Microsatellite Unstable Colorectal Cancer, Microsatellite Stable Colorectal Cancer, Mismatch Repair Proficient Colorectal Cancer, Mismatch Repair Deficient Colorectal Cancer
Conditions
Brief summary
The purpose of this study is to examine if Nivolumab by itself, or Nivolumab in combination with other anti-cancer drugs, will result in meaningful tumor size reduction, in participants with colon cancer that has come back or has spread, and who have a specific biomarker in their tumors.
Interventions
DRUGIpilimumab
Specified dose on specified days
DRUGNivolumab
Specified dose on specified days
DRUGCobimetinib
Specified dose on specified days
DRUGDaratumumab
Specified dose on specified days
DRUGBMS-986016
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 * Histologically confirmed recurrent or metastatic colorectal cancer * Measurable disease per RECIST v1.1 * Microsatellite instability expression detected by an accredited laboratory * Participants enrolled into the C3 Cohort must have not had treatment for their metastatic disease
Exclusion criteria
* Active brain metastases or leptomeningeal metastases are not allowed * Prior treatment with an anti-Programmed Death Receptor (PD)-1, anti-PD-L1, anti-PD-L2, anti-Cytotoxic T-Cell Lymphoma-4 Antigen (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways * Prior malignancy active within the previous 3 years except for locally curable cancers * Participants with active, known or suspected autoimmune disease * Participants with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of study drug administration Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Per Investigator Assessment | From date of randomization to the date of objectively documented progression or the date of subsequent systemic cancer therapy, whichever occurs first (Up to approximately 127 months) | Objective Response Rate (ORR) is defined as the number of randomized participants who achieve a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), based on investigator assessments \\\[using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1\\\], divided by the number of all randomized participants. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \\\<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Per Independent Review Committee (IRC) | From date of randomization to the date of objectively documented progression or the date of subsequent systemic cancer therapy, whichever occurs first (Up to approximately 127 months) | Objective Response Rate (ORR) is defined as the number of randomized participants who achieve a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), based on IRC\\\[using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1\\\], divided by the number of all randomized participants. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \\\<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
Countries
Australia, Belgium, Canada, France, Ireland, Italy, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Nivolumab Monotherapy Nivolumab 3 mg/kg | 74 |
| Cohort 2: Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg | 119 |
| Cohort 3: Nivolumab 3 mg/kg Q2W with Ipilimumab 1 mg/kg Q6W Nivolumab 3 mg/kg Q2W with Ipilimumab 1 mg/kg twice in six weeks Q6W | 45 |
| MSS: Nivolumab 3 mg/kg Q2W with Ipilimumab 1 mg/kg Q6W Nivolumab 3 mg/kg Q2W with Ipilimumab 1 mg/kg Q6W | 10 |
| Non-MSI-H: Nivolumab 1 mg/kg + Ipilimumab 3 mg/kg Nivolumab 1 mg/kg + Ipilimumab 3 mg/kg | 10 |
| Non-MSI-H: Nivolumab 1 mg/kg + Ipilimumab 1 mg/kg Nivolumab 1 mg/kg + Ipilimumab 1 mg/kg | 3 |
| Cohort 4: Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg + Cobimetinib 60 mg Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg + Cobimetinib 60 mg | 30 |
| Cohort 5: Nivolumab 240 mg + BMS-986016 80 mg Nivolumab 240 mg + BMS-986016 80 mg | 50 |
| Cohort 6: Nivolumab FD + Daratumumab 16 mg/kg Nivolumab FD + Daratumumab 16 mg/kg | 44 |
| Total | 385 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Administrative reasons by sponsor | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Adverse event unrelated to study drug | 2 | 5 | 6 | 0 | 1 | 0 | 4 | 4 | 1 |
| Overall Study | Death | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Disease Progression | 36 | 42 | 8 | 5 | 6 | 3 | 23 | 20 | 43 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Maximum clinical benefit | 13 | 38 | 19 | 0 | 0 | 0 | 0 | 10 | 0 |
| Overall Study | Other reason | 3 | 7 | 0 | 1 | 0 | 0 | 0 | 9 | 0 |
| Overall Study | Participant request to discontinue study treatment | 7 | 7 | 4 | 0 | 0 | 0 | 1 | 1 | 0 |
| Overall Study | Participant withdrew consent | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Study Drug Toxicity | 10 | 18 | 7 | 4 | 3 | 0 | 2 | 5 | 0 |
Baseline characteristics
| Characteristic | Total | Cohort 1: Nivolumab Monotherapy | Cohort 2: Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg | Cohort 3: Nivolumab 3 mg/kg Q2W with Ipilimumab 1 mg/kg Q6W | MSS: Nivolumab 3 mg/kg Q2W with Ipilimumab 1 mg/kg Q6W | Non-MSI-H: Nivolumab 1 mg/kg + Ipilimumab 3 mg/kg | Non-MSI-H: Nivolumab 1 mg/kg + Ipilimumab 1 mg/kg | Cohort 4: Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg + Cobimetinib 60 mg | Cohort 5: Nivolumab 240 mg + BMS-986016 80 mg | Cohort 6: Nivolumab FD + Daratumumab 16 mg/kg |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized >= 65 and < 75 years | 80 Participants | 13 Participants | 27 Participants | 10 Participants | 1 Participants | 1 Participants | 0 Participants | 9 Participants | 10 Participants | 9 Participants |
| Age, Customized < 65 years | 268 Participants | 57 Participants | 81 Participants | 22 Participants | 9 Participants | 9 Participants | 3 Participants | 21 Participants | 34 Participants | 32 Participants |
| Age, Customized >= 75 years | 37 Participants | 4 Participants | 11 Participants | 13 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants | 3 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 7 Participants | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 16 Participants | 7 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 7 Participants | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 354 Participants | 65 Participants | 110 Participants | 43 Participants | 10 Participants | 10 Participants | 3 Participants | 23 Participants | 49 Participants | 41 Participants |
| Sex: Female, Male Female | 155 Participants | 30 Participants | 49 Participants | 22 Participants | 2 Participants | 3 Participants | 1 Participants | 12 Participants | 22 Participants | 14 Participants |
| Sex: Female, Male Male | 230 Participants | 44 Participants | 70 Participants | 23 Participants | 8 Participants | 7 Participants | 2 Participants | 18 Participants | 28 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 44 / 74 | 46 / 119 | 16 / 45 | 9 / 10 | 3 / 3 | 10 / 10 | 29 / 30 | 27 / 50 | 43 / 44 |
| other Total, other adverse events | 73 / 74 | 116 / 119 | 45 / 45 | 10 / 10 | 3 / 3 | 10 / 10 | 27 / 30 | 48 / 50 | 43 / 44 |
| serious Total, serious adverse events | 46 / 74 | 72 / 119 | 22 / 45 | 8 / 10 | 3 / 3 | 9 / 10 | 20 / 30 | 28 / 50 | 29 / 44 |
Outcome results
Primary
Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Per Investigator Assessment
Objective Response Rate (ORR) is defined as the number of randomized participants who achieve a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), based on investigator assessments \\\[using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1\\\], divided by the number of all randomized participants. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \\\<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From date of randomization to the date of objectively documented progression or the date of subsequent systemic cancer therapy, whichever occurs first (Up to approximately 127 months)
Population: All treated participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Nivolumab Monotherapy | Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Per Investigator Assessment | 40.5 percentage of participants |
| Cohort 2: Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg | Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Per Investigator Assessment | 66.4 percentage of participants |
| Cohort 3: Nivolumab 3 mg/kg Q2W with Ipilimumab 1 mg/kg Q6W | Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Per Investigator Assessment | 71.1 percentage of participants |
| Cohort 4: Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg + Cobimetinib 60 mg | Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Per Investigator Assessment | 3.3 percentage of participants |
| Cohort 5: Nivolumab 240 mg + BMS-986016 80 mg | Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Per Investigator Assessment | 50.0 percentage of participants |
| Cohort 6: Nivolumab FD + Daratumumab 16 mg/kg | Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Per Investigator Assessment | 0 percentage of participants |
| MSS: Nivolumab 3 mg/kg Q2W with Ipilimumab 1 mg/kg Q6W | Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Per Investigator Assessment | 0 percentage of participants |
| Non-MSI-H: Nivolumab 1 mg/kg + Ipilimumab 3 mg/kg | Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Per Investigator Assessment | 0 percentage of participants |
| Non-MSI-H: Nivolumab 1 mg/kg + Ipilimumab 1 mg/kg | Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Per Investigator Assessment | 10.0 percentage of participants |
Secondary
Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Per Independent Review Committee (IRC)
Objective Response Rate (ORR) is defined as the number of randomized participants who achieve a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), based on IRC\\\[using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1\\\], divided by the number of all randomized participants. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \\\<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From date of randomization to the date of objectively documented progression or the date of subsequent systemic cancer therapy, whichever occurs first (Up to approximately 127 months)
Population: All treated participants. As pre-specified only applicable for Cohort 1, 2, 3, 4, 5 and 6
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Nivolumab Monotherapy | Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Per Independent Review Committee (IRC) | 37.8 percentage of participants |
| Cohort 2: Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg | Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Per Independent Review Committee (IRC) | 61.3 percentage of participants |
| Cohort 3: Nivolumab 3 mg/kg Q2W with Ipilimumab 1 mg/kg Q6W | Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Per Independent Review Committee (IRC) | 62.2 percentage of participants |
| Cohort 4: Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg + Cobimetinib 60 mg | Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Per Independent Review Committee (IRC) | 6.7 percentage of participants |
| Cohort 5: Nivolumab 240 mg + BMS-986016 80 mg | Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Per Independent Review Committee (IRC) | 50.0 percentage of participants |
| Cohort 6: Nivolumab FD + Daratumumab 16 mg/kg | Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Per Independent Review Committee (IRC) | 0 percentage of participants |