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

Bristol-Myers Squibb325 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

325

Conditions

Colorectal Cancer Colorectal Tumors Colorectal Carcinoma Colorectal Neoplasm

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: 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).

Time frame: Approximately up to 30 Months

Secondary Outcomes

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).

Time frame: 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)

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

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

Overview

Conditions

Interventions

Eligibility

Locations (47)

Outcomes

Primary Outcomes

Secondary Outcomes