Metastatic Colorectal Cancer
Conditions
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.
Interventions
BIOLOGICALIpilimumab
Specified dose on specified days
DRUGOxaliplatin
Specified dose on specified days
DRUGLeucovorin
Specified dose on specified days
DRUGFluorouracil
Specified dose on specified days
DRUGIrinotecan
Specified dose on specified days
DRUGBevacizumab
Specified dose on specified days
DRUGCetuximab
Specified dose on specified days
BIOLOGICALNivolumab
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Ono Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Czechia, Denmark, France, Germany, Greece, Ireland, Italy, Japan, Netherlands, Norway, Puerto Rico, Romania, Spain, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm A - Nivolumab Monotherapy Nivolumab 240 mg infusion on Day 1 and every two weeks during cycles 1 and 2 for a total of 6 doses. Starting from Cycle 3 Day 1 participants received Nivolumab 480 mg infusion every 4 weeks. | 353 |
| Arm B - Nivolumab + Ipilimumab Nivolumab 240 mg infusion followed by Ipilimumab 1 mg/kg IV on Day 1 and every three weeks during cycles 1 and 2 for a total of 4 doses. Starting from Cycle 3 Day 1, participants received Nivolumab 480 mg infusion every 4 weeks. | 354 |
| Arm C - Investigator's Choice Chemotherapy Participants received standard of care chemotherapy | 132 |
| Total | 839 |
Baseline characteristics
| Characteristic | Arm A - Nivolumab Monotherapy | Arm B - Nivolumab + Ipilimumab | Arm C - Investigator's Choice Chemotherapy | Total |
|---|---|---|---|---|
| Age, Continuous | 60.3 Years STANDARD_DEVIATION 13.76 | 60.5 Years STANDARD_DEVIATION 13.14 | 61.3 Years STANDARD_DEVIATION 14.93 | 60.5 Years STANDARD_DEVIATION 13.69 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 34 Participants | 32 Participants | 11 Participants | 77 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 189 Participants | 165 Participants | 67 Participants | 421 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 130 Participants | 157 Participants | 54 Participants | 341 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 36 Participants | 27 Participants | 15 Participants | 78 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 4 Participants | 2 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 12 Participants | 2 Participants | 19 Participants |
| Race (NIH/OMB) White | 305 Participants | 311 Participants | 113 Participants | 729 Participants |
| Sex: Female, Male Female | 163 Participants | 192 Participants | 68 Participants | 423 Participants |
| Sex: Female, Male Male | 190 Participants | 162 Participants | 64 Participants | 416 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 150 / 353 | 103 / 354 | 62 / 132 | 24 / 60 |
| other Total, other adverse events | 311 / 351 | 330 / 352 | 114 / 115 | 52 / 60 |
| serious Total, serious adverse events | 161 / 351 | 174 / 352 | 58 / 115 | 38 / 60 |
Outcome results
Primary
Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - Arm B vs. Arm A All Lines Centrally Confirmed MSI-H/dMMR
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.
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)
Population: All randomized participants with centrally confirmed DNA mismatch repairdeficient/microsatellite instability-high metastatic colorectal cancer (dMMR/MSI-H mCRC) in Arm A and Arm B only
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A - Nivolumab Monotherapy | Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - Arm B vs. Arm A All Lines Centrally Confirmed MSI-H/dMMR | 39.26 Months |
| Arm B - Nivolumab + Ipilimumab | Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - Arm B vs. Arm A All Lines Centrally Confirmed MSI-H/dMMR | NA Months |
p-value: 0.000395% CI: [0.48, 0.81]Log Rank
Primary
Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - Arm B vs. Arm C 1L Participants Centrally Confirmed MSI-H/dMMR
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.
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)
Population: All randomized participants with centrally confirmed DNA mismatch repairdeficient/microsatellite instability-high metastatic colorectal cancer (dMMR/MSI-H mCRC) who have not received prior therapy for metastatic disease (1L) in Arm B and Arm C only
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A - Nivolumab Monotherapy | Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - Arm B vs. Arm C 1L Participants Centrally Confirmed MSI-H/dMMR | NA Months |
| Arm B - Nivolumab + Ipilimumab | Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - Arm B vs. Arm C 1L Participants Centrally Confirmed MSI-H/dMMR | 5.85 Months |
p-value: <0.000195% CI: [0.14, 0.32]Log Rank
Secondary
Objective Response Rate (ORR) by Blinded Independent Review Center (BICR) - 1L Participants
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.
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)
Population: All randomized participants with centrally confirmed DNA mismatch repairdeficient/microsatellite instability-high metastatic colorectal cancer (dMMR/MSI-H mCRC) who have not received prior therapy for metastatic disease (1L)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A - Nivolumab Monotherapy | Objective Response Rate (ORR) by Blinded Independent Review Center (BICR) - 1L Participants | 61.2 Percentage of participants |
| Arm B - Nivolumab + Ipilimumab | Objective Response Rate (ORR) by Blinded Independent Review Center (BICR) - 1L Participants | 72.5 Percentage of participants |
| Arm C - Investigator's Choice Chemotherapy | Objective Response Rate (ORR) by Blinded Independent Review Center (BICR) - 1L Participants | 27.4 Percentage of participants |
95% CI: [3.91, 12.62]
95% CI: [1.06, 2.63]
Secondary
Objective Response Rate (ORR) by Blinded Independent Review Center (BICR) - Arm A and Arm B All Lines With dMMR/MSI-H mCRC
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.
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)
Population: All randomized participants with centrally confirmed DNA mismatch repairdeficient/microsatellite instability-high metastatic colorectal cancer (dMMR/MSI-H mCRC) in Arm A and Arm B only
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A - Nivolumab Monotherapy | Objective Response Rate (ORR) by Blinded Independent Review Center (BICR) - Arm A and Arm B All Lines With dMMR/MSI-H mCRC | 57.7 Percentage of participants |
| Arm B - Nivolumab + Ipilimumab | Objective Response Rate (ORR) by Blinded Independent Review Center (BICR) - Arm A and Arm B All Lines With dMMR/MSI-H mCRC | 70.6 Percentage of participants |
p-value: 0.001195% CI: [1.26, 2.5]Cochran-Mantel-Haenszel
Secondary
Overall Survival (OS) - 1L Participants
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.
Time frame: From randomization to the date of death due to any cause
Secondary
Overall Survival (OS) - Arm B vs. Arm A All Lines With dMMR/MSI-H mCRC
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.
Time frame: From randomization to the date of death due to any cause (Up to approximately 60 months)
Population: All randomized participants with centrally confirmed DNA mismatch repairdeficient/microsatellite instability-high metastatic colorectal cancer (dMMR/MSI-H mCRC) in Arm A and Arm B only
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A - Nivolumab Monotherapy | Overall Survival (OS) - Arm B vs. Arm A All Lines With dMMR/MSI-H mCRC | NA Months |
| Arm B - Nivolumab + Ipilimumab | Overall Survival (OS) - Arm B vs. Arm A All Lines With dMMR/MSI-H mCRC | NA Months |
95% CI: [0.45, 0.83]
Secondary
Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - 1L Participants
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.
Time frame: From date of randomization to the date of first objectively documented disease progression or death due to any cause, whichever occurs first
Secondary
Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - 1L Randomized Participants
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.
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)
Population: All randomized participants who have not received prior therapy for metastatic disease (1L)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A - Nivolumab Monotherapy | Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - 1L Randomized Participants | 44.85 Months |
| Arm B - Nivolumab + Ipilimumab | Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - 1L Randomized Participants | NA Months |
| Arm C - Investigator's Choice Chemotherapy | Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - 1L Randomized Participants | 6.21 Months |
95% CI: [0.23, 0.46]
Secondary
Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - Arm B vs. Arm A All Randomized Participants
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.
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)
Population: All randomized participants in Arm A and Arm B only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A - Nivolumab Monotherapy | Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - Arm B vs. Arm A All Randomized Participants | 18.43 Months |
| Arm B - Nivolumab + Ipilimumab | Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - Arm B vs. Arm A All Randomized Participants | 54.08 Months |
95% CI: [0.52, 0.79]
Secondary
Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) by Immunohistochemistry (IHC) - Arm B vs. Arm A
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.
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)
Population: All randomized participants with centrally confirmed DNA mismatch repairdeficient (dMMR) in Arm A and Arm B only
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A - Nivolumab Monotherapy | Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) by Immunohistochemistry (IHC) - Arm B vs. Arm A | 44.29 Months |
| Arm B - Nivolumab + Ipilimumab | Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) by Immunohistochemistry (IHC) - Arm B vs. Arm A | NA Months |
95% CI: [0.48, 0.83]
Secondary
Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) by Immunohistochemistry (IHC) - Arm B vs. Arm C
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.
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)
Population: All randomized participants with centrally confirmed DNA mismatch repairdeficient (dMMR) who have not received prior therapy for metastatic disease (1L) in Arm B and Arm C only
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A - Nivolumab Monotherapy | Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) by Immunohistochemistry (IHC) - Arm B vs. Arm C | NA Months |
| Arm B - Nivolumab + Ipilimumab | Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) by Immunohistochemistry (IHC) - Arm B vs. Arm C | 6.21 Months |
95% CI: [0.12, 0.31]
Secondary
Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) by Polymerase Chain Reaction (PCR) - Arm B vs. Arm A
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.
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)
Population: All randomized participants with centrally confirmed microsatellite instability-high (MSI-H) in Arm A and Arm B only
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A - Nivolumab Monotherapy | Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) by Polymerase Chain Reaction (PCR) - Arm B vs. Arm A | NA Months |
| Arm B - Nivolumab + Ipilimumab | Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) by Polymerase Chain Reaction (PCR) - Arm B vs. Arm A | NA Months |
95% CI: [0.45, 0.8]
Secondary
Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) by Polymerase Chain Reaction (PCR) - Arm B vs. Arm C
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.
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)
Population: All randomized participants with centrally confirmed microsatellite instability-high (MSI-H) who have not received prior therapy for metastatic disease (1L) in Arm B and Arm C only
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A - Nivolumab Monotherapy | Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) by Polymerase Chain Reaction (PCR) - Arm B vs. Arm C | NA Months |
| Arm B - Nivolumab + Ipilimumab | Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) by Polymerase Chain Reaction (PCR) - Arm B vs. Arm C | 6.21 Months |
95% CI: [0.12, 0.31]
Secondary
Progression-free Survival (PFS) by Blinded Independent Review Center (BICR) - Crossover and First Line Arm
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.
Time frame: From date of randomization to the date of first objectively documented disease progression or death due to any cause, whichever occurs first
Secondary
Progression-free Survival (PFS) by Investigator - 1L Participants
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.
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)
Secondary
Progression-free Survival (PFS) by Investigator - Arm A and Arm B All Lines With dMMR/MSI-H mCRC
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.
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)
Population: All randomized participants with centrally confirmed DNA mismatch repairdeficient/microsatellite instability-high metastatic colorectal cancer (dMMR/MSI-H mCRC) in Arm A and Arm B only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A - Nivolumab Monotherapy | Progression-free Survival (PFS) by Investigator - Arm A and Arm B All Lines With dMMR/MSI-H mCRC | 38.14 Months |
| Arm B - Nivolumab + Ipilimumab | Progression-free Survival (PFS) by Investigator - Arm A and Arm B All Lines With dMMR/MSI-H mCRC | NA Months |
95% CI: [0.48, 0.8]
Secondary
Progression-free Survival (PFS) by Investigator- Arm B vs. Arm A All Lines
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.
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)
Population: All randomized participants in Arm A and Arm B only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A - Nivolumab Monotherapy | Progression-free Survival (PFS) by Investigator- Arm B vs. Arm A All Lines | 22.18 Months |
| Arm B - Nivolumab + Ipilimumab | Progression-free Survival (PFS) by Investigator- Arm B vs. Arm A All Lines | 54.08 Months |
95% CI: [0.52, 0.79]