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

NCT03377361 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: CA209-9N92017-001830-24
• Study Type: interventional
• Target: 325
• Locations: 10 countries
• Sites: 47

Brief Summary

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.

Conditions

Colorectal Cancer; Colorectal Tumors; Colorectal Carcinoma; Colorectal Neoplasm

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (9)

• Objective Response Rate in Part 1 and Part 1A

  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

  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

  Approximately up to 20 Months

• Time to Response in Part 1 and Part 1A

  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

  from the first dosing date to the date of first objectively documented disease progression or death, whichever occurs first (Approximately up to 21 months)

Study Arms (6)

Part 1 Cohort 1 3rd Line (3L): nivolumab + trametinib

EXPERIMENTAL

Biological: Nivolumab; Drug: Trametinib

Part 1A Cohort 2 2nd Line (2L): nivolumab + ipilimumab + trametinib

EXPERIMENTAL

Biological: Nivolumab; Drug: Trametinib; Biological: Ipilimumab

Part 1A Cohort 3 (2L): nivolumab + ipilimumab + trametinib

EXPERIMENTAL

Biological: Nivolumab; Drug: Trametinib; Biological: Ipilimumab

Part 2 Cohort 4 (3L): nivolumab + ipilimumab + trametinib

EXPERIMENTAL

Biological: Nivolumab; Drug: Trametinib; Biological: Ipilimumab

Part 2 Cohort 5 (3L): Regorafenib

EXPERIMENTAL

Drug: Regorafenib

Part 1B Cohort 6 (2L): nivolumab + ipilimumab + trametinib

EXPERIMENTAL

Biological: Nivolumab; Drug: Trametinib; Biological: Ipilimumab

Interventions

Nivolumab BIOLOGICAL

Specified dose on specified days

Also known as: Opdivo, BMS-936558

Part 1 Cohort 1 3rd Line (3L): nivolumab + trametinib; Part 1A Cohort 2 2nd Line (2L): nivolumab + ipilimumab + trametinib; Part 1A Cohort 3 (2L): nivolumab + ipilimumab + trametinib; Part 1B Cohort 6 (2L): nivolumab + ipilimumab + trametinib; Part 2 Cohort 4 (3L): nivolumab + ipilimumab + trametinib

Trametinib DRUG

Specified dose on specified days

Also known as: Mekinist

Part 1 Cohort 1 3rd Line (3L): nivolumab + trametinib; Part 1A Cohort 2 2nd Line (2L): nivolumab + ipilimumab + trametinib; Part 1A Cohort 3 (2L): nivolumab + ipilimumab + trametinib; Part 1B Cohort 6 (2L): nivolumab + ipilimumab + trametinib; Part 2 Cohort 4 (3L): nivolumab + ipilimumab + trametinib

Ipilimumab BIOLOGICAL

Specified dose on specified days

Also known as: Yervoy, BMS-734016

Part 1A Cohort 2 2nd Line (2L): nivolumab + ipilimumab + trametinib; Part 1A Cohort 3 (2L): nivolumab + ipilimumab + trametinib; Part 1B Cohort 6 (2L): nivolumab + ipilimumab + trametinib; Part 2 Cohort 4 (3L): nivolumab + ipilimumab + trametinib

Regorafenib DRUG

Specified dose on specified days

Part 2 Cohort 5 (3L): Regorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead
• Novartis: collaborator

Study Sites (47)

Local Institution - 0022

Birmingham, Alabama, 35249, United States

Location

Local Institution - 0027

Los Angeles, California, 90033, United States

Location

Local Institution - 0067

Los Angeles, California, 90089, United States

Location

Local Institution - 0001

San Francisco, California, 94158, United States

Location

Local Institution - 0107

Gainesville, Florida, 32610, United States

Location

Local Institution - 0111

Miami, Florida, 33136, United States

Location

Local Institution - 0028

Baltimore, Maryland, 21287, United States

Location

Local Institution - 0116

Hattiesburg, Mississippi, 39401-7233, United States

Location

Local Institution - 0103

St Louis, Missouri, 63110, United States

Location

Local Institution - 0104

New York, New York, 10016, United States

Location

Local Institution - 0029

Charlotte, North Carolina, 28204, United States

Location

Local Institution - 0100

Lancaster, Pennsylvania, 17604, United States

Location

Local Institution - 0003

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University - Clinical Research Institute

Philadelphia, Pennsylvania, 19107, United States

Location

Local Institution - 0101

Temple, Texas, 76508, United States

Location

Local Institution - 0002

Madison, Wisconsin, 53792-0001, United States

Location

Local Institution - 0120

Ciudad Autónoma de Buenos Aires, Buenos Aires, C1426ANZ, Argentina

Location

Local Institution - 0123

Buenos Aires, Distrito Federal, 1181, Argentina

Location

Local Institution - 0122

Buenos Aires, Distrito Federal, C1096AAS, Argentina

Location

Local Institution - 0119

Buenos Aires, 1431, Argentina

Location

Local Institution - 0044

Blacktown, New South Wales, 2148, Australia

Location

Local Institution - 0043

Southport, Queensland, 4215, Australia

Location

Local Institution - 0068

Elizabeth Vale, South Australia, 05112, Australia

Location

Local Institution - 0055

Clayton, Victoria, 0, Australia

Location

Local Institution - 0069

Heidelberg, Victoria, 3084, Australia

Location

Local Institution

Woluwe-Saint-Lambert, 1200, Belgium

Location

Local Institution - 0113

Edmonton, Alberta, T6G 1Z2, Canada

Location

Local Institution - 0070

Toronto, Ontario, M5G 2M9, Canada

Location

Local Institution - 0077

Montreal, Quebec, H2X 0A9, Canada

Location

Local Institution - 0076

Ottawa, K1H 8L6, Canada

Location

Local Institution - 0117

Santiago, Santiago Metropolitan, 000000, Chile

Location

Local Institution - 0118

Santiago, Santiago Metropolitan, 8420383, Chile

Location

Local Institution - 0072

Olomouc, Olomoucký kraj, 779 00, Czechia

Location

Local Institution - 0071

Brno, 65653, Czechia

Location

Local Institution - 0073

Hradec Králové, 500 05, Czechia

Location

Local Institution - 0004

Hanover, 30625, Germany

Location

Local Institution - 0095

Catania, 95124, Italy

Location

Local Institution - 0093

Milan, 20133, Italy

Location

Local Institution - 0092

Padua, 35128, Italy

Location

Local Institution - 0094

Rozzano, 20089, Italy

Location

Local Institution - 0079

Badalona, Barcelona [Barcelona], 08916, Spain

Location

Local Institution - 0080

Pamplona, Navarre, 31009, Spain

Location

Local Institution - 0052

Barcelona, 08035, Spain

Location

Local Institution - 0114

Madrid, 28007, Spain

Location

Local Institution - 0051

Madrid, 28041, Spain

Location

Local Institution - 0115

Madrid, 28050, Spain

Location

Local Institution - 0096

Seville, 41013, Spain

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Nivolumab; trametinib; Ipilimumab; regorafenib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please Email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2017
• First Posted: December 19, 2017
• Study Start: January 31, 2018
• Primary Completion: November 4, 2024
• Study Completion: November 4, 2024
• Last Updated: December 3, 2025
• Results First Posted: December 3, 2025

Record last verified: 2025-11

Locations

AU (5); AR (4); CL (2); CA (4); BE (1); CZ (3); IT (4); US (16); ES (7); DE (1)