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OpenTrials
Active, Not Recruiting

NCT Number: 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)

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Conditions

Metastatic Colorectal Cancer Colonic Diseases Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Neoplasms Neoplasms by Site Rectal Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Local Institution - 0073, Ciudad Autonoma Beunos Aires, Buenos Aires, Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Ipilimumab

Biological

Specified dose on specified days

Oxaliplatin

Drug

Specified dose on specified days

Leucovorin

Drug

Specified dose on specified days

Fluorouracil

Drug

Specified dose on specified days

Irinotecan

Drug

Specified dose on specified days

Bevacizumab

Drug

Specified dose on specified days

Cetuximab

Drug

Specified dose on specified days

Nivolumab

Biological

Specified dose on specified days

Primary outcomes

  1. 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)

    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.

  2. 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)

    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.

Secondary outcomes

  1. 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

    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.

  2. 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)

    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.

  3. 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)

    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.

  4. 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

    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.

  5. 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)

    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.

  6. 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)

    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.

  7. 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)

    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.

  8. 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)

    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.

  9. 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)

    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.

  10. 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)

    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.

  11. 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)

    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.

  12. 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)

    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.

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

    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)

    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.

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

    Time frame: From randomization to the date of death due to any cause (Up to approximately 60 months)

    Overall Survival (OS) is defined as the time from the randomization date to the date of death due to any cause. A participant who has not died will be censored at last known date alive.

  15. Overall Survival (OS) - 1L Participants

    Time frame: From randomization to the date of death due to any cause

    Overall Survival (OS) is defined as the time from the randomization date to the date of death due to any cause. A participant who has not died will be censored at last known date alive.

Sponsors and collaborators

Lead sponsor

Bristol-Myers Squibb

Industry

Collaborators

  • Ono Pharmaceutical Co., Ltd.

Registry information

Official study 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

Acronym: CheckMate 8HW

Important dates

Study start
2019
Primary completion
2024
Study completion
2026
First posted
Jul 5, 2019
Registry last updated
Oct 3, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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