An Investigational Immuno-therapy Study of Nivolumab, Compared to Placebo, in Patients With Bladder or Upper Urinary Tract Cancer, Following Surgery to Remove the Cancer (CheckMate 274)

A Phase 3 Randomized, Double-blind, Multi-center Study of Adjuvant Nivolumab Versus Placebo in Subjects With High Risk Invasive Urothelial Carcinoma (CheckMate 274: CHECKpoint Pathway and nivoluMAb Clinical Trial Evaluation 274)

The purpose of this study is to determine the effectiveness and safety of Nivolumab compared to placebo in participants who have undergone radical surgery for invasive urothelial cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Various Advanced Cancer
• Intervention / Treatment: Other: Placebo; Biological: Nivolumab

• Study Type: Interventional
• Enrollment (Actual): 709
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Berazategui, Buenos Aires, Argentina, 1880
      • Local Institution - 0021
    • Capital Federal, Buenos Aires, Argentina, 1426
      • Local Institution - 0090
    • Ciudad Autonoma De Buenos Aire, Buenos Aires, Argentina, 1181
      • Local Institution - 0089
    • Ciudad Autónoma de BuenosAires, Buenos Aires, Argentina, C1280AEB
      • Local Institution - 0022
  • RIO Negro
    • Viedma, RIO Negro, Argentina, 8500
      • Local Institution - 0102
  • Tucuman
    • San Miguel De Tucuman, Tucuman, Argentina, 4000
      • Local Institution - 0020
• Australia
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Local Institution - 0048
    • St. Leonards, New South Wales, Australia, 2065
      • Local Institution - 0047
    • Waratah, New South Wales, Australia, 2298
      • Local Institution - 0046
  • South Australia
    • Elizabeth Vale, South Australia, Australia, 5112
      • Local Institution - 0050
  • Victoria
    • Frankston, Victoria, Australia, 3199
      • Local Institution - 0184
  • Western Australia
    • Perth, Western Australia, Australia, 6150
      • Local Institution - 0175
• Austria
  • Linz, Austria, 4010
    • Local Institution - 0133
  • Salzburg, Austria, 5020
    • Local Institution - 0136
  • Vienna, Austria, 1090
    • Local Institution - 0132
  • Wien, Austria, 1090
    • Local Institution - 0183
• Belgium
  • Hasselt, Belgium, 3500
    • Local Institution - 0029
  • Liege, Belgium, 4000
    • Local Institution - 0027
• Brazil
  • Rio De Janeiro, Brazil, 20231-050
    • Local Institution - 0231
  • São Paulo, Brazil, 04014-002
    • Local Institution - 0100
  • RIO Grande DO SUL
    • Ijui, RIO Grande DO SUL, Brazil, 98700-000
      • Local Institution - 0071
    • Porto Alegre, RIO Grande DO SUL, Brazil, 90610000
      • Local Institution - 0072
  • SAO Paulo
    • Cerqueira Cesar, SAO Paulo, Brazil, 01246-000
      • Local Institution - 0073
  • Sao Paulo
    • Barretos, Sao Paulo, Brazil, 14780-070
      • Local Institution - 0070
• Canada
  • Montreal, Canada, H2X 0A9
    • Local Institution - 0101
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Local Institution - 0139
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Local Institution - 0109
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Local Institution - 0112
• Chile
  • Temuco, Chile, 4810297
    • Local Institution - 0137
  • Metropolitana
    • Santiago, Metropolitana, Chile
      • Local Institution - 0099
  • Valparaiso
    • Vina Del Mar, Valparaiso, Chile, 2540364
      • Local Institution - 0038
• China
  • Beijing
    • Beijing, Beijing, China, 100001
      • Local Institution - 0191
    • Beijing, Beijing, China, 100034
      • Local Institution - 0206
    • Beijing, Beijing, China, 100050
      • Local Institution - 0192
  • Chongqing
    • Chongqing, Chongqing, China, 400030
      • Local Institution - 0210
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Local Institution - 0198
  • Guangdong
    • Guangzhou, Guangdong, China, 510230
      • Local Institution - 0222
    • Guangzhou, Guangdong, China, 510288
      • Local Institution - 0203
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • Local Institution - 0227
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Local Institution - 0196
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Local Institution - 0220
    • Nanjing, Jiangsu, China, 210029
      • Local Institution - 0204
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Local Institution - 0223
  • Shan3xi
    • Xi'an, Shan3xi, China, 710061
      • Local Institution
  • Shandong
    • Yantai, Shandong, China, 264000
      • Local Institution - 0212
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Local Institution - 0193
    • Shanghai, Shanghai, China, 200032
      • Local Institution - 0202
    • Shanghai, Shanghai, China, 200040
      • Local Institution - 0199
    • Shanghai, Shanghai, China, 200040
      • Local Institution - 0217
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Local Institution - 0229
    • Chengdu, Sichuan, China, 610072
      • Local Institution - 0219
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Local Institution - 0221
    • Hangzhou, Zhejiang, China, 310014
      • Local Institution - 0195
    • Wenzhou, Zhejiang, China, 32500
      • Local Institution - 0230
• Colombia
  • Bogota, Colombia
    • Local Institution - 0092
  • Floridablanca, Colombia, 681004
    • Local Institution - 0093
  • Medellin, Colombia, 050034
    • Local Institution - 0091
• Denmark
  • Aalborg, Denmark, 9100
    • Local Institution - 0108
  • Aarhus N, Denmark, 8200
    • Local Institution - 0106
  • Copenhagen, Denmark, 2100
    • Local Institution - 0107
• France
  • Clermont-ferrand, France, 63000
    • Local Institution - 0233
  • La Roche-sur-Yon, France, 85000
    • Local Institution - 0115
  • Marseille Cedex 9, France, 13273
    • Local Institution - 0080
  • Paris, France, 75475
    • Local Institution - 0081
  • Strasbourg, France, 67200
    • Local Institution - 0113
  • Suresnes, France, 92151
    • Local Institution - 0097
  • Villejuif, France, 94800
    • Local Institution - 0098
• Germany
  • Chemnitz, Germany, 09130
    • Local Institution - 0131
  • Essen, Germany, 45136
    • Local Institution - 0125
  • Greifswald, Germany, 17475
    • Local Institution - 0127
  • Hamburg, Germany, 20246
    • Local Institution - 0126
  • Heidelberg, Germany, 69126
    • Local Institution - 0124
  • Jena, Germany, 07747
    • Local Institution - 0123
  • Marburg, Germany, 35043
    • Local Institution - 0188
  • Muenster, Germany, 48149
    • Local Institution - 0128
  • Munich, Germany, 81675
    • Local Institution - 0122
  • Nuernberg, Germany, 90419
    • Local Institution - 0185
  • Regensburg, Germany, 93053
    • Local Institution - 0130
  • Stuttgart, Germany, 70174
    • Local Institution - 0129
• Greece
  • Athens, Greece, 11528
    • Local Institution - 0110
  • Thessaloniki, Greece, 54007
    • Local Institution - 0111
• Ireland
  • Dublin, Ireland
    • Local Institution - 0052
  • Cork
    • Wilton, Cork, Ireland
      • Local Institution - 0054
• Israel
  • Haifa, Israel, 3109601
    • Local Institution - 0118
  • Jerusalem, Israel, 91120
    • Local Institution - 0121
  • Ramat Gan, Israel, 5262100
    • Local Institution - 0120
  • Zerifin, Israel, 70300
    • Local Institution - 0119
• Italy
  • Arezzo, Italy, 52100
    • Local Institution - 0088
  • Bergamo, Italy, 24127
    • Local Institution - 0197
  • Milano, Italy, 20133
    • Local Institution - 0082
  • Pisa, Italy, 56126
    • Local Institution - 0084
  • Reggio Emilia, Italy, 42100
    • Local Institution - 0189
  • Roma, Italy, 00144
    • Local Institution - 0085
  • Roma, Italy, 00152
    • Local Institution - 0086
  • Siena, Italy, 53100
    • Local Institution - 0083
• Japan
  • Chiba, Japan, 260-8717
    • Local Institution - 0143
  • Osaka, Japan, 5418567
    • Local Institution - 0164
  • Akita
    • Akita-shi, Akita, Japan, 0108543
      • Local Institution - 0142
  • Aomori
    • Hirosaki, Aomori, Japan, 0368563
      • Local Institution - 0144
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan, 8128582
      • Local Institution - 0162
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8543
      • Local Institution - 0160
    • Sapporo-shi, Hokkaido, Japan, 0608648
      • Local Institution - 0161
  • Ibaraki
    • Tsukuba-shi, Ibaraki, Japan, 3058576
      • Local Institution - 0148
  • Nagasaki
    • Nagasaki-shi, Nagasaki, Japan, 8528501
      • Local Institution - 0163
  • Niigata
    • Niigata-shi, Niigata, Japan, 9518520
      • Local Institution - 0150
  • Okayama
    • Okayama-city, Okayama, Japan, 700-8558
      • Local Institution - 0141
  • Osaka
    • Osakasayama, Osaka, Japan, 589-8511
      • Local Institution - 0149
  • Shizuoka
    • Hamamatasu, Shizuoka, Japan, 431-3192
      • Local Institution - 0151
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 1138603
      • Local Institution - 0146
    • Shinjuku-Ku, Tokyo, Japan, 1608582
      • Local Institution - 0145
    • Shinjuku-ku, Tokyo, Japan, 1628666
      • Local Institution - 0147
• Korea, Republic of
  • Seongnam-si, Korea, Republic of, 13620
    • Local Institution - 0155
  • Seoul, Korea, Republic of, 03722
    • Local Institution - 0154
  • Seoul, Korea, Republic of, 05505
    • Local Institution - 0152
  • Seoul, Korea, Republic of, 06351
    • Local Institution - 0156
• Mexico
  • Distrito Federal
    • Df, Distrito Federal, Mexico, 06720
      • Local Institution - 0138
    • Mexico, Distrito Federal, Mexico, 06700
      • Local Institution - 0116
    • Mexico, Distrito Federal, Mexico, 14080
      • Local Institution - 0039
    • Mexico City, Distrito Federal, Mexico, 14080
      • Local Institution - 0034
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44270
      • Local Institution - 0035
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64460
      • Local Institution - 0032
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Local Institution - 0069
  • Maastrict, Netherlands, 6229 HX
    • Local Institution - 0068
  • Nijmegen, Netherlands, 6500 HB
    • Local Institution - 0041
• Peru
  • Lima, Peru, Lima 41
    • Local Institution - 0043
• Poland
  • Gdansk, Poland, 80-214
    • Local Institution - 0055
  • Lodz, Poland, 93-513
    • Local Institution - 0057
  • Warsaw, Poland, 02-797
    • Local Institution - 0187
  • Wroclaw, Poland, 50-556
    • Local Institution - 0058
  • Wroclaw, Poland, 53-413
    • Local Institution - 0186
• Romania
  • Bucuresti, Romania, 021389
    • Local Institution - 0182
  • Craiova, Romania, 200347
    • Local Institution - 0096
  • Floresti, Romania, 407280
    • Local Institution - 0078
  • Timisoara, Timis, Romania, 300239
    • Local Institution - 0181
• Russian Federation
  • Moscow, Russian Federation, 125284
    • Local Institution - 0140
  • Saint-Petersburg, Russian Federation, 197758
    • Local Institution - 0031
• Spain
  • Badalona-barcelona, Spain, 08916
    • Local Institution - 0067
  • Barcelona, Spain, 08035
    • Local Institution - 0066
  • Madrid, Spain, 28007
    • Local Institution - 0064
  • Madrid, Spain, 28034
    • Local Institution - 0062
  • Madrid, Spain, 28041
    • Local Institution - 0063
  • Santander, Spain, 39008
    • Local Institution - 0232
  • Sevilla, Spain, 41013
    • Local Institution - 0065
• Sweden
  • Lund, Sweden, 221 85
    • Local Institution - 0105
• Switzerland
  • Basel, Switzerland, 4031
    • Local Institution - 0134
  • Zuerich, Switzerland, 8038
    • Local Institution - 0135
• Taiwan
  • Kaohsiung, Taiwan, 807
    • Local Institution - 0158
  • Taichung, Taiwan, 404
    • Local Institution - 0159
  • Taipei, Taiwan, 100
    • Local Institution - 0153
• United Kingdom
  • London, United Kingdom, SE1 9RT
    • Local Institution - 0036
  • London, United Kingdom, SW3 6JJ
    • Local Institution - 0114
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M20 4BX
      • Local Institution - 0025
  • Midlothian
    • Edinburgh, Midlothian, United Kingdom, EH4 2XU
      • Local Institution - 0076
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • Local Institution - 0024
  • Yorkshire
    • Sheffield, Yorkshire, United Kingdom, S10 2SJ
      • Local Institution - 0059
• United States
  • Alaska
    • Anchorage, Alaska, United States, 99503
      • Alaska Urological Institute dba Alaska Clinical Research Center
  • Arizona
    • Tucson, Arizona, United States, 85704
      • Local Institution - 0179
  • California
    • Clovis, California, United States, 93611
      • Local Institution - 0061
    • Sacramento, California, United States, 95817
      • Local Institution - 0172
    • San Francisco, California, United States, 94115
      • Local Institution - 0005
  • Colorado
    • Lakewood, Colorado, United States, 80228
      • Local Institution - 0178
  • Florida
    • Gainesville, Florida, United States, 32610
      • Local Institution - 0167
    • Miami Beach, Florida, United States, 33140
      • Local Institution - 0030
    • Tampa, Florida, United States, 33612
      • Local Institution - 0008
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Local Institution - 0168
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Local Institution - 0094
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Local Institution - 0171
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Local Institution - 0173
  • Minnesota
    • Burnsville, Minnesota, United States, 55337
      • Local Institution - 0051
    • Rochester, Minnesota, United States, 55905
      • Local Institution - 0004
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Local Institution - 0003
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Local Institution - 0177
  • New York
    • Albany, New York, United States, 12208
      • Local Institution - 0176
    • Buffalo, New York, United States, 14263
      • Local Institution - 0157
    • Mineola, New York, United States, 11501
      • Local Institution - 0007
    • New York, New York, United States, 10021
      • Local Institution - 0001
    • New York, New York, United States, 10029
      • Local Institution - 0006
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7305
      • Local Institution - 0166
    • Durham, North Carolina, United States, 27708
      • Local Institution
  • Oregon
    • Portland, Oregon, United States, 97213
      • Local Institution - 0044
    • Portland, Oregon, United States, 97239
      • Local Institution - 0010
    • Tigard, Oregon, United States, 97223
      • Local Institution - 0180
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Local Institution - 0074
    • Pittsburgh, Pennsylvania, United States, 15212
      • Local Institution - 0011
    • Pittsburgh, Pennsylvania, United States, 15232
      • Local Institution - 0040
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Local Institution - 0169
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Local Institution - 0009
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Local Institution - 0234

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Must have had invasive urothelial cancer at high risk of recurrence originating in the bladder, ureter, or renal pelvis
• Must have had radical surgical resection (e.g. radical cystectomy), performed within the last 120 days
• Must have disease free status as determined by imaging within 4 weeks of dosing
• Tumor tissue must be provided for biomarker analysis
• Patients who have not received prior neoadjuvant cisplatin chemotherapy must be ineligible for or refuse cisplatin-based adjuvant chemotherapy

Exclusion Criteria:

• Partial bladder or partial kidney removal (eg, partial cystectomy or partial nephrectomy)
• Secondary Treatment (eg, adjuvant systemic chemotherapy for bladder cancer) following surgical removal of bladder cancer
• Subjects with active, known or suspected autoimmune disease
• Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured
• Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 day of study drug administration
• Positive test for hepatitis B virus surface antigen (HBV s Ag) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nivolumab; Nivolumab dose as specified	Biological: Nivolumab
Placebo Comparator: Placebo; Placebo dose as specified	Other: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Free Survival (DFS)	The time between the date of randomization and the date of first documented recurrence (local urothelial tract, local non-urothelial tract or distant), or death due to any cause, whichever occurs first.	approximately up to 48 months
Disease Free Survival (DFS) in PD-L1 Expression ≥ 1% Population	The time between the date of randomization and the date of first documented recurrence (local urothelial tract, local non-urothelial tract or distant), or death due to any cause, whichever occurs first.	approximately up to 48 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-Urothelial Tract Recurrence Free Survival	The time between the date of randomization and the date of first documented recurrence (local non-urothelial tract or distant), or death due to any cause, whichever occurs first.	up to 53 months
Non-Urothelial Tract Recurrence Free Survival in PD-L1 Expression ≥ 1% Population	The time between the date of randomization and the date of first documented recurrence (local non-urothelial tract or distant), or death due to any cause, whichever occurs first.	up to 53 months
Overall Survival	the time from randomization to the date of death from any cause.	on going
Overall Survival in Participants With PD-L1 Expression ≥ 1%	the time from randomization to the date of death from any cause.	on going
Disease Specific Survival	the time from randomization to the date of death due to disease (urothelial cancer).	on going
Disease Specific Survival in Participants With PD-L1 Expression ≥ 1%	the time from randomization to the date of death due to disease (urothelial cancer).	on going

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: Ono Pharmaceutical Co. Ltd
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

General Publications

• Bajorin DF, Witjes JA, Gschwend JE, Schenker M, Valderrama BP, Tomita Y, Bamias A, Lebret T, Shariat SF, Park SH, Ye D, Agerbaek M, Enting D, McDermott R, Gajate P, Peer A, Milowsky MI, Nosov A, Neif Antonio J Jr, Tupikowski K, Toms L, Fischer BS, Qureshi A, Collette S, Unsal-Kacmaz K, Broughton E, Zardavas D, Koon HB, Galsky MD. Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma. N Engl J Med. 2021 Jun 3;384(22):2102-2114. doi: 10.1056/NEJMoa2034442. Erratum In: N Engl J Med. 2021 Aug 26;385(9):864.

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2016
• Primary Completion (Actual): July 17, 2020
• Study Completion (Estimated): May 27, 2027

Study Registration Dates

• First Submitted: December 14, 2015
• First Submitted That Met QC Criteria: December 15, 2015
• First Posted (Estimated): December 16, 2015

Study Record Updates

• Last Update Posted (Estimated): January 8, 2024
• Last Update Submitted That Met QC Criteria: January 2, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: CA209-274; 2014-003626-40 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No