A Study of Nivolumab, Nivolumab Plus Ipilimumab, or Investigator's Choice Chemotherapy for the Treatment of Participants With Deficient Mismatch Repair (dMMR)/Microsatellite Instability High (MSI-H) Metastatic Colorectal Cancer (mCRC)
- Conditions
- Metastatic Colorectal Cancer
- Interventions
- Registration Number
- NCT04008030
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The main purpose of this study is to compare the clinical benefit, as measured by Progression-Free Survival (PFS), Objective Response Rate (ORR), and Overall Survival (OS), achieved by nivolumab in combination with ipilimumab or by nivolumab monotherapy in participants with Microsatellite Instability High (MSI-H) or Mismatch Repair Deficient (dMMR) metastatic colorectal cancer (mCRC). This study will also compare nivolumab plus ipilimumab combination vs chemotherapy for treatment of MSI-H/dMMR mCRC participants.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 1147
- Histologically confirmed recurrent or metastatic colorectal cancer (CRC) irrespective of prior treatment history with chemotherapy and/or targeted agents not amenable to surgery (Applicable only during Part 1 enrollment of the study)
- Histologically confirmed recurrent or metastatic CRC with no prior treatment history with chemotherapy and/or targeted agents for metastatic disease and not amenable to surgery (Applicable during Part 2 enrollment of the study)
- Known tumor microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) status per local standard of practice
- Eastern cooperative oncology group (ECOG) performance status lower than or equal to 1
- An active, known or suspected autoimmune disease
- History of interstitial lung disease or pneumonitis
- Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
Other protocol-defined inclusion/exclusion criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Nivolumab Monotherapy Nivolumab - Arm B: Nivolumab + Ipilimumab Combination Ipilimumab - Arm B: Nivolumab + Ipilimumab Combination Nivolumab - Arm C: Investigator's Choice Chemotherapy Leucovorin Participants in Arm C would be allowed to receive Nivolumab + Ipilimumab if they progress Arm C: Investigator's Choice Chemotherapy Fluorouracil Participants in Arm C would be allowed to receive Nivolumab + Ipilimumab if they progress Arm C: Investigator's Choice Chemotherapy Irinotecan Participants in Arm C would be allowed to receive Nivolumab + Ipilimumab if they progress Arm C: Investigator's Choice Chemotherapy Oxaliplatin Participants in Arm C would be allowed to receive Nivolumab + Ipilimumab if they progress Arm C: Investigator's Choice Chemotherapy Bevacizumab Participants in Arm C would be allowed to receive Nivolumab + Ipilimumab if they progress Arm C: Investigator's Choice Chemotherapy Cetuximab Participants in Arm C would be allowed to receive Nivolumab + Ipilimumab if they progress
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) (arm B vs A, all lines, centrally confirmed) Up to 5 years PFS by BICR (arm B vs C, 1L, centrally confirmed) Up to 5 years
- Secondary Outcome Measures
Name Time Method OS (arm B vs A, 1L, centrally confirmed) Up to 5 years Overall Survival (OS) (arm B vs A, all lines, centrally confirmed) Up to 5 years OS (arm A vs C, 1L, centrally confirmed) Up to 5 years PFS by Investigator (arm A, B and C, 1L, centrally confirmed) Up to 5 years PFS by BICR among all randomized participants who have not received prior treatment (arm B vs A, 1L, per local testing) Up to 5 years PFS by Investigator Assessment (arm B vs A, all lines, centrally confirmed) Up to 5 years PFS by BICR among all randomized participants (arm B vs A, all lines, per local testing) Up to 5 years ORR by BICR (arm B vs A, 1L, centrally confirmed) Up to 5 years ORR by BICR (arm A vs C, 1L, centrally confirmed) Up to 5 years Overall Response Rate (ORR) by BICR (arm B vs A, all lines, centrally confirmed) Up to 5 years PFS by BICR (arm A vs C, 1L, centrally confirmed) Up to 5 years OS (arm B vs C, 1L, centrally confirmed) Up to 5 years PFS by BICR (arm B vs A, 1L, centrally confirmed) Up to 5 years ORR by BICR (arm B vs C, 1L, centrally confirmed) Up to 5 years PFS by BICR (arm B vs C, 1L, by each central test) Up to 5 years PFS by BICR (arm B vs A, all lines, by each central test) Up to 5 years ORR by BICR (crossover cohort, centrally confirmed) Up to 5 years PFS by BICR among all randomized participants who have not received prior treatment (arm B vs C, 1L, per local testing) Up to 5 years PFS by BICR (crossover cohort, centrally confirmed) Up to 5 years
Trial Locations
- Locations (158)
Local Institution - 0084
🇦🇷Buenos Aires, Argentina
Local Institution - 0100
🇦🇷Caba, Argentina
Local Institution - 0072
🇦🇷Caba, Argentina
Local Institution - 0068
🇦🇹Linz, Austria
Local Institution - 0120
🇦🇹Salzburg, Austria
Local Institution - 0067
🇦🇹Wiener Neustadt, Austria
Local Institution - 0065
🇦🇹Wien, Austria
Local Institution - 0153
🇨🇳Guangzhou, Guangdong, China
Local Institution - 0149
🇨🇳Guangzhou, Guangdong, China
Local Institution - 0164
🇨🇳Changchun, Jilin, China
Local Institution - 0137
🇨🇳Hangzhou, Zhejiang, China
Local Institution - 0086
🇨🇿Olomouc, Czechia
Local Institution - 0038
🇩🇰Herlev, Denmark
Local Institution - 0036
🇩🇰Vejle, Denmark
Local Institution - 0028
🇫🇷Besancon Cedex, France
Local Institution - 0029
🇫🇷Lyon Cedex 08, France
Local Institution - 0183
🇫🇷Lyon, France
Local Institution - 0066
🇫🇷Marseille, France
Local Institution - 0030
🇫🇷Montpellier, France
Local Institution - 0032
🇫🇷Nantes, France
Local Institution - 0027
🇫🇷Paris, France
Local Institution - 0061
🇫🇷Pessac Cedex, France
Local Institution - 0031
🇫🇷Poitiers, France
Local Institution - 0184
🇫🇷Strasbourg, France
Local Institution - 0040
🇫🇷Toulouse, France
Local Institution - 0042
🇩🇪Dresden, Germany
Local Institution - 0007
🇩🇪Essen, Germany
Local Institution - 0043
🇩🇪Hamburg, Germany
Local Institution - 0117
🇩🇪Hamburg, Germany
Local Institution - 0008
🇩🇪Hannover, Germany
Local Institution - 0009
🇩🇪Heidelberg, Germany
Local Institution - 0044
🇩🇪Marburg, Germany
Local Institution - 0010
🇩🇪Munich, Germany
Local Institution - 0035
🇳🇴Oslo, Norway
Local Institution - 0058
🇵🇷Rio Piedras, Puerto Rico
Local Institution - 0076
🇷🇴Cluj-Napoca, Cluj, Romania
Local Institution - 0081
🇷🇴Craiova, Dolj, Romania
Local Institution - 0168
🇷🇴Brasov, Romania
Local Institution - 0080
🇷🇴Bucharest, Romania
Local Institution - 0205
🇷🇴Iași, Romania
Local Institution - 0089
🇷🇴Suceava, Romania
Local Institution - 0211
🇨🇳Lanzhou, Gansu, China
Local Institution - 0059
🇺🇸Los Angeles, California, United States
Local Institution - 0130
🇺🇸Sacramento, California, United States
Local Institution - 0103
🇺🇸Denver, Colorado, United States
Local Institution - 0119
🇺🇸Arlington Heights, Illinois, United States
Local Institution - 0060
🇺🇸New York, New York, United States
Local Institution - 0105
🇺🇸Portland, Oregon, United States
Local Institution - 0121
🇺🇸Pittsburgh, Pennsylvania, United States
Local Institution - 0106
🇺🇸Dallas, Texas, United States
Local Institution - 0104
🇺🇸Roanoke, Virginia, United States
Local Institution - 0073
🇦🇷Ciudad Autonoma Beunos Aires, Buenos Aires, Argentina
Local Institution - 0074
🇦🇷Viedma, RIO Negro, Argentina
Local Institution - 0019
🇦🇺Westmead, New South Wales, Australia
Local Institution - 0053
🇦🇺Woolloongabba, Queensland, Australia
Local Institution - 0018
🇦🇺Elizabeth Vale, South Australia, Australia
Local Institution - 0041
🇦🇺Clayton, Victoria, Australia
Local Institution - 0017
🇦🇺Heidelberg, Victoria, Australia
Local Institution - 0064
🇦🇹Graz, Austria
Local Institution - 0045
🇧🇪Bonheiden, Antwerpen, Belgium
Local Institution - 0025
🇧🇪Anderlecht, Bruxelles-Capitale, Région De, Belgium
Local Institution - 0024
🇧🇪Leuven, Belgium
Local Institution - 0096
🇧🇷Ipatinga, Minas Gerais, Brazil
Local Institution - 0200
🇧🇷Natal, RIO Grande DO Norte, Brazil
Local Institution - 0192
🇧🇷Porto Alegre, RIO Grande DO SUL, Brazil
Local Institution - 0102
🇧🇷Barretos, Sao Paulo, Brazil
Local Institution - 0095
🇧🇷Sao Paulo, São Paulo, Brazil
Local Institution - 0094
🇧🇷São José do Rio Preto, São Paulo, Brazil
Local Institution - 0199
🇧🇷Rio de Janeiro, Brazil
Local Institution - 0193
🇧🇷São Paulo, Brazil
Local Institution - 0011
🇨🇦Edmonton, Alberta, Canada
Local Institution - 0039
🇨🇦Vancouver, British Columbia, Canada
Local Institution - 0013
🇨🇦Toronto, Ontario, Canada
Local Institution - 0016
🇨🇦Montreal, Quebec, Canada
Local Institution - 0015
🇨🇦Sherbrooke, Quebec, Canada
Local Institution - 0071
🇨🇱Santiago, Metropolitana, Chile
Local Institution - 0069
🇨🇱Santiago, Metropolitana, Chile
Local Institution - 0070
🇨🇱Independencia, Santiago, Chile
Local Institution - 0146
🇨🇳Hefei, Anhui, China
Local Institution
🇨🇳Fuzhou, Fujian, China
Local Institution - 0163
🇨🇳Xiamen, Fujian, China
Local Institution - 0207
🇨🇳Zhangzhou, Fujian, China
Local Institution - 0158
🇨🇳Foshan, Guangdong, China
Local Institution - 0167
🇨🇳Guangzhou, Guangdong, China
Local Institution - 0160
🇨🇳Nanning, Guangxi, China
Local Institution - 0196
🇨🇳Nanning, Guangxi, China
Local Institution - 0180
🇨🇳Harbin, Heilongjiang, China
Local Institution - 0181
🇨🇳Zhengzhou, Henan, China
Local Institution - 0197
🇨🇳Changsha, Hunan, China
Local Institution - 0145
🇨🇳Changzhou, Jiangsu, China
Local Institution - 0151
🇨🇳Nanchang, Jiangxi, China
Local Institution - 0116
🇯🇵Fukuoka-shi, Fukuoka, Japan
Local Institution - 0162
🇨🇳Shenyang, Liaoning, China
Local Institution - 0188
🇨🇳Xi'an, Shaanxi, China
Local Institution - 0210
🇨🇳Jinan, Shandong, China
Local Institution - 0212
🇨🇳Linyi, Shandong, China
Local Institution - 0154
🇨🇳Qingdao, Shandong, China
Local Institution - 0165
🇨🇳Yantai, Shandong, China
Local Institution - 0143
🇨🇳Shanghai, Shanghai, China
Local Institution - 0131
🇨🇳Shanghai, Shanghai, China
Local Institution - 0221
🇨🇳Shanghai, Shanghai, China
Local Institution - 0195
🇨🇳Kunming, Yunnan, China
Local Institution - 0206
🇨🇳Ningbo, Zhejiang, China
Local Institution - 0087
🇨🇿Brno, Czechia
Local Institution - 0085
🇨🇿Hradec Kralove, Czechia
Local Institution - 0088
🇨🇿Novy Jicin, Czechia
Local Institution - 0176
🇫🇷Limoges, Haute-Vienne, France
Local Institution - 0138
🇫🇷Lille, Nord, France
Local Institution - 0186
🇫🇷Bayonne, France
Local Institution - 0222
🇬🇷Athens, Greece
Local Institution - 0123
🇬🇷Athens, Greece
Local Institution - 0125
🇬🇷Heraklion, Greece
Local Institution - 0124
🇬🇷Holargos, Greece
Local Institution - 0126
🇬🇷Ioannina, Greece
Local Institution - 0091
🇮🇪Dublin 8, Dublin, Ireland
Local Institution - 0022
🇮🇪Dublin, Ireland
Local Institution - 0026
🇮🇪Limerick, Ireland
Local Institution - 0055
🇮🇹Catania, Italy
Local Institution - 0003
🇮🇹Genova, Italy
Local Institution - 0001
🇮🇹Milan, Italy
Local Institution - 0004
🇮🇹Napoli, Italy
Local Institution - 0002
🇮🇹Padova, Italy
Local Institution - 0054
🇮🇹Roma, Italy
Local Institution - 0109
🇯🇵Nagoya-shi, Aichi, Japan
Local Institution - 0112
🇯🇵Chiba-shi, Chiba, Japan
Local Institution - 0107
🇯🇵Kashiwa-shi, Chiba, Japan
Local Institution - 0132
🇯🇵Matsuyama, Ehime, Japan
Local Institution - 0174
🇯🇵Sapporo-shi, Hokkaido, Japan
Local Institution - 0128
🇯🇵Kanazawa-city, Ishikawa, Japan
Local Institution - 0111
🇯🇵Kawasaki, Kanagawa, Japan
Local Institution - 0175
🇯🇵Yokohama, Kanagawa, Japan
Local Institution - 0133
🇯🇵Kumamoto-shi, Kumamoto, Japan
Local Institution - 0189
🇯🇵Osaki, Miyagi, Japan
Local Institution - 0177
🇯🇵Kurashiki, Okayama, Japan
Local Institution - 0115
🇯🇵Suita-shi, Osaka, Japan
Local Institution - 0187
🇯🇵Hidaka, Saitama, Japan
Local Institution - 0110
🇯🇵Kitaadachigun, Saitama, Japan
Local Institution - 0108
🇯🇵Sunto-gun, Shizuoka, Japan
Local Institution - 0118
🇯🇵Chuo-ku, Tokyo, Japan
Local Institution - 0113
🇯🇵Koto-ku, Tokyo, Japan
Local Institution - 0129
🇯🇵Minato-ku, Tokyo, Japan
Local Institution - 0114
🇯🇵Osaka, Japan
Local Institution - 0052
🇳🇱Amsterdam, Noord-Holland, Netherlands
Local Institution - 0051
🇳🇱Amsterdam, Noord-Holland, Netherlands
Local Institution - 0050
🇳🇱Utrecht, Netherlands
Local Institution - 0033
🇳🇴Bergen, Norway
Local Institution - 0034
🇳🇴Lorenskog, Norway
Local Institution - 0056
🇪🇸Badalona, Barcelona [Barcelona], Spain
Local Institution - 0173
🇪🇸A Coruna, Spain
Local Institution - 0006
🇪🇸Barcelona, Spain
Local Institution - 0005
🇪🇸Madrid, Spain
Local Institution - 0172
🇪🇸Malaga, Spain
Local Institution - 0063
🇪🇸Sevilla, Spain
Local Institution - 0171
🇪🇸Valencia, Spain
Local Institution - 0092
🇹🇷Adana, Turkey
Local Institution - 0101
🇹🇷Istanbul, Turkey
Local Institution - 0127
🇬🇧London, United Kingdom
Local Institution - 0049
🇬🇧Oxford, United Kingdom