Saint Petersburg, 197758
Local Institution - 0027
Saint Petersburg, 198255
Local Institution - 0143
Ufa, 450054
Belgium6 sites
Local Institution - 0034
Charleroi, Hainaut, 6060
Local Institution - 0030
Edegem, 2650
Local Institution - 0031
Ghent, 9000
Local Institution - 0117
Hasselt, 3500
Local Institution - 0121
Roeselare, West-Vlaanderen, 8800
Local Institution - 0033
Sint-Niklaas, 9100
Spain6 sites
Local Institution - 0066
Barcelona, 08035
Local Institution - 0067
Barcelona, 08916
Local Institution - 0065
Madrid, 28041
Local Institution - 0064
Majadahonda, Madrid, 28222
Local Institution - 0069
Seville, 41013
Local Institution - 0068
Valencia, 46014
Israel5 sites
Local Institution - 0187
Jerusalem, 91120
Local Institution - 0186
Kfar Saba, 44281
Local Institution - 0185
Petah Tikva, 49100
Local Institution - 0184
Tel HaShomer, 52621
Local Institution - 0188
Tsrifin, 70300
Netherlands5 sites
Local Institution - 0036
Amsterdam, 1066 CX
Local Institution - 0189
Amsterdam, 1081 HV
Local Institution - 0169
Breda, 4818 CK
Local Institution - 0037
Rotterdam, 3014 GD
Local Institution - 0039
Veldhoven, 5504 DB
Peru5 sites
Local Institution - 0262
Lima, 0
Local Institution - 0263
Lima, 0
Local Institution - 0350
Lima, 27
Local Institution - 0261
Lima, 34
Local Institution - 0351
Lima, Lima 41
South Korea5 sites
Local Institution - 0249
Cheongju-si, 28644
Local Institution - 0133
Gangnam-gu, 06351
Local Institution - 0136
Seongnam-si, Kyǒnggi-do, 436-707
Local Institution - 0132
Seoul, 05505
Local Institution - 0135
Seoul, 06591
Taiwan5 sites
Local Institution - 0139
Taichung, 407
Local Institution - 0138
Taipei, 100
Local Institution - 0140
Taipei, 112
Local Institution - 0310
Taipei, 235
Local Institution - 0141
Taoyuan City, 333
Colombia4 sites
Local Institution - 0237
Bogotá, 0
Local Institution - 0238
Bogotá, 0
Local Institution - 0282
Medellín, 050034
Local Institution - 0273
Pereira, Risaralda Department, 0
Czechia4 sites
Local Institution - 0112
Hradec Králové, 500 05
Local Institution - 0113
Olomouc, 779 00
Local Institution - 0111
Prague, 140 59
Local Institution - 0232
Příbram, 261 01
Greece4 sites
Local Institution - 0094
Athens, Attikí, 115 27
Local Institution - 0095
Heraklion, 711 10
Local Institution - 0190
Neo Faliro, 18547
Local Institution - 0101
Thessaloniki, 54007
Ireland4 sites
Local Institution - 0053
Beaumont, Dublin 9
Local Institution - 0054
Dublin, Dublin
Local Institution - 0055
Galway, 0
Local Institution - 0100
Limerick, 0
Romania4 sites
Local Institution - 0167
Craiova, 200542
Local Institution - 0250
Floreşti, 407280
Local Institution - 0166
Romania, 400015
Local Institution - 0284
Sector 2, 022328
South Africa4 sites
Local Institution - 0264
Pretoria, Gauteng, 0002
Local Institution - 0234
Sandton, Gauteng, 2196
Local Institution - 0233
Saxonwold, Johannesburg, Gauteng, 2196
Local Institution - 0305
Vereeniging, 1936
Switzerland4 sites
Local Institution - 0243
Basel, 4031
Local Institution - 0246
Chur, 7000
Local Institution - 0244
Lausanne, 1011
Local Institution - 0245
Winterthur, 8401
Austria3 sites
Local Institution - 0241
Graz, 8036
Local Institution - 0240
Vienna, 1090
Local Institution - 0239
Wels, 4600
Chile3 sites
Local Institution - 0173
Santiago, Santiago Metropolitan, 7500921
Local Institution - 0131
Santiago, Santiago Metropolitan, 8420383
Local Institution - 0174
Viña del Mar, Valparaiso, 254 0364
Hungary3 sites
Local Institution - 0025
Budapest, 1083
Local Institution - 0024
Budapest, 1121
Local Institution - 0026
Mátraháza, 3233
Finland2 sites
Local Institution - 0270
Oulu, 90029
Local Institution - 0271
Turku, 20520
Lebanon2 sites
Local Institution - 0287
Beirut, 00961
Local Institution - 0286
Beirut, 166830
About this study
Official title: An Open-Label, Randomized Phase 3 Trial of Nivolumab, or Nivolumab Plus Ipilimumab, or Nivolumab Plus Platinum Doublet Chemotherapy Versus Platinum Doublet Chemotherapy in Subjects With Chemotherapy-Naïve Stage IV or Recurrent Non-Small Cell Lung Cancer (NSCLC)
The purpose of this study is to show that Nivolumab, or Nivolumab plus Ipilimumab, or Nivolumab plus Platinum-Doublet Chemotherapy improves progression free survival and/or overall survival compared with chemotherapy in patients with advanced lung cancer.
- Conditions
- Non-Small Cell Lung Cancer
- Being tested
- Nivolumab, Ipilimumab, Carboplatin, Cisplatin, Gemcitabine
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called Opdivo
IpilimumabDrug
Also called Yervoy
CarboplatinDrug
CisplatinDrug
GemcitabineDrug
PemetrexedDrug
PaclitaxelDrug
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Nivolumab | Experimental | Nivolumab intravenously (IV) as specified Receives: Drug: Nivolumab |
| Arm B: Nivolumab + Ipilimumab | Experimental | Nivolumab + Ipilimumab IV as specified Receives: Drug: Nivolumab; Drug: Ipilimumab |
| Arm C: Nivolumab + Platinum doublet chemotherapy | Experimental | Nivolumab + Platinum doublet chemotherapy (IV) dose as specified Receives: Drug: Nivolumab; Drug: Carboplatin; Drug: Cisplatin; Drug: Gemcitabine; Drug: Pemetrexed; Drug: Paclitaxel |
| Arm D: Platinum doublet chemotherapy | Experimental | Chemotherapy administered on specified days of IV chemotherapy Receives: Drug: Carboplatin; Drug: Cisplatin; Drug: Gemcitabine; Drug: Pemetrexed; Drug: Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Survival Per BICR
Progression-Free Survival then (PFS) is defined as the time between the date of randomization and the date of first documented disease progression, based on BICR assessments (per RECIST v1.1), or death due to any cause, whichever occurs first based on Kaplan-Meier estimates. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Measured: From randomization untill disease progression or death, whichever occurs first (up to approximately 481 weeks)
Overall Survival
OS for all randomized participants is the time between randomization date and the date of death from any cause.
Measured: From randomization untill death or last follow up whichever occurs first (up to approximately 481 weeks)
Secondary outcomes (2)
Objective Response Rate (ORR) Per BICR
Objective response rate (ORR) is defined as the number of participants who achieve a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), based on blinded independent central review (BICR) assessments using Response Evaluation Criteria in Solid Tumors (RECIST 1.1), divided by the number of all randomized participants.
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.
Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Measured: From randomization untill disease progression or death, whichever occurs first (up to approximately 481 weeks)
Percentage of Participants With Symptom Deterioration at Week 12 Assessed Via Lung Cancer Symptom Scale
The Lung Cancer Symptom Scale (LCSS) is a disease measure of quality of life which evaluates six major lung cancer symptoms and their effect on overall distress and symptom severity, impact on day-to-day activities, and overall quality of life. This patient reported outcome (PRO) questionnaire assesses the following 6 symptoms items (appetite loss, fatigue, cough, dyspnea, hemoptysis, pain) and 3 summary global items (symptom distress, activity level, overall quality of life) for patients using visual analogue scales (VAS) (100 mm horizontal line) ranging from 0 (best rating) to 100 (worst rating). The LCSS average total score is sum of items 1 to 9 divided by the total number of items ((sum of items 1 to 9)/9) ranging from 0 to 100 where high score represent worst outcome. Disease-Related Symptom Deterioration by Week 12 defined as a 10 points or more increase from baseline in LCSS average score at any time (on or off-treatment) up to 95 days from randomization date.
Measured: Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2015 (estimated)
- Study start5 Aug 2015
- Primary completion25 Oct 2024
- Study completion25 Oct 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 (8)Papers the sponsor has linked to this study.
- Other trials for Non-Small Cell Lung 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
- 2,747 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ono Pharmaceutical Co., Ltd.
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02477826
- Sponsor's protocol ID
- CA209-227
- Other IDs
- 2014-003630-23, 2014
- Acronym
- CheckMate 227
- Status last verified
- Oct 2025
- First submitted
- 18 Jun 2015
- Last updated
- 30 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Nishio M, Hayashi H, Goto Y, Ikeda S, Yokoyama T, Tanaka H, Tambo Y, Hotta K, Fukuhara T, Daga H, Masubuchi K, Aoyama T, Tschaika M, Hu N, Mizutani H. Nivolumab plus ipilimumab-based treatment in Japanese patients with metastatic non-small cell lung cancer and tumor PD-L1 < 1%: a pooled analysis. Int J Clin Oncol. 2026 Aug 11. doi: 10.1007/s10147-026-03116-w. Online ahead of print.
PubMed 42579028Peters S, Paz-Ares LG, Reck M, Carbone DP, Brahmer JR, Borghaei H, Lu S, O'Byrne KJ, John T, Ciuleanu TE, Schenker M, Bernabe Caro R, Nishio M, Cobo M, Lee JS, Zurawski B, Pluzanski A, Aoyama T, Tschaika M, Devas V, Grootendorst DJ, Ramalingam SS. Long-Term Survival Outcomes With First-Line Nivolumab Plus Ipilimumab-Based Treatment in Patients With Metastatic NSCLC and Tumor Programmed Death-Ligand 1 Lower Than 1%: A Pooled Analysis. J Thorac Oncol. 2025 Jan;20(1):94-108. doi: 10.1016/j.jtho.2024.09.1439. Epub 2024 Oct 4.
PubMed 39369790Mason M, Lapuente-Santana O, Halkola AS, Wang W, Mall R, Xiao X, Kaufman J, Fu J, Pfeil J, Banerjee J, Chung V, Chang H, Chasalow SD, Lin HY, Chai R, Yu T, Finotello F, Mirtti T, Mayranpaa MI, Bao J, Verschuren EW, Ahmed EI, Ceccarelli M, Miller LD, Monaco G, Hendrickx WRL, Sherif S, Yang L, Tang M, Gu SS, Zhang W, Zhang Y, Zeng Z, Das Sahu A, Liu Y, Yang W, Bedognetti D, Tang J, Eduati F, Laajala TD, Geese WJ, Guinney J, Szustakowski JD, Vincent BG, Carbone DP. A community challenge to predict clinical outcomes after immune checkpoint blockade in non-small cell lung cancer. J Transl Med. 2024 Feb 21;22(1):190. doi: 10.1186/s12967-023-04705-3.
PubMed 38383458Brahmer JR, Lee JS, Ciuleanu TE, Bernabe Caro R, Nishio M, Urban L, Audigier-Valette C, Lupinacci L, Sangha R, Pluzanski A, Burgers J, Mahave M, Ahmed S, Schoenfeld AJ, Paz-Ares LG, Reck M, Borghaei H, O'Byrne KJ, Gupta RG, Bushong J, Li L, Blum SI, Eccles LJ, Ramalingam SS. Five-Year Survival Outcomes With Nivolumab Plus Ipilimumab Versus Chemotherapy as First-Line Treatment for Metastatic Non-Small-Cell Lung Cancer in CheckMate 227. J Clin Oncol. 2023 Feb 20;41(6):1200-1212. doi: 10.1200/JCO.22.01503. Epub 2022 Oct 12.
PubMed 36223558Reck M, Ciuleanu TE, Lee JS, Schenker M, Audigier-Valette C, Zurawski B, Linardou H, Otterson GA, Salman P, Nishio M, de la Mora Jimenez E, Lesniewski-Kmak K, Albert I, Ahmed S, Syrigos K, Penrod JR, Yuan Y, Blum SI, Nathan FE, Sun X, Moreno-Koehler A, Taylor F, O'Byrne KJ. First-Line Nivolumab Plus Ipilimumab Versus Chemotherapy in Advanced NSCLC With 1% or Greater Tumor PD-L1 Expression: Patient-Reported Outcomes From CheckMate 227 Part 1. J Thorac Oncol. 2021 Apr;16(4):665-676. doi: 10.1016/j.jtho.2020.12.019. Epub 2021 Jan 21.
PubMed 33485960Hellmann MD, Paz-Ares L, Bernabe Caro R, Zurawski B, Kim SW, Carcereny Costa E, Park K, Alexandru A, Lupinacci L, de la Mora Jimenez E, Sakai H, Albert I, Vergnenegre A, Peters S, Syrigos K, Barlesi F, Reck M, Borghaei H, Brahmer JR, O'Byrne KJ, Geese WJ, Bhagavatheeswaran P, Rabindran SK, Kasinathan RS, Nathan FE, Ramalingam SS. Nivolumab plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2019 Nov 21;381(21):2020-2031. doi: 10.1056/NEJMoa1910231. Epub 2019 Sep 28.
PubMed 31562796Reck M, Schenker M, Lee KH, Provencio M, Nishio M, Lesniewski-Kmak K, Sangha R, Ahmed S, Raimbourg J, Feeney K, Corre R, Franke FA, Richardet E, Penrod JR, Yuan Y, Nathan FE, Bhagavatheeswaran P, DeRosa M, Taylor F, Lawrance R, Brahmer J. Nivolumab plus ipilimumab versus chemotherapy as first-line treatment in advanced non-small-cell lung cancer with high tumour mutational burden: patient-reported outcomes results from the randomised, open-label, phase III CheckMate 227 trial. Eur J Cancer. 2019 Jul;116:137-147. doi: 10.1016/j.ejca.2019.05.008. Epub 2019 Jun 11.
PubMed 31195357Hellmann MD, Ciuleanu TE, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C, Minenza E, Linardou H, Burgers S, Salman P, Borghaei H, Ramalingam SS, Brahmer J, Reck M, O'Byrne KJ, Geese WJ, Green G, Chang H, Szustakowski J, Bhagavatheeswaran P, Healey D, Fu Y, Nathan F, Paz-Ares L. Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden. N Engl J Med. 2018 May 31;378(22):2093-2104. doi: 10.1056/NEJMoa1801946. Epub 2018 Apr 16.
PubMed 29658845
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Randomized Phase 3 Trial of Nivolumab, or Nivolumab Plus Ipilimumab, or Nivolumab Plus Platinum Doublet Chemotherapy Versus Platinum Doublet Chemotherapy in Subjects With Chemotherapy-Naïve Stage IV or Recurrent Non-Small Cell Lung Cancer (NSCLC)
- ClinicalTrials.gov ID
- NCT02477826
- Acronym / sponsor ID
- CheckMate 227 / CA209-227
- Conditions
- Non-Small Cell Lung Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,747 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Collaborators
- Ono Pharmaceutical Co., Ltd.
- Study start
- 5 Aug 2015 (actual)
- Primary completion
- 25 Oct 2024 (actual)
- Study completion
- 25 Oct 2024 (actual)
- First posted
- 23 Jun 2015 (estimated)
- Results
- Posted 30 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to show that Nivolumab, or Nivolumab plus Ipilimumab, or Nivolumab plus Platinum-Doublet Chemotherapy improves progression free survival and/or overall survival compared with chemotherapy in patients with advanced lung cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm A: Nivolumab | Experimental | Drug: NivolumabNivolumab intravenously (IV) as specified |
| Arm B: Nivolumab + Ipilimumab | Experimental | Drug: Nivolumab, Drug: IpilimumabNivolumab + Ipilimumab IV as specified |
| Arm C: Nivolumab + Platinum doublet chemotherapy | Experimental | Drug: Nivolumab, Drug: Carboplatin, Drug: Cisplatin, Drug: Gemcitabine, Drug: Pemetrexed, Drug: PaclitaxelNivolumab + Platinum doublet chemotherapy (IV) dose as specified |
| Arm D: Platinum doublet chemotherapy | Experimental | Drug: Carboplatin, Drug: Cisplatin, Drug: Gemcitabine, Drug: Pemetrexed, Drug: PaclitaxelChemotherapy administered on specified days of IV chemotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Subjects with histologically confirmed Stage IV or recurrent NSCLC squamous or non-squamous histology, with no prior systemic anticancer therapy
- Subjects must have programmed death-ligand 1 (PD -L1) immunohistochemical (IHC) testing, with results, performed by the central lab during the Screening period
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1
- Measurable disease by CT or MRI per response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) criteria
Key exclusion criteria (4 listed)
- Subjects with untreated Central nervous system (CNS) metastases are excluded
- Subjects with an active, known or suspected autoimmune disease are excluded
- Any positive test for hepatitis B virus or hepatitis C virus or human immunodeficiency virus (HIV) indicating acute or chronic infection
- Other protocol defined inclusion/exclusion criteria apply
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 | Drug | Arm A: Nivolumab, Arm B: Nivolumab + Ipilimumab, Arm C: Nivolumab + Platinum doublet chemotherapy |
| IpilimumabAlso: Yervoy | Drug | Arm B: Nivolumab + Ipilimumab |
| Carboplatin | Drug | Arm C: Nivolumab + Platinum doublet chemotherapy, Arm D: Platinum doublet chemotherapy |
| Cisplatin | Drug | Arm C: Nivolumab + Platinum doublet chemotherapy, Arm D: Platinum doublet chemotherapy |
| Gemcitabine | Drug | Arm C: Nivolumab + Platinum doublet chemotherapy, Arm D: Platinum doublet chemotherapy |
| Pemetrexed | Drug | Arm C: Nivolumab + Platinum doublet chemotherapy, Arm D: Platinum doublet chemotherapy |
| Paclitaxel | Drug | Arm C: Nivolumab + Platinum doublet chemotherapy, Arm D: Platinum doublet chemotherapy |
Primary outcome
Progression-Free Survival Per BICR
Time frame: From randomization untill disease progression or death, whichever occurs first (up to approximately 481 weeks)
Progression-Free Survival then (PFS) is defined as the time between the date of randomization and the date of first documented disease progression, based on BICR assessments (per RECIST v1.1), or death due to any cause, whichever occurs first based on Kaplan-Meier estimates. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Overall Survival
Time frame: From randomization untill death or last follow up whichever occurs first (up to approximately 481 weeks)
OS for all randomized participants is the time between randomization date and the date of death from any cause.
2 secondary outcomes
Objective Response Rate (ORR) Per BICR
Time frame: From randomization untill disease progression or death, whichever occurs first (up to approximately 481 weeks)
Percentage of Participants With Symptom Deterioration at Week 12 Assessed Via Lung Cancer Symptom Scale
Time frame: Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42579028Nishio M, Hayashi H, Goto Y, Ikeda S, Yokoyama T, Tanaka H, Tambo Y, Hotta K, Fukuhara T, Daga H, Masubuchi K, Aoyama T, Tschaika M, Hu N, Mizutani H. Nivolumab plus ipilimumab-based treatment in Japanese patients with metastatic non-small cell lung cancer and tumor PD-L1 < 1%: a pooled analysis. Int J Clin Oncol. 2026 Aug 11. doi: 10.1007/s10147-026-03116-w. Online ahead of print.
- Derived from this study: PubMed 39369790Peters S, Paz-Ares LG, Reck M, Carbone DP, Brahmer JR, Borghaei H, Lu S, O'Byrne KJ, John T, Ciuleanu TE, Schenker M, Bernabe Caro R, Nishio M, Cobo M, Lee JS, Zurawski B, Pluzanski A, Aoyama T, Tschaika M, Devas V, Grootendorst DJ, Ramalingam SS. Long-Term Survival Outcomes With First-Line Nivolumab Plus Ipilimumab-Based Treatment in Patients With Metastatic NSCLC and Tumor Programmed Death-Ligand 1 Lower Than 1%: A Pooled Analysis. J Thorac Oncol. 2025 Jan;20(1):94-108. doi: 10.1016/j.jtho.2024.09.1439. Epub 2024 Oct 4.
- Derived from this study: PubMed 38383458Mason M, Lapuente-Santana O, Halkola AS, Wang W, Mall R, Xiao X, Kaufman J, Fu J, Pfeil J, Banerjee J, Chung V, Chang H, Chasalow SD, Lin HY, Chai R, Yu T, Finotello F, Mirtti T, Mayranpaa MI, Bao J, Verschuren EW, Ahmed EI, Ceccarelli M, Miller LD, Monaco G, Hendrickx WRL, Sherif S, Yang L, Tang M, Gu SS, Zhang W, Zhang Y, Zeng Z, Das Sahu A, Liu Y, Yang W, Bedognetti D, Tang J, Eduati F, Laajala TD, Geese WJ, Guinney J, Szustakowski JD, Vincent BG, Carbone DP. A community challenge to predict clinical outcomes after immune checkpoint blockade in non-small cell lung cancer. J Transl Med. 2024 Feb 21;22(1):190. doi: 10.1186/s12967-023-04705-3.
- Derived from this study: PubMed 36223558Brahmer JR, Lee JS, Ciuleanu TE, Bernabe Caro R, Nishio M, Urban L, Audigier-Valette C, Lupinacci L, Sangha R, Pluzanski A, Burgers J, Mahave M, Ahmed S, Schoenfeld AJ, Paz-Ares LG, Reck M, Borghaei H, O'Byrne KJ, Gupta RG, Bushong J, Li L, Blum SI, Eccles LJ, Ramalingam SS. Five-Year Survival Outcomes With Nivolumab Plus Ipilimumab Versus Chemotherapy as First-Line Treatment for Metastatic Non-Small-Cell Lung Cancer in CheckMate 227. J Clin Oncol. 2023 Feb 20;41(6):1200-1212. doi: 10.1200/JCO.22.01503. Epub 2022 Oct 12.
- Derived from this study: PubMed 33485960Reck M, Ciuleanu TE, Lee JS, Schenker M, Audigier-Valette C, Zurawski B, Linardou H, Otterson GA, Salman P, Nishio M, de la Mora Jimenez E, Lesniewski-Kmak K, Albert I, Ahmed S, Syrigos K, Penrod JR, Yuan Y, Blum SI, Nathan FE, Sun X, Moreno-Koehler A, Taylor F, O'Byrne KJ. First-Line Nivolumab Plus Ipilimumab Versus Chemotherapy in Advanced NSCLC With 1% or Greater Tumor PD-L1 Expression: Patient-Reported Outcomes From CheckMate 227 Part 1. J Thorac Oncol. 2021 Apr;16(4):665-676. doi: 10.1016/j.jtho.2020.12.019. Epub 2021 Jan 21.
- Derived from this study: PubMed 31562796Hellmann MD, Paz-Ares L, Bernabe Caro R, Zurawski B, Kim SW, Carcereny Costa E, Park K, Alexandru A, Lupinacci L, de la Mora Jimenez E, Sakai H, Albert I, Vergnenegre A, Peters S, Syrigos K, Barlesi F, Reck M, Borghaei H, Brahmer JR, O'Byrne KJ, Geese WJ, Bhagavatheeswaran P, Rabindran SK, Kasinathan RS, Nathan FE, Ramalingam SS. Nivolumab plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2019 Nov 21;381(21):2020-2031. doi: 10.1056/NEJMoa1910231. Epub 2019 Sep 28.
- Derived from this study: PubMed 31195357Reck M, Schenker M, Lee KH, Provencio M, Nishio M, Lesniewski-Kmak K, Sangha R, Ahmed S, Raimbourg J, Feeney K, Corre R, Franke FA, Richardet E, Penrod JR, Yuan Y, Nathan FE, Bhagavatheeswaran P, DeRosa M, Taylor F, Lawrance R, Brahmer J. Nivolumab plus ipilimumab versus chemotherapy as first-line treatment in advanced non-small-cell lung cancer with high tumour mutational burden: patient-reported outcomes results from the randomised, open-label, phase III CheckMate 227 trial. Eur J Cancer. 2019 Jul;116:137-147. doi: 10.1016/j.ejca.2019.05.008. Epub 2019 Jun 11.
- Derived from this study: PubMed 29658845Hellmann MD, Ciuleanu TE, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C, Minenza E, Linardou H, Burgers S, Salman P, Borghaei H, Ramalingam SS, Brahmer J, Reck M, O'Byrne KJ, Geese WJ, Green G, Chang H, Szustakowski J, Bhagavatheeswaran P, Healey D, Fu Y, Nathan F, Paz-Ares L. Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden. N Engl J Med. 2018 May 31;378(22):2093-2104. doi: 10.1056/NEJMoa1801946. Epub 2018 Apr 16.
- 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
290 sites in 33 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 Carboplatin in people with Non-Small Cell Lung Cancer, run by Bristol-Myers Squibb at 290 sites in 33 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 4 inclusion and 4 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 30 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 290 sites in China, Japan, United States, France, Germany and 28 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 30 Oct 2025). 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?
Progression-Free Survival Per BICR (time frame: From randomization untill disease progression or death, whichever occurs first (up to approximately 481 weeks)). 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 NCT02477826, which also lists 8 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 30 Oct 2025.