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)
Clinicaltrials.gov identifier recruitment status First Posted Last update posted
NCT02477826 Recruiting June 23, 2015 September 21, 2021

study description
Brief 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.

Condition or Disease: Non-Small Cell Lung Cancer
Intervention/treatment: Drug: Nivolumab
Drug: Ipilimumab
Drug: Carboplatin
Drug: Cisplatin
Drug: Gemcitabine
Drug: Pemetrexed
Drug: Paclitaxel
Phase: Phase 3
Detailed Description

N/A


study design
Study Type: Interventional
Estimated Enrollment : 1980 participants
Intervention Model : Parallel Assignment
Masking: None (Open Label) ()
Primary Purpose: Treatment
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)
Actual Study Start Date: August 2015
Estimated Primary Completion Date: August 2024
Estimated Study Completion Date: August 2024

Arms and interventions
Arm Intervention/treatment
Experimental: Arm A: Nivolumab
Nivolumab intravenously (IV) as specified
Drug: Nivolumab
Experimental: Arm B: Nivolumab + Ipilimumab
Nivolumab + Ipilimumab IV as specified
Drug: Nivolumab


Drug: Ipilimumab
Experimental: Arm C: Nivolumab + Platinum doublet chemotherapy
Nivolumab + Platinum doublet chemotherapy (IV) dose as specified
Drug: Nivolumab


Drug: Carboplatin


Drug: Cisplatin


Drug: Gemcitabine


Drug: Pemetrexed


Drug: Paclitaxel
Experimental: Arm D: Platinum doublet chemotherapy
Chemotherapy administered on specified days of IV chemotherapy
Drug: Carboplatin


Drug: Cisplatin


Drug: Gemcitabine


Drug: Pemetrexed


Drug: Paclitaxel
outcome measures
Primary Outcome Measures: 1. Overall survival (OS) [ Time Frame: approximately 48 months ]
2. Progression-free Survival (PFS) as determined by blinded independent central review (BICR) [ Time Frame: approximately 40 months ]
Secondary Outcome Measures: 1. Objective response rate (ORR) [ Time Frame: Up to 48 months ]
ORR of nivolumab monotherapy and nivolumab in combination with ipilimumab to platinum-doublet chemotherapy in subjects with advanced lung cancer
2. Disease related symptom improvement as measured by the Lung Cancer Symptom Score (LCSS) in all subjects [ Time Frame: Up to 48 months ]
Disease related symptom improvement assessed at each dosing for 6 months, then every 6 weeks while on treatment

Eligibility Criteria
Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
Criteria

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

Inclusion Criteria:

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

Exclusion Criteria:

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 could apply


Contacts and Locations
Contacts

Contact: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email: Clinical.Trials@bms.com

Contact: First line of the email MUST contain NCT# and Site #.

Locations
United States, Alabama Southern Cancer Center, Inc. Mobile
United States, California Local Institution La Jolla
United States, California California Pacific Medical Center San Francisco
United States, Connecticut Yale University New Haven
United States, Georgia Emory University Hospital Atlanta
United States, Georgia Northwest Georgia Oncology Centers, P.C. Marietta
United States, Kentucky Baptist Health Lexington Lexington
United States, Maryland Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins Baltimore
United States, Massachusetts Local Institution Boston
United States, Massachusetts Local Institution Boston
United States, Michigan Local Institution Southfield
United States, Minnesota Local Institution Rochester
United States, Missouri Washington University School Of Medicine Saint Louis
United States, New York Roswell Park Cancer Institute Buffalo
United States, New York Memorial Sloan Kettering Nassau New York
United States, North Carolina Duke University Medical Center Durham
United States, Ohio University Hospitals Cleveland
United States, Ohio The Ohio State University Columbus
United States, Pennsylvania Lehigh Valley Health Network Allentown
United States, Pennsylvania St. Mary Medical Center Langhorne
United States, Pennsylvania Fox Chase Cancer Center Philadelphia
United States, Pennsylvania Thomas Jefferson University Philadelphia
United States, Pennsylvania Guthrie Medical Group, Pc Sayre
United States, South Carolina Hollings Cancer Center Charleston
United States, South Carolina Greenville Health System Greenville
United States, South Carolina St Francis Hospital Greenville
United States, Tennessee Vanderbilt University Medical Center Nashville
United States, Texas The University Of Texas Dallas
United States, Texas University Of Texas Southwestern Medical Center Dallas
United States, Texas University Of Texas Md Anderson Cancer Ctr Houston
United States, Utah Huntsman Cancer Institute At The Univ. Of Utah Salt Lake City
United States, Washington Kadlec Clinical Hematology and Oncology Kennewick
Argentina, Buenos Aires COIBA Berazategui
Argentina, Buenos Aires Instituto Alexander Fleming Capital Federal
Argentina, Buenos Aires Hospital Italiano De Buenos Aires Ciudad Autonoma De Buenos Aire
Argentina, Buenos Aires Fundacion Investigar Ciudad de Buenos Aires
Argentina, Buenos Aires Hospital Privado De Comunidad Mar Del Plata
Argentina, Cordoba Hospital Privado Centro Medico De Cordoba Córdoba
Argentina, RIO Negro Clinica Viedma S.A. Viedma
Argentina, Tucuman Centro Medico San Roque San Miguel de Tucuman
Argentina Local Institution Caba
Argentina Instituto Oncologico De Cordoba Cordoba
Argentina Clinica Privada Universitaria Reina Fabiola Cordoba
Australia, Australian Capital Territory Local Institution Garran
Australia, New South Wales Blacktown Hospital Blacktown
Australia, New South Wales Local Institution Gosford
Australia, New South Wales Tamworth Hospital Tamworth
Australia, Queensland Princess Alexandra Hospital Brisbane
Australia, South Australia Local Institution Elizabeth Vale
Australia, Victoria Local Institution Clayton
Australia, Victoria St Vincent's Hospital Fitzroy
Australia, Western Australia Local Institution Perth
Australia Local Institution Murdoch
Austria Medizinische Universitatsklinik Graz
Austria Akh Wien Vienna
Austria Klinikum Wels-Grieskirchen Gmbh Wels
Belgium Local Institution Charleroi
Belgium Local Institution Edegem
Belgium Local Institution Gent
Belgium Local Institution Hasselt
Belgium Local Institution Roeselare
Belgium Local Institution Sint Niklaas
Brazil, Bahia Local Institution Salvador
Brazil, RIO Grande DO SUL Local Institution Ijui
Brazil, RIO Grande DO SUL Local Institution Porto Alegre
Brazil, SAO Paulo Local Institution Barretos
Brazil Local Institution Rio De Janeiro
Brazil Local Institution Sao Paulo
Brazil Local Institution Sao Paulo
Brazil Local Institution Sao Paulo
Canada, Alberta Cross Cancer Institute Edmonton
Canada, Newfoundland and Labrador Dr. H.Bliss Murphy Cancer Centre St. John's
Canada, Ontario London Regional Cancer Program London
Canada, Quebec Jewish General Hospital Montreal
Canada, Quebec CISSS du Bas-Saint-Laurent Hopital Regional de Rimouski Rimouski
Canada, Quebec Centre integre universitaire de sante et de service sociaux de l'estrie - CHUS Sherbrooke
Canada, Quebec Centre integre universitaire de sante et de services sociaux de la Mauricie-et-du-Centre-du-Quebec Trois-Rivieres
Canada Institut Universitaire de Cardiologie et de Pneumologie de Quebec - Universite Laval Quebec
Canada CHU de Quebec - Universite Laval Quebec
Chile, Metropolitana Fundacion Arturo Lopez Perez Santiago
Chile, Santiago DE Chile Centro Internacional de Estudios Clinicos Recoleta
Chile, Valparaiso Instituto Oncologico Vina Del Mar
China, Anhui Local Institution Hefei
China, Beijing Local Institution Beijing
China, Beijing Local Institution Beijing
China, Beijing Local Institution Beijing
China, Chongqing Local Institution Chongqing
China, Guangdong Local Institution Guangzhou
China, Guangdong Local Institution Guangzhou
China, Guangdong Local Institution Guanzhou
China, Hainan Local Institution Haikou
China, Heilongjiang Local Institution Haerbin
China, Henan Local Institution Zhengzhou
China, Henan Local Institution Zhengzhou
China, Hunan Local Institution Changsha
China, Hunan Local Institution Changsha
China, Jiangsu Local Institution Nanjing
China, Jiangxi Local Institution Nanchang
China, Jilin Local Institution Changchun
China, Jilin Local Institution Changchun
China, Liaoning Local Institution Shenyang
China, Shaanxi Local Institution Xi'an
China, Shan3xi Local Institution Xi'an
China, Shandong Local Institution Qingdao
China, Shanghai Local Institution Shanghai
China, Shanghai Local Institution Shanghai
China, Shanghai Local Institution Shanghai
China, Xinjiang Local Institution Urumqi
China, Zhejiang Local Institution Hanghzou
China, Zhejiang Local Institution Hangzhou
China, Zhejiang Local Institution Hangzhou
China Local Institution Beijing
China Local Institution Beijing
China Local Institution Chongqing
China Local Institution Chongqing
China Local Institution Hangzhou
China Local Institution Hangzhou
China Local Institution Kunming
China Local Institution Shanghai
China Local Institution Shantou
Colombia, Risaralda Oncologos Del Occidente Sa Pereira
Colombia Administradora Del Country S.A. - Clinica Del Country Bogota
Colombia Hospital Universitario San Ignacio Bogota
Colombia Hospital Pablo Tobon Uribe Medellin
Czechia Plicni klinika Hradec Kralove
Czechia Klinika plicnich nemoci a tuberkulozy Olomouc
Czechia Pneumologicka klinika 1. LF a TN Praha 4
Czechia Oddeleni Onkologie Pribram
Finland Local Institution Oulu
Finland Local Institution Turku
France Local Institution ANGERS Cedex 2
France Local Institution Besançon Cedex
France Local Institution Bron Cedex
France Local Institution Caen
France Local Institution Creteil
France Local Institution Limoges cedex
France Hopital Nord Marseille Cedex 20
France Local Institution Paris
France Local Institution Pessac
France Local Institution Rennes Cedex 9
France Local Institution Rouen
France Local Institution Saint Herblain
France Local Institution Saint Priest En Jarez
France Local Institution Strasbourg
France Local Institution Toulon
Germany, Thuringen Zentralklinik Bad Berka Gmbh Bad Berka
Germany Local Institution Berlin
Germany Universitaetsklinikum Essen Essen
Germany Universitatsklinikum Frankfurt Frankfurt
Germany SRH WALD KLINIKUM GERA gGmbH Gera
Germany Klinik Schillerhoehe Gerlingen
Germany Krankenhaus Grosshansdorf Grosshansdorf
Germany Stadtisches Krankenhaus Martha Maria Halle-Dolau Halle
Germany Thoraxklinik-Heidelberg Ggmbh Heidelberg
Germany Lungenklinik Hemer Hemer
Germany Klinikverbund Kempten-Oberallgau Immenstadt
Germany Universitaetsklinikum Magdeburg A. o. R. Magdeburg
Germany Klinikum Bogenhausen Muenchen
Germany Hsk Dr.-Horst-Schmidt-Kliniken Wiesbaden Wiesbaden
Greece Sotiria General Hospital Athens
Greece University Hospital Of Heraklion Heraklio
Greece Metropolitan Hospital Neo Faliro
Greece Local Institution Thessaloniki
Hungary Local Institution Budapest
Hungary Local Institution Budapest
Hungary Local Institution Matrahaza
Ireland, Dublin Local Institution Dublin 8
Ireland Local Institution Dublin
Ireland Local Institution Galway
Ireland Local Institution Limerick
Israel Local Institution Jerusalem
Israel Local Institution Kfar-saba
Israel Local Institution Petach Tikva
Israel Local Institution Tel-hashomer
Israel Local Institution Zerifin
Italy Local Institution Avellino
Italy Local Institution Bergamo
Italy Local Institution Bologna
Italy Local Institution Livorno
Italy Local Institution Messina
Italy Local Institution Milano
Italy Local Institution Milan
Italy Local Institution Napoli
Italy Ospedale Santa Maria delle Croci Ravenna
Italy Local Institution Roma
Italy Local Institution Roma
Italy Local Institution S.Andrea Fratte PG
Italy Ospedale S.Maria Terni
Japan, Aichi Local Institution Nagoya-shi
Japan, Aichi Local Institution Nagoya-shi
Japan, Chiba Local Institution Chiba-shi
Japan, Chiba Local Institution Kashiwa-shi
Japan, Ehime Local Institution Matsuyama-shi
Japan, Fukuoka Local Institution Fukuoka-shi
Japan, Fukuoka Local Institution Kurume-shi
Japan, Gunma Local Institution Ota-shi
Japan, Hiroshima Local Institution Hiroshima-shi
Japan, Hokkaido Local Institution Sapporo-shi
Japan, Hokkaido Local Institution Sapporo-shi
Japan, Hyogo Local Institution Akashi-shi
Japan, Hyogo Local Institution Kobe-shi
Japan, Ishikawa Local Institution Kanazawa-shi
Japan, Kanagawa Local Institution Yokohama-shi
Japan, Kanagawa Local Institution Yokohama-Shi
Japan, Miyagi Local Institution Natori-shi
Japan, Miyagi Local Institution Sendai-shi
Japan, Miyagi Local Institution Sendai-shi
Japan, Niigata Local Institution Niigata-shi
Japan, Okayama Local Institution Kurashiki-shi
Japan, Okayama Local Institution Okayama-shi
Japan, Osaka Local Institution Hirakata-shi
Japan, Osaka Local Institution Osaka-shi
Japan, Osaka Local Institution Osakasayama-shi
Japan, Osaka Local Institution Takatsuki-shi
Japan, Saitama Local Institution Hidaka-shi
Japan, Saitama Local Institution Kitaadachi-gun
Japan, Shizuoka Local Institution Sunto-gun
Japan, Tokyo Local Institution Bunkyo-ku
Japan, Tokyo Local Institution Chuo-ku
Japan, Tokyo Local Institution Koto-ku
Japan, Tokyo Local Institution Shinjuku-ku
Japan, Wakayama Local Institution Wakayama-shi
Japan, Yamaguchi Local Institution Ube-shi
Korea, Republic of, Chungcheonbuk-do Local Institution Cheongju-si
Korea, Republic of, Gyeonggi-do Local Institution Seongnam-si
Korea, Republic of Local Institution Seoul
Korea, Republic of Local Institution Seoul
Korea, Republic of Local Institution Seoul
Lebanon Local Institution Beirut
Lebanon Local Institution Beirut
Mexico, Distrito Federal Local Institution Df
Mexico, Distrito Federal Local Institution Mexico
Mexico, Estado DE Mexico Phylasis Clinicas Research S de R. L. de C. V. Cuautitlan
Mexico, Estado DE Mexico Local Institution Toluca
Mexico, Jalisco Instituto Jalisciense De Cancerologia Guadalajara
Mexico, Michoacan Local Institution Morelia
Mexico, Nuevo LEON Axis Heilsa S de Rl de Cv Monterrey
Mexico, Yucatan Medical Care & Research Merida
Mexico Local Institution Chihuahua
Mexico Centro de Alta Especialidad en Reumatologia e Investigacion del Potosi S.C. San Luis Potosi
Mexico Local Institution San Luis Potosi
Netherlands Local Institution Amsterdam
Netherlands Local Institution Amsterdam
Netherlands Local Institution Breda
Netherlands Local Institution Rotterdam
Netherlands Local Institution Veldhoven
Peru Clinica Ricardo Palma Lima
Peru Instituto Nacional De Enfermedades Neoplasicas Lima
Peru Clinica San Felipe- Unidad de Oncologia Medica Lima
Peru Instituto Oncologico Miraflores Lima
Peru Oncocenter Peru SAC - Oncosalud Lima
Poland Ambulatorium Chemioterapii Bydgoszcz
Poland Wojewodzkie Centrum Onkologii Gdansk
Poland Oddzial Onkologii I Radioterapii Szpital Morski Im. Pck Gdynia
Poland Centrum Onkologii-Inst.Im.M.Sklodowskiej-Curie O.W Gliwicach Gliwice
Poland Regionalny Osrodek Onkologiczny Lodz
Poland Klinika Nowotworow Pluca i Klatki Piersiowej Warszawa
Poland ORTHOS Szpital Wielospecjalistyczny Sp. z o.o. Wroclaw
Romania Institutul Clinic Fundeni Bucharest
Romania Sf. Nectarie Oncology Center Craiova
Romania S.C. Radiotherapy Center Cluj S.R.L. Floresti
Romania Prof. Dr. Ion Chiricuta Institute Of Oncology Day Care Dep Romania
Russian Federation Local Institution Chelyabinsk
Russian Federation Local Institution Kazan
Russian Federation Local Institution Moscow
Russian Federation Local Institution Saint-Petersburg
Russian Federation Local Institution St. Petersburg
Russian Federation Local Institution St. Petersburg
Russian Federation Local Institution Ufa
Saudi Arabia Local Institution Riyadh 11426
Saudi Arabia Local Institution Riyadh-11211
South Africa, Gauteng Local Institution Johannesburg
South Africa, Gauteng Local Institution Pretoria
South Africa, Gauteng Local Institution Saxonwold, Johannesburg
South Africa Local Institution Vereeniging
Spain, Madrid Local Institution Majadahonda
Spain Local Institution Badalona (Barcelona)
Spain Local Institution Barcelona
Spain Local Institution Madrid
Spain Local Institution Sevilla
Spain Local Institution Valencia
Switzerland Klinik Fur Onkologie Basel
Switzerland Kantonsspital Graubuenden Chur
Switzerland Centre hospitalier universitaire Vaudois (CHUV) Lausanne
Switzerland Local Institution Winterthur
Taiwan Local Institution Taichung
Taiwan Local Institution Taipei
Taiwan Local Institution Taipei
Taiwan Local Institution Taipei
Taiwan Local Institution Tao-Yuan County
Turkey Local Institution Ankara
Turkey Local Institution Antalya
Turkey Local Institution Kayseri
United Arab Emirates Local Institution Al Ain
United Kingdom, Cleveland Local Institution Middlesborough
United Kingdom, Greater London Local Institution London
United Kingdom, Greater London Local Institution London
United Kingdom, Greater London Local Institution London
United Kingdom, Hampshire Local Institution Southampton
United Kingdom, Leicestershire Local Institution Leicester
United Kingdom, WEST Midlands Local Institution Birmingham
United Kingdom Local Institution Cambridgeshire
United Kingdom Local Institution Edinburgh
United Kingdom Local Institution Surrey
Sponsors and Collaborators
Bristol-Myers Squibb
Ono Pharmaceutical Co. Ltd
Investigator
Study Director : Bristol-Myers Squibb Bristol-Myers Squibb
More Information
Other Publications

Reck 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.

Hellmann 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.

Reck 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.

Hellmann 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.

Responsible Party : Bristol-Myers Squibb
ClinicalTrials.gov Identifier : NCT02477826     
Other Study ID Numbers : CA209-227, 2014-003630-23
First Posted : June 23, 2015
Last Update Posted : September 21, 2021
Last Verified : September 2021
Additional relevant MeSH terms :
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms