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

NCT03642067 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: J18119IRB00173537CA224-068
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

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

Keywords

Relatlimab; Nivolumab; Immunotherapy; Anti-PD-1; Anti-LAG-3; Antibody; MSS; PD-L1; Microsatellite stability; Colorectal cancer; Colon cancer; Rectal cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on RECIST 1.1 criteria. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions. Participants who discontinue due to toxicity or clinical progression prior to post-baseline tumor assessments will be considered as non-responders. Participants who discontinue for other reasons prior to their first dose of study drug will not included in the analysis.

  12 months

Secondary Outcomes (1)

• Number of Participants Experiencing Drug-Related Adverse Events (AEs) Requiring Treatment Discontinuation

  12 months

Study Arms (3)

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

EXPERIMENTAL

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.

Drug: Nivolumab; Drug: Relatlimab

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

EXPERIMENTAL

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.

Drug: Nivolumab; Drug: Relatlimab

Cohort C: Colorectal cancer with no biomarker evaluation required

EXPERIMENTAL

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).

Drug: Nivolumab; Drug: Relatlimab

Interventions

Nivolumab DRUG

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

Also known as: OPDIVO, BMS-936558, anti-PD-1

Cohort A: Composite PD-L1/Mucin (CPM) positive colorectal cancer; Cohort B: Composite PD-L1/Mucin (CPM) negative colorectal cancer; Cohort C: Colorectal cancer with no biomarker evaluation required

Relatlimab DRUG

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

Also known as: BMS-986016, anti-LAG-3

Cohort A: Composite PD-L1/Mucin (CPM) positive colorectal cancer; Cohort B: Composite PD-L1/Mucin (CPM) negative colorectal cancer; Cohort C: Colorectal cancer with no biomarker evaluation required

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

MeSH Terms

Conditions

Spinocerebellar Degenerations; Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

Nivolumab; relatlimab

Condition Hierarchy (Ancestors)

Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; 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: Dung Le, MD
• Organization: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

dle@jhmi.edu

443-287-0002

Study Officials

• Dung Le, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2018
• First Posted: August 22, 2018
• Study Start: February 12, 2019
• Primary Completion: February 23, 2024
• Study Completion: September 18, 2024
• Last Updated: June 15, 2025
• Results First Posted: January 28, 2025

Record last verified: 2025-06

Locations

US (1)