Study of Nivolumab and Relatlimab in Patients With Microsatellite Stable (MSS) Advanced Colorectal Cancer

NCT ID: NCT03642067

Last Updated: 2025-06-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-12
• Study Completion Date: 2024-09-18

Brief Summary

The purpose of this study is to evaluate the safety and clinical activity of nivolumab and relatlimab in patients with metastatic or locally advanced microsatellite stable (MSS) colorectal cancer.

Conditions

Microsatellite Stable (MSS) Colorectal Adenocarcinomas; Colorectal Adenocarcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A: Composite PD-L1/Mucin (CPM) positive colorectal cancer

Participants were pre-screened for CPM score. The CPM score integrates the percent of PD-L1 expression at the tumor interface and the percent of acellular mucin in the tumor area ([%PD-L1 + % acellular mucin]/2) using each participant's primary tumor tissue. A CPM score cutoff of greater than or equal to 15% was used to determine CPM positivity.

Participants received 480mg Nivolumab and 160mg Relatlimab.

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

Nivolumab was administered IV on day 1 of each 28 day cycle.

Relatlimab

Intervention Type: DRUG

Relatlimab was administered IV on day 1 of each 28 day cycle.

Cohort B: Composite PD-L1/Mucin (CPM) negative colorectal cancer

Participants were pre-screened for CPM score. The CPM score integrates the percent of PD-L1 expression at the tumor interface and the percent of acellular mucin in the tumor area ([%PD-L1 + % acellular mucin]/2) using each participant's primary tumor tissue. A CPM score cutoff of less than 15% was used to determine CPM negativity.

Participants received 480mg Nivolumab and 160mg Relatlimab.

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

Nivolumab was administered IV on day 1 of each 28 day cycle.

Relatlimab

Intervention Type: DRUG

Relatlimab was administered IV on day 1 of each 28 day cycle.

Cohort C: Colorectal cancer with no biomarker evaluation required

Participants were not pre-screened for composite PD-L1/mucin (CPM) score.

Participants received 480mg Nivolumab and 960mg Relatlimab (dose reduced to 480mg or 160mg).

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

Nivolumab was administered IV on day 1 of each 28 day cycle.

Relatlimab

Intervention Type: DRUG

Relatlimab was administered IV on day 1 of each 28 day cycle.

Interventions

Nivolumab

Nivolumab was administered IV on day 1 of each 28 day cycle.

Intervention Type: DRUG

Relatlimab

Relatlimab was administered IV on day 1 of each 28 day cycle.

Intervention Type: DRUG

Other Intervention Names

OPDIVO, BMS-936558, anti-PD-1; BMS-986016, anti-LAG-3

Eligibility Criteria

Inclusion Criteria

• Age ≥18 years.
• ECOG performance status 0 or 1
• Have metastatic or locally advanced microsatellite stable (MSS) colorectal adenocarcinoma.
• Cohort A: Primary lesion has a composite PD-L1/Mucin (CPM) score ≥ 15%.
• Cohort B: Primary lesion has a composite PD-L1/Mucin (CPM) score < 15%.
• Cohort C: Prior surgical resection of primary tumor. Prospective biomarker evaluation not required.
• Must have received at least one chemotherapy regimen.
• Patients with the presence of at least one measurable lesion using RECIST 1.1.
• Patients must have available archival tissue from the surgical resection of their primary tumor.
• Patient's acceptance of tumor biopsies.
• Life expectancy of greater than 3 months.
• Patients must have adequate organ and marrow function defined by study - specified laboratory tests.
• Documented LVEF ≥ 50% - 6 month prior to drug administration.
• Must use acceptable form of birth control while on study.
• Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria

• Known history or evidence of brain metastases. Patients with previously treated brain metastases may participate if they are stable for 4 weeks prior to beginning treatment, have no new or enlarging brain metastases, and are not using steroids for at least 1 week prior to initiation of study treatment.
• Require any antineoplastic therapy.
• History of prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, or anti-Lag-3 antibodies.
• Had chemotherapy, radiation, or steroids within 14 days prior to study treatment.
• Had any cytotoxic drug within 4 weeks prior to initiation of study treatment.
• Hypersensitivity reaction to any monoclonal antibody.
• Has uncontrolled intercurrent acute or chronic medical illness.
• Has an active known or suspected autoimmune disease.
• Has a diagnosis of immunodeficiency.
• Prior tissue or organ allograft or allogeneic bone marrow transplantation.
• Requires daily supplemental oxygen
• History of interstitial lung disease.
• Requires daily supplemental oxygen.
• Significant heart disease
• History of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent.
• Infection with HIV or hepatitis B or C at screening.
• Has an active infection.
• Unable to have blood drawn.
• Patient with uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Woman who are pregnant or breastfeeding.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dung Le, MD

Role: PRINCIPAL_INVESTIGATOR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB00173537

Identifier Type: OTHER

Identifier Source: secondary_id

CA224-068

Identifier Type: OTHER

Identifier Source: secondary_id

J18119

Identifier Type: -

Identifier Source: org_study_id