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

Lung Cancer Clinical Trial

— CheckMate 451  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02538666
• Other study ID #: CA209-451
• Secondary ID: 2015-002441-61
• Status: Completed
• Phase: Phase 3
• Start date: October 13, 2015
• Est. completion date: November 11, 2021

Study information

• Verified date: December 2022
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 907
• Est. completion date: November 11, 2021
• Est. primary completion date: October 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms
• Small Cell Lung Carcinoma

Intervention

Biological:
• Nivolumab

• Ipilimumab

Other:
• Placebo

Locations

Country	Name	City	State
Argentina	Local Institution - 0110	Berazategui	Buenos Aires
Argentina	Local Institution - 0088	Capital Federal	Buenos Aires
Argentina	Local Institution - 0109	Ciudad Autonoma De Buenos Aire	Buenos Aires
Argentina	Local Institution - 0188	Cordoba
Argentina	Local Institution - 0029	Tucuman
Australia	Local Institution - 0137	Adelaide	South Australia
Australia	Local Institution	Birtinya	Queensland
Australia	Princess Alexandra Hospital	Brisbane	Queensland
Australia	Local Institution - 0035	East Melbourne	Victoria
Australia	Local Institution	Kogarah	New South Wales
Australia	Local Institution	Wollongong	New South Wales
Austria	Local Institution - 0174	Innsbruck
Austria	Local Institution - 0173	Salzburg
Austria	Local Institution - 0172	Wien
Belgium	Local Institution - 0057	Brussels
Belgium	Local Institution - 0059	Charleroi
Belgium	Local Institution - 0060	Roeselare
Brazil	Local Institution - 0081	Barretos	Sao Paulo
Brazil	Local Institution - 0068	Belo Horizonte	Minas Gerais
Brazil	Local Institution - 0067	Fortaleza	Ceara
Brazil	Local Institution - 0063	Ijui	RIO Grande DO SUL
Brazil	Local Institution - 0017	Itajai	Santa Catarina
Brazil	Local Institution - 0064	Porto Alegre	RIO Grande DO SUL
Brazil	Local Institution	Rio de Janeiro
Brazil	Local Institution	Salvador
Canada	Local Institution - 0094	Edmonton	Alberta
Canada	Local Institution - 0136	Moncton	New Brunswick
Canada	Local Institution - 0123	Oshawa	Ontario
Canada	Local Institution - 0102	Sudbury	Ontario
Canada	Local Institution - 0111	Windsor	Ontario
China	Local Institution	Beijing	Beijing
China	Local Institution	Beijing	Beijing
China	Local Institution	Changchun	Jilin
China	Local Institution - 0247	Changsha
China	Local Institution - 0240	Guangzhou
China	Local Institution - 0227	Hangzhou	Zhejiang
China	Local Institution - 0239	Hangzhou	Zhejiang
China	Local Institution - 0221	Harbin	Heilongjiang
China	Local Institution - 0238	Hefei	Anhui
China	Local Institution - 0243	Hefei	Anhui
China	Local Institution - 0232	Kunming	Yunnan
China	Local Institution - 0230	Nanchang	Jiangxi
China	Local Institution - 0248	Nantong	Jiangsu
China	Local Institution - 0220	Shanghai	Shanghai
China	Local Institution - 0228	Shanghai	Shanghai
China	Local Institution - 0233	Shanghai	Shanghai
China	Local Institution - 0245	Shanghai	Shanghai
China	Local Institution - 0237	Shenyang	Liaoning
China	Local Institution - 0246	Wenzhou	Zhejiang
China	Local Institution - 0244	Wuhang	Hubei
Colombia	Local Institution - 0078	Bogota
Colombia	Local Institution	Medellin
Colombia	Local Institution	Monteria	Cordoba
Finland	Local Institution - 0044	Oulu
Finland	Local Institution - 0043	Tampere
Finland	Local Institution - 0045	Turku
Finland	Local Institution - 0046	Vaasa
France	Local Institution - 0208	Avignon Cedes 9
France	Local Institution - 0099	Lyon Cedex 08
France	Local Institution - 0098	Marseille Cedex 20
France	Local Institution - 0097	Paris Cedex 20
France	Local Institution - 0095	Pierre Benite
France	Local Institution - 0100	Rennes Cedex 9
France	Local Institution - 0150	Saint Herblain
France	Local Institution - 0149	Strasbourg	Alsace
France	Local Institution - 0096	Toulouse
Germany	Local Institution - 0171	Augsburg
Germany	Local Institution - 0170	Bad Berka
Germany	Local Institution - 0168	Berlin
Germany	Local Institution - 0164	Bochum
Germany	Local Institution - 0166	Gauting
Germany	Local Institution - 0165	Grosshansdorf
Germany	Local Institution - 0169	Immenhausen
Germany	Local Institution - 0167	Tübingen
Greece	Local Institution - 0080	N.Kifissia
Greece	Interbalkan European Medical Center	Thessaloniki
Hong Kong	Local Institution - 0052	Hong Kong
Ireland	Local Institution	Dublin
Ireland	Local Institution - 0175	Dublin
Ireland	Local Institution - 0162	Galway
Ireland	Local Institution - 0214	Limerick
Ireland	Local Institution - 0161	Wilton	Cork
Israel	Local Institution	Haifa
Israel	Local Institution - 0093	Jerusalem
Israel	Local Institution	Petach Tikva
Israel	Local Institution - 0090	Tel Aviv
Israel	Local Institution - 0089	Zerifin
Italy	Local Institution - 0026	Avellino
Italy	Local Institution - 0025	Bologna
Italy	Local Institution - 0112	Messina
Italy	Local Institution - 0027	Milan	Lombardia
Italy	Local Institution - 0082	Perugia
Japan	Local Institution - 0141	Bunkyo-ku	Tokyo
Japan	Local Institution - 0071	Chuo-ku	Tokyo
Japan	Local Institution - 0146	Fukuoka-shi	Fukuoka
Japan	Local Institution - 0198	Gifu-shi	Gifu
Japan	Local Institution - 0193	Hidaka	Saitama
Japan	Local Institution	Hirakata-shi	Osaka
Japan	Local Institution - 0138	Kanazawa-shi	Ishikawa
Japan	Local Institution - 0139	Kashiwa-shi	Chiba
Japan	Local Institution - 0076	Kobe-shi	Hyogo
Japan	Local Institution - 0140	Koto-ku	Tokyo
Japan	Local Institution - 0077	Kurashiki-shi	Okayama
Japan	Local Institution - 0200	Kurume-shi	Fukuoka
Japan	Local Institution - 0142	Matsuyama-shi	Ehime
Japan	Local Institution - 0075	Osaka-sayama-shi	Osaka
Japan	Local Institution - 0145	Osaka-shi	Osaka
Japan	Local Institution - 0143	Sapporo-shi	Hokkaido
Japan	Local Institution - 0069	Sendai-shi	Miyagi
Japan	Local Institution - 0070	Sendai-shi	Miyagi
Japan	Local Institution - 0144	Shinjuku-ku	Tokyo
Japan	Local Institution - 0083	Takatsuki-shi	Osaka
Japan	Local Institution - 0216	Wakayama
Japan	Local Institution - 0072	Yokohama-shi	Kanagawa
Korea, Republic of	Local Institution - 0021	Gangnam-gu
Korea, Republic of	Local Institution - 0047	Seongnam-si	Gyeonggi-do
Korea, Republic of	Local Institution - 0022	Seoul
Korea, Republic of	Local Institution - 0154	Seoul
Korea, Republic of	Local Institution - 0024	Suwon	Kyonggi-do
Mexico	Local Institution - 0020	Leon de los Aldama	Guanajuato
Mexico	Local Institution - 0019	Mexico	Distrito Federal
Mexico	Local Institution - 0028	Monterrey	Nuevo Leon
Mexico	Local Institution - 0135	Queretaro
Netherlands	Local Institution - 0158	's-Hertogenbosch
Netherlands	Local Institution	Eindhoven
Netherlands	Local Institution - 0159	Rotterdam
Peru	Local Institution	Lima
Peru	Local Institution	Lima
Peru	Local Institution	Miraflores	Lima
Poland	Local Institution - 0041	Gdansk
Poland	Local Institution - 0054	Gdynia
Poland	Local Institution - 0053	Olsztyn
Poland	Local Institution - 0187	Warszawa
Romania	Local Institution - 0186	Bucharest
Romania	Local Institution - 0199	Bucharest
Romania	Local Institution - 0182	Craiova
Romania	Local Institution - 0178	Lasi
Romania	Local Institution - 0212	Romania
Romania	Local Institution - 0181	Timisoara, Timis
Russian Federation	Local Institution - 0148	Moscow
Russian Federation	Local Institution - 0209	Moscow
Russian Federation	Local Institution - 0217	Moscow
Russian Federation	Local Institution - 0115	St Petersburg
Russian Federation	Local Institution - 0157	St Petersburg
Russian Federation	Local Institution - 0116	St. Petersburg
Singapore	Local Institution - 0050	Singapore
South Africa	Local Institution - 0084	Cape Town	Western Cape
South Africa	Local Institution - 0085	Cape Town	Western CAPE
South Africa	Local Institution - 0086	George	Western CAPE
South Africa	Local Institution - 0087	Sandton	Gauteng
Spain	Local Institution	Barcelona
Spain	Local Institution - 0132	Barcelona
Spain	Local Institution	Madrid
Spain	Local Institution	Malaga
Spain	Local Institution	Sevilla
Sweden	Local Institution - 0124	Lund
Sweden	Local Institution - 0185	Uppsala
Switzerland	Local Institution - 0179	Aarau
Switzerland	Local Institution - 0180	Geneve
Switzerland	Local Institution - 0191	St. Gallen
Taiwan	Local Institution - 0049	Tainan	TNN
Taiwan	Local Institution - 0048	Taoyuan
United Kingdom	Local Institution - 0118	London	Greater London
United Kingdom	Local Institution - 0201	London	Greater London
United Kingdom	Local Institution - 0152	Oxford	Oxfordshire
United Kingdom	Local Institution - 0192	Sheffield
United Kingdom	Local Institution - 0151	Sutton	Surrey
United Kingdom	Local Institution - 0153	Truro	Cornwall
United Kingdom	Local Institution - 0121	Wirral	Lancashire
United States	Local Institution - 0004	Allentown	Pennsylvania
United States	Local Institution - 0010	Atlanta	Georgia
United States	Local Institution - 0051	Baltimore	Maryland
United States	Local Institution - 0107	Boston	Massachusetts
United States	Local Institution - 0207	Boston	Massachusetts
United States	Local Institution - 0005	Charleston	South Carolina
United States	Local Institution - 0129	Cincinnati	Ohio
United States	Local Institution - 0009	Columbus	Ohio
United States	Local Institution - 0014	Durham	North Carolina
United States	Local Institution - 0061	Fairway	Kansas
United States	Local Institution - 0215	Fargo	North Dakota
United States	Local Institution - 0127	Fort Myers	Florida
United States	Local Institution - 0013	Indianapolis	Indiana
United States	Local Institution - 0007	Jacksonville	Florida
United States	Local Institution - 0032	Lexington	Kentucky
United States	Local Institution - 0202	New Haven	Connecticut
United States	Local Institution - 0008	New York	New York
United States	Local Institution - 0001	Portland	Oregon
United States	Local Institution - 0034	Portland	Oregon
United States	Local Institution - 0006	Richmond	Virginia
United States	Local Institution - 0003	Sacramento	California
United States	Local Institution - 0015	Saint Louis	Missouri
United States	Local Institution - 0128	Saint Petersburg	Florida
United States	Local Institution - 0011	Salt Lake City	Utah
United States	Local Institution - 0002	Sayre	Pennsylvania
United States	Local Institution - 0213	Sioux Falls	South Dakota
United States	Local Institution - 0012	Wichita	Kansas
United States	Local Institution - 0016	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	Ono Pharmaceutical Co. Ltd

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  China,  Colombia,  Finland,  France,  Germany,  Greece,  Hong Kong,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Peru,  Poland,  Romania,  Russian Federation,  Singapore,  South Africa,  Spain,  Sweden,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS) of Nivolumab + Ipilimumab Versus Placebo In The Global Population	OS was defined as the time from randomization to the date of death. A participant who had not died was censored at last known alive date. OS was followed up during the blinded study drug treatment and every 3 months via in-person or phone contact after participant discontinued the blinded study drug	From randomization to 400 deaths across the two treatment groups (Nivo+Ipi vs Placebo) (up to approximately 37 months)
Secondary	Overall Survival (OS) of Nivolumab Versus Placebo	Overall Survival (OS) comparing nivolumab monotherapy versus placebo. OS was defined as the time from randomization to the date of death. A participant who had not died was censored at last known alive date. OS was followed up during the blinded study drug treatment and every 3 months via in-person or phone contact after participant discontinued the blinded study drug.	From randomization to the date of death or last known alive date (up to approximately 73 months)
Secondary	Overall Survival (OS) of Nivolumab + Ipilimumab Versus Nivolumab	Overall Survival (OS) comparing Nivolumab + Ipilimumab Versus Nivolumab. OS was defined as the time from randomization to the date of death. A participant who had not died was censored at last known alive date. OS was followed up during the blinded study drug treatment and every 3 months via in-person or phone contact after participant discontinued the blinded study drug.	From randomization to the date of death or last known alive date (up to approximately 73 months)
Secondary	Progression Free Survival (PFS) Per BICR	PFS was defined as the time between the date of randomization and the first date of documented progression as determined by Blind Independent Central Review (BICR) or death due to any cause, whichever occurred first. Participants who died with no reported progression were considered to have progressed on the date of death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment on or prior to initiation of the subsequent anti-cancer therapy. Participants who did not have any on study tumor assessments and did not die (or died after initiation of the subsequent anti- cancer therapy) were censored on their date of randomization. Participants who started any subsequent anti- cancer therapy without a prior reported Progressive Disease (PD) per BICR were censored at the last evaluable tumor assessment on or prior to initiation of the subsequent anti-cancer therapy.	From randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 73 months)
Secondary	Overall Survival (OS) in Tumor Mutational Burden (TMB) High and Low Subgroups by TMB Cutoff In The Global Population	Tumor mutational burden (TMB) is measured using FoundationOne CDxTM (F1CDx) assay, a comprehensive genomic profile (CGP) assay based on baseline tumor tissue. TMB is defined as the number of somatic, coding, base substitution, and indel mutations per megabase of genome examined.; OS in TMB by the following cutoff points: =10 mutations/mb, < 10 mutations/mb, =13 mutations/mb, <13 mutations/mb	From randomization to the date of death or last known alive date (up to approximately 73 months)
Secondary	Progression Free Survival (PFS) Per BICR in Tumor Mutational Burden (TMB) High and Low Subgroups by TMB Cutoff In The Global Population	Tumor mutational burden (TMB) is measured using FoundationOne CDxTM (F1CDx) assay, a comprehensive genomic profile (CGP) assay based on baseline tumor tissue. TMB is defined as the number of somatic, coding, base substitution, and indel mutations per megabase of genome examined.; PFS in TMB by the following cutoff points: =10 mutations/mb, < 10 mutations/mb, =13 mutations/mb, <13 mutations/mb.	From randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 73 months)

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting