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 (CheckMate 9N9)

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

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Colorectal Neoplasm; Colorectal Tumors; Colorectal Carcinoma
• Intervention / Treatment: Biological: Nivolumab; Drug: Trametinib; Biological: Ipilimumab; Drug: Regorafenib

• Study Type: Interventional
• Enrollment (Actual): 325
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1431
    • Local Institution - 0119
  • Buenos Aires
    • Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1426ANZ
      • Local Institution - 0120
  • Distrito Federal
    • Buenos Aires, Distrito Federal, Argentina, C1096AAS
      • Local Institution - 0122
    • Buenos Aires, Distrito Federal, Argentina, 1181
      • Local Institution - 0123
• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Local Institution - 0044
  • Queensland
    • Southport, Queensland, Australia, 4215
      • Local Institution - 0043
  • South Australia
    • Elizabeth Vale, South Australia, Australia, 05112
      • Local Institution - 0068
  • Victoria
    • Clayton, Victoria, Australia
      • Local Institution - 0055
    • Heidelberg, Victoria, Australia, 3084
      • Local Institution - 0069
• Belgium
  • Woluwe-Saint-Lambert, Belgium, 1200
    • Local Institution
• Canada
  • Ottawa, Canada, K1H 8L6
    • Local Institution - 0076
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Local Institution - 0113
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Local Institution - 0070
  • Quebec
    • Montreal, Quebec, Canada, H2X 0A9
      • Local Institution - 0077
• Chile
  • Santiago Metropolitan
    • Santiago, Santiago Metropolitan, Chile, 000000
      • Local Institution - 0117
    • Santiago, Santiago Metropolitan, Chile, 8420383
      • Local Institution - 0118
• Czechia
  • Brno, Czechia, 65653
    • Local Institution - 0071
  • Hradec Králové, Czechia, 500 05
    • Local Institution - 0073
  • Olomoucký kraj
    • Olomouc, Olomoucký kraj, Czechia, 779 00
      • Local Institution - 0072
• Germany
  • Hanover, Germany, 30625
    • Local Institution - 0004
• Italy
  • Catania, Italy, 95124
    • Local Institution - 0095
  • Milan, Italy, 20133
    • Local Institution - 0093
  • Padua, Italy, 35128
    • Local Institution - 0092
  • Rozzano, Italy, 20089
    • Local Institution - 0094
• Spain
  • Barcelona, Spain, 08035
    • Local Institution - 0052
  • Madrid, Spain, 28007
    • Local Institution - 0114
  • Madrid, Spain, 28041
    • Local Institution - 0051
  • Madrid, Spain, 28050
    • Local Institution - 0115
  • Seville, Spain, 41013
    • Local Institution - 0096
  • Barcelona [Barcelona]
    • Badalona, Barcelona [Barcelona], Spain, 08916
      • Local Institution - 0079
  • Navarre
    • Pamplona, Navarre, Spain, 31009
      • Local Institution - 0080
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • Local Institution - 0022
  • California
    • Los Angeles, California, United States, 90033
      • Local Institution - 0027
    • Los Angeles, California, United States, 90089
      • Local Institution - 0067
    • San Francisco, California, United States, 94158
      • Local Institution - 0001
  • Florida
    • Gainesville, Florida, United States, 32610
      • Local Institution - 0107
    • Miami, Florida, United States, 33136
      • Local Institution - 0111
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Local Institution - 0028
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401-7233
      • Local Institution - 0116
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Local Institution - 0103
  • New York
    • New York, New York, United States, 10016
      • Local Institution - 0104
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Local Institution - 0029
  • Pennsylvania
    • Lancaster, Pennsylvania, United States, 17604
      • Local Institution - 0100
    • Philadelphia, Pennsylvania, United States, 19104
      • Local Institution - 0003
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University - Clinical Research Institute
  • Texas
    • Temple, Texas, United States, 76508
      • Local Institution - 0101
  • Wisconsin
    • Madison, Wisconsin, United States, 53792-0001
      • Local Institution - 0002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limiting Toxicities in Part 1 and Part 1A	Dose Limiting Toxicities are defined as adverse events have to be at least possibly related to study treatment, and not to disease progression, be clinically relevant and a clinically relevant shift from baseline.	4 weeks for Doublet Reginmen and 8 weeks for triplet Regimen
Safety Related Events in Part 1 and Part 1 A	Safety-related events in clinical trials include Adverse Events (AEs), Serious Adverse Events (SAEs), and deaths. An AE is any new or worsening medical issue in a participant receiving the study drug, regardless of its relation to the drug. This includes abnormal lab results, symptoms, or diseases. An SAE is a more severe AE that results in death, is life-threatening, requires or prolongs hospitalization, causes significant disability, involves a birth defect, or is deemed medically important-potentially jeopardizing the participant or requiring intervention, even if not immediately life-threatening. These definitions help ensure consistent reporting and evaluation of safety during clinical studies.	Assessed from first dose date to 100 days after last dose of study therapy. (Approximately: Part 1: ~ 6.5 Months Part 1A: ~ 5.5 Months)
Clinical Laboratory Abnormalities in Part 1 and Part 1A: Specific Thyroid Tests	Number of participants with clinical laboratory abnormalities in specific thyroid tests	Assessed from first dose date to 100 days after last dose of study therapy. (Approximately: Part 1: ~ 6.5 Months Part 1A: ~ 5.5 Months)
Clinical Laboratory Abnormalities in Part 1 and Part 1A: Specific Liver Tests	Number of participants with clinical laboratory abnormalities in specific liver tests.	Assessed from first dose date to 100 days after last dose of study therapy. (Approximately: Part 1: ~ 6.5 Months Part 1A: ~ 5.5 Months)
Overal Response Rate in Part 1B and Part 2	ORR is defined as the proportion of all treated participants whose BOR is either confirmed complete response (CR) or confirmed partial response (PR).	Approximately up to 30 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate in Part 1 and Part 1A	ORR is defined as the proportion of all treated participants whose BOR is either confirmed complete response (CR) or confirmed partial response (PR).	From the first dosing date and the date of the initial objectively documented tumor progression or subsequent therapy date (Approximately up to 21 Months)
Disease Control Rate in Part 1 and Part 1A	The disease control rate (DCR) is defined as the percentage of participants whose BOR is either confirmed CR or confirmed PR or stable disease (SD)	From the first dosing date and the date of the initial objectively documented tumor progression or subsequent therapy date (Approximately up to 21 Months)
Duration of Response in Part 1 and Part 1A	DOR for a participant with a BOR of confirmed CR or PR, is defined as the time between the date of first confirmed response and the date of the first objectively documented tumor progression per RECIST 1.1 or death, whichever occurs first.	Approximately up to 20 Months
Time to Response in Part 1 and Part 1A	Time to response (TTR) is defined for participants who had a confirmed CR or PR as the time from the first dosing date to the date of first documented CR or PR per RECIST 1.1.	From the first dosing date to the date of first documented CR or PR per RECIST 1.1. (Approximately on average 10 months)
Progression Free Survival in Part 1 and Part 1A	PFS for a participant is defined as the time from the first dosing date to the date of first objectively documented disease progression per RECIST 1.1 (ie, radiologic) or death due to any cause, whichever occurs first.	from the first dosing date to the date of first objectively documented disease progression or death, whichever occurs first (Approximately up to 21 months)
Overall Survival in Part 1 and Part 1A	OS for a participant is defined as the time from the first dosing date to the date of death due to any cause. A participant who has not died will be censored at last known date alive.	Approximately up to 69 Months
Safety Related Events in Part 1B and Part 2	Safety-related events in clinical trials include Adverse Events (AEs), Serious Adverse Events (SAEs), and deaths. An AE is any new or worsening medical issue in a participant receiving the study drug, regardless of its relation to the drug. This includes abnormal lab results, symptoms, or diseases. An SAE is a more severe AE that results in death, is life-threatening, requires or prolongs hospitalization, causes significant disability, involves a birth defect, or is deemed medically important-potentially jeopardizing the participant or requiring intervention, even if not immediately life-threatening. These definitions help ensure consistent reporting and evaluation of safety during clinical studies.	Assessed from first dose date to 100 days after last dose of study therapy. (Approximately: 6.8 Months)
Clinical Laboratory Abnormalities in Part 1B and Part 2: Specific Thyroid Tests	Number of participants with clinical laboratory abnormalities in specific thyroid tests	Assessed from first dose date to 100 days after last dose of study therapy. (Approximately: 6.8 Months)
Clinical Laboratory Abnormalities in Part 1B and Part 2: Specific Liver Tests	Number of participants with clinical laboratory abnormalities in specific liver tests.	Assessed from first dose date to 100 days after last dose of study therapy. (Approximately: 6.8 Months)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: Novartis
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2018
• Primary Completion (Actual): November 4, 2024
• Study Completion (Actual): November 4, 2024

Study Registration Dates

• First Submitted: December 14, 2017
• First Submitted That Met QC Criteria: December 14, 2017
• First Posted (Actual): December 19, 2017

Study Record Updates

• Last Update Posted (Estimated): December 3, 2025
• Last Update Submitted That Met QC Criteria: November 20, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab; Ipilimumab; trametinib; regorafenib
• Other Study ID Numbers: CA209-9N9; 2017-001830-24 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No