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)
- Conditions
- Metastatic Colorectal Cancer
- Interventions
- Registration Number
- NCT04008030
- Lead Sponsor
- Bristol-Myers Squibb
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 839
- 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
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Nivolumab Monotherapy Nivolumab - Arm B: Nivolumab + Ipilimumab Combination Ipilimumab - Arm B: Nivolumab + Ipilimumab Combination Nivolumab - Arm C: Investigator's Choice Chemotherapy Leucovorin Participants in Arm C would be allowed to receive Nivolumab + Ipilimumab if they progress Arm C: Investigator's Choice Chemotherapy Fluorouracil Participants in Arm C would be allowed to receive Nivolumab + Ipilimumab if they progress Arm C: Investigator's Choice Chemotherapy Irinotecan Participants in Arm C would be allowed to receive Nivolumab + Ipilimumab if they progress Arm C: Investigator's Choice Chemotherapy Oxaliplatin Participants in Arm C would be allowed to receive Nivolumab + Ipilimumab if they progress Arm C: Investigator's Choice Chemotherapy Bevacizumab Participants in Arm C would be allowed to receive Nivolumab + Ipilimumab if they progress Arm C: Investigator's Choice Chemotherapy Cetuximab Participants in Arm C would be allowed to receive Nivolumab + Ipilimumab if they progress
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - Arm B vs. Arm A All Lines Centrally Confirmed MSI-H/dMMR 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.
Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - Arm B vs. Arm C 1L Participants Centrally Confirmed MSI-H/dMMR 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 Outcome Measures
Name Time Method Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - 1L Participants 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.
Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - Arm B vs. Arm A All Randomized Participants 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.
Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - 1L Randomized Participants 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.
Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - Crossover and First Line Arm 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.
Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) by Polymerase Chain Reaction (PCR) - Arm B vs. Arm A 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.
Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) by Immunohistochemistry (IHC) - Arm B vs. Arm A 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.
Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) by Polymerase Chain Reaction (PCR) - Arm B vs. Arm C 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.
Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) by Immunohistochemistry (IHC) - Arm B vs. Arm C 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.
Progression-free Survival (PFS) by Investigator- Arm B vs. Arm A All Lines 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.
Progression-free Survival (PFS) by Investigator - Arm A and Arm B All Lines With dMMR/MSI-H mCRC 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.
Progression-free Survival (PFS) by Investigator - 1L Participants 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.
Objective Response Rate (ORR) by Blinded Independent Review Center (BICR) - Arm A and Arm B All Lines With dMMR/MSI-H mCRC 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.Objective Response Rate (ORR) by Blinded Independent Review Center (BICR) - 1L Participants 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.Overall Survival (OS) - Arm B vs. Arm A All Lines With dMMR/MSI-H mCRC 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.
Overall Survival (OS) - 1L Participants 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.
Trial Locations
- Locations (157)
Local Institution - 0059
🇺🇸Los Angeles, California, United States
Local Institution - 0130
🇺🇸Sacramento, California, United States
Local Institution - 0103
🇺🇸Denver, Colorado, United States
Local Institution - 0119
🇺🇸Arlington Heights, Illinois, United States
Local Institution - 0060
🇺🇸New York, New York, United States
Local Institution - 0105
🇺🇸Portland, Oregon, United States
Local Institution - 0121
🇺🇸Pittsburgh, Pennsylvania, United States
Local Institution - 0106
🇺🇸Dallas, Texas, United States
Local Institution - 0104
🇺🇸Roanoke, Virginia, United States
Local Institution - 0073
🇦🇷Ciudad Autonoma Beunos Aires, Buenos Aires, Argentina
Scroll for more (147 remaining)Local Institution - 0059🇺🇸Los Angeles, California, United States