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

NCT02538666 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: CA209-4512015-002441-61
• Study Type: interventional
• Target: 907
• Locations: 31 countries
• Sites: 194

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.

Conditions

Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Overall Survival (OS) of Nivolumab Versus Placebo

  From randomization to the date of death or last known alive date (up to approximately 73 months)

• Overall Survival (OS) of Nivolumab + Ipilimumab Versus Nivolumab

  From randomization to the date of death or last known alive date (up to approximately 73 months)

• Progression Free Survival (PFS) Per BICR

  From randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 73 months)

• Overall Survival (OS) in Tumor Mutational Burden (TMB) High and Low Subgroups by TMB Cutoff In The Global Population

  From randomization to the date of death or last known alive date (up to approximately 73 months)

• Progression Free Survival (PFS) Per BICR in Tumor Mutational Burden (TMB) High and Low Subgroups by TMB Cutoff In The Global Population

  From randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 73 months)

Study Arms (3)

Nivolumab monotherapy

EXPERIMENTAL

Nivolumab intravenous fusion

Biological: Nivolumab

Nivolumab and ipilimumab combination therapy

EXPERIMENTAL

Nivolumab and ipilimumab intravenous fusion

Biological: Nivolumab; Biological: Ipilimumab

Placebo

PLACEBO COMPARATOR

Placebo

Other: Placebo

Interventions

Nivolumab BIOLOGICAL

Also known as: Opdivo

Nivolumab and ipilimumab combination therapy; Nivolumab monotherapy

Ipilimumab BIOLOGICAL

Also known as: Yervoy

Nivolumab and ipilimumab combination therapy

Placebo OTHER

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead
• Ono Pharmaceutical Co. Ltd: collaborator

Study Sites (197)

Local Institution - 0003

Sacramento, California, 95816, United States

Location

Local Institution - 0202

New Haven, Connecticut, 06520, United States

Location

Local Institution - 0127

Fort Myers, Florida, 33901, United States

Location

Local Institution - 0007

Jacksonville, Florida, 32256, United States

Location

Local Institution - 0128

St. Petersburg, Florida, 33705, United States

Location

Local Institution - 0010

Atlanta, Georgia, 30322, United States

Location

Local Institution - 0013

Indianapolis, Indiana, 46237, United States

Location

Local Institution - 0061

Fairway, Kansas, 66205, United States

Location

Local Institution - 0012

Wichita, Kansas, 67214, United States

Location

Local Institution - 0032

Lexington, Kentucky, 40503, United States

Location

Local Institution - 0051

Baltimore, Maryland, 21287, United States

Location

Local Institution - 0107

Boston, Massachusetts, 02215, United States

Location

Local Institution - 0207

Boston, Massachusetts, 02215, United States

Location

Local Institution - 0015

St Louis, Missouri, 63110, United States

Location

Local Institution - 0008

New York, New York, 10065, United States

Location

Local Institution - 0014

Durham, North Carolina, 27710, United States

Location

Local Institution - 0016

Winston-Salem, North Carolina, 27103, United States

Location

Local Institution - 0215

Fargo, North Dakota, 58102, United States

Location

Local Institution - 0129

Cincinnati, Ohio, 45242, United States

Location

Local Institution - 0009

Columbus, Ohio, 43210, United States

Location

Local Institution - 0001

Portland, Oregon, 97213, United States

Location

Local Institution - 0034

Portland, Oregon, 97239, United States

Location

Local Institution - 0004

Allentown, Pennsylvania, 18103, United States

Location

Local Institution - 0002

Sayre, Pennsylvania, 18840, United States

Location

Local Institution - 0005

Charleston, South Carolina, 29425, United States

Location

Local Institution - 0213

Sioux Falls, South Dakota, 57104, United States

Location

Local Institution - 0011

Salt Lake City, Utah, 84112, United States

Location

Local Institution - 0006

Richmond, Virginia, 23226, United States

Location

Local Institution - 0110

Berazategui, Buenos Aires, 1880, Argentina

Location

Local Institution - 0088

Capital Federal, Buenos Aires, 1426, Argentina

Location

Local Institution - 0109

Ciudad Autonoma de Buenos Aire, Buenos Aires, 1181, Argentina

Location

Local Institution - 0188

Córdoba, 5004, Argentina

Location

Local Institution - 0029

San Miguel de Tucumán, 4000, Argentina

Location

Local Institution

Kogarah, New South Wales, Australia

Location

Local Institution

Wollongong, New South Wales, 2500, Australia

Location

Local Institution

Birtinya, Queensland, 4575, Australia

Location

Princess Alexandra Hospital

Brisbane, Queensland, 4102, Australia

Location

Local Institution - 0137

Adelaide, South Australia, 5000, Australia

Location

Local Institution - 0035

East Melbourne, Victoria, 3165, Australia

Location

Local Institution - 0174

Innsbruck, 6020, Austria

Location

Local Institution - 0173

Salzburg, 5020, Austria

Location

Local Institution - 0172

Vienna, 1130, Austria

Location

Local Institution - 0057

Brussels, 1090, Belgium

Location

Local Institution - 0059

Charleroi, 6000, Belgium

Location

Local Institution - 0060

Roeselare, 8800, Belgium

Location

Local Institution - 0067

Fortaleza, Ceará, 60430-230, Brazil

Location

Local Institution - 0068

Belo Horizonte, Minas Gerais, 30110-022, Brazil

Location

Local Institution - 0063

Ijuí, Rio Grande do Sul, 98700-000, Brazil

Location

Local Institution - 0064

Porto Alegre, Rio Grande do Sul, 90610000, Brazil

Location

Local Institution - 0017

Itajaí, Santa Catarina, 88301-220, Brazil

Location

Local Institution - 0081

Barretos, São Paulo, 14784-400, Brazil

Location

Local Institution

Rio de Janeiro, 22793-080, Brazil

Location

Local Institution

Salvador, 40170-110, Brazil

Location

Local Institution - 0094

Edmonton, Alberta, T6G 1Z2, Canada

Location

Local Institution - 0136

Moncton, New Brunswick, E1C 6Z8, Canada

Location

Local Institution - 0102

Greater Sudbury, Ontario, P3E 5J1, Canada

Location

Local Institution - 0123

Oshawa, Ontario, L1G 2B9, Canada

Location

Local Institution - 0111

Windsor, Ontario, N8W 1L9, Canada

Location

Local Institution - 0238

Hefei, Anhui, 230001, China

Location

Local Institution - 0243

Hefei, Anhui, 230022, China

Location

Local Institution

Beijing, Beijing Municipality, 100001, China

Location

Local Institution

Beijing, Beijing Municipality, 100142, China

Location

Local Institution - 0221

Harbin, Heilongjiang, 155040, China

Location

Local Institution - 0244

Wuhang, Hubei, 430030, China

Location

Local Institution - 0248

Nantong, Jiangsu, 226361, China

Location

Local Institution - 0230

Nanchang, Jiangxi, 330006, China

Location

Local Institution

Changchun, Jilin, 130021, China

Location

Local Institution - 0237

Shenyang, Liaoning, 110046, China

Location

Local Institution - 0220

Shanghai, Shanghai Municipality, 200030, China

Location

Local Institution - 0228

Shanghai, Shanghai Municipality, 200030, China

Location

Local Institution - 0233

Shanghai, Shanghai Municipality, 200032, China

Location

Local Institution - 0245

Shanghai, Shanghai Municipality, 200433, China

Location

Local Institution - 0232

Kunming, Yunnan, 650118, China

Location

Local Institution - 0239

Hangzhou, Zhejiang, 310003, China

Location

Local Institution - 0227

Hangzhou, Zhejiang, 310016, China

Location

Local Institution - 0246

Wenzhou, Zhejiang, 325000, China

Location

Local Institution - 0247

Changsha, 0, China

Location

Local Institution - 0240

Guangzhou, 510515, China

Location

Local Institution

Montería, Departamento de Córdoba, Colombia

Location

Local Institution - 0078

Bogotá, 0, Colombia

Location

Local Institution

Medellín, MEDELLIN, Colombia

Location

Local Institution - 0044

Oulu, 90029, Finland

Location

Local Institution - 0043

Tampere, 33521, Finland

Location

Local Institution - 0045

Turku, FIN-20521, Finland

Location

Local Institution - 0046

Vaasa, 65130, Finland

Location

Local Institution - 0149

Strasbourg, Alsace, 67091, France

Location

Local Institution - 0208

Avignon Cedes 9, 84918, France

Location

Local Institution - 0099

Lyon, 69373, France

Location

Local Institution - 0098

Marseille, 13915, France

Location

Local Institution - 0097

Paris, 75970, France

Location

Local Institution - 0095

Pierre-Bénite, 69495, France

Location

Local Institution - 0100

Rennes, 35033, France

Location

Local Institution - 0150

Saint-Herblain, 44805, France

Location

Local Institution - 0096

Toulouse, 31059, France

Location

Local Institution - 0171

Augsburg, 86156, Germany

Location

Local Institution - 0170

Bad Berka, 99437, Germany

Location

Local Institution - 0168

Berlin, 14165, Germany

Location

Local Institution - 0164

Bochum, 44791, Germany

Location

Local Institution - 0166

Gauting, 82131, Germany

Location

Local Institution - 0165

Großhansdorf, 22927, Germany

Location

Local Institution - 0169

Immenhausen, 34376, Germany

Location

Local Institution - 0167

Tübingen, 72076, Germany

Location

Local Institution - 0080

N.Kifissia, 14564, Greece

Location

Interbalkan European Medical Center

Thessaloniki, 57001, Greece

Location

Local Institution - 0052

Hong Kong, 0, Hong Kong

Location

Local Institution - 0161

Wilton, CORK, 0, Ireland

Location

Local Institution - 0175

Dublin, 24, Ireland

Location

Local Institution

Dublin, 4, Ireland

Location

Local Institution - 0162

Galway, ST4 6QG, Ireland

Location

Local Institution - 0214

Limerick, 0, Ireland

Location

Local Institution

Haifa, 31096, Israel

Location

Local Institution - 0093

Jerusalem, 91031, Israel

Location

Local Institution

Petah Tikva, 49100, Israel

Location

Local Institution - 0090

Tel Aviv, 64239, Israel

Location

Local Institution - 0089

Ẕerifin, 70300, Israel

Location

Local Institution - 0027

Milan, Lombardy, 20141, Italy

Location

Local Institution - 0026

Avellino, 83100, Italy

Location

Local Institution - 0025

Bologna, 40138, Italy

Location

Local Institution - 0112

Messina, 98158, Italy

Location

Local Institution - 0082

Perugia, 06132, Italy

Location

Local Institution - 0139

Kashiwa-shi, Chiba, 2778577, Japan

Location

Local Institution - 0142

Matsuyama, Ehime, 7910280, Japan

Location

Local Institution - 0146

Fukuoka, Fukuoka, 8128582, Japan

Location

Local Institution - 0200

Kurume-shi, Fukuoka, 8300011, Japan

Location

Local Institution - 0198

Gifu, Gifu, 5008513, Japan

Location

Local Institution - 0143

Sapporo, Hokkaido, 0608648, Japan

Location

Local Institution - 0076

Kobe, Hyōgo, 6500047, Japan

Location

Local Institution - 0138

Kanazawa, Ishikawa-ken, 9208641, Japan

Location

Local Institution - 0072

Yokohama, Kanagawa, 2408555, Japan

Location

Local Institution - 0070

Sendai, Miyagi, 9800873, Japan

Location

Local Institution - 0069

Sendai, Miyagi, 9808574, Japan

Location

Local Institution - 0077

Kurashiki-shi, Okayama-ken, 7108602, Japan

Location

Local Institution

Hirakata-shi, Osaka, 5731191, Japan

Location

Local Institution - 0145

Osaka, Osaka, 5340021, Japan

Location

Local Institution - 0075

Osaka-sayama-shi, Osaka, 5898511, Japan

Location

Local Institution - 0083

Takatsuki-shi, Osaka, 5698686, Japan

Location

Local Institution - 0193

Hidaka, Saitama, 350-1298, Japan

Location

Local Institution - 0141

Bunkyo-ku, Tokyo, 113-8603, Japan

Location

Local Institution - 0071

Chuo-ku, Tokyo, 1040045, Japan

Location

Local Institution - 0140

Koto-ku, Tokyo, 1358550, Japan

Location

Local Institution - 0144

Shinjuku-ku, Tokyo, 1600023, Japan

Location

Local Institution - 0216

Wakayama, 641-8510, Japan

Location

Local Institution - 0020

León, Guanajuato, 37000, Mexico

Location

Local Institution - 0019

Mexico City, Mexico City, 14050, Mexico

Location

Local Institution - 0028

Monterrey, Nuevo León, 64000, Mexico

Location

Local Institution - 0135

Querétaro, 76090, Mexico

Location

Local Institution - 0158

's-Hertogenbosch, 5223 GZ, Netherlands

Location

Local Institution

Eindhoven, 5623 EJ, Netherlands

Location

Local Institution - 0159

Rotterdam, 3000 CA, Netherlands

Location

Local Institution

Miraflores, Lima region, 18, Peru

Location

Local Institution

Lima, 27, Peru

Location

Local Institution

Lima, 34, Peru

Location

Local Institution - 0041

Gdansk, 80-19, Poland

Location

Local Institution - 0054

Gdynia, 81-519, Poland

Location

Local Institution - 0053

Olsztyn, 10-357, Poland

Location

Local Institution - 0187

Warsaw, 02-781, Poland

Location

Local Institution - 0199

Bucharest, 010991, Romania

Location

Local Institution - 0186

Bucharest, 020122, Romania

Location

Local Institution - 0182

Craiova, 200347, Romania

Location

Local Institution - 0178

Lasi, 700106, Romania

Location

Local Institution - 0212

Romania, 400015, Romania

Location

Local Institution - 0181

Timisoara, Timis, 300239, Romania

Location

Local Institution - 0148

Moscow, 105229, Russia

Location

Local Institution - 0217

Moscow, 115478, Russia

Location

Local Institution - 0209

Moscow, 121309, Russia

Location

Local Institution - 0116

Saint Petersburg, 194291, Russia

Location

Local Institution - 0157

Saint Petersburg, 197758, Russia

Location

Local Institution - 0115

Saint Petersburg, 198255, Russia

Location

Local Institution - 0050

Singapore, 169610, Singapore

Location

Local Institution - 0087

Sandton, Gauteng, 2199, South Africa

Location

Local Institution - 0084

Cape Town, Western Cape, 7570, South Africa

Location

Local Institution - 0085

Cape Town, Western Cape, 7700, South Africa

Location

Local Institution - 0086

George, Western Cape, 6530, South Africa

Location

Local Institution - 0047

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

Local Institution - 0024

Suwon, Kyǒnggi-do, 16499, South Korea

Location

Local Institution - 0021

Gangnam-gu, 06351, South Korea

Location

Local Institution - 0022

Seoul, 03722, South Korea

Location

Local Institution - 0154

Seoul, 05505, South Korea

Location

Local Institution - 0132

Barcelona, 08035, Spain

Location

Local Institution

Barcelona, 08036, Spain

Location

Local Institution

Madrid, 28040, Spain

Location

Local Institution

Málaga, 29011, Spain

Location

Local Institution

Seville, 41013, Spain

Location

Local Institution - 0124

Lund, 221 85, Sweden

Location

Local Institution - 0185

Uppsala, 751 85, Sweden

Location

Local Institution - 0179

Aarau, 5001, Switzerland

Location

Local Institution - 0180

Geneva, 1205, Switzerland

Location

Local Institution - 0191

Sankt Gallen, 9007, Switzerland

Location

Local Institution - 0049

Tainan, TNN, 704, Taiwan

Location

Local Institution - 0048

Taoyuan District, 333, Taiwan

Location

Local Institution - 0153

Truro, Cornwall, TR1 3LJ, United Kingdom

Location

Local Institution - 0118

London, Greater London, NW1 2PG, United Kingdom

Location

Local Institution - 0201

London, Greater London, SW3 6JJ, United Kingdom

Location

Local Institution - 0121

Metropolitan Borough of Wirral, Lancashire, CH63 4JY, United Kingdom

Location

Local Institution - 0152

Oxford, Oxfordshire, OX3 7LJ, United Kingdom

Location

Local Institution - 0151

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Local Institution - 0192

Sheffield, S10 2SJ, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 35383114 DERIVED

• 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.

  PMID: 33683919 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please Email

Study Officials

• Bristol Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: August 26, 2015
• First Posted: September 2, 2015
• Study Start: October 13, 2015
• Primary Completion: October 1, 2018
• Study Completion: November 11, 2021
• Last Updated: January 5, 2023
• Results First Posted: October 22, 2019

Record last verified: 2022-12

Locations

CA (5); CH (3); BR (8); DE (8); KR (5); BE (3); ES (5); TW (2); AU (6); JP (22); RO (6); RU (6); IE (5); US (28); SG (1); IT (5); PL (4); CO (3); ME (4); NL (3); HK (1); GB (7); AR (5); FI (4); FR (9); PE (3); SE (2); CN (20); ZA (4); GR (2); IL (5)