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Efficacy Study of Nivolumab Plus Ipilimumab or Nivolumab Plus Chemotherapy Against Chemotherapy in Stomach Cancer or Stomach/Esophagus Junction Cancer

Phase 3
Completed
Conditions
Gastric Cancer
Gastroesophageal Junction Cancer
Esophageal Adenocarcinoma
Interventions
Registration Number
NCT02872116
Lead Sponsor
Bristol-Myers Squibb
Brief Summary

The main purpose of this study is to compare how long patients with gastric or gastroesophageal junction cancer live after receiving nivolumab and ipilimumab or nivolumab and chemotherapy compared with patients receiving chemotherapy alone.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
2031
Inclusion Criteria
  • Male or Female at least 18 years of age
  • Must have gastric cancer or gastroesophageal junction cancer that cannot be operated on and that is advanced or has spread out
  • Did not receive neoadjuvant or adjuvant treatment (chemotherapy, radiotherapy, or both) for their disease within the last 6 months
  • 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
Exclusion Criteria
  • Presence of tumor cells in the brain or spinal cord that have not been treated
  • 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

Other protocol-defined inclusion/exclusion criteria apply

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Nivolumab + XELOXCapecitabine-
FOLFOX (Oxaliplatin + Leucovorin + Fluorouracil)Fluorouracil-
XELOX (Oxaliplatin + Capecitabine)Oxaliplatin-
FOLFOX (Oxaliplatin + Leucovorin + Fluorouracil)Oxaliplatin-
Nivolumab + XELOXOxaliplatin-
XELOX (Oxaliplatin + Capecitabine)Capecitabine-
Nivolumab + IpilimumabNivolumabNivolumab + Ipilimumab for 4 doses, followed by Nivolumab monotherapy Enrollment is closed for this arm
FOLFOX (Oxaliplatin + Leucovorin + Fluorouracil)Leucovorin-
Nivolumab + IpilimumabIpilimumabNivolumab + Ipilimumab for 4 doses, followed by Nivolumab monotherapy Enrollment is closed for this arm
Nivolumab + XELOXNivolumab-
Nivolumab + FOLFOXOxaliplatin-
Nivolumab + FOLFOXNivolumab-
Nivolumab + FOLFOXLeucovorin-
Nivolumab + FOLFOXFluorouracil-
Primary Outcome Measures
NameTimeMethod
Overall Survival (OS) in Participants Treated With Nivolumab Plus Chemotherapy vs Chemotherapy With PD-L1 CPS ≥ 5From the date of randomization up to the date of death, up to approximately 17 months

Overall survival (OS), defined as the time from randomization to the time of death, in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy with PD-L1 CPS (combined positive score) ≥ 5. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.

Progression Free Survival (PFS) in Participants Treated With Nivolumab Plus Chemotherapy vs Chemotherapy With PD-L1 CPS ≥ 5From randomization to the date of the first documented progressive disease (PD) per BICR or death due to any cause (up to approximately 10 months)

Progression Free Survival (PFS) is defined as the time from randomization to the date of the first documented PD or death due to any cause. PD is determined by blinded independent committee review (BICR) per RECIST1.1 criteria in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy with PD-L1 CPS ≥ 5. Progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking in reference the smallest sum on study that also demonstrated an absolute increase of at least 5 mm. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.

Secondary Outcome Measures
NameTimeMethod
OS in Participants Treated With Nivolumab Plus Chemotherapy vs ChemotherapyFrom the date of randomization up to the date of death, up to approximately 17 months

Overall survival (OS), defined as the time from randomization to the time of death, in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy with PD-L1 CPS ≥ 1, 10, and all randomized participants. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.

OS in Participants Treated With Nivolumab Plus Ipilimumab vs ChemotherapyFrom the date of randomization up to the date of death, up to approximately 14 months

Overall survival (OS), defined as the time from randomization to the time of death, in participants treated with Nivolumab plus Ipilimumab vs Chemotherapy with PD-L1 CPS (combined positive score) ≥ 1, 5, 10, and all randomized participants. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.

PFS in Participants Treated With Nivolumab Plus Chemotherapy vs ChemotherapyFrom randomization to the date of the first documented progressive disease (PD) per BICR or death due to any cause (up to approximately 10 months)

Progression free survival (PFS), defined as the time from randomization to the date of the first documented progressive disease (PD) or death due to any cause, in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy by BICR per RECIST1.1 in participants with PD-L1 CPS ≥ 10, 1, or all randomized subjects. Progreessive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking in reference the smallest sum on study that also demonstrated an absolute increase of at least 5 mm. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.

PFS in Participants Treated With Nivolumab Plus Ipilimumab vs ChemotherapyFrom randomization to the date of the first documented progressive disease (PD) per BICR or death due to any cause (up to approximately 9 months)

Progression Free Survival (PFS) is defined as the time from randomization to the date of the first documented PD or death due to any cause. PD is determined by blinded independent committee review (BICR) per RECIST1.1 criteria in participants treated with Nivolumab plus Ipilumab vs Chemotherapy with PD-L1 CPS ≥ 10, 5, 1 or all randomized participants. Progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking in reference the smallest sum on study that also demonstrated an absolute increase of at least 5 mm. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.

Objective Response RateFrom randomization to the date of objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first (up to approximately 43 months)

Objective response rate (ORR) as assessed by BICR in participants with PD-L1 CPS ≥ 10, 5, 1, or all randomized participants. ORR is a percentage of participants determined by the number of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of measurable participants with target lesion at baseline. BOR is defined as the best response designation as determined by the BICR, recorded between the date of randomization and the date of objectively documented progression (per RECIST 1.1 as determined by the BICR) or the date of subsequent anti-cancer therapy, whichever occurs first. CR is defined as the disappearance of all target lesions. PR is define as at 30% decrease in the sum of diameters of target lesions. The 806 chemotherapy treated participants are split into two separate arms (Arm 2a and Arm 2b) to act as comparison groups to the other treatment arms.

Time to Symptom Deterioration (TTSD)From randomization until a clinically meaningful decline from baseline in GaCS score

TTSD is defined as the the time from randomization until a clinically meaningful decline from baseline in Gastric Cancer Subscale (GaCS) score. A clinically meaningful deterioration is defined as a reduction of 8.2 points in the GaCS score. Subjects who do not deteriorate will be censored at the time of their last GACS assessment. Subjects without baseline GaCS assessment will be censored on the randomization date. Those with baseline GaCS, who do not have any GaCS assessments after randomization will be censored on the day after randomization.

Trial Locations

Locations (179)

Local Institution - 0122

🇯🇵

Minato-ku, Tokyo, Japan

Local Institution - 0017

🇬🇷

Nea Kifissia, Attikí, Greece

Local Institution - 0016

🇵🇱

Lublin, Poland

Local Institution - 0127

🇯🇵

Kita-Gun, Kagawa, Japan

Local Institution - 0024

🇨🇴

Pasto, Colombia

Local Institution - 0077

🇫🇷

Lille, Nord, France

Local Institution - 0056

🇬🇷

Athens, Greece

Local Institution - 0019

🇬🇷

Ioannina, Greece

Local Institution - 0108

🇭🇺

Debrecen, Hungary

Local Institution - 0128

🇯🇵

Chiba-shi, Chiba, Japan

Local Institution - 0215

🇲🇽

Mexico City, Distrito Federal, Mexico

Local Institution - 0018

🇬🇷

Patras, Greece

Local Institution - 0008

🇭🇺

Budapest, Hungary

Local Institution - 0007

🇭🇺

Budapest, Hungary

Local Institution - 0116

🇮🇱

Jerusalem, Israel

Local Institution - 0115

🇮🇱

Petach Tikva, Israel

Local Institution - 0039

🇵🇪

Lima, Peru

Local Institution - 0012

🇷🇴

Baia Mare, Jud Maramures, Romania

Local Institution - 0117

🇮🇱

Ramat-gan, Israel

Local Institution - 0137

🇯🇵

Sapporo-shi, Hokkaido, Japan

Local Institution - 0114

🇮🇱

Tel Aviv, Israel

Local Institution - 0125

🇯🇵

Kashiwa, Chiba, Japan

Local Institution - 0124

🇯🇵

Suita-shi, Osaka, Japan

Local Institution - 0123

🇯🇵

Kitaadachi-gun, Saitama, Japan

Local Institution - 0210

🇵🇹

Porto, Portugal

Local Institution - 0041

🇷🇴

Craiova, Dolj, Romania

Local Institution - 0129

🇯🇵

Tokyo, Japan

Local Institution - 0217

🇲🇽

Toluca, Estado DE Mexico, Mexico

Local Institution - 0216

🇲🇽

Queretaro, Mexico

Local Institution - 0139

🇵🇪

Lima, Peru

Local Institution - 0042

🇷🇴

Cluj-Napoca, Romania

Local Institution - 0071

🇷🇺

Chelyabinsk, Russian Federation

Local Institution - 0194

🇸🇬

Singapore, Singapore

Local Institution - 0211

🇹🇷

Ankara, Turkey

Local Institution - 0037

🇵🇪

Lima, Peru

Local Institution - 0203

🇹🇷

Ankara, Turkey

Local Institution - 0207

🇹🇷

Edrine, Turkey

Local Institution - 0043

🇵🇹

Lisboa, Portugal

Local Institution - 0069

🇷🇺

Moscow, Russian Federation

Local Institution - 0055

🇷🇴

Suceava, Romania

Local Institution - 0086

🇷🇺

Moscow, Russian Federation

Local Institution - 0105

🇷🇺

Moscow, Russian Federation

Local Institution - 0148

🇨🇳

Tainan, Taiwan

Local Institution - 0201

🇹🇷

Antalya, Turkey

Local Institution - 0133

🇨🇳

Taipei, Taiwan

Local Institution - 0208

🇹🇷

Diyarbakır, Turkey

Local Institution - 0005

🇺🇸

Los Angeles, California, United States

Local Institution - 0021

🇺🇸

Baltimore, Maryland, United States

Florida Cancer Specialists S.

🇺🇸

Fort Myers, Florida, United States

Local Institution - 0101

🇦🇺

Adelaide, South Australia, Australia

Local Institution - 0193

🇸🇬

Singapore, Central Singapore, Singapore

Local Institution - 0120

🇺🇸

Chicago, Illinois, United States

Local Institution - 0002

🇺🇸

Boston, Massachusetts, United States

Local Institution - 0065

🇺🇸

Pittsburgh, Pennsylvania, United States

Local Institution - 0135

🇺🇸

Boston, Massachusetts, United States

Local Institution - 0004

🇺🇸

Houston, Texas, United States

Local Institution - 0003

🇺🇸

New York, New York, United States

Local Institution - 0205

🇮🇹

Modena, Italy

Local Institution - 0219

🇺🇸

Arlington Heights, Illinois, United States

Local Institution - 0035

🇨🇦

Edmonton, Alberta, Canada

Local Institution - 0036

🇨🇦

London, Ontario, Canada

Local Institution - 0058

🇨🇱

Independencia, Santiago, Chile

Local Institution - 0067

🇨🇦

Toronto, Ontario, Canada

Local Institution - 0196

🇨🇦

Montreal, Quebec, Canada

Local Institution - 0034

🇨🇦

Trois-Rivieres, Quebec, Canada

Local Institution - 0096

🇩🇪

Freiburg, Germany

Local Institution - 0022

🇨🇴

Bogota, Colombia

Local Institution - 0078

🇫🇷

Paris, France

Local Institution - 0081

🇫🇷

Dijon, France

Local Institution - 0083

🇫🇷

Montpellier, France

Local Institution - 0054

🇧🇷

Sao Paulo, Brazil

Local Institution - 0068

🇨🇦

Sherbrooke, Quebec, Canada

Local Institution - 0032

🇨🇱

Temuco, Araucania, Chile

Local Institution - 0093

🇩🇪

Hamburg, Germany

Local Institution - 0089

🇩🇪

Dresden, Germany

Local Institution - 0197

🇨🇿

Brno, Czechia

Local Institution - 0132

🇰🇷

Seoul, Korea, Republic of

Local Institution - 0025

🇨🇴

Bogota, Cundinamarca, Colombia

Local Institution - 0158

🇨🇳

Changzhou, Jiangsu, China

Local Institution - 0094

🇩🇪

Berlin, Germany

Local Institution - 0080

🇫🇷

Caen, France

Local Institution - 0113

🇫🇷

Nantes, France

Local Institution - 0095

🇩🇪

Cologne, Germany

Local Institution - 0149

🇩🇪

Muenchen, Germany

Local Institution - 0079

🇫🇷

Nice Cedex 2, France

Local Institution - 0200

🇨🇿

Brno, Czechia

Local Institution - 0092

🇩🇪

Mainz, Rheinland-Pfalz, Germany

Local Institution - 0091

🇩🇪

Essen, Germany

Local Institution - 0130

🇯🇵

Nagoya, Aichi, Japan

Local Institution - 0131

🇰🇷

Seoul, Korea, Republic of

Local Institution - 0212

🇪🇸

Zaragoza, Spain

Local Institution - 0072

🇬🇧

Southampton, United Kingdom

Local Institution - 0049

🇪🇸

Pozuelo De Alarcon, Madrid, Spain

Local Institution - 0050

🇪🇸

Badajoz, Spain

Local Institution - 0126

🇯🇵

Chuo-ku, Tokyo, Japan

Local Institution - 0189

🇵🇪

Lima, Peru

Local Institution - 0040

🇷🇴

Bucharest, Romania

Local Institution - 0134

🇨🇳

Taoyuan County, Taiwan

Local Institution - 0073

🇬🇧

Manchester, Greater Manchester, United Kingdom

Local Institution - 0209

🇪🇸

Badalona-barcelona, Spain

Local Institution - 0013

🇵🇱

Tarnobrzeg, Poland

Local Institution - 0014

🇵🇱

Warszawa, Poland

Local Institution - 0045

🇪🇸

Valencia, Spain

Local Institution - 0085

🇷🇺

St. Petersburg, Russian Federation

Local Institution - 0075

🇬🇧

Sutton, Surrey, United Kingdom

Local Institution - 0074

🇬🇧

London, Greater London, United Kingdom

Local Institution - 0044

🇪🇸

Barcelona, Spain

Local Institution - 0178

🇨🇳

Beijing, Beijing, China

Local Institution - 0176

🇨🇳

Beijing, Beijing, China

Local Institution - 0171

🇨🇳

Beijing, Beijing, China

Local Institution - 0185

🇨🇳

Fuzhou, Fujian, China

Local Institution - 0167

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Urumqi, Xinjiang, China

Local Institution - 0166

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Guangzhou, Guangdong, China

Local Institution - 0175

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Shanghai, Shanghai, China

Local Institution - 0161

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Hangzhou, Zhejiang, China

Local Institution - 0160

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Harbin, Heilongjiang, China

Local Institution - 0155

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Changchun, Jilin, China

Local Institution - 0159

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Zhengzhou, Henan, China

Local Institution - 0156

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Changchun, Jilin, China

Local Institution - 0181

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Shenyang, Liaoning, China

Local Institution - 0173

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Changsha, Hunan, China

Local Institution - 0187

🇨🇳

Nanjing, Jiangsu, China

Local Institution - 0154

🇨🇳

Nanjing, Jiangsu, China

Local Institution - 0182

🇨🇳

Qingdao, Shandong, China

Local Institution - 0165

🇨🇳

Shanghai, Shanghai, China

Local Institution - 0168

🇨🇳

Hangzhou, Zhejiang, China

Local Institution - 0174

🇨🇳

Hangzhou, China

Local Institution - 0172

🇨🇳

Tianjin, China

Local Institution - 0046

🇧🇷

Ijui, RIO Grande DO SUL, Brazil

Local Institution - 0053

🇧🇷

Salvador, Bahia, Brazil

Local Institution - 0099

🇦🇺

Perth, Western Australia, Australia

Local Institution - 0151

🇺🇸

Denver, Colorado, United States

Local Institution - 0001

🇺🇸

San Francisco, California, United States

Local Institution - 0104

🇺🇸

Nashville, Tennessee, United States

Local Institution - 0059

🇮🇹

Roma, Italy

Local Institution - 0062

🇮🇹

Bergamo, Italy

Local Institution - 0061

🇮🇹

Napoli, Italy

Local Institution - 0063

🇮🇹

Pisa, Italy

Local Institution - 0064

🇮🇹

San Giovanni Rotondo, Italy

Local Institution - 0119

🇫🇷

Plérin, France

Local Institution - 0066

🇺🇸

Aurora, Colorado, United States

Local Institution - 0136

🇺🇸

Washington, District of Columbia, United States

Local Institution - 0147

🇺🇸

Miami, Florida, United States

Florida Cancer Specialists

🇺🇸

Saint Petersburg, Florida, United States

Local Institution - 0179

🇺🇸

Marietta, Georgia, United States

Local Institution - 0138

🇺🇸

Cleveland, Ohio, United States

Local Institution - 0146

🇺🇸

Eugene, Oregon, United States

Local Institution - 0186

🇺🇸

Cleveland, Ohio, United States

Lehigh Valley Health Network

🇺🇸

Allentown, Pennsylvania, United States

Local Institution - 0140

🇺🇸

Bedford, Texas, United States

Local Institution - 0213

🇺🇸

Dallas, Texas, United States

Local Institution - 0143

🇺🇸

Dallas, Texas, United States

Local Institution - 0028

🇦🇷

Capital Federal, Buenos Aires, Argentina

Local Institution - 0150

🇺🇸

Newport News, Virginia, United States

Texas Oncology-Plano East

🇺🇸

Plano, Texas, United States

Local Institution - 0030

🇦🇷

Caba, Buenos Aires, Argentina

Local Institution - 0029

🇦🇷

Capital Federal, Buenos Aires, Argentina

Local Institution - 0183

🇦🇷

Viedma, RIO Negro, Argentina

Local Institution - 0027

🇦🇷

Cordoba, Argentina

Local Institution - 0026

🇦🇷

San Miguel De Tucuman, Tucuman, Argentina

Local Institution - 0184

🇦🇷

La Rioja, Argentina

Local Institution - 0202

🇦🇺

Blacktown, New South Wales, Australia

Local Institution - 0100

🇦🇺

Gosford, New South Wales, Australia

Local Institution - 0190

🇦🇺

Southport, Queensland, Australia

Local Institution - 0103

🇦🇺

Ballarat, Victoria, Australia

Local Institution - 0214

🇦🇺

St Albans, Victoria, Australia

Local Institution - 0102

🇦🇺

Shepparton, Victoria, Australia

Local Institution - 0048

🇧🇷

Barretos, Sao Paulo, Brazil

Local Institution - 0057

🇨🇱

Santiago, Metropolitana, Chile

Local Institution - 0188

🇩🇪

Dusseldorf, Germany

Local Institution - 0118

🇮🇱

Haifa, Israel

Local Institution - 0052

🇨🇦

Montréal, Quebec, Canada

Local Institution - 0051

🇨🇦

Quebec City, Quebec, Canada

Local Institution - 0031

🇨🇱

Santiago, Metropolitana, Chile

Local Institution - 0033

🇨🇱

Vina Del Mar, Valparaiso, Chile

Local Institution - 0076

🇬🇧

Nottingham, Nottinghamshire, United Kingdom

Local Institution - 0047

🇧🇷

Porto Alegre, RIO Grande DO SUL, Brazil

Local Institution - 0195

🇭🇰

Hong Kong, Hong Kong

Local Institution - 0191

🇭🇰

Hong Kong, Hong Kong

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