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)

NCT ID: NCT04008030

Last Updated: 2025-10-03

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

839 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-08-05

Study Completion Date

2026-06-10

Brief Summary

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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

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Conditions

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Metastatic Colorectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A: Nivolumab Monotherapy

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

Specified dose on specified days

Arm B: Nivolumab + Ipilimumab Combination

Group Type EXPERIMENTAL

Ipilimumab

Intervention Type BIOLOGICAL

Specified dose on specified days

Nivolumab

Intervention Type BIOLOGICAL

Specified dose on specified days

Arm C: Investigator's Choice Chemotherapy

Participants in Arm C would be allowed to receive Nivolumab + Ipilimumab if they progress

Group Type ACTIVE_COMPARATOR

Oxaliplatin

Intervention Type DRUG

Specified dose on specified days

Leucovorin

Intervention Type DRUG

Specified dose on specified days

Fluorouracil

Intervention Type DRUG

Specified dose on specified days

Irinotecan

Intervention Type DRUG

Specified dose on specified days

Bevacizumab

Intervention Type DRUG

Specified dose on specified days

Cetuximab

Intervention Type DRUG

Specified dose on specified days

Interventions

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Ipilimumab

Specified dose on specified days

Intervention Type BIOLOGICAL

Oxaliplatin

Specified dose on specified days

Intervention Type DRUG

Leucovorin

Specified dose on specified days

Intervention Type DRUG

Fluorouracil

Specified dose on specified days

Intervention Type DRUG

Irinotecan

Specified dose on specified days

Intervention Type DRUG

Bevacizumab

Specified dose on specified days

Intervention Type DRUG

Cetuximab

Specified dose on specified days

Intervention Type DRUG

Nivolumab

Specified dose on specified days

Intervention Type BIOLOGICAL

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ono Pharmaceutical Co. Ltd

INDUSTRY

Sponsor Role collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

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Local Institution - 0210

Jinan, Shandong, China

Site Status

Local Institution - 0212

Linyi, Shandong, China

Site Status

Local Institution - 0154

Qingdao, Shandong, China

Site Status

Local Institution - 0165

Yantai, Shandong, China

Site Status

Local Institution - 0153

Guangzhou, Guangdong, China

Site Status

Local Institution - 0149

Guangzhou, Guangdong, China

Site Status

Local Institution - 0160

Nanning, Guangxi, China

Site Status

Local Institution - 0196

Nanning, Guangxi, China

Site Status

Local Institution - 0180

Harbin, Heilongjiang, China

Site Status

Local Institution - 0181

Zhengzhou, Henan, China

Site Status

Local Institution - 0197

Changsha, Hunan, China

Site Status

Local Institution - 0145

Changzhou, Jiangsu, China

Site Status

Local Institution - 0151

Nanchang, Jiangxi, China

Site Status

Local Institution - 0164

Changchun, Jilin, China

Site Status

Local Institution - 0162

Shenyang, Liaoning, China

Site Status

Local Institution - 0188

Xi'an, Shaanxi, China

Site Status

Local Institution - 0059

Los Angeles, California, United States

Site Status

Local Institution - 0130

Sacramento, California, United States

Site Status

Local Institution - 0103

Denver, Colorado, United States

Site Status

Local Institution - 0119

Arlington Heights, Illinois, United States

Site Status

Local Institution - 0060

New York, New York, United States

Site Status

Local Institution - 0105

Portland, Oregon, United States

Site Status

Local Institution - 0121

Pittsburgh, Pennsylvania, United States

Site Status

Local Institution - 0106

Dallas, Texas, United States

Site Status

Local Institution - 0104

Roanoke, Virginia, United States

Site Status

Local Institution - 0073

Ciudad Autonoma Beunos Aires, Buenos Aires, Argentina

Site Status

Local Institution - 0074

Viedma, Río Negro Province, Argentina

Site Status

Local Institution - 0084

Buenos Aires, , Argentina

Site Status

Local Institution - 0100

CABA, , Argentina

Site Status

Local Institution - 0072

CABA, , Argentina

Site Status

Local Institution - 0019

Westmead, New South Wales, Australia

Site Status

Local Institution - 0053

Woolloongabba, Queensland, Australia

Site Status

Local Institution - 0018

Elizabeth Vale, South Australia, Australia

Site Status

Local Institution - 0041

Clayton, Victoria, Australia

Site Status

Local Institution - 0017

Heidelberg, Victoria, Australia

Site Status

Local Institution - 0064

Graz, , Austria

Site Status

Local Institution - 0068

Linz, , Austria

Site Status

Local Institution - 0120

Salzburg, , Austria

Site Status

Local Institution - 0065

Vienna, , Austria

Site Status

Local Institution - 0067

Wiener Neustadt, , Austria

Site Status

Local Institution - 0045

Bonheiden, Antwerpen, Belgium

Site Status

Local Institution - 0025

Anderlecht, Bruxelles-Capitale, Région de, Belgium

Site Status

Local Institution - 0024

Leuven, , Belgium

Site Status

Local Institution - 0096

Ipatinga, Minas Gerais, Brazil

Site Status

Local Institution - 0200

Natal, Rio Grande do Norte, Brazil

Site Status

Local Institution - 0192

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Local Institution - 0102

Barretos, São Paulo, Brazil

Site Status

Local Institution - 0094

São José do Rio Preto, São Paulo, Brazil

Site Status

Local Institution - 0095

São Paulo, São Paulo, Brazil

Site Status

Local Institution - 0199

Rio de Janeiro, , Brazil

Site Status

Local Institution - 0193

São Paulo, , Brazil

Site Status

Local Institution - 0011

Edmonton, Alberta, Canada

Site Status

Local Institution - 0039

Vancouver, British Columbia, Canada

Site Status

Local Institution - 0013

Toronto, Ontario, Canada

Site Status

Local Institution - 0016

Montreal, Quebec, Canada

Site Status

Local Institution - 0015

Sherbrooke, Quebec, Canada

Site Status

Local Institution - 0070

Independencia, Santiago Metropolitan, Chile

Site Status

Local Institution - 0071

Santiago, Santiago Metropolitan, Chile

Site Status

Local Institution - 0069

Santiago, Santiago Metropolitan, Chile

Site Status

Local Institution - 0146

Hefei, Anhui, China

Site Status

Local Institution - 0163

Xiamen, Fujian, China

Site Status

Local Institution - 0207

Zhangzhou, Fujian, China

Site Status

Local Institution - 0211

Lanzhou, Gansu, China

Site Status

Local Institution - 0158

Foshan, Guangdong, China

Site Status

Local Institution - 0167

Guangzhou, Guangdong, China

Site Status

Local Institution - 0143

Shanghai, Shanghai Municipality, China

Site Status

Local Institution - 0131

Shanghai, Shanghai Municipality, China

Site Status

Local Institution - 0221

Shanghai, Shanghai Municipality, China

Site Status

Local Institution - 0195

Kunming, Yunnan, China

Site Status

Local Institution - 0137

Hangzhou, Zhejiang, China

Site Status

Local Institution - 0206

Ningbo, Zhejiang, China

Site Status

Local Institution - 0087

Brno, , Czechia

Site Status

Local Institution - 0085

Hradec Králové, , Czechia

Site Status

Local Institution - 0088

Nový Jičín, , Czechia

Site Status

Local Institution - 0086

Olomouc, , Czechia

Site Status

Local Institution - 0038

Herlev, , Denmark

Site Status

Local Institution - 0036

Vejle, , Denmark

Site Status

Local Institution - 0176

Limoges, Haute-Vienne, France

Site Status

Local Institution - 0138

Lille, Nord, France

Site Status

Local Institution - 0186

Bayonne, , France

Site Status

Local Institution - 0028

Besançon, , France

Site Status

Local Institution - 0183

Lyon, , France

Site Status

Local Institution - 0029

Lyon, , France

Site Status

Local Institution - 0066

Marseille, , France

Site Status

Local Institution - 0030

Montpellier, , France

Site Status

Local Institution - 0032

Nantes, , France

Site Status

Local Institution - 0027

Paris, , France

Site Status

Local Institution - 0061

Pessac, , France

Site Status

Local Institution - 0031

Poitiers, , France

Site Status

Local Institution - 0184

Strasbourg, , France

Site Status

Local Institution - 0040

Toulouse, , France

Site Status

Local Institution - 0042

Dresden, , Germany

Site Status

Local Institution - 0007

Essen, , Germany

Site Status

Local Institution - 0043

Hamburg, , Germany

Site Status

Local Institution - 0117

Hamburg, , Germany

Site Status

Local Institution - 0008

Hanover, , Germany

Site Status

Local Institution - 0009

Heidelberg, , Germany

Site Status

Local Institution - 0044

Marburg, , Germany

Site Status

Local Institution - 0010

Munich, , Germany

Site Status

Local Institution - 0222

Athens, , Greece

Site Status

Local Institution - 0123

Athens, , Greece

Site Status

Local Institution - 0124

Cholargós, , Greece

Site Status

Local Institution - 0125

Heraklion, , Greece

Site Status

Local Institution - 0126

Ioannina, , Greece

Site Status

Local Institution - 0091

Dublin, Dublin, Ireland

Site Status

Local Institution - 0022

Dublin, , Ireland

Site Status

Local Institution - 0026

Limerick, , Ireland

Site Status

Local Institution - 0055

Catania, , Italy

Site Status

Local Institution - 0003

Genova, , Italy

Site Status

Local Institution - 0001

Milan, , Italy

Site Status

Local Institution - 0004

Napoli, , Italy

Site Status

Local Institution - 0002

Padua, , Italy

Site Status

Local Institution - 0054

Roma, , Italy

Site Status

Local Institution - 0109

Nagoya, Aichi-ken, Japan

Site Status

Local Institution - 0112

Chiba, Chiba, Japan

Site Status

Local Institution - 0107

Kashiwa-shi, Chiba, Japan

Site Status

Local Institution - 0132

Matsuyama, Ehime, Japan

Site Status

Local Institution - 0116

Fukuoka, Fukuoka, Japan

Site Status

Local Institution - 0174

Sapporo, Hokkaido, Japan

Site Status

Local Institution - 0128

Kanazawa, Ishikawa-ken, Japan

Site Status

Local Institution - 0111

Kawasaki, Kanagawa, Japan

Site Status

Local Institution - 0175

Yokohama, Kanagawa, Japan

Site Status

Local Institution - 0133

Kumamoto, Kumamoto, Japan

Site Status

Local Institution - 0189

Ōsaki, Miyagi, Japan

Site Status

Local Institution - 0177

Kurashiki, Okayama-ken, Japan

Site Status

Local Institution - 0115

Suita-shi, Osaka, Japan

Site Status

Local Institution - 0187

Hidaka, Saitama, Japan

Site Status

Local Institution - 0110

Kitaadachigun, Saitama, Japan

Site Status

Local Institution - 0108

Sunto-gun, Shizuoka, Japan

Site Status

Local Institution - 0118

Chuo-ku, Tokyo, Japan

Site Status

Local Institution - 0113

Koto-ku, Tokyo, Japan

Site Status

Local Institution - 0129

Minato-ku, Tokyo, Japan

Site Status

Local Institution - 0114

Osaka, , Japan

Site Status

Local Institution - 0052

Amsterdam, North Holland, Netherlands

Site Status

Local Institution - 0051

Amsterdam, North Holland, Netherlands

Site Status

Local Institution - 0050

Utrecht, , Netherlands

Site Status

Local Institution - 0033

Bergen, , Norway

Site Status

Local Institution - 0034

Lorenskog, , Norway

Site Status

Local Institution - 0035

Oslo, , Norway

Site Status

Local Institution - 0058

Rio Piedras, , Puerto Rico

Site Status

Local Institution - 0076

Cluj-Napoca, Cluj, Romania

Site Status

Local Institution - 0081

Craiova, Dolj, Romania

Site Status

Local Institution - 0168

Brasov, , Romania

Site Status

Local Institution - 0080

Bucharest, , Romania

Site Status

Local Institution - 0205

Iași, , Romania

Site Status

Local Institution - 0089

Suceava, , Romania

Site Status

Local Institution - 0056

Badalona, Barcelona [Barcelona], Spain

Site Status

Local Institution - 0173

A Coruña, , Spain

Site Status

Local Institution - 0006

Barcelona, , Spain

Site Status

Local Institution - 0005

Madrid, , Spain

Site Status

Local Institution - 0172

Málaga, , Spain

Site Status

Local Institution - 0063

Seville, , Spain

Site Status

Local Institution - 0171

Valencia, , Spain

Site Status

Local Institution - 0092

Adana, , Turkey (Türkiye)

Site Status

Local Institution - 0101

Istanbul, , Turkey (Türkiye)

Site Status

Local Institution - 0127

London, , United Kingdom

Site Status

Local Institution - 0049

Oxford, , United Kingdom

Site Status

Countries

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United States Argentina Australia Austria Belgium Brazil Canada Chile China Czechia Denmark France Germany Greece Ireland Italy Japan Netherlands Norway Puerto Rico Romania Spain Turkey (Türkiye) United Kingdom

References

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Andre T, Elez E, Lenz HJ, Jensen LH, Touchefeu Y, Van Cutsem E, Garcia-Carbonero R, Tougeron D, Mendez GA, Schenker M, de la Fouchardiere C, Limon ML, Yoshino T, Li J, Manzano Mozo JL, Dahan L, Tortora G, Chalabi M, Goekkurt E, Braghiroli MI, Joshi R, Cil T, Aubin F, Cela E, Chen T, Lei M, Jin L, Blum SI, Lonardi S. Nivolumab plus ipilimumab versus nivolumab in microsatellite instability-high metastatic colorectal cancer (CheckMate 8HW): a randomised, open-label, phase 3 trial. Lancet. 2025 Feb 1;405(10476):383-395. doi: 10.1016/S0140-6736(24)02848-4. Epub 2025 Jan 25.

Reference Type DERIVED
PMID: 39874977 (View on PubMed)

Andre T, Elez E, Van Cutsem E, Jensen LH, Bennouna J, Mendez G, Schenker M, de la Fouchardiere C, Limon ML, Yoshino T, Li J, Lenz HJ, Manzano Mozo JL, Tortora G, Garcia-Carbonero R, Dahan L, Chalabi M, Joshi R, Goekkurt E, Braghiroli MI, Cil T, Cela E, Chen T, Lei M, Dixon M, Abdullaev S, Lonardi S; CheckMate 8HW Investigators. Nivolumab plus Ipilimumab in Microsatellite-Instability-High Metastatic Colorectal Cancer. N Engl J Med. 2024 Nov 28;391(21):2014-2026. doi: 10.1056/NEJMoa2402141.

Reference Type DERIVED
PMID: 39602630 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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2018-000040-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CA209-8HW

Identifier Type: -

Identifier Source: org_study_id

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