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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)

NCT04008030

Description:

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.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief 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)
  • Official Title: A Phase 3 Randomized Clinical Trial of Nivolumab Alone, Nivolumab in Combination With Ipilimumab, or an Investigator's Choice Chemotherapy in Participants With Microsatellite Instability High (MSI-H) or Mismatch Repair Deficient (dMMR) Metastatic Colorectal Cancer

Clinical Trial IDs

  • ORG STUDY ID: CA209-8HW
  • SECONDARY ID: 2018-000040-26
  • NCT ID: NCT04008030

Conditions

  • Metastatic Colorectal Cancer

Interventions

DrugSynonymsArms
IpilimumabArm B: Nivolumab + Ipilimumab Combination
OxaliplatinArm C: Investigator's Choice Chemotherapy
LeucovorinArm C: Investigator's Choice Chemotherapy
FluorouracilArm C: Investigator's Choice Chemotherapy
IrinotecanArm C: Investigator's Choice Chemotherapy
BevacizumabArm C: Investigator's Choice Chemotherapy
CetuximabArm C: Investigator's Choice Chemotherapy
NivolumabArm A: Nivolumab Monotherapy

Purpose

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 Arms

NameTypeDescriptionInterventions
Arm A: Nivolumab MonotherapyExperimentalSpecified dose on specified days
  • Nivolumab
Arm B: Nivolumab + Ipilimumab CombinationExperimentalSpecified dose on specified days
  • Ipilimumab
  • Nivolumab
Arm C: Investigator's Choice ChemotherapyActive ComparatorSpecified dose on specified days. Participants in Arm C would be allowed to receive Nivolumab + Ipilimumab if they progress
  • Oxaliplatin
  • Leucovorin
  • Fluorouracil
  • Irinotecan
  • Bevacizumab
  • Cetuximab

Eligibility Criteria

        For more information regarding Bristol-Myers Squibb Clinical Trial participation, please
        visit www.BMSStudyConnect.com

        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 MSI-H or dMMR status per local standard of practice

          -  Eastern cooperative oncology group (ECOG) performance status lower than or equal to 1

        Exclusion Criteria:

          -  Participants with 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) (arm B vs A, all lines, centrally confirmed)
Time Frame:Up to 5 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall Response Rate (ORR) by BICR (arm B vs A, all lines, centrally confirmed)
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:Overall Survival (OS) (arm B vs A, all lines, centrally confirmed)
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:PFS by Investigator Assessment (arm B vs A, all lines, centrally confirmed)
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:PFS by BICR among all randomized participants (arm B vs A, all lines, per local testing)
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:PFS by BICR (arm B vs A, 1L, centrally confirmed)
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:ORR by BICR (arm B vs C, 1L, centrally confirmed)
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:ORR by BICR (arm B vs A, 1L, centrally confirmed)
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:OS (arm B vs A, 1L, centrally confirmed)
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:PFS by BICR (arm A vs C, 1L, centrally confirmed)
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:OS (arm B vs C, 1L, centrally confirmed)
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:ORR by BICR (arm A vs C, 1L, centrally confirmed)
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:OS (arm A vs C, 1L, centrally confirmed)
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:PFS by Investigator (arm A, B and C, 1L, centrally confirmed)
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:PFS by BICR among all randomized participants who have not received prior treatment (arm B vs C, 1L, per local testing)
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:PFS by BICR among all randomized participants who have not received prior treatment (arm B vs A, 1L, per local testing)
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:PFS by BICR (arm B vs C, 1L, by each central test)
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:PFS by BICR (arm B vs A, all lines, by each central test)
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:PFS by BICR (crossover cohort, centrally confirmed)
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:ORR by BICR (crossover cohort, centrally confirmed)
Time Frame:Up to 5 years
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Bristol-Myers Squibb

Last Updated

November 3, 2020