Clinical trial NCT02538666: An Investigational Immuno-therapy Study of Nivolumab, or Nivolumab in Combination With Ipilimumab, or Placebo in Patients With Extensive-Stage Disease Small Cell Lung Cancer (ED-SCLC) After Completion of Platinum-based Chemotherapy
Official title: A Randomized, Multicenter, Double-Blind, Phase 3 Study of Nivolumab, Nivolumab in Combination With Ipilimumab, or Placebo as Maintenance Therapy in Subjects With Extensive-Stage Disease Small Cell Lung Cancer (ED-SCLC) After Completion of Platinum-based First Line Chemotherapy (CheckMate 451: CHECKpoint Pathway and nivoluMAb Clinical Trial Evaluation 451)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lung Cancer
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Ono Pharmaceutical Co. Ltd
First posted: 2015-09-02
Enrollment: 907
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In this study, all patients must have already completed first-line chemotherapy to treat extensive-stage disease small cell lung cancer. The purpose of this study is to show that nivolumab, or nivolumab plus ipilimumab followed by nivolumab by itself, will prolong overall survival when administered as consolidation treatment in patients that are stable or responding after chemotherapy. Patients receiving treatment will be compared with patients taking placebo.


Eligibility criteria: Inclusion Criteria:

* Subjects with histologically or cytologically confirmed extensive stage disease SCLC
* Ongoing response of stable disease or better following 4 cycles of platinum-based first line chemotherapy
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria:

* Subjects with symptomatic Central Nervous System (CNS) metastases
* Subjects receiving consolidative chest radiation
* Subjects with active, known, or suspected autoimmune disease are excluded
* All side effects attributed to prior anti-cancer therapy must have resolved to Grade 1 or baseline

Other protocol-defined inclusion/exclusion criteria apply

Primary outcomes:
measure: Overall Survival (OS) of Nivolumab + Ipilimumab Versus Placebo In The Global Population
timeFrame: From randomization to 400 deaths across the two treatment groups (Nivo+Ipi vs Placebo) (up to approximately 37 months)
Secondary outcomes:
measure: Overall Survival (OS) of Nivolumab Versus Placebo
timeFrame: From randomization to the date of death or last known alive date (up to approximately 73 months)
measure: Overall Survival (OS) of Nivolumab + Ipilimumab Versus Nivolumab
timeFrame: From randomization to the date of death or last known alive date (up to approximately 73 months)
measure: Progression Free Survival (PFS) Per BICR
timeFrame: From randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 73 months)
measure: Overall Survival (OS) in Tumor Mutational Burden (TMB) High and Low Subgroups by TMB Cutoff In The Global Population
timeFrame: From randomization to the date of death or last known alive date (up to approximately 73 months)
measure: Progression Free Survival (PFS) Per BICR in Tumor Mutational Burden (TMB) High and Low Subgroups by TMB Cutoff In The Global Population
timeFrame: From randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 73 months)
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: Local Institution - 0003
state: California
city: New Haven
country: United States
facility: Local Institution - 0202
state: Connecticut
city: Fort Myers
country: United States
facility: Local Institution - 0127
state: Florida
city: Jacksonville
country: United States
facility: Local Institution - 0007
state: Florida
city: Saint Petersburg
country: United States
facility: Local Institution - 0128
state: Florida
city: Atlanta
country: United States
facility: Local Institution - 0010
state: Georgia
city: Indianapolis
country: United States
facility: Local Institution - 0013
state: Indiana
city: Fairway
country: United States
facility: Local Institution - 0061
state: Kansas
city: Wichita
country: United States
facility: Local Institution - 0012
state: Kansas
city: Lexington
country: United States
facility: Local Institution - 0032
state: Kentucky
city: Baltimore
country: United States
facility: Local Institution - 0051
state: Maryland
city: Boston
country: United States
facility: Local Institution - 0107
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0207
state: Massachusetts
city: Saint Louis
country: United States
facility: Local Institution - 0015
state: Missouri
city: New York
country: United States
facility: Local Institution - 0008
state: New York
city: Durham
country: United States
facility: Local Institution - 0014
state: North Carolina
city: Winston-Salem
country: United States
facility: Local Institution - 0016
state: North Carolina
city: Fargo
country: United States
facility: Local Institution - 0215
state: North Dakota
city: Cincinnati
country: United States
facility: Local Institution - 0129
state: Ohio
city: Columbus
country: United States
facility: Local Institution - 0009
state: Ohio
city: Portland
country: United States
facility: Local Institution - 0001
state: Oregon
city: Portland
country: United States
facility: Local Institution - 0034
state: Oregon
city: Allentown
country: United States
facility: Local Institution - 0004
state: Pennsylvania
city: Sayre
country: United States
facility: Local Institution - 0002
state: Pennsylvania
city: Charleston
country: United States
facility: Local Institution - 0005
state: South Carolina
city: Sioux Falls
country: United States
facility: Local Institution - 0213
state: South Dakota
city: Salt Lake City
country: United States
facility: Local Institution - 0011
state: Utah
city: Richmond
country: United States
facility: Local Institution - 0006
state: Virginia
city: Berazategui
country: Argentina
facility: Local Institution - 0110
state: Buenos Aires
city: Capital Federal
country: Argentina
facility: Local Institution - 0088
state: Buenos Aires
city: Ciudad Autonoma De Buenos Aire
country: Argentina
facility: Local Institution - 0109
state: Buenos Aires
city: Cordoba
country: Argentina
facility: Local Institution - 0188
city: Tucuman
country: Argentina
facility: Local Institution - 0029
city: Kogarah
country: Australia
facility: Local Institution
state: New South Wales
city: Wollongong
country: Australia
facility: Local Institution
state: New South Wales
city: Birtinya
country: Australia
facility: Local Institution
state: Queensland
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Local Institution - 0137
state: South Australia
city: East Melbourne
country: Australia
facility: Local Institution - 0035
state: Victoria
city: Innsbruck
country: Austria
facility: Local Institution - 0174
city: Salzburg
country: Austria
facility: Local Institution - 0173
city: Wien
country: Austria
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city: Brussels
country: Belgium
facility: Local Institution - 0057
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country: Belgium
facility: Local Institution - 0059
city: Roeselare
country: Belgium
facility: Local Institution - 0060
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country: Brazil
facility: Local Institution - 0067
state: Ceara
city: Belo Horizonte
country: Brazil
facility: Local Institution - 0068
state: Minas Gerais
city: Ijui
country: Brazil
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state: RIO Grande DO SUL
city: Porto Alegre
country: Brazil
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state: RIO Grande DO SUL
city: Itajai
country: Brazil
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state: Santa Catarina
city: Barretos
country: Brazil
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state: Sao Paulo
city: Rio de Janeiro
country: Brazil
facility: Local Institution
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city: Edmonton
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facility: Local Institution - 0094
state: Alberta
city: Moncton
country: Canada
facility: Local Institution - 0136
state: New Brunswick
city: Oshawa
country: Canada
facility: Local Institution - 0123
state: Ontario
city: Sudbury
country: Canada
facility: Local Institution - 0102
state: Ontario
city: Windsor
country: Canada
facility: Local Institution - 0111
state: Ontario
city: Hefei
country: China
facility: Local Institution - 0238
state: Anhui
city: Hefei
country: China
facility: Local Institution - 0243
state: Anhui
city: Beijing
country: China
facility: Local Institution
state: Beijing
city: Beijing
country: China
facility: Local Institution
state: Beijing
city: Harbin
country: China
facility: Local Institution - 0221
state: Heilongjiang
city: Wuhang
country: China
facility: Local Institution - 0244
state: Hubei
city: Nantong
country: China
facility: Local Institution - 0248
state: Jiangsu
city: Nanchang
country: China
facility: Local Institution - 0230
state: Jiangxi
city: Changchun
country: China
facility: Local Institution
state: Jilin
city: Shenyang
country: China
facility: Local Institution - 0237
state: Liaoning
city: Shanghai
country: China
facility: Local Institution - 0220
state: Shanghai
city: Shanghai
country: China
facility: Local Institution - 0228
state: Shanghai
city: Shanghai
country: China
facility: Local Institution - 0233
state: Shanghai
city: Shanghai
country: China
facility: Local Institution - 0245
state: Shanghai
city: Kunming
country: China
facility: Local Institution - 0232
state: Yunnan
city: Hangzhou
country: China
facility: Local Institution - 0239
state: Zhejiang
city: Hangzhou
country: China
facility: Local Institution - 0227
state: Zhejiang
city: Wenzhou
country: China
facility: Local Institution - 0246
state: Zhejiang
city: Changsha
country: China
facility: Local Institution - 0247
city: Guangzhou
country: China
facility: Local Institution - 0240
city: Monteria
country: Colombia
facility: Local Institution
state: Cordoba
city: Bogota
country: Colombia
facility: Local Institution - 0078
city: Medellin
country: Colombia
facility: Local Institution
city: Oulu
country: Finland
facility: Local Institution - 0044
city: Tampere
country: Finland
facility: Local Institution - 0043
city: Turku
country: Finland
facility: Local Institution - 0045
city: Vaasa
country: Finland
facility: Local Institution - 0046
city: Strasbourg
country: France
facility: Local Institution - 0149
state: Alsace
city: Avignon Cedes 9
country: France
facility: Local Institution - 0208
city: Lyon Cedex 08
country: France
facility: Local Institution - 0099
city: Marseille Cedex 20
country: France
facility: Local Institution - 0098
city: Paris Cedex 20
country: France
facility: Local Institution - 0097
city: Pierre Benite
country: France
facility: Local Institution - 0095
city: Rennes Cedex 9
country: France
facility: Local Institution - 0100
city: Saint Herblain
country: France
facility: Local Institution - 0150
city: Toulouse
country: France
facility: Local Institution - 0096
city: Augsburg
country: Germany
facility: Local Institution - 0171
city: Bad Berka
country: Germany
facility: Local Institution - 0170
city: Berlin
country: Germany
facility: Local Institution - 0168
city: Bochum
country: Germany
facility: Local Institution - 0164
city: Gauting
country: Germany
facility: Local Institution - 0166
city: Grosshansdorf
country: Germany
facility: Local Institution - 0165
city: Immenhausen
country: Germany
facility: Local Institution - 0169
city: Tübingen
country: Germany
facility: Local Institution - 0167
city: N.Kifissia
country: Greece
facility: Local Institution - 0080
city: Thessaloniki
country: Greece
facility: Interbalkan European Medical Center
city: Hong Kong
country: Hong Kong
facility: Local Institution - 0052
city: Wilton
country: Ireland
facility: Local Institution - 0161
state: Cork
city: Dublin
country: Ireland
facility: Local Institution - 0175
city: Dublin
country: Ireland
facility: Local Institution
city: Galway
country: Ireland
facility: Local Institution - 0162
city: Limerick
country: Ireland
facility: Local Institution - 0214
city: Haifa
country: Israel
facility: Local Institution
city: Jerusalem
country: Israel
facility: Local Institution - 0093
city: Petach Tikva
country: Israel
facility: Local Institution
city: Tel Aviv
country: Israel
facility: Local Institution - 0090
city: Zerifin
country: Israel
facility: Local Institution - 0089
city: Milan
country: Italy
facility: Local Institution - 0027
state: Lombardia
city: Avellino
country: Italy
facility: Local Institution - 0026
city: Bologna
country: Italy
facility: Local Institution - 0025
city: Messina
country: Italy
facility: Local Institution - 0112
city: Perugia
country: Italy
facility: Local Institution - 0082
city: Kashiwa-shi
country: Japan
facility: Local Institution - 0139
state: Chiba
city: Matsuyama-shi
country: Japan
facility: Local Institution - 0142
state: Ehime
city: Fukuoka-shi
country: Japan
facility: Local Institution - 0146
state: Fukuoka
city: Kurume-shi
country: Japan
facility: Local Institution - 0200
state: Fukuoka
city: Gifu-shi
country: Japan
facility: Local Institution - 0198
state: Gifu
city: Sapporo-shi
country: Japan
facility: Local Institution - 0143
state: Hokkaido
city: Kobe-shi
country: Japan
facility: Local Institution - 0076
state: Hyogo
city: Kanazawa-shi
country: Japan
facility: Local Institution - 0138
state: Ishikawa
city: Yokohama-shi
country: Japan
facility: Local Institution - 0072
state: Kanagawa
city: Sendai-shi
country: Japan
facility: Local Institution - 0070
state: Miyagi
city: Sendai-shi
country: Japan
facility: Local Institution - 0069
state: Miyagi
city: Kurashiki-shi
country: Japan
facility: Local Institution - 0077
state: Okayama
city: Hirakata-shi
country: Japan
facility: Local Institution
state: Osaka
city: Osaka-sayama-shi
country: Japan
facility: Local Institution - 0075
state: Osaka
city: Osaka-shi
country: Japan
facility: Local Institution - 0145
state: Osaka
city: Takatsuki-shi
country: Japan
facility: Local Institution - 0083
state: Osaka
city: Hidaka
country: Japan
facility: Local Institution - 0193
state: Saitama
city: Bunkyo-ku
country: Japan
facility: Local Institution - 0141
state: Tokyo
city: Chuo-ku
country: Japan
facility: Local Institution - 0071
state: Tokyo
city: Koto-ku
country: Japan
facility: Local Institution - 0140
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Local Institution - 0144
state: Tokyo
city: Wakayama
country: Japan
facility: Local Institution - 0216
city: Seongnam-si
country: Korea, Republic of
facility: Local Institution - 0047
state: Gyeonggi-do
city: Suwon
country: Korea, Republic of
facility: Local Institution - 0024
state: Kyǒnggi-do
city: Gangnam-gu
country: Korea, Republic of
facility: Local Institution - 0021
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0022
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0154
city: Mexico
country: Mexico
facility: Local Institution - 0019
state: Distrito Federal
city: Leon de los Aldama
country: Mexico
facility: Local Institution - 0020
state: Guanajuato
city: Monterrey
country: Mexico
facility: Local Institution - 0028
state: Nuevo Leon
city: Queretaro
country: Mexico
facility: Local Institution - 0135
city: 's-Hertogenbosch
country: Netherlands
facility: Local Institution - 0158
city: Eindhoven
country: Netherlands
facility: Local Institution
city: Rotterdam
country: Netherlands
facility: Local Institution - 0159
city: Miraflores
country: Peru
facility: Local Institution
state: Lima
city: Lima
country: Peru
facility: Local Institution
city: Lima
country: Peru
facility: Local Institution
city: Gdansk
country: Poland
facility: Local Institution - 0041
city: Gdynia
country: Poland
facility: Local Institution - 0054
city: Olsztyn
country: Poland
facility: Local Institution - 0053
city: Warszawa
country: Poland
facility: Local Institution - 0187
city: Bucharest
country: Romania
facility: Local Institution - 0199
city: Bucharest
country: Romania
facility: Local Institution - 0186
city: Craiova
country: Romania
facility: Local Institution - 0182
city: Lasi
country: Romania
facility: Local Institution - 0178
city: Romania
country: Romania
facility: Local Institution - 0212
city: Timisoara, Timis
country: Romania
facility: Local Institution - 0181
city: Moscow
country: Russian Federation
facility: Local Institution - 0148
city: Moscow
country: Russian Federation
facility: Local Institution - 0217
city: Moscow
country: Russian Federation
facility: Local Institution - 0209
city: St Petersburg
country: Russian Federation
facility: Local Institution - 0157
city: St Petersburg
country: Russian Federation
facility: Local Institution - 0115
city: St. Petersburg
country: Russian Federation
facility: Local Institution - 0116
city: Singapore
country: Singapore
facility: Local Institution - 0050
city: Sandton
country: South Africa
facility: Local Institution - 0087
state: Gauteng
city: Cape Town
country: South Africa
facility: Local Institution - 0084
state: Western Cape
city: Cape Town
country: South Africa
facility: Local Institution - 0085
state: Western CAPE
city: George
country: South Africa
facility: Local Institution - 0086
state: Western CAPE
city: Barcelona
country: Spain
facility: Local Institution - 0132
city: Barcelona
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Malaga
country: Spain
facility: Local Institution
city: Sevilla
country: Spain
facility: Local Institution
city: Lund
country: Sweden
facility: Local Institution - 0124
city: Uppsala
country: Sweden
facility: Local Institution - 0185
city: Aarau
country: Switzerland
facility: Local Institution - 0179
city: Geneve
country: Switzerland
facility: Local Institution - 0180
city: St. Gallen
country: Switzerland
facility: Local Institution - 0191
city: Tainan
country: Taiwan
facility: Local Institution - 0049
state: TNN
city: Taoyuan
country: Taiwan
facility: Local Institution - 0048
city: Truro
country: United Kingdom
facility: Local Institution - 0153
state: Cornwall
city: London
country: United Kingdom
facility: Local Institution - 0118
state: Greater London
city: London
country: United Kingdom
facility: Local Institution - 0201
state: Greater London
city: Wirral
country: United Kingdom
facility: Local Institution - 0121
state: Lancashire
city: Oxford
country: United Kingdom
facility: Local Institution - 0152
state: Oxfordshire
city: Sutton
country: United Kingdom
facility: Local Institution - 0151
state: Surrey
city: Sheffield
country: United Kingdom
facility: Local Institution - 0192
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Kang YK, Reck M, Nghiem P, Feng Y, Plautz G, Kim HR, Owonikoko TK, Boku N, Chen LT, Lei M, Chang H, Lin WH, Roy A, Bello A, Sheng J. Assessment of hyperprogression versus the natural course of disease development with nivolumab with or without ipilimumab versus placebo in phase III, randomized, controlled trials. J Immunother Cancer. 2022 Apr;10(4):e004273. doi: 10.1136/jitc-2021-004273.
citation: Owonikoko TK, Park K, Govindan R, Ready N, Reck M, Peters S, Dakhil SR, Navarro A, Rodriguez-Cid J, Schenker M, Lee JS, Gutierrez V, Percent I, Morgensztern D, Barrios CH, Greillier L, Baka S, Patel M, Lin WH, Selvaggi G, Baudelet C, Baden J, Pandya D, Doshi P, Kim HR. Nivolumab and Ipilimumab as Maintenance Therapy in Extensive-Disease Small-Cell Lung Cancer: CheckMate 451. J Clin Oncol. 2021 Apr 20;39(12):1349-1359. doi: 10.1200/JCO.20.02212. Epub 2021 Mar 8.