Clinical trial NCT04008030: 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)
Official title: A Phase 3 Randomized Clinical Trial of Nivolumab Alone, Nivolumab in Combination With Ipilimumab, or Investigator's Choice Chemotherapy in Participants With Microsatellite Instability High (MSI-H) or Mismatch Repair Deficient (dMMR) Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Metastatic Colorectal Cancer
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Ono Pharmaceutical Co. Ltd
First posted: 2019-07-05
Enrollment: 881
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) (arm B vs A, all lines, centrally confirmed)
timeFrame: Up to 5 years
measure: PFS by BICR (arm B vs C, 1L, centrally confirmed)
timeFrame: Up to 5 years
Secondary outcomes:
measure: Overall Response Rate (ORR) by BICR (arm B vs A, all lines, centrally confirmed)
timeFrame: Up to 5 years
measure: Overall Survival (OS) (arm B vs A, all lines, centrally confirmed)
timeFrame: Up to 5 years
measure: PFS by Investigator Assessment (arm B vs A, all lines, centrally confirmed)
timeFrame: Up to 5 years
measure: PFS by BICR among all randomized participants (arm B vs A, all lines, per local testing)
timeFrame: Up to 5 years
measure: PFS by BICR (arm B vs A, 1L, centrally confirmed)
timeFrame: Up to 5 years
measure: ORR by BICR (arm B vs C, 1L, centrally confirmed)
timeFrame: Up to 5 years
measure: ORR by BICR (arm B vs A, 1L, centrally confirmed)
timeFrame: Up to 5 years
measure: OS (arm B vs A, 1L, centrally confirmed)
timeFrame: Up to 5 years
measure: PFS by BICR (arm A vs C, 1L, centrally confirmed)
timeFrame: Up to 5 years
measure: OS (arm B vs C, 1L, centrally confirmed)
timeFrame: Up to 5 years
measure: ORR by BICR (arm A vs C, 1L, centrally confirmed)
timeFrame: Up to 5 years
measure: OS (arm A vs C, 1L, centrally confirmed)
timeFrame: Up to 5 years
measure: PFS by Investigator (arm A, B and C, 1L, centrally confirmed)
timeFrame: Up to 5 years
measure: PFS by BICR among all randomized participants who have not received prior treatment (arm B vs C, 1L, per local testing)
timeFrame: Up to 5 years
measure: PFS by BICR among all randomized participants who have not received prior treatment (arm B vs A, 1L, per local testing)
timeFrame: Up to 5 years
measure: PFS by BICR (arm B vs C, 1L, by each central test)
timeFrame: Up to 5 years
measure: PFS by BICR (arm B vs A, all lines, by each central test)
timeFrame: Up to 5 years
measure: PFS by BICR (crossover cohort, centrally confirmed)
timeFrame: Up to 5 years
measure: ORR by BICR (crossover cohort, centrally confirmed)
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Local Institution - 0059
state: California
city: Sacramento
country: United States
facility: Local Institution - 0130
state: California
city: Denver
country: United States
facility: Local Institution - 0103
state: Colorado
city: Arlington Heights
country: United States
facility: Local Institution - 0119
state: Illinois
city: New York
country: United States
facility: Local Institution - 0060
state: New York
city: Portland
country: United States
facility: Local Institution - 0105
state: Oregon
city: Pittsburgh
country: United States
facility: Local Institution - 0121
state: Pennsylvania
city: Dallas
country: United States
facility: Local Institution - 0106
state: Texas
city: Roanoke
country: United States
facility: Local Institution - 0104
state: Virginia
city: Ciudad Autonoma Beunos Aires
country: Argentina
facility: Local Institution - 0073
state: Buenos Aires
city: Viedma
country: Argentina
facility: Local Institution - 0074
state: RIO Negro
city: Buenos Aires
country: Argentina
facility: Local Institution - 0084
city: Caba
country: Argentina
facility: Local Institution - 0100
city: Caba
country: Argentina
facility: Local Institution - 0072
city: Westmead
country: Australia
facility: Local Institution - 0019
state: New South Wales
city: Woolloongabba
country: Australia
facility: Local Institution - 0053
state: Queensland
city: Elizabeth Vale
country: Australia
facility: Local Institution - 0018
state: South Australia
city: Clayton
country: Australia
facility: Local Institution - 0041
state: Victoria
city: Heidelberg
country: Australia
facility: Local Institution - 0017
state: Victoria
city: Graz
country: Austria
facility: Local Institution - 0064
city: Linz
country: Austria
facility: Local Institution - 0068
city: Salzburg
country: Austria
facility: Local Institution - 0120
city: Wiener Neustadt
country: Austria
facility: Local Institution - 0067
city: Wien
country: Austria
facility: Local Institution - 0065
city: Bonheiden
country: Belgium
facility: Local Institution - 0045
state: Antwerpen
city: Anderlecht
country: Belgium
facility: Local Institution - 0025
state: Bruxelles-Capitale, Région De
city: Leuven
country: Belgium
facility: Local Institution - 0024
city: Ipatinga
country: Brazil
facility: Local Institution - 0096
state: Minas Gerais
city: Natal
country: Brazil
facility: Local Institution - 0200
state: RIO Grande DO Norte
city: Porto Alegre
country: Brazil
facility: Local Institution - 0192
state: RIO Grande DO SUL
city: Barretos
country: Brazil
facility: Local Institution - 0102
state: Sao Paulo
city: Sao Paulo
country: Brazil
facility: Local Institution - 0095
state: São Paulo
city: São José do Rio Preto
country: Brazil
facility: Local Institution - 0094
state: São Paulo
city: Rio de Janeiro
country: Brazil
facility: Local Institution - 0199
city: São Paulo
country: Brazil
facility: Local Institution - 0193
city: Edmonton
country: Canada
facility: Local Institution - 0011
state: Alberta
city: Vancouver
country: Canada
facility: Local Institution - 0039
state: British Columbia
city: Toronto
country: Canada
facility: Local Institution - 0013
state: Ontario
city: Montreal
country: Canada
facility: Local Institution - 0016
state: Quebec
city: Sherbrooke
country: Canada
facility: Local Institution - 0015
state: Quebec
city: Santiago
country: Chile
facility: Local Institution - 0071
state: Metropolitana
city: Santiago
country: Chile
facility: Local Institution - 0069
state: Metropolitana
city: Independencia
country: Chile
facility: Local Institution - 0070
state: Santiago
city: Hefei
country: China
facility: Local Institution - 0146
state: Anhui
city: Xiamen
country: China
facility: Local Institution - 0163
state: Fujian
city: Zhangzhou
country: China
facility: Local Institution - 0207
state: Fujian
city: Lanzhou
country: China
facility: Local Institution - 0211
state: Gansu
city: Foshan
country: China
facility: Local Institution - 0158
state: Guangdong
city: Guangzhou
country: China
facility: Local Institution - 0167
state: Guangdong
city: Guangzhou
country: China
facility: Local Institution - 0153
state: Guangdong
city: Guangzhou
country: China
facility: Local Institution - 0149
state: Guangdong
city: Nanning
country: China
facility: Local Institution - 0160
state: Guangxi
city: Nanning
country: China
facility: Local Institution - 0196
state: Guangxi
city: Harbin
country: China
facility: Local Institution - 0180
state: Heilongjiang
city: Zhengzhou
country: China
facility: Local Institution - 0181
state: Henan
city: Changsha
country: China
facility: Local Institution - 0197
state: Hunan
city: Changzhou
country: China
facility: Local Institution - 0145
state: Jiangsu
city: Nanchang
country: China
facility: Local Institution - 0151
state: Jiangxi
city: Changchun
country: China
facility: Local Institution - 0164
state: Jilin
city: Shenyang
country: China
facility: Local Institution - 0162
state: Liaoning
city: Xi'an
country: China
facility: Local Institution - 0188
state: Shaanxi
city: Jinan
country: China
facility: Local Institution - 0210
state: Shandong
city: Linyi
country: China
facility: Local Institution - 0212
state: Shandong
city: Qingdao
country: China
facility: Local Institution - 0154
state: Shandong
city: Yantai
country: China
facility: Local Institution - 0165
state: Shandong
city: Shanghai
country: China
facility: Local Institution - 0143
state: Shanghai
city: Shanghai
country: China
facility: Local Institution - 0131
state: Shanghai
city: Shanghai
country: China
facility: Local Institution - 0221
state: Shanghai
city: Kunming
country: China
facility: Local Institution - 0195
state: Yunnan
city: Hangzhou
country: China
facility: Local Institution - 0137
state: Zhejiang
city: Ningbo
country: China
facility: Local Institution - 0206
state: Zhejiang
city: Brno
country: Czechia
facility: Local Institution - 0087
city: Hradec Kralove
country: Czechia
facility: Local Institution - 0085
city: Novy Jicin
country: Czechia
facility: Local Institution - 0088
city: Olomouc
country: Czechia
facility: Local Institution - 0086
city: Herlev
country: Denmark
facility: Local Institution - 0038
city: Vejle
country: Denmark
facility: Local Institution - 0036
city: Limoges
country: France
facility: Local Institution - 0176
state: Haute-Vienne
city: Lille
country: France
facility: Local Institution - 0138
state: Nord
city: Bayonne
country: France
facility: Local Institution - 0186
city: Besancon Cedex
country: France
facility: Local Institution - 0028
city: Lyon Cedex 08
country: France
facility: Local Institution - 0029
city: Lyon
country: France
facility: Local Institution - 0183
city: Marseille
country: France
facility: Local Institution - 0066
city: Montpellier
country: France
facility: Local Institution - 0030
city: Nantes
country: France
facility: Local Institution - 0032
city: Paris
country: France
facility: Local Institution - 0027
city: Pessac Cedex
country: France
facility: Local Institution - 0061
city: Poitiers
country: France
facility: Local Institution - 0031
city: Strasbourg
country: France
facility: Local Institution - 0184
city: Toulouse
country: France
facility: Local Institution - 0040
city: Dresden
country: Germany
facility: Local Institution - 0042
city: Essen
country: Germany
facility: Local Institution - 0007
city: Hamburg
country: Germany
facility: Local Institution - 0043
city: Hamburg
country: Germany
facility: Local Institution - 0117
city: Hannover
country: Germany
facility: Local Institution - 0008
city: Heidelberg
country: Germany
facility: Local Institution - 0009
city: Marburg
country: Germany
facility: Local Institution - 0044
city: Munich
country: Germany
facility: Local Institution - 0010
city: Athens
country: Greece
facility: Local Institution - 0222
city: Athens
country: Greece
facility: Local Institution - 0123
city: Heraklion
country: Greece
facility: Local Institution - 0125
city: Holargos
country: Greece
facility: Local Institution - 0124
city: Ioannina
country: Greece
facility: Local Institution - 0126
city: Dublin 8
country: Ireland
facility: Local Institution - 0091
state: Dublin
city: Dublin
country: Ireland
facility: Local Institution - 0022
city: Limerick
country: Ireland
facility: Local Institution - 0026
city: Catania
country: Italy
facility: Local Institution - 0055
city: Genova
country: Italy
facility: Local Institution - 0003
city: Milan
country: Italy
facility: Local Institution - 0001
city: Napoli
country: Italy
facility: Local Institution - 0004
city: Padova
country: Italy
facility: Local Institution - 0002
city: Roma
country: Italy
facility: Local Institution - 0054
city: Nagoya-shi
country: Japan
facility: Local Institution - 0109
state: Aichi
city: Chiba-shi
country: Japan
facility: Local Institution - 0112
state: Chiba
city: Kashiwa-shi
country: Japan
facility: Local Institution - 0107
state: Chiba
city: Matsuyama
country: Japan
facility: Local Institution - 0132
state: Ehime
city: Fukuoka-shi
country: Japan
facility: Local Institution - 0116
state: Fukuoka
city: Sapporo-shi
country: Japan
facility: Local Institution - 0174
state: Hokkaido
city: Kanazawa-city
country: Japan
facility: Local Institution - 0128
state: Ishikawa
city: Kawasaki
country: Japan
facility: Local Institution - 0111
state: Kanagawa
city: Yokohama
country: Japan
facility: Local Institution - 0175
state: Kanagawa
city: Kumamoto-shi
country: Japan
facility: Local Institution - 0133
state: Kumamoto
city: Osaki
country: Japan
facility: Local Institution - 0189
state: Miyagi
city: Kurashiki
country: Japan
facility: Local Institution - 0177
state: Okayama
city: Suita-shi
country: Japan
facility: Local Institution - 0115
state: Osaka
city: Hidaka
country: Japan
facility: Local Institution - 0187
state: Saitama
city: Kitaadachigun
country: Japan
facility: Local Institution - 0110
state: Saitama
city: Sunto-gun
country: Japan
facility: Local Institution - 0108
state: Shizuoka
city: Chuo-ku
country: Japan
facility: Local Institution - 0118
state: Tokyo
city: Koto-ku
country: Japan
facility: Local Institution - 0113
state: Tokyo
city: Minato-ku
country: Japan
facility: Local Institution - 0129
state: Tokyo
city: Osaka
country: Japan
facility: Local Institution - 0114
city: Amsterdam
country: Netherlands
facility: Local Institution - 0052
state: Noord-Holland
city: Amsterdam
country: Netherlands
facility: Local Institution - 0051
state: Noord-Holland
city: Utrecht
country: Netherlands
facility: Local Institution - 0050
city: Bergen
country: Norway
facility: Local Institution - 0033
city: Lorenskog
country: Norway
facility: Local Institution - 0034
city: Oslo
country: Norway
facility: Local Institution - 0035
city: Rio Piedras
country: Puerto Rico
facility: Local Institution - 0058
city: Cluj-Napoca
country: Romania
facility: Local Institution - 0076
state: Cluj
city: Craiova
country: Romania
facility: Local Institution - 0081
state: Dolj
city: Brasov
country: Romania
facility: Local Institution - 0168
city: Bucharest
country: Romania
facility: Local Institution - 0080
city: Iași
country: Romania
facility: Local Institution - 0205
city: Suceava
country: Romania
facility: Local Institution - 0089
city: Badalona
country: Spain
facility: Local Institution - 0056
state: Barcelona [Barcelona]
city: A Coruna
country: Spain
facility: Local Institution - 0173
city: Barcelona
country: Spain
facility: Local Institution - 0006
city: Madrid
country: Spain
facility: Local Institution - 0005
city: Malaga
country: Spain
facility: Local Institution - 0172
city: Sevilla
country: Spain
facility: Local Institution - 0063
city: Valencia
country: Spain
facility: Local Institution - 0171
city: Adana
country: Turkey
facility: Local Institution - 0092
city: Istanbul
country: Turkey
facility: Local Institution - 0101
city: London
country: United Kingdom
facility: Local Institution - 0127
city: Oxford
country: United Kingdom
facility: Local Institution - 0049
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: