Study of Nivolumab and Relatlimab in Advanced Mismatch Repair Deficient Cancers Resistant to Prior PD-(L)1 Inhibitor

NCT03607890 | Active Not Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: J18102IRB00173534P50CA062924
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to evaluate the safety and clinical activity of nivolumab and relatlimab in patients with microsatellite instability high (MSI-H) solid tumors refractory to prior PD-(L)1 therapy.

Conditions

MSI-H Tumors; Refractory MSI - H Solid Tumors Prior of PD-(L) 1 Therapy

Keywords

Relatlimab; Nivolumab; Immunotherapy; Anti - PD-1; Anti - LAG-3; Antibodies; MSI; MMR deficient; Microsatellite instability

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

  4 years

Secondary Outcomes (1)

• Number of participants experiencing study drug-related toxicities

  4 years

Study Arms (3)

Cohort 1: Nivolumab and Relatlimab

EXPERIMENTAL

480mg/160mg (co-administered)

Drug: Nivolumab; Drug: Relatlimab

Cohort 2: Nivolumab and Relatlimab

EXPERIMENTAL

480mg/960mg or 480mg/160mg (sequential administration)

Drug: Nivolumab; Drug: Relatlimab

Cohort 3: Nivolumab and Relatlimab

EXPERIMENTAL

480mg/480mg (sequential administration)

Drug: Nivolumab; Drug: Relatlimab

Interventions

Nivolumab DRUG

Patients will receive treatment every 28 days for up to 2 years. Nivolumab will be administered IV on day 1 (28 day cycle).

Also known as: anti-PD-1, OPDIVO

Cohort 1: Nivolumab and Relatlimab

Relatlimab DRUG

Patients will receive treatment every 28 days up to 2 years. Relatlimab will be administered IV on day 1 (28 day cycle).

Also known as: BMS-986016

Cohort 1: Nivolumab and Relatlimab

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.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Have metastatic or locally advanced mismatch repair deficient/MSI-H disease.
• Patients must have received prior PD-1/PD-L1 inhibitor therapy
• Patients with the presence of at least one measurable lesion.
• Life expectancy of greater than 3 months.
• Patients must have adequate organ and marrow function defined by study - specified laboratory tests.
• Documented left ventricular ejection fraction (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.
• Require any antineoplastic therapy.
• History of prior treatment with anti-LAG3.
• Had chemotherapy, radiation, or steroids within 14 days prior to study treatment.
• Had any investigational cytotoxic drug within 4 weeks prior to study treatment.
• Have received any investigational drugs, a live vaccine, any allergen hyposensitization therapy, growth factors or major surgery within 28 days prior to study treatment.
• Major surgery
• Hypersensitivity reaction to any monoclonal antibody.
• 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.
• 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
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

MeSH Terms

Conditions

Turcot syndrome; Microsatellite Instability

Interventions

Nivolumab; relatlimab

Condition Hierarchy (Ancestors)

Genomic Instability; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Dung Le, MD

  Johns Hopkins Medical Institution

  PRINCIPAL INVESTIGATOR

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: July 24, 2018
• First Posted: July 31, 2018
• Study Start: November 16, 2018
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: March 16, 2026

Record last verified: 2026-03

Locations

US (2)