A Study of Nivolumab Alone or Nivolumab Combination Therapy in Colon Cancer That Has Come Back or Has Spread

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 2 Clinical Trial of Nivolumab, or Nivolumab Combinations in Recurrent and Metastatic Microsatellite Instability High (MSI-H) and Non-MSI-H Colon Cancer

Conditions
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Microsatellite Unstable Colorectal Cancer, Microsatellite Stable Colorectal Cancer, Mismatch Repair Proficient Colorectal Cancer, Mismatch Repair Deficient Colorectal Cancer

Intervention / Treatment
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* Drug: Ipilimumab
* Drug: Nivolumab
* Drug: Cobimetinib
* Drug: Daratumumab
* Drug: BMS-986016


Participation Criteria
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Eligibility Criteria
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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/exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nivolumab Monotherapy<br> | Drug: Nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;|
| Experimental: Nivolumab + Ipilimumab<br> | Drug: Ipilimumab<br>* Specified dose on specified days<br>* Other names: Yervoy;Drug: Nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;|
| Experimental: Nivolumab + Ipilimumab Cohort C3<br> | Drug: Ipilimumab<br>* Specified dose on specified days<br>* Other names: Yervoy;Drug: Nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;|
| Experimental: Nivolumab + Ipilimumab + Cobimetinib Cohort C4<br> | Drug: Ipilimumab<br>* Specified dose on specified days<br>* Other names: Yervoy;Drug: Nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;Drug: Cobimetinib<br>* Specified dose on specified days<br>* Other names: Cotellic;|
| Experimental: Nivolumab + BMS-986016 Cohort C5<br> | Drug: Nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;Drug: BMS-986016<br>* Specified dose on specified days<br>|
| Experimental: Nivolumab + Daratumumab Cohort C6<br> | Drug: Nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;Drug: Daratumumab<br>* Specified dose on specified days<br>* Other names: Darzalex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by Investigator |  | The final analysis of the primary endpoint will occur at least 6 months after the last enrolled subject's first dose of study therapy (Approximately up to 34 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR by RECIST v1.1 by Independent Radiology Review Committee (IRRC) |  | The final analysis of the secondary endpoint will occur the time of the primary endpoint analysis (Approximately up to 34 months) |