A Study to Evaluate Efficacy in Subjects With Esophageal Cancer Treated With Nivolumab and Ipilimumab or Nivolumab Combined With Fluorouracil Plus Cisplatin Versus Fluorouracil Plus Cisplatin

NCT03143153 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: CA209-6482016-001514-20
• Study Type: interventional
• Target: 970
• Locations: 26 countries
• Sites: 187

Brief Summary

The main purpose of this study is to compare how long subjects with esophageal cancer live overall or live without disease progression after receiving nivolumab and ipilimumab or nivolumab combined with fluorouracil plus cisplatin versus fluorouracil plus cisplatin

Conditions

Various Advanced Cancer

Outcome Measures

Primary Outcomes (2)

• Overall Survival (OS) in Participants With Tumor Cell PD-L1

  Overall Survival (OS) is defined as the time between the date of randomization and the date of death. For participants without documentation of death, OS will be censored on the last date the subject was known to be alive.

  From the date of randomization to up to the date of death (up to approximately 20 months)

• Progression-free Survival (PFS) as Assessed by BICR in Participants With Tumor Cell PD-L1

  Progression-free survival (PFS) is defined as the time from randomization to the date of the first documented progressive disease (PD) per Blinded Independent Central Review (BICR) or death due to any cause. Participants who die without a reported prior PD per BICR (and die without start of subsequent therapy) will be considered to have progressed on the date of death. Participants who did not have documented PD per BICR per RECIST1.1 criteria and who did not die, will be censored at the date of the 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) will be censored at the randomization date. Participants who started any subsequent anti-cancer therapy without a prior reported PD per BICR will be censored at the last tumor assessment on or prior to initiation of the subsequent anti-cancer therapy.

  From the date of randomization to up to the date of the first documented disease progression or death (up to approximately 9 months)

Secondary Outcomes (3)

• Overall Survival (OS) in All Randomized Participants

  From the date of randomization to up to the date of death (up to approximately 88 months)

• Progression-free Survival (PFS) in All Randomized Participants as Assessed by BICR

  From the date of randomization to up to the date of the first documented disease progression or death (up to approximately 88 months)

• Objective Response Rate (ORR) as Assessed by BICR

  From the date of randomization to up to the date of objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first (up to 88 months)

Study Arms (3)

Nivolumab + Ipilimumab

EXPERIMENTAL

Biological: Nivolumab; Biological: Ipilimumab

Nivolumab + Cisplatin + Fluorouacil

EXPERIMENTAL

Biological: Nivolumab; Drug: Cisplatin; Drug: Fluorouracil

Cisplatin + Fluorouracil

ACTIVE COMPARATOR

Drug: Cisplatin; Drug: Fluorouracil

Interventions

Nivolumab BIOLOGICAL

Specified dose on specified days

Also known as: BMS-936558 (Nivolumab), Opdivo (Nivolumab)

Nivolumab + Cisplatin + Fluorouacil; Nivolumab + Ipilimumab

Ipilimumab BIOLOGICAL

Specified dose on specified days

Also known as: BMS-734016 (Ipilimumab), Yervoy (Ipilimumab)

Nivolumab + Ipilimumab

Cisplatin DRUG

Specified dose on specified days

Cisplatin + Fluorouracil; Nivolumab + Cisplatin + Fluorouacil

Fluorouracil DRUG

Specified dose on specified days

Cisplatin + Fluorouracil; Nivolumab + Cisplatin + Fluorouacil

Eligibility Criteria

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

You may qualify if:

• Must have histologically confirmed squamous cell carcinoma or adenosquamous cell carcinoma of esophagus
• Male or Female at least 18 years of age
• Must have esophageal cancer that cannot be operated on, or treated with definitive chemoradiation with curative intent, that is advanced, reoccurring or has spread out
• Must have full activity or, if limited, must be able to walk and carry out light activities such as light house work or office work
• Must agree to provide tumor tissue sample, either from a previous surgery or biopsy within 6 months or fresh, prior to the start of treatment in this study

You may not qualify if:

• Presence of tumor cells in the brain or spinal cord which are symptomatic or require treatment
• Active known or suspected autoimmune disease
• Any serious or uncontrolled medical disorder or active infection
• Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• Any positive test result for hepatitis B or C indicating acute or chronic infection and/or detectable virus

Sponsors & Collaborators

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

Study Sites (190)

Local Institution - 0191

Mobile, Alabama, 36608, United States

Location

Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

Usc/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Local Institution - 0188

Denver, Colorado, 80218, United States

Location

University Of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Local Institution - 0186

Miami, Florida, 33176, United States

Location

Local Institution - 0225

Tampa, Florida, 33612, United States

Location

Local Institution - 0074

Atlanta, Georgia, 30322, United States

Location

Local Institution - 0032

Marietta, Georgia, 30060, United States

Location

Hackensack Meridian Jersey Shore University Medical Center

Neptune City, New Jersey, 07753, United States

Location

Oncology Associates Of Oregon, Pc

Eugene, Oregon, 97401, United States

Location

Northwest Cancer Specialists, P.C.

Portland, Oregon, 97227, United States

Location

Local Institution - 0210

Dallas, Texas, 75246, United States

Location

Local Institution - 0028

Houston, Texas, 77030, United States

Location

Local Institution - 0190

Roanoke, Virginia, 24014, United States

Location

Local Institution - 0203

Morgantown, West Virginia, 26506-9162, United States

Location

Local Institution - 0048

Buenos Aires, Buenos Aires, 1417, Argentina

Location

Local Institution - 0050

Capital Federal, Buenos Aires, 1264, Argentina

Location

Local Institution - 0087

La Rioja, La Rioja Province, 5300, Argentina

Location

Local Institution - 0086

Rosario, Santa Fe Province, 2000, Argentina

Location

Local Institution - 0232

Tamworth, New South Wales, 2340, Australia

Location

Local Institution - 0011

Douglas, Queensland, 4814, Australia

Location

Local Institution - 0010

Murdoch, Western Australia, 6150, Australia

Location

Local Institution - 0241

Salzburg, 5020, Austria

Location

Local Institution - 0017

Salvador, Estado de Bahia, 41950-640, Brazil

Location

Local Institution - 0227

Ipatinga, Minas Gerais, 35160-158, Brazil

Location

Local Institution - 0228

Rio de Janeiro, Rio de Janeiro, 22793-080, Brazil

Location

Local Institution - 0021

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

Location

Local Institution - 0016

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

Location

Local Institution - 0019

Barretos, São Paulo, 14780-070, Brazil

Location

Local Institution - 0226

Jaú, São Paulo, 17210-080, Brazil

Location

Local Institution - 0018

São José do Rio Preto, São Paulo, 15090000, Brazil

Location

Local Institution - 0020

São Paulo, São Paulo, 01246-000, Brazil

Location

Local Institution - 0095

Moncton, New Brunswick, E1C 6Z8, Canada

Location

Local Institution - 0082

Montreal, Quebec, H3T 1E2, Canada

Location

Local Institution - 0222

Montreal, Quebec, H4A 3J1, Canada

Location

Local Institution - 0037

Trois-Rivières, Quebec, G8Z 3R9, Canada

Location

Local Institution - 0053

Santiago, Santiago Metropolitan, 8320000, Chile

Location

Local Institution - 0214

Santiago, Santiago Metropolitan, Chile

Location

Local Institution - 0207

Hefei, Anhui, 230022, China

Location

Local Institution - 0197

Hefei, Anhui, 230061, China

Location

Local Institution - 0182

Beijing, Beijing Municipality, 100032, China

Location

Local Institution - 0179

Beijing, Beijing Municipality, 100071, China

Location

Local Institution - 0216

Beijing, Beijing Municipality, 100853, China

Location

Local Institution - 0217

Fuzhou, Fujian, 350014, China

Location

Local Institution - 0219

Fuzhou, Fujian, 350025, China

Location

Local Institution - 0199

Shantou, Guangdong, 515041, China

Location

Local Institution - 0185

Harbin, Heilongjiang, 155040, China

Location

Local Institution - 0193

Zhengzhou, Henan, 0, China

Location

Local Institution - 0195

Zhengzhou, Henan, 450008, China

Location

Local Institution - 0194

Zhengzhou, Henan, 450052, China

Location

Local Institution - 0249

Changsha, Hunan, 410000, China

Location

Local Institution - 0212

Changsha, Hunan, 410008, China

Location

Local Institution - 0201

Nanjing, Jiangsu, 210000, China

Location

Local Institution - 0180

Changchun, Jilin, 130021, China

Location

Local Institution - 0183

Xi'an, Shan3xi, 710038, China

Location

Local Institution - 0215

Shanghai, Shanghai Municipality, 200030, China

Location

Local Institution - 0200

Shanghai, Shanghai Municipality, 200032, China

Location

Local Institution - 0184

Hangzhou, Zhejiang, 310003, China

Location

Local Institution - 0247

Linhai, Zhejiang, 317000, China

Location

Local Institution - 0220

Shenyang, 110042, China

Location

Local Institution - 0248

Xi'an, 0, China

Location

Local Institution - 0059

Bogotá, Bogota D.C., 0, Colombia

Location

Local Institution - 0058

Medellín, 050034, Colombia

Location

Local Institution - 0224

Montería, 230001, Colombia

Location

Local Institution - 0094

Pereira, 660004, Colombia

Location

Local Institution - 0083

Brno, 625 00, Czechia

Location

Local Institution - 0008

Brno, 656 53, Czechia

Location

Local Institution - 0006

Nový Jičín, 741 01, Czechia

Location

Local Institution - 0099

Odense, 5000, Denmark

Location

Local Institution - 0116

Lille, Nord, 59000, France

Location

Local Institution - 0114

Caen, 14076, France

Location

Local Institution - 0112

Montpellier, 34090, France

Location

Local Institution - 0113

Rennes, 35042, France

Location

Local Institution - 0242

Toulouse, 31059, France

Location

Local Institution - 0115

Villejuif, 94800, France

Location

Local Institution - 0035

Hong Kong, 0, Hong Kong

Location

Local Institution - 0070

Kowloon, Hong Kong

Location

Local Institution - 0085

Bergamo, 24127, Italy

Location

Local Institution - 0039

Milan, 20133, Italy

Location

Local Institution - 0084

Padua, Padova, Italy

Location

Local Institution - 0240

Pisa, 56126, Italy

Location

Local Institution - 0152

Akita, Akita, 010-8543, Japan

Location

Local Institution - 0104

Hirosaki-shi, Aomori, 0368563, Japan

Location

Local Institution - 0101

Chiba, Chiba, 260-8717, Japan

Location

Local Institution - 0153

Chiba, Chiba, 2608670, Japan

Location

Local Institution - 0173

Kashiwa-shi, Chiba, 2778577, Japan

Location

Local Institution - 0169

Matsuyama, Ehime, 7900024, Japan

Location

Local Institution - 0119

Matsuyama, Ehime, 7910280, Japan

Location

Local Institution - 0174

Fukuoka, Fukuoka, 8111395, Japan

Location

Local Institution - 0142

Fukuoka, Fukuoka, 8128582, Japan

Location

Local Institution - 0103

Fukushima, Fukushima, 9601295, Japan

Location

Local Institution - 0154

Gifu, Gifu, 5011194, Japan

Location

Local Institution - 0176

Ōta, Gunma, 3738550, Japan

Location

Local Institution - 0100

Hiroshima, Hiroshima, 7348551, Japan

Location

Local Institution - 0111

Sapporo, Hokkaido, 060-8648, Japan

Location

Local Institution - 0170

Akashi-shi, Hyōgo, 6738558, Japan

Location

Local Institution - 0172

Kobe, Hyōgo, 6500017, Japan

Location

Local Institution - 0118

Kobe, Hyōgo, 6500047, Japan

Location

Local Institution - 0171

Kanazawa, Ishikawa-ken, 920-8530, Japan

Location

Local Institution - 0229

Kagoshima, Kagoshima-ken, 8908520, Japan

Location

Local Institution - 0127

Isehara, Kanagawa, 259-1193, Japan

Location

Local Institution - 0109

Kawasaki-shi, Kanagawa, 216-8511, Japan

Location

Local Institution - 0105

Sagamihara-shi, Kanagawa, 2520375, Japan

Location

Local Institution - 0147

Yokohama, Kanagawa, 2360004, Japan

Location

Local Institution - 0117

Yokohama, Kanagawa, 2418515, Japan

Location

Local Institution - 0141

Kumamoto, Kumamoto, 8608556, Japan

Location

Local Institution - 0120

Kamigyō-ku, Kyoto, 602-8566, Japan

Location

Local Institution - 0145

Kyoto, Kyoto, 606-8507, Japan

Location

Local Institution - 0144

Sendai, Miyagi, 9808575, Japan

Location

Local Institution - 0146

Niigata, Niigata, 9518566, Japan

Location

Local Institution - 0135

Kurashiki-shi, Okayama-ken, 7010192, Japan

Location

Local Institution - 0137

Okayama, Okayama-ken, 7008558, Japan

Location

Local Institution - 0221

Hirakata, Osaka, 573-1191, Japan

Location

Local Institution - 0138

Osaka, Osaka, 5418567, Japan

Location

Local Institution - 0098

Sayama, Osaka, 589-8511, Japan

Location

Local Institution - 0107

Suita, Osaka, 5650871, Japan

Location

Local Institution - 0139

Takatsuki, Osaka, 569-8686, Japan

Location

Local Institution - 0230

Hidaka-shi, Saitama, 3501298, Japan

Location

Local Institution - 0175

Kitaadachi-gun, Saitama, 3620806, Japan

Location

Local Institution - 0108

Shizuoka, Shizuoka, 4208527, Japan

Location

Local Institution - 0143

Sunto-gun, Shizuoka, 411-8777, Japan

Location

Local Institution - 0148

Shimotsuga-gun, Tochigi, 321-0293, Japan

Location

Local Institution - 0106

Bunkyo-ku, Tokyo, 1138519, Japan

Location

Local Institution - 0110

Bunkyo-ku, Tokyo, 1138677, Japan

Location

Local Institution - 0136

Chuo-ku, Tokyo, 1040045, Japan

Location

Local Institution - 0128

Chuo-ku, Tokyo, 1048560, Japan

Location

Local Institution - 0126

Koto-ku, Tokyo, 1358550, Japan

Location

Local Institution - 0156

Minato-ku, Tokyo, 1058470, Japan

Location

Local Institution - 0245

Ōta-ku, Tokyo, 1438541, Japan

Location

Local Institution - 0140

Shinagawa-ku, Tokyo, 142-8666, Japan

Location

Local Institution - 0196

Shinjuku-Ku, Tokyo, 1608582, Japan

Location

Local Institution - 0155

Shinjuku-ku, Tokyo, 1628666, Japan

Location

Local Institution - 0231

Toyama, Toyama, 9300194, Japan

Location

Local Institution - 0178

Wakayama, Wakayama, 641-8510, Japan

Location

Local Institution - 0238

Ube-shi, Yamaguchi, 7558505, Japan

Location

Local Institution - 0090

Tuxtla Gutiérrez, Chiapas, 29038, Mexico

Location

Local Institution - 0102

Mexico City, Mexico City, 14000, Mexico

Location

Local Institution - 0234

San Luis Potosí City, San Luis Potosí, 78200, Mexico

Location

Local Institution - 0071

Mérida, Yucatán, 97138, Mexico

Location

Local Institution - 0060

Lima, Lima Province, 34, Peru

Location

Local Institution - 0093

Lima, Lima Province, Lima 11, Peru

Location

Local Institution - 0092

Callao, Provincia Constitucional del Callao, 02, Peru

Location

Local Institution - 0024

Lublin, 20-081, Poland

Location

Local Institution - 0022

Warsaw, 02-781, Poland

Location

Local Institution - 0243

Porto, Porto District, 4200-072, Portugal

Location

Local Institution - 0081

Bucharest, 021389, Romania

Location

Local Institution - 0079

Cluj-Napoca, 400015, Romania

Location

Local Institution - 0076

Craiova, 200347, Romania

Location

Local Institution - 0080

Suceava, 720237, Romania

Location

Local Institution - 0089

Moscow, 121309, Russia

Location

Local Institution - 0088

Saint Petersburg, 198255, Russia

Location

Local Institution - 0033

Singapore, Central Singapore, 168583, Singapore

Location

Local Institution - 0034

Singapore, 119228, Singapore

Location

Local Institution - 0129

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

Location

Local Institution - 0165

Seoul, Seoul-teukbyeolsi [Seoul], 02841, South Korea

Location

Local Institution - 0166

Busan, 49241, South Korea

Location

Local Institution - 0150

Daegu, 41404, South Korea

Location

Local Institution - 0149

Daejeon, 35015, South Korea

Location

Local Institution - 0236

Jeonju, 54907, South Korea

Location

Local Institution - 0235

Seoul, 01812, South Korea

Location

Local Institution - 0130

Seoul, 05505, South Korea

Location

Local Institution - 0177

Seoul, 06351, South Korea

Location

Local Institution - 0168

Seoul, 06591, South Korea

Location

Local Institution - 0151

Seoul, 07345, South Korea

Location

Local Institution - 0131

Seoul, 08308, South Korea

Location

Local Institution - 0123

Seoul, 120-752, South Korea

Location

Local Institution - 0157

Ulsan, 44033, South Korea

Location

Local Institution - 0063

Barcelona, 08035, Spain

Location

Local Institution - 0062

Madrid, 28050, Spain

Location

Local Institution - 0158

Changhua County, Changhua, 50006, Taiwan

Location

Local Institution - 0161

Tainan, TNN, 704, Taiwan

Location

Local Institution - 0167

Kaohsiung City, 807, Taiwan

Location

Local Institution - 0133

Kaohsiung City, 833, Taiwan

Location

Local Institution - 0163

Kaohsiung County, 0, Taiwan

Location

Local Institution - 0164

Keelung, 204, Taiwan

Location

Local Institution - 0132

Taichung, 40447, Taiwan

Location

Local Institution - 0160

Tainan, 71004, Taiwan

Location

Local Institution - 0124

Taipei, 100, Taiwan

Location

Local Institution - 0162

Taipei, 10449, Taiwan

Location

Local Institution - 0134

Taipei, 11217, Taiwan

Location

Local Institution - 0159

Taoyuan District, 333, Taiwan

Location

Local Institution - 0096

Ankara, 06100, Turkey (Türkiye)

Location

Local Institution - 0125

Diyarbakır, 21280, Turkey (Türkiye)

Location

Local Institution - 0122

Edrine, 22010, Turkey (Türkiye)

Location

Local Institution - 0069

London, Greater London, NW1 2PG, United Kingdom

Location

Local Institution - 0066

London, Greater London, SW3 6JJ, United Kingdom

Location

Local Institution - 0031

Manchester, Greater Manchester, M20 4BX, United Kingdom

Location

Local Institution - 0237

London, EC1A 7BE, United Kingdom

Location

Local Institution - 0029

Surrey, SM2 5PT, United Kingdom

Location

Related Publications (3)

• Zhang Y, Li C, Du K, Pengkhun N, Huang Z, Gong M, Li Y, Liu X, Li L, Wang D, Wang C, Chen F, Li J. Comparative analysis of immune checkpoint inhibitors in first-line treatment of esophageal squamous cell carcinoma: a network meta-analysis. Immunotherapy. 2023 Jul;15(10):737-750. doi: 10.2217/imt-2022-0236. Epub 2023 May 4.

  PMID: 37139963 DERIVED

• Kato K, Doki Y, Ogata T, Motoyama S, Kawakami H, Ueno M, Kojima T, Shirakawa Y, Okada M, Ishihara R, Kubota Y, Amaya-Chanaga C, Chen T, Matsumura Y, Kitagawa Y. First-line nivolumab plus ipilimumab or chemotherapy versus chemotherapy alone in advanced esophageal squamous cell carcinoma: a Japanese subgroup analysis of open-label, phase 3 trial (CheckMate 648/ONO-4538-50). Esophagus. 2023 Apr;20(2):291-301. doi: 10.1007/s10388-022-00970-1. Epub 2022 Nov 19.

  PMID: 36401133 DERIVED

• Doki Y, Ajani JA, Kato K, Xu J, Wyrwicz L, Motoyama S, Ogata T, Kawakami H, Hsu CH, Adenis A, El Hajbi F, Di Bartolomeo M, Braghiroli MI, Holtved E, Ostoich SA, Kim HR, Ueno M, Mansoor W, Yang WC, Liu T, Bridgewater J, Makino T, Xynos I, Liu X, Lei M, Kondo K, Patel A, Gricar J, Chau I, Kitagawa Y; CheckMate 648 Trial Investigators. Nivolumab Combination Therapy in Advanced Esophageal Squamous-Cell Carcinoma. N Engl J Med. 2022 Feb 3;386(5):449-462. doi: 10.1056/NEJMoa2111380.

  PMID: 35108470 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Interventions

Nivolumab; Ipilimumab; Cisplatin; Fluorouracil

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

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

Clinical.Trails@bms.com

Please email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: May 4, 2017
• First Posted: May 8, 2017
• Study Start: June 29, 2017
• Primary Completion: January 18, 2021
• Study Completion: January 13, 2025
• Last Updated: February 17, 2026
• Results First Posted: March 2, 2022

Record last verified: 2026-02

Locations

AR (4); TW (12); CO (4); JP (54); RO (4); SG (2); CN (23); CA (4); ES (2); GB (5); IT (4); CZ (3); ME (4); PL (2); RU (2); DK (1); PE (3); HK (2); KR (14); CL (2); BR (9); US (16); FR (6); AU (1); PT (1); TU (3)