Trial Review

Did you know?

The ANZCTR now automatically displays published trial results and simplifies the addition of trial documents such as unpublished protocols and statistical analysis plans.

These enhancements will offer a more comprehensive view of trials, regardless of whether their results are positive, negative, or inconclusive.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02538666




Registration number
NCT02538666
Ethics application status
Date submitted
26/08/2015
Date registered
2/09/2015
Date last updated
5/01/2023

Titles & IDs
Public title
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
Scientific 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)
Secondary ID [1] 0 0
2015-002441-61
Secondary ID [2] 0 0
CA209-451
Universal Trial Number (UTN)
Trial acronym
CheckMate 451
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Experimental: Nivolumab monotherapy - Nivolumab intravenous fusion

Experimental: Nivolumab and ipilimumab combination therapy - Nivolumab and ipilimumab intravenous fusion

Placebo comparator: Placebo - Placebo
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS) of Nivolumab + Ipilimumab Versus Placebo In The Global Population
Timepoint [1] 0 0
From randomization to 400 deaths across the two treatment groups (Nivo+Ipi vs Placebo) (up to approximately 37 months)
Secondary outcome [1] 0 0
Overall Survival (OS) of Nivolumab Versus Placebo
Timepoint [1] 0 0
From randomization to the date of death or last known alive date (up to approximately 73 months)
Secondary outcome [2] 0 0
Overall Survival (OS) of Nivolumab + Ipilimumab Versus Nivolumab
Timepoint [2] 0 0
From randomization to the date of death or last known alive date (up to approximately 73 months)
Secondary outcome [3] 0 0
Progression Free Survival (PFS) Per BICR
Timepoint [3] 0 0
From randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 73 months)
Secondary outcome [4] 0 0
Overall Survival (OS) in Tumor Mutational Burden (TMB) High and Low Subgroups by TMB Cutoff In The Global Population
Timepoint [4] 0 0
From randomization to the date of death or last known alive date (up to approximately 73 months)
Secondary outcome [5] 0 0
Progression Free Survival (PFS) Per BICR in Tumor Mutational Burden (TMB) High and Low Subgroups by TMB Cutoff In The Global Population
Timepoint [5] 0 0
From randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 73 months)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/10/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
11/11/2021
Sample size
Target
Accrual to date
Final
907
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Local Institution - Kogarah
Recruitment hospital [2] 0 0
Local Institution - Wollongong
Recruitment hospital [3] 0 0
Local Institution - Birtinya
Recruitment hospital [4] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [5] 0 0
Local Institution - 0137 - Adelaide
Recruitment hospital [6] 0 0
Local Institution - 0035 - East Melbourne
Recruitment postcode(s) [1] 0 0
- Kogarah
Recruitment postcode(s) [2] 0 0
2500 - Wollongong
Recruitment postcode(s) [3] 0 0
4575 - Birtinya
Recruitment postcode(s) [4] 0 0
4102 - Brisbane
Recruitment postcode(s) [5] 0 0
5000 - Adelaide
Recruitment postcode(s) [6] 0 0
3165 - East Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Kansas
Country [7] 0 0
United States of America
State/province [7] 0 0
Kentucky
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Missouri
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
North Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
North Dakota
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Oregon
Country [16] 0 0
United States of America
State/province [16] 0 0
Pennsylvania
Country [17] 0 0
United States of America
State/province [17] 0 0
South Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
South Dakota
Country [19] 0 0
United States of America
State/province [19] 0 0
Utah
Country [20] 0 0
United States of America
State/province [20] 0 0
Virginia
Country [21] 0 0
Argentina
State/province [21] 0 0
Buenos Aires
Country [22] 0 0
Argentina
State/province [22] 0 0
Cordoba
Country [23] 0 0
Argentina
State/province [23] 0 0
Tucuman
Country [24] 0 0
Austria
State/province [24] 0 0
Innsbruck
Country [25] 0 0
Austria
State/province [25] 0 0
Salzburg
Country [26] 0 0
Austria
State/province [26] 0 0
Wien
Country [27] 0 0
Belgium
State/province [27] 0 0
Brussels
Country [28] 0 0
Belgium
State/province [28] 0 0
Charleroi
Country [29] 0 0
Belgium
State/province [29] 0 0
Roeselare
Country [30] 0 0
Brazil
State/province [30] 0 0
Ceara
Country [31] 0 0
Brazil
State/province [31] 0 0
Minas Gerais
Country [32] 0 0
Brazil
State/province [32] 0 0
RIO Grande DO SUL
Country [33] 0 0
Brazil
State/province [33] 0 0
Santa Catarina
Country [34] 0 0
Brazil
State/province [34] 0 0
Sao Paulo
Country [35] 0 0
Brazil
State/province [35] 0 0
Rio de Janeiro
Country [36] 0 0
Brazil
State/province [36] 0 0
Salvador
Country [37] 0 0
Canada
State/province [37] 0 0
Alberta
Country [38] 0 0
Canada
State/province [38] 0 0
New Brunswick
Country [39] 0 0
Canada
State/province [39] 0 0
Ontario
Country [40] 0 0
China
State/province [40] 0 0
Anhui
Country [41] 0 0
China
State/province [41] 0 0
Beijing
Country [42] 0 0
China
State/province [42] 0 0
Heilongjiang
Country [43] 0 0
China
State/province [43] 0 0
Hubei
Country [44] 0 0
China
State/province [44] 0 0
Jiangsu
Country [45] 0 0
China
State/province [45] 0 0
Jiangxi
Country [46] 0 0
China
State/province [46] 0 0
Jilin
Country [47] 0 0
China
State/province [47] 0 0
Liaoning
Country [48] 0 0
China
State/province [48] 0 0
Shanghai
Country [49] 0 0
China
State/province [49] 0 0
Yunnan
Country [50] 0 0
China
State/province [50] 0 0
Zhejiang
Country [51] 0 0
China
State/province [51] 0 0
Changsha
Country [52] 0 0
China
State/province [52] 0 0
Guangzhou
Country [53] 0 0
Colombia
State/province [53] 0 0
Cordoba
Country [54] 0 0
Colombia
State/province [54] 0 0
Bogota
Country [55] 0 0
Colombia
State/province [55] 0 0
Medellin
Country [56] 0 0
Finland
State/province [56] 0 0
Oulu
Country [57] 0 0
Finland
State/province [57] 0 0
Tampere
Country [58] 0 0
Finland
State/province [58] 0 0
Turku
Country [59] 0 0
Finland
State/province [59] 0 0
Vaasa
Country [60] 0 0
France
State/province [60] 0 0
Alsace
Country [61] 0 0
France
State/province [61] 0 0
Avignon Cedes 9
Country [62] 0 0
France
State/province [62] 0 0
Lyon Cedex 08
Country [63] 0 0
France
State/province [63] 0 0
Marseille Cedex 20
Country [64] 0 0
France
State/province [64] 0 0
Paris Cedex 20
Country [65] 0 0
France
State/province [65] 0 0
Pierre Benite
Country [66] 0 0
France
State/province [66] 0 0
Rennes Cedex 9
Country [67] 0 0
France
State/province [67] 0 0
Saint Herblain
Country [68] 0 0
France
State/province [68] 0 0
Toulouse
Country [69] 0 0
Germany
State/province [69] 0 0
Augsburg
Country [70] 0 0
Germany
State/province [70] 0 0
Bad Berka
Country [71] 0 0
Germany
State/province [71] 0 0
Berlin
Country [72] 0 0
Germany
State/province [72] 0 0
Bochum
Country [73] 0 0
Germany
State/province [73] 0 0
Gauting
Country [74] 0 0
Germany
State/province [74] 0 0
Grosshansdorf
Country [75] 0 0
Germany
State/province [75] 0 0
Immenhausen
Country [76] 0 0
Germany
State/province [76] 0 0
Tübingen
Country [77] 0 0
Greece
State/province [77] 0 0
N.Kifissia
Country [78] 0 0
Greece
State/province [78] 0 0
Thessaloniki
Country [79] 0 0
Hong Kong
State/province [79] 0 0
Hong Kong
Country [80] 0 0
Ireland
State/province [80] 0 0
Cork
Country [81] 0 0
Ireland
State/province [81] 0 0
Dublin
Country [82] 0 0
Ireland
State/province [82] 0 0
Galway
Country [83] 0 0
Ireland
State/province [83] 0 0
Limerick
Country [84] 0 0
Israel
State/province [84] 0 0
Haifa
Country [85] 0 0
Israel
State/province [85] 0 0
Jerusalem
Country [86] 0 0
Israel
State/province [86] 0 0
Petach Tikva
Country [87] 0 0
Israel
State/province [87] 0 0
Tel Aviv
Country [88] 0 0
Israel
State/province [88] 0 0
Zerifin
Country [89] 0 0
Italy
State/province [89] 0 0
Lombardia
Country [90] 0 0
Italy
State/province [90] 0 0
Avellino
Country [91] 0 0
Italy
State/province [91] 0 0
Bologna
Country [92] 0 0
Italy
State/province [92] 0 0
Messina
Country [93] 0 0
Italy
State/province [93] 0 0
Perugia
Country [94] 0 0
Japan
State/province [94] 0 0
Chiba
Country [95] 0 0
Japan
State/province [95] 0 0
Ehime
Country [96] 0 0
Japan
State/province [96] 0 0
Fukuoka
Country [97] 0 0
Japan
State/province [97] 0 0
Gifu
Country [98] 0 0
Japan
State/province [98] 0 0
Hokkaido
Country [99] 0 0
Japan
State/province [99] 0 0
Hyogo
Country [100] 0 0
Japan
State/province [100] 0 0
Ishikawa
Country [101] 0 0
Japan
State/province [101] 0 0
Kanagawa
Country [102] 0 0
Japan
State/province [102] 0 0
Miyagi
Country [103] 0 0
Japan
State/province [103] 0 0
Okayama
Country [104] 0 0
Japan
State/province [104] 0 0
Osaka
Country [105] 0 0
Japan
State/province [105] 0 0
Saitama
Country [106] 0 0
Japan
State/province [106] 0 0
Tokyo
Country [107] 0 0
Japan
State/province [107] 0 0
Wakayama
Country [108] 0 0
Korea, Republic of
State/province [108] 0 0
Gyeonggi-do
Country [109] 0 0
Korea, Republic of
State/province [109] 0 0
Kyonggi-do
Country [110] 0 0
Korea, Republic of
State/province [110] 0 0
Gangnam-gu
Country [111] 0 0
Korea, Republic of
State/province [111] 0 0
Seoul
Country [112] 0 0
Mexico
State/province [112] 0 0
Distrito Federal
Country [113] 0 0
Mexico
State/province [113] 0 0
Guanajuato
Country [114] 0 0
Mexico
State/province [114] 0 0
Nuevo Leon
Country [115] 0 0
Mexico
State/province [115] 0 0
Queretaro
Country [116] 0 0
Netherlands
State/province [116] 0 0
's-Hertogenbosch
Country [117] 0 0
Netherlands
State/province [117] 0 0
Eindhoven
Country [118] 0 0
Netherlands
State/province [118] 0 0
Rotterdam
Country [119] 0 0
Peru
State/province [119] 0 0
Lima
Country [120] 0 0
Poland
State/province [120] 0 0
Gdansk
Country [121] 0 0
Poland
State/province [121] 0 0
Gdynia
Country [122] 0 0
Poland
State/province [122] 0 0
Olsztyn
Country [123] 0 0
Poland
State/province [123] 0 0
Warszawa
Country [124] 0 0
Romania
State/province [124] 0 0
Bucharest
Country [125] 0 0
Romania
State/province [125] 0 0
Craiova
Country [126] 0 0
Romania
State/province [126] 0 0
Lasi
Country [127] 0 0
Romania
State/province [127] 0 0
Romania
Country [128] 0 0
Romania
State/province [128] 0 0
Timisoara, Timis
Country [129] 0 0
Russian Federation
State/province [129] 0 0
Moscow
Country [130] 0 0
Russian Federation
State/province [130] 0 0
St Petersburg
Country [131] 0 0
Russian Federation
State/province [131] 0 0
St. Petersburg
Country [132] 0 0
Singapore
State/province [132] 0 0
Singapore
Country [133] 0 0
South Africa
State/province [133] 0 0
Gauteng
Country [134] 0 0
South Africa
State/province [134] 0 0
Western Cape
Country [135] 0 0
South Africa
State/province [135] 0 0
Western CAPE
Country [136] 0 0
Spain
State/province [136] 0 0
Barcelona
Country [137] 0 0
Spain
State/province [137] 0 0
Madrid
Country [138] 0 0
Spain
State/province [138] 0 0
Malaga
Country [139] 0 0
Spain
State/province [139] 0 0
Sevilla
Country [140] 0 0
Sweden
State/province [140] 0 0
Lund
Country [141] 0 0
Sweden
State/province [141] 0 0
Uppsala
Country [142] 0 0
Switzerland
State/province [142] 0 0
Aarau
Country [143] 0 0
Switzerland
State/province [143] 0 0
Geneve
Country [144] 0 0
Switzerland
State/province [144] 0 0
St. Gallen
Country [145] 0 0
Taiwan
State/province [145] 0 0
TNN
Country [146] 0 0
Taiwan
State/province [146] 0 0
Taoyuan
Country [147] 0 0
United Kingdom
State/province [147] 0 0
Cornwall
Country [148] 0 0
United Kingdom
State/province [148] 0 0
Greater London
Country [149] 0 0
United Kingdom
State/province [149] 0 0
Lancashire
Country [150] 0 0
United Kingdom
State/province [150] 0 0
Oxfordshire
Country [151] 0 0
United Kingdom
State/province [151] 0 0
Surrey
Country [152] 0 0
United Kingdom
State/province [152] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bristol-Myers Squibb
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Ono Pharmaceutical Co. Ltd
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT02538666
Trial related presentations / publications
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Bristol Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02538666