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

NCT ID: NCT03607890

Last Updated: 2025-12-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-16
• Study Completion Date: 2026-10-31

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

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

Study Design

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

Study Groups

Cohort 1: Nivolumab and Relatlimab

480mg/160mg (co-administered)

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

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

Relatlimab

Intervention Type: DRUG

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

Cohort 2: Nivolumab and Relatlimab

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

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

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

Relatlimab

Intervention Type: DRUG

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

Cohort 3: Nivolumab and Relatlimab

480mg/480mg (sequential administration)

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

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

Relatlimab

Intervention Type: DRUG

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

Interventions

Nivolumab

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

Intervention Type: DRUG

Relatlimab

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

Intervention Type: DRUG

Nivolumab

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

Intervention Type: DRUG

Relatlimab

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

Intervention Type: DRUG

Nivolumab

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

Intervention Type: DRUG

Relatlimab

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

Intervention Type: DRUG

Other Intervention Names

anti-PD-1, OPDIVO; BMS-986016; anti-PD-1, OPDIVO; BMS-986016; anti-PD-1, OPDIVO; BMS-986016

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• 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.
• Prior life-threatening toxicity to anti-PD-1, anti-PD-L1, anti-PD-L2,or anti-CTLA4
• Woman who are pregnant or breastfeeding.

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

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

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

Johns Hopkins Medical Institution

Locations

Cedars Sinai Medical Center

Los Angeles, California, United States

Site Status: RECRUITING

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Colleen Apostal, RN

Role: CONTACT

GIClinicaltrials@jhmi.edu

410-614-3644

Facility Contacts

Abraham Levi

Role: primary

Abraham.levi@cshs.org

310-248-8084

Colleen Apostal, RN

Role: primary

GIClinicaltrials@jhmi.edu

410-614-3644

Other Identifiers

IRB00173534

Identifier Type: OTHER

Identifier Source: secondary_id

P50CA062924

Identifier Type: NIH

Identifier Source: secondary_id

View Link

J18102

Identifier Type: -

Identifier Source: org_study_id