An Investigational Immuno-therapy Study Of Nivolumab In Combination With Trametinib With Or Without Ipilimumab In Participants With Previously Treated Cancer of the Colon or Rectum That Has Spread

Study Overview
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Brief Summary
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The purpose of this study is to investigate treatment with nivolumab in combination with trametinib with or without ipilimumab in participants with previously treated cancer of the colon or rectum that has spread.

Official Title
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A Study Of Nivolumab In Combination With Trametinib With Or Without Ipilimumab In Participants With Previously Treated Metastatic Colorectal Cancers

Conditions
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Colorectal Cancer, Colorectal Tumors, Colorectal Carcinoma, Colorectal Neoplasm

Intervention / Treatment
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* Biological: Nivolumab
* Drug: Trametinib
* Biological: Ipilimumab
* Drug: Regorafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed previously treated metastatic colorectal cancer with adenocarcinoma histology and in Stage IV per American Joint Committee on Cancer (version 4.0) at study entry Microsatellite status should be performed per local standard of practice, immunohistochemistry (IHC) and/or PCR. If IHC results are equivocal, PCR is required for determining microsatellite stable (MSS) status Must have measurable disease per RECIST 1.1. Participants with lesions in a previously irradiated field as the sole site of measurable disease will be permitted to enroll provided the lesion(s) have demonstrated clear progression and can be measured accurately Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 at screening and on cycle 1 day 1 (C1D1) Exclusion Criteria: BRAF V600 mutant colorectal cancer Active brain metastases or leptomeningeal metastases Active, known or suspected autoimmune disease Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study treatment administration History of interstitial lung disease or pneumonitis Prior treatment with immune checkpoint inhibitors and mitogen-activated protein kinase enzymes (MEK) inhibitors History of allergy or hypersensitivity to study drug components 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 Cohort 1 3rd Line (3L): nivolumab + trametinib<br> | Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;Drug: Trametinib<br>* Specified dose on specified days<br>* Other names: Mekinist;|
| Experimental: Part 1A Cohort 2 2nd Line (2L): nivolumab + ipilimumab + trametinib<br> | Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;Drug: Trametinib<br>* Specified dose on specified days<br>* Other names: Mekinist;Biological: Ipilimumab<br>* Specified dose on specified days<br>* Other names: BMS-734016;|
| Experimental: Part 1A Cohort 3 (2L): nivolumab + ipilimumab + trametinib<br> | Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;Drug: Trametinib<br>* Specified dose on specified days<br>* Other names: Mekinist;Biological: Ipilimumab<br>* Specified dose on specified days<br>* Other names: BMS-734016;|
| Experimental: Part 2 Cohort 4 (3L): nivolumab + ipilimumab + trametinib<br> | Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;Drug: Trametinib<br>* Specified dose on specified days<br>* Other names: Mekinist;Biological: Ipilimumab<br>* Specified dose on specified days<br>* Other names: BMS-734016;|
| Experimental: Part 2 Cohort 5 (3L): Regorafenib<br> | Drug: Regorafenib<br>* Specified dose on specified days<br>|
| Experimental: Part 1B Cohort 6 (2L): nivolumab + ipilimumab + trametinib<br> | Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;Drug: Trametinib<br>* Specified dose on specified days<br>* Other names: Mekinist;Biological: Ipilimumab<br>* Specified dose on specified days<br>* Other names: BMS-734016;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose limiting toxicity (DLTs) |  | Up to 23 months | 
| Incidence of Adverse Events (AEs) |  | Approximately 100 months | 
| Incidence of Serious Adverse Events (SAEs) |  | Approximately 100 months | 
| Incidence of Deaths |  | Up to 100 months | 
| Incidence of clinically significant changes in clinical laboratory results: Hematology tests |  | Up to 77 months | 
| Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests |  | Up to 77 months | 
| Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests |  | Up to 77 months | 
| Objective response rate (ORR) by investigator (Part 1B and Part 2) |  | Approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) (Part 1A and Part 1) |  | Approximately 24 months | 
| Disease control rate (DCR) |  | Approximately 24 months | 
| Duration of response (DOR) |  | Approximately 24 months | 
| Time to response (TTR) |  | Approximately 24 months | 
| Progression-free survival (PFS) by investigator per response evaluation criteria in solid tumors (RECIST) v1.1 |  | Approximately 24 months | 
| Best overall response (BOR) |  | Up to 24 months | 
| Overall survival (OS) |  | Approximately 40 months | 
| Incidence of Adverse Events (AEs) |  | Approximately 100 months | 
| Incidence of Serious Adverse Events (SAEs) |  | Approximately 100 months | 
| Incidence of Deaths |  | Up to 100 months | 
| Incidence of clinically significant changes in clinical laboratory results: Hematology tests |  | Up to 77 months | 
| Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests |  | Up to 77 months | 
| Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests |  | Up to 77 months |