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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04008030




Registration number
NCT04008030
Ethics application status
Date submitted
2/07/2019
Date registered
5/07/2019
Date last updated
3/05/2024

Titles & IDs
Public title
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)
Scientific 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
Secondary ID [1] 0 0
2018-000040-26
Secondary ID [2] 0 0
CA209-8HW
Universal Trial Number (UTN)
Trial acronym
CheckMate 8HW
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Ipilimumab
Treatment: Drugs - Oxaliplatin
Treatment: Drugs - Leucovorin
Treatment: Drugs - Fluorouracil
Treatment: Drugs - Irinotecan
Treatment: Drugs - Bevacizumab
Treatment: Drugs - Cetuximab
Other interventions - Nivolumab

Experimental: Arm A: Nivolumab Monotherapy -

Experimental: Arm B: Nivolumab + Ipilimumab Combination -

Active Comparator: Arm C: Investigator's Choice Chemotherapy - Participants in Arm C would be allowed to receive Nivolumab + Ipilimumab if they progress


Other interventions: Ipilimumab
Specified dose on specified days

Treatment: Drugs: Oxaliplatin
Specified dose on specified days

Treatment: Drugs: Leucovorin
Specified dose on specified days

Treatment: Drugs: Fluorouracil
Specified dose on specified days

Treatment: Drugs: Irinotecan
Specified dose on specified days

Treatment: Drugs: Bevacizumab
Specified dose on specified days

Treatment: Drugs: Cetuximab
Specified dose on specified days

Other interventions: Nivolumab
Specified dose on specified days
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) (arm B vs A, all lines, centrally confirmed)
Timepoint [1] 0 0
Up to 5 years
Primary outcome [2] 0 0
PFS by BICR (arm B vs C, 1L, centrally confirmed)
Timepoint [2] 0 0
Up to 5 years
Secondary outcome [1] 0 0
Overall Response Rate (ORR) by BICR (arm B vs A, all lines, centrally confirmed)
Timepoint [1] 0 0
Up to 5 years
Secondary outcome [2] 0 0
Overall Survival (OS) (arm B vs A, all lines, centrally confirmed)
Timepoint [2] 0 0
Up to 5 years
Secondary outcome [3] 0 0
PFS by Investigator Assessment (arm B vs A, all lines, centrally confirmed)
Timepoint [3] 0 0
Up to 5 years
Secondary outcome [4] 0 0
PFS by BICR among all randomized participants (arm B vs A, all lines, per local testing)
Timepoint [4] 0 0
Up to 5 years
Secondary outcome [5] 0 0
PFS by BICR (arm B vs A, 1L, centrally confirmed)
Timepoint [5] 0 0
Up to 5 years
Secondary outcome [6] 0 0
ORR by BICR (arm B vs C, 1L, centrally confirmed)
Timepoint [6] 0 0
Up to 5 years
Secondary outcome [7] 0 0
ORR by BICR (arm B vs A, 1L, centrally confirmed)
Timepoint [7] 0 0
Up to 5 years
Secondary outcome [8] 0 0
OS (arm B vs A, 1L, centrally confirmed)
Timepoint [8] 0 0
Up to 5 years
Secondary outcome [9] 0 0
PFS by BICR (arm A vs C, 1L, centrally confirmed)
Timepoint [9] 0 0
Up to 5 years
Secondary outcome [10] 0 0
OS (arm B vs C, 1L, centrally confirmed)
Timepoint [10] 0 0
Up to 5 years
Secondary outcome [11] 0 0
ORR by BICR (arm A vs C, 1L, centrally confirmed)
Timepoint [11] 0 0
Up to 5 years
Secondary outcome [12] 0 0
OS (arm A vs C, 1L, centrally confirmed)
Timepoint [12] 0 0
Up to 5 years
Secondary outcome [13] 0 0
PFS by Investigator (arm A, B and C, 1L, centrally confirmed)
Timepoint [13] 0 0
Up to 5 years
Secondary outcome [14] 0 0
PFS by BICR among all randomized participants who have not received prior treatment (arm B vs C, 1L, per local testing)
Timepoint [14] 0 0
Up to 5 years
Secondary outcome [15] 0 0
PFS by BICR among all randomized participants who have not received prior treatment (arm B vs A, 1L, per local testing)
Timepoint [15] 0 0
Up to 5 years
Secondary outcome [16] 0 0
PFS by BICR (arm B vs C, 1L, by each central test)
Timepoint [16] 0 0
Up to 5 years
Secondary outcome [17] 0 0
PFS by BICR (arm B vs A, all lines, by each central test)
Timepoint [17] 0 0
Up to 5 years
Secondary outcome [18] 0 0
PFS by BICR (crossover cohort, centrally confirmed)
Timepoint [18] 0 0
Up to 5 years
Secondary outcome [19] 0 0
ORR by BICR (crossover cohort, centrally confirmed)
Timepoint [19] 0 0
Up to 5 years

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/08/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
10/06/2026
Actual
Sample size
Target
831
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Local Institution - 0019 - Westmead
Recruitment hospital [2] 0 0
Local Institution - 0053 - Woolloongabba
Recruitment hospital [3] 0 0
Local Institution - 0018 - Elizabeth Vale
Recruitment hospital [4] 0 0
Local Institution - 0041 - Clayton
Recruitment hospital [5] 0 0
Local Institution - 0017 - Heidelberg
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [4] 0 0
3168 - Clayton
Recruitment postcode(s) [5] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
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United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Oregon
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Virginia
Country [12] 0 0
Argentina
State/province [12] 0 0
Buenos Aires
Country [13] 0 0
Argentina
State/province [13] 0 0
RIO Negro
Country [14] 0 0
Argentina
State/province [14] 0 0
Caba
Country [15] 0 0
Austria
State/province [15] 0 0
Graz
Country [16] 0 0
Austria
State/province [16] 0 0
Linz
Country [17] 0 0
Austria
State/province [17] 0 0
Salzburg
Country [18] 0 0
Austria
State/province [18] 0 0
Wiener Neustadt
Country [19] 0 0
Austria
State/province [19] 0 0
Wien
Country [20] 0 0
Belgium
State/province [20] 0 0
Antwerpen
Country [21] 0 0
Belgium
State/province [21] 0 0
Brussel
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Belgium
State/province [22] 0 0
Bruxelles
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Belgium
State/province [23] 0 0
Leuven
Country [24] 0 0
Brazil
State/province [24] 0 0
Minas Gerais
Country [25] 0 0
Brazil
State/province [25] 0 0
RIO Grande DO Norte
Country [26] 0 0
Brazil
State/province [26] 0 0
Rio Grande Do Sul
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Brazil
State/province [27] 0 0
RIO Grande DO SUL
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Brazil
State/province [28] 0 0
Sao Paulo
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Brazil
State/province [29] 0 0
São Paulo
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Brazil
State/province [30] 0 0
Rio de Janeiro
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Canada
State/province [31] 0 0
Alberta
Country [32] 0 0
Canada
State/province [32] 0 0
British Columbia
Country [33] 0 0
Canada
State/province [33] 0 0
Nova Scotia
Country [34] 0 0
Canada
State/province [34] 0 0
Ontario
Country [35] 0 0
Canada
State/province [35] 0 0
Quebec
Country [36] 0 0
Chile
State/province [36] 0 0
Metropolitana
Country [37] 0 0
Chile
State/province [37] 0 0
Santiago
Country [38] 0 0
China
State/province [38] 0 0
Anhui
Country [39] 0 0
China
State/province [39] 0 0
Fujian
Country [40] 0 0
China
State/province [40] 0 0
Gansu
Country [41] 0 0
China
State/province [41] 0 0
Guangdong
Country [42] 0 0
China
State/province [42] 0 0
Guangxi
Country [43] 0 0
China
State/province [43] 0 0
Heilongjiang
Country [44] 0 0
China
State/province [44] 0 0
Henan
Country [45] 0 0
China
State/province [45] 0 0
Hunan
Country [46] 0 0
China
State/province [46] 0 0
Jiangsu
Country [47] 0 0
China
State/province [47] 0 0
Jiangxi
Country [48] 0 0
China
State/province [48] 0 0
Jilin
Country [49] 0 0
China
State/province [49] 0 0
Liaoning
Country [50] 0 0
China
State/province [50] 0 0
Shaanxi
Country [51] 0 0
China
State/province [51] 0 0
Shandong
Country [52] 0 0
China
State/province [52] 0 0
Shanghai
Country [53] 0 0
China
State/province [53] 0 0
Yunnan
Country [54] 0 0
China
State/province [54] 0 0
Zhejiang
Country [55] 0 0
Czechia
State/province [55] 0 0
Brno
Country [56] 0 0
Czechia
State/province [56] 0 0
Hradec Kralove
Country [57] 0 0
Czechia
State/province [57] 0 0
Novy Jicin
Country [58] 0 0
Czechia
State/province [58] 0 0
Olomouc
Country [59] 0 0
Denmark
State/province [59] 0 0
Herlev
Country [60] 0 0
Denmark
State/province [60] 0 0
Odense
Country [61] 0 0
Denmark
State/province [61] 0 0
Vejle
Country [62] 0 0
France
State/province [62] 0 0
Haute-Vienne
Country [63] 0 0
France
State/province [63] 0 0
Nord
Country [64] 0 0
France
State/province [64] 0 0
Bayonne
Country [65] 0 0
France
State/province [65] 0 0
Besancon Cedex
Country [66] 0 0
France
State/province [66] 0 0
Lyon Cedex 08
Country [67] 0 0
France
State/province [67] 0 0
Lyon
Country [68] 0 0
France
State/province [68] 0 0
Marseille
Country [69] 0 0
France
State/province [69] 0 0
Montpellier
Country [70] 0 0
France
State/province [70] 0 0
Nantes
Country [71] 0 0
France
State/province [71] 0 0
Paris
Country [72] 0 0
France
State/province [72] 0 0
Pessac Cedex
Country [73] 0 0
France
State/province [73] 0 0
Poitiers
Country [74] 0 0
France
State/province [74] 0 0
Rouen
Country [75] 0 0
France
State/province [75] 0 0
Strasbourg
Country [76] 0 0
France
State/province [76] 0 0
Toulouse
Country [77] 0 0
Germany
State/province [77] 0 0
Dresden
Country [78] 0 0
Germany
State/province [78] 0 0
Essen
Country [79] 0 0
Germany
State/province [79] 0 0
Hamburg
Country [80] 0 0
Germany
State/province [80] 0 0
Hannover
Country [81] 0 0
Germany
State/province [81] 0 0
Heidelberg
Country [82] 0 0
Germany
State/province [82] 0 0
Marburg
Country [83] 0 0
Germany
State/province [83] 0 0
Munich
Country [84] 0 0
Greece
State/province [84] 0 0
Athens
Country [85] 0 0
Greece
State/province [85] 0 0
Heraklion
Country [86] 0 0
Greece
State/province [86] 0 0
Holargos
Country [87] 0 0
Greece
State/province [87] 0 0
Ioannina
Country [88] 0 0
Ireland
State/province [88] 0 0
Dublin
Country [89] 0 0
Ireland
State/province [89] 0 0
Limerick
Country [90] 0 0
Italy
State/province [90] 0 0
Catania
Country [91] 0 0
Italy
State/province [91] 0 0
Genova
Country [92] 0 0
Italy
State/province [92] 0 0
Milan
Country [93] 0 0
Italy
State/province [93] 0 0
Napoli
Country [94] 0 0
Italy
State/province [94] 0 0
Padova
Country [95] 0 0
Italy
State/province [95] 0 0
Roma
Country [96] 0 0
Japan
State/province [96] 0 0
Aichi
Country [97] 0 0
Japan
State/province [97] 0 0
Chiba
Country [98] 0 0
Japan
State/province [98] 0 0
Ehime
Country [99] 0 0
Japan
State/province [99] 0 0
Fukuoka
Country [100] 0 0
Japan
State/province [100] 0 0
Hokkaido
Country [101] 0 0
Japan
State/province [101] 0 0
Ishikawa
Country [102] 0 0
Japan
State/province [102] 0 0
Kanagawa
Country [103] 0 0
Japan
State/province [103] 0 0
Kumamoto
Country [104] 0 0
Japan
State/province [104] 0 0
Miyagi
Country [105] 0 0
Japan
State/province [105] 0 0
Okayama
Country [106] 0 0
Japan
State/province [106] 0 0
Osaka
Country [107] 0 0
Japan
State/province [107] 0 0
Saitama
Country [108] 0 0
Japan
State/province [108] 0 0
Shizuoka
Country [109] 0 0
Japan
State/province [109] 0 0
Tokyo
Country [110] 0 0
Netherlands
State/province [110] 0 0
Amsterdam
Country [111] 0 0
Netherlands
State/province [111] 0 0
Utrecht
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Norway
State/province [112] 0 0
Bergen
Country [113] 0 0
Norway
State/province [113] 0 0
Lorenskog
Country [114] 0 0
Norway
State/province [114] 0 0
Oslo
Country [115] 0 0
Puerto Rico
State/province [115] 0 0
Rio Piedras
Country [116] 0 0
Romania
State/province [116] 0 0
Cluj
Country [117] 0 0
Romania
State/province [117] 0 0
Dolj
Country [118] 0 0
Romania
State/province [118] 0 0
Brasov
Country [119] 0 0
Romania
State/province [119] 0 0
Bucharest
Country [120] 0 0
Romania
State/province [120] 0 0
Constanta
Country [121] 0 0
Romania
State/province [121] 0 0
Ia?i
Country [122] 0 0
Romania
State/province [122] 0 0
Suceava
Country [123] 0 0
Spain
State/province [123] 0 0
Barcelona [Barcelona]
Country [124] 0 0
Spain
State/province [124] 0 0
A Coruna
Country [125] 0 0
Spain
State/province [125] 0 0
Barcelona
Country [126] 0 0
Spain
State/province [126] 0 0
Madrid
Country [127] 0 0
Spain
State/province [127] 0 0
Malaga
Country [128] 0 0
Spain
State/province [128] 0 0
Sevilla
Country [129] 0 0
Spain
State/province [129] 0 0
Valencia
Country [130] 0 0
Turkey
State/province [130] 0 0
Adana
Country [131] 0 0
Turkey
State/province [131] 0 0
Istanbul
Country [132] 0 0
United Kingdom
State/province [132] 0 0
Greater London
Country [133] 0 0
United Kingdom
State/province [133] 0 0
Yorkshire
Country [134] 0 0
United Kingdom
State/province [134] 0 0
London
Country [135] 0 0
United Kingdom
State/province [135] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bristol-Myers Squibb
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Ono Pharmaceutical Co. Ltd
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04008030
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
BMS Study Connect Contact Center www.BMSStudyConnect.com
Address 0 0
Country 0 0
Phone 0 0
855-907-3286
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04008030