Metastatic Colorectal Cancer Clinical Trial
— CheckMate 8HWOfficial 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
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.
| Status | Recruiting |
| Enrollment | 831 |
| Est. completion date | June 10, 2026 |
| Est. primary completion date | June 9, 2025 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Argentina | Local Institution - 0084 | Buenos Aires | |
| Argentina | Local Institution - 0072 | Caba | |
| Argentina | Local Institution - 0100 | Caba | |
| Argentina | Local Institution - 0073 | Ciudad Autonoma Beunos Aires | Buenos Aires |
| Argentina | Local Institution - 0074 | Viedma | RIO Negro |
| Australia | Local Institution - 0041 | Clayton | Victoria |
| Australia | Local Institution - 0018 | Elizabeth Vale | South Australia |
| Australia | Local Institution - 0017 | Heidelberg | Victoria |
| Australia | Local Institution - 0019 | Westmead | New South Wales |
| Australia | Local Institution - 0053 | Woolloongabba | Queensland |
| Austria | Local Institution - 0064 | Graz | |
| Austria | Local Institution - 0068 | Linz | |
| Austria | Local Institution - 0120 | Salzburg | |
| Austria | Local Institution - 0065 | Wien | |
| Austria | Local Institution - 0067 | Wiener Neustadt | |
| Belgium | Local Institution - 0045 | Bonheiden | Antwerpen |
| Belgium | Local Institution | Brussel | |
| Belgium | Local Institution - 0025 | Bruxelles | |
| Belgium | Local Institution - 0024 | Leuven | |
| Brazil | Local Institution - 0102 | Barretos | Sao Paulo |
| Brazil | Local Institution - 0096 | Ipatinga | Minas Gerais |
| Brazil | Local Institution - 0200 | Natal | RIO Grande DO Norte |
| Brazil | Local Institution - 0097 | Porto Alegre | Rio Grande Do Sul |
| Brazil | Local Institution - 0192 | Porto Alegre | RIO Grande DO SUL |
| Brazil | Local Institution - 0199 | Rio de Janeiro | |
| Brazil | Local Institution - 0094 | São José do Rio Preto | São Paulo |
| Brazil | Local Institution - 0095 | Sao Paulo | São Paulo |
| Brazil | Local Institution - 0193 | São Paulo | |
| Canada | Local Institution - 0011 | Edmonton | Alberta |
| Canada | Local Institution | Halifax | Nova Scotia |
| Canada | Local Institution - 0016 | Montreal | Quebec |
| Canada | Local Institution | Quebec | |
| Canada | Local Institution - 0015 | Sherbrooke | Quebec |
| Canada | Local Institution - 0013 | Toronto | Ontario |
| Canada | Local Institution - 0039 | Vancouver | British Columbia |
| Chile | Local Institution - 0070 | Independencia | Santiago |
| Chile | Local Institution - 0069 | Santiago | Metropolitana |
| Chile | Local Institution - 0071 | Santiago | Metropolitana |
| China | The 1st Hospital Of Jilin University | Changchun | Jilin |
| China | Hunan Cancer Hospital | Changsha | Hunan |
| China | The First People's Hospital of Changzhou | Changzhou | Jiangsu |
| China | Local Institution - 0158 | Foshan | Guangdong |
| China | Local Institution | Fuzhou | Fujian |
| China | Local Institution - 0153 | Guangzhou | Guangdong |
| China | Local Institution - 0167 | Guangzhou | Guangdong |
| China | Local Institution - 0194 | Guangzhou | Guangdong |
| China | The Sixth Affiliated Hospital of Sun Yat-sen University | Guangzhou | Guangdong |
| China | The 2nd Affiliated Hospital Of Z.U.S.M | Hangzhou | Zhejiang |
| China | Harbin Medical University Cancer Hospital | Harbin | Heilongjiang |
| China | Local Institution - 0146 | Hefei | Anhui |
| China | Shandong Cancer Hospital | Jinan | Shandong |
| China | Yunnan Province Cancer Hospital | Kunming | Yunnan |
| China | Local Institution - 0211 | Lanzhou | Gansu |
| China | Local Institution - 0212 | Linyi | Shandong |
| China | The 1st Affiliate Hospital Of Nanchang University | Nanchang | Jiangxi |
| China | Guangxi Medical University Affiliated Tumor Hospital | Nanning | Guangxi |
| China | The people's hospital of Guangxi Zhuang autonomous region | Nanning | Guangxi |
| China | Local Institution - 0206 | Ningbo | Zhejiang |
| China | Local Institution - 0154 | Qingdao | Shandong |
| China | Local Institution - 0143 | Shanghai | Shanghai |
| China | Local Institution - 0221 | Shanghai | Shanghai |
| China | Shanghai East Hospital | Shanghai | Shanghai |
| China | Liaoning Cancer Hospital and Institute | Shenyang | Liaoning |
| China | Local Institution - 0188 | Xi'an | Shaanxi |
| China | The First Affiliated hospital of Xiamen University | Xiamen | Fujian |
| China | Local Institution - 0165 | Yantai | Shandong |
| China | Zhangzhou Municipal Hospital of Fujian Province | Zhangzhou | Fujian |
| China | The First Affiliated Hospital of Zhengzhou University | Zhengzhou | Henan |
| Czechia | Local Institution - 0087 | Brno | |
| Czechia | Local Institution - 0085 | Hradec Kralove | |
| Czechia | Local Institution - 0088 | Novy Jicin | |
| Czechia | Local Institution - 0086 | Olomouc | |
| Denmark | Local Institution - 0038 | Herlev | |
| Denmark | Local Institution | Odense | |
| Denmark | Local Institution - 0036 | Vejle | |
| France | Local Institution - 0186 | Bayonne | |
| France | Local Institution - 0028 | Besancon Cedex | |
| France | Local Institution - 0138 | Lille | Nord |
| France | Local Institution - 0176 | Limoges | Haute-Vienne |
| France | Local Institution - 0183 | Lyon | |
| France | Local Institution - 0029 | Lyon Cedex 08 | |
| 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 | Rouen | |
| France | Local Institution - 0184 | Strasbourg | |
| France | Local Institution - 0040 | Toulouse | |
| Germany | 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 | |
| Greece | Local Institution - 0123 | Athens | |
| Greece | Local Institution - 0125 | Heraklion | |
| Greece | Local Institution - 0124 | Holargos | |
| Greece | Local Institution - 0126 | Ioannina | |
| Ireland | Local Institution - 0022 | Dublin | |
| Ireland | Local Institution - 0091 | Dublin 8 | Dublin |
| Ireland | Local Institution - 0026 | Limerick | |
| Italy | 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 | |
| Japan | Local Institution - 0112 | Chiba-shi | Chiba |
| Japan | Local Institution - 0118 | Chuo-ku | Tokyo |
| Japan | Local Institution - 0116 | Fukuoka-shi | Fukuoka |
| Japan | Local Institution - 0187 | Hidaka | Saitama |
| Japan | Local Institution - 0128 | Kanazawa-city | Ishikawa |
| Japan | Local Institution - 0107 | Kashiwa-shi | Chiba |
| Japan | Local Institution - 0111 | Kawasaki-shi | Kanagawa |
| Japan | Local Institution - 0110 | Kitaadachigun | Saitama |
| Japan | Local Institution - 0113 | Koto-ku | Tokyo |
| Japan | Local Institution - 0133 | Kumamoto-shi | Kumamoto |
| Japan | Local Institution - 0177 | Kurashiki | Okayama |
| Japan | Local Institution - 0132 | Matsuyama | Ehime |
| Japan | Local Institution - 0129 | Minato-ku | Tokyo |
| Japan | Local Institution - 0109 | Nagoya-shi | Aichi |
| Japan | Local Institution - 0114 | Osaka | |
| Japan | Local Institution - 0189 | Osaki | Miyagi |
| Japan | Local Institution - 0174 | Sapporo-shi | Hokkaido |
| Japan | Local Institution - 0115 | Suita-shi | Osaka |
| Japan | Local Institution - 0108 | Sunto-gun | Shizuoka |
| Japan | Local Institution - 0175 | Yokohama | Kanagawa |
| Netherlands | Local Institution - 0051 | Amsterdam | |
| Netherlands | Local Institution - 0052 | Amsterdam | |
| Netherlands | Local Institution - 0050 | Utrecht | |
| Norway | Local Institution - 0033 | Bergen | |
| Norway | Local Institution - 0034 | Lorenskog | |
| Norway | Local Institution - 0035 | Oslo | |
| Puerto Rico | Local Institution - 0058 | Rio Piedras | |
| Romania | Local Institution - 0168 | Brasov | |
| Romania | Local Institution - 0080 | Bucharest | |
| Romania | Local Institution - 0076 | Cluj-Napoca | Cluj |
| Romania | Local Institution | Constanta | |
| Romania | Local Institution - 0081 | Craiova | Dolj |
| Romania | Local Institution - 0205 | Ia?i | |
| Romania | Local Institution - 0089 | Suceava | |
| Spain | Local Institution - 0173 | A Coruna | |
| Spain | Local Institution - 0056 | Badalona | Barcelona [Barcelona] |
| Spain | Local Institution - 0006 | Barcelona | |
| Spain | Local Institution | Madrid | |
| Spain | Local Institution - 0005 | Madrid | |
| Spain | Local Institution - 0172 | Malaga | |
| Spain | Local Institution - 0063 | Sevilla | |
| Spain | Local Institution - 0171 | Valencia | |
| Turkey | Local Institution - 0092 | Adana | |
| Turkey | Local Institution - 0101 | Istanbul | |
| United Kingdom | Local Institution | Leeds | Yorkshire |
| United Kingdom | Local Institution | London | Greater London |
| United Kingdom | Local Institution - 0127 | London | |
| United Kingdom | Local Institution - 0049 | Oxford | |
| United States | Local Institution - 0119 | Arlington Heights | Illinois |
| United States | Local Institution - 0106 | Dallas | Texas |
| United States | Local Institution - 0103 | Denver | Colorado |
| United States | Local Institution | Fort Worth | Texas |
| United States | Banner MD Anderson Cancer Center | Gilbert | Arizona |
| United States | Local Institution - 0059 | Los Angeles | California |
| United States | Local Institution | Marietta | Georgia |
| United States | Local Institution | Miami | Florida |
| United States | Local Institution - 0060 | New York | New York |
| United States | Local Institution | Philadelphia | Pennsylvania |
| United States | Local Institution - 0121 | Pittsburgh | Pennsylvania |
| United States | Local Institution - 0105 | Portland | Oregon |
| United States | Local Institution - 0104 | Roanoke | Virginia |
| United States | Local Institution - 0130 | Sacramento | California |
| Lead Sponsor | Collaborator |
|---|---|
| Bristol-Myers Squibb | Ono Pharmaceutical Co. Ltd |
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, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) (arm B vs A, all lines, centrally confirmed) | Up to 5 years | ||
| Primary | PFS by BICR (arm B vs C, 1L, centrally confirmed) | Up to 5 years | ||
| Secondary | Overall Response Rate (ORR) by BICR (arm B vs A, all lines, centrally confirmed) | Up to 5 years | ||
| Secondary | Overall Survival (OS) (arm B vs A, all lines, centrally confirmed) | Up to 5 years | ||
| Secondary | PFS by Investigator Assessment (arm B vs A, all lines, centrally confirmed) | Up to 5 years | ||
| Secondary | PFS by BICR among all randomized participants (arm B vs A, all lines, per local testing) | Up to 5 years | ||
| Secondary | PFS by BICR (arm B vs A, 1L, centrally confirmed) | Up to 5 years | ||
| Secondary | ORR by BICR (arm B vs C, 1L, centrally confirmed) | Up to 5 years | ||
| Secondary | ORR by BICR (arm B vs A, 1L, centrally confirmed) | Up to 5 years | ||
| Secondary | OS (arm B vs A, 1L, centrally confirmed) | Up to 5 years | ||
| Secondary | PFS by BICR (arm A vs C, 1L, centrally confirmed) | Up to 5 years | ||
| Secondary | OS (arm B vs C, 1L, centrally confirmed) | Up to 5 years | ||
| Secondary | ORR by BICR (arm A vs C, 1L, centrally confirmed) | Up to 5 years | ||
| Secondary | OS (arm A vs C, 1L, centrally confirmed) | Up to 5 years | ||
| Secondary | PFS by Investigator (arm A, B and C, 1L, centrally confirmed) | Up to 5 years | ||
| Secondary | 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 | ||
| Secondary | 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 | ||
| Secondary | PFS by BICR (arm B vs C, 1L, by each central test) | Up to 5 years | ||
| Secondary | PFS by BICR (arm B vs A, all lines, by each central test) | Up to 5 years | ||
| Secondary | PFS by BICR (crossover cohort, centrally confirmed) | Up to 5 years | ||
| Secondary | ORR by BICR (crossover cohort, centrally confirmed) | Up to 5 years |
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|---|---|---|---|
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