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
- 881
- 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 Central Review (BICR) (arm B vs A, all lines, centrally confirmed) Up to 5 years PFS by BICR (arm B vs C, 1L, centrally confirmed) Up to 5 years
- Secondary Outcome Measures
Name Time Method OS (arm B vs A, 1L, centrally confirmed) Up to 5 years Overall Survival (OS) (arm B vs A, all lines, centrally confirmed) Up to 5 years OS (arm A vs C, 1L, centrally confirmed) Up to 5 years PFS by Investigator (arm A, B and C, 1L, centrally confirmed) Up to 5 years PFS by BICR among all randomized participants who have not received prior treatment (arm B vs A, 1L, per local testing) Up to 5 years PFS by Investigator Assessment (arm B vs A, all lines, centrally confirmed) Up to 5 years PFS by BICR among all randomized participants (arm B vs A, all lines, per local testing) Up to 5 years ORR by BICR (arm B vs A, 1L, centrally confirmed) Up to 5 years ORR by BICR (arm A vs C, 1L, centrally confirmed) Up to 5 years Overall Response Rate (ORR) by BICR (arm B vs A, all lines, centrally confirmed) Up to 5 years PFS by BICR (arm A vs C, 1L, centrally confirmed) Up to 5 years OS (arm B vs C, 1L, centrally confirmed) Up to 5 years PFS by BICR (arm B vs A, 1L, centrally confirmed) Up to 5 years ORR by BICR (arm B vs C, 1L, centrally confirmed) Up to 5 years PFS by BICR (arm B vs C, 1L, by each central test) Up to 5 years PFS by BICR (arm B vs A, all lines, by each central test) Up to 5 years ORR by BICR (crossover cohort, centrally confirmed) Up to 5 years PFS by BICR among all randomized participants who have not received prior treatment (arm B vs C, 1L, per local testing) Up to 5 years PFS by BICR (crossover cohort, centrally confirmed) Up to 5 years
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