NCT04008030 · CITED IN SOURCE DOCUMENTS

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)

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2026-08-20

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - Arm B vs. Arm A All Lines Centrally Confirmed MSI-H/dMMR

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outcome · POSTED

Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - Arm B vs. Arm C 1L Participants Centrally Confirmed MSI-H/dMMR

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outcome · NOT POSTED

Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - 1L Participants

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outcome · POSTED

Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - Arm B vs. Arm A All Randomized Participants

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outcome · POSTED

Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - 1L Randomized Participants

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outcome · NOT POSTED

Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - Crossover and First Line Arm

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outcome · POSTED

Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) by Polymerase Chain Reaction (PCR) - Arm B vs. Arm A

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outcome · POSTED

Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) by Immunohistochemistry (IHC) - Arm B vs. Arm A

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outcome · POSTED

Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) by Polymerase Chain Reaction (PCR) - Arm B vs. Arm C

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outcome · POSTED

Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) by Immunohistochemistry (IHC) - Arm B vs. Arm C

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outcome · POSTED

Progression-free Survival (PFS) by Investigator- Arm B vs. Arm A All Lines

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outcome · POSTED

Progression-free Survival (PFS) by Investigator - Arm A and Arm B All Lines With dMMR/MSI-H mCRC

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outcome · NOT POSTED

Progression-free Survival (PFS) by Investigator - 1L Participants

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outcome · POSTED

Objective Response Rate (ORR) by Blinded Independent Review Center (BICR) - Arm A and Arm B All Lines With dMMR/MSI-H mCRC

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outcome · POSTED

Objective Response Rate (ORR) by Blinded Independent Review Center (BICR) - 1L Participants

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outcome · POSTED

Overall Survival (OS) - Arm B vs. Arm A All Lines With dMMR/MSI-H mCRC

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outcome · NOT POSTED

Overall Survival (OS) - 1L Participants

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

intervention Names
Biological: Nivolumab
label
Arm A: Nivolumab Monotherapy
type
EXPERIMENTAL
intervention Names
Biological: Ipilimumab
Biological: Nivolumab
label
Arm B: Nivolumab + Ipilimumab Combination
type
EXPERIMENTAL
description
Participants in Arm C would be allowed to receive Nivolumab + Ipilimumab if they progress
intervention Names
Drug: Oxaliplatin
Drug: Leucovorin
Drug: Fluorouracil
Drug: Irinotecan
Drug: Bevacizumab
Drug: Cetuximab
label
Arm C: Investigator's Choice Chemotherapy
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Arm B: Nivolumab + Ipilimumab Combination
description
Specified dose on specified days
name
Ipilimumab
type
BIOLOGICAL
arm Group Labels
Arm C: Investigator's Choice Chemotherapy
description
Specified dose on specified days
name
Oxaliplatin
type
DRUG
arm Group Labels
Arm C: Investigator's Choice Chemotherapy
description
Specified dose on specified days
name
Leucovorin
type
DRUG
arm Group Labels
Arm C: Investigator's Choice Chemotherapy
description
Specified dose on specified days
name
Fluorouracil
type
DRUG
arm Group Labels
Arm C: Investigator's Choice Chemotherapy
description
Specified dose on specified days
name
Irinotecan
type
DRUG
arm Group Labels
Arm C: Investigator's Choice Chemotherapy
description
Specified dose on specified days
name
Bevacizumab
type
DRUG
arm Group Labels
Arm C: Investigator's Choice Chemotherapy
description
Specified dose on specified days
name
Cetuximab
type
DRUG
arm Group Labels
Arm A: Nivolumab Monotherapy
Arm B: Nivolumab + Ipilimumab Combination
description
Specified dose on specified days
name
Nivolumab
type
BIOLOGICAL

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 839
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
BICR-assessed Progression-free survival (PFS) is defined as the time from the randomization date to the date of first objectively documented disease progression per RECIST 1.1 (i.e, radiologic) or death due to any cause, whichever occurs first.
measure
Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - Arm B vs. Arm A All Lines Centrally Confirmed MSI-H/dMMR
time Frame
From date of randomization to the date of first objectively documented disease progression or death due to any cause, whichever occurs first (Up to approximately 60 months)
description
BICR-assessed Progression-free survival (PFS) is defined as the time from the randomization date to the date of first objectively documented disease progression per RECIST 1.1 (i.e, radiologic) or death due to any cause, whichever occurs first.
measure
Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - Arm B vs. Arm C 1L Participants Centrally Confirmed MSI-H/dMMR
time Frame
From date of randomization to the date of first objectively documented disease progression or death due to any cause, whichever occurs first (Up to approximately 32 months)

secondary Outcomes

description
BICR-assessed Progression-free survival (PFS) is defined as the time from the randomization date to the date of first objectively documented disease progression per RECIST 1.1 (i.e, radiologic) or death due to any cause, whichever occurs first.
measure
Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - 1L Participants
time Frame
From date of randomization to the date of first objectively documented disease progression or death due to any cause, whichever occurs first
description
BICR-assessed Progression-free survival (PFS) is defined as the time from the randomization date to the date of first objectively documented disease progression per RECIST 1.1 (i.e, radiologic) or death due to any cause, whichever occurs first.
measure
Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - Arm B vs. Arm A All Randomized Participants
time Frame
From date of randomization to the date of first objectively documented disease progression or death due to any cause, whichever occurs first (Up to approximately 60 months)
description
BICR-assessed Progression-free survival (PFS) is defined as the time from the randomization date to the date of first objectively documented disease progression per RECIST 1.1 (i.e, radiologic) or death due to any cause, whichever occurs first.
measure
Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - 1L Randomized Participants
time Frame
From date of randomization to the date of first objectively documented disease progression or death due to any cause, whichever occurs first (Up to approximately 60 months)
description
BICR-assessed Progression-free survival (PFS) is defined as the time from the randomization date to the date of first objectively documented disease progression per RECIST 1.1 (i.e, radiologic) or death due to any cause, whichever occurs first.
measure
Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - Crossover and First Line Arm
time Frame
From date of randomization to the date of first objectively documented disease progression or death due to any cause, whichever occurs first
description
BICR-assessed Progression-free survival (PFS) is defined as the time from the randomization date to the date of first objectively documented disease progression per RECIST 1.1 (i.e, radiologic) or death due to any cause, whichever occurs first.
measure
Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) by Polymerase Chain Reaction (PCR) - Arm B vs. Arm A
time Frame
From date of randomization to the date of first objectively documented disease progression or death due to any cause, whichever occurs first (Up to approximately 60 months)
description
BICR-assessed Progression-free survival (PFS) is defined as the time from the randomization date to the date of first objectively documented disease progression per RECIST 1.1 (i.e, radiologic) or death due to any cause, whichever occurs first.
measure
Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) by Immunohistochemistry (IHC) - Arm B vs. Arm A
time Frame
From date of randomization to the date of first objectively documented disease progression or death due to any cause, whichever occurs first (Up to approximately 60 months)
description
BICR-assessed Progression-free survival (PFS) is defined as the time from the randomization date to the date of first objectively documented disease progression per RECIST 1.1 (i.e, radiologic) or death due to any cause, whichever occurs first.
measure
Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) by Polymerase Chain Reaction (PCR) - Arm B vs. Arm C
time Frame
From date of randomization to the date of first objectively documented disease progression or death due to any cause, whichever occurs first (Up to approximately 32 months)
description
BICR-assessed Progression-free survival (PFS) is defined as the time from the randomization date to the date of first objectively documented disease progression per RECIST 1.1 (i.e, radiologic) or death due to any cause, whichever occurs first.
measure
Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) by Immunohistochemistry (IHC) - Arm B vs. Arm C
time Frame
From date of randomization to the date of first objectively documented disease progression or death due to any cause, whichever occurs first (Up to approximately 32 months)
description
Investigator-assessed Progression-free survival (PFS) is defined as the time from the randomization date to the date of first objectively documented disease progression per RECIST 1.1 (i.e, radiologic) or death due to any cause, whichever occurs first.
measure
Progression-free Survival (PFS) by Investigator- Arm B vs. Arm A All Lines
time Frame
From date of randomization to the date of first objectively documented disease progression or death due to any cause, whichever occurs first (Up to approximately 60 months)
description
Investigator-assessed Progression-free survival (PFS) is defined as the time from the randomization date to the date of first objectively documented disease progression per RECIST 1.1 (i.e, radiologic) or death due to any cause, whichever occurs first.
measure
Progression-free Survival (PFS) by Investigator - Arm A and Arm B All Lines With dMMR/MSI-H mCRC
time Frame
From date of randomization to the date of first objectively documented disease progression or death due to any cause, whichever occurs first (Up to approximately 60 months)
description
Investigator-assessed Progression-free survival (PFS) is defined as the time from the randomization date to the date of first objectively documented disease progression per RECIST 1.1 (i.e, radiologic) or death due to any cause, whichever occurs first.
measure
Progression-free Survival (PFS) by Investigator - 1L Participants
time Frame
From date of randomization to the date of first objectively documented disease progression or death due to any cause, whichever occurs first (Up to approximately 60 months for arm A and arm B; up to 32 months for arm C)
description
Objective Response Rate (ORR) is defined as the percentage of all randomized participants whose best overall response is either confirmed complete response (CR) or confirmed partial response (PR). CR= Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR= At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease (PD)=At least a 20% increase in the sum of diameters of target lesions. the sum must also demonstrate an absolute increase of at least 5 mm.
measure
Objective Response Rate (ORR) by Blinded Independent Review Center (BICR) - Arm A and Arm B All Lines With dMMR/MSI-H mCRC
time Frame
From date of randomization to the date of the initial objectively documented tumor progression, or the date of initiation of subsequent therapy, whichever occurs first (Up to approximately 60 months)

Full study description

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.

Source references

references

citation
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.
pmid
39874977
type
DERIVED
citation
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.
pmid
39602630
type
DERIVED