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

Study Overview
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Brief Summary
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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.

Official Title
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Phase 2 Study of Nivolumab and Relatlimab in Advanced Mismatch Repair Deficient Cancers Resistant to Prior PD-(L)1 Inhibitor

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

Intervention / Treatment
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* Drug: Nivolumab
* Drug: Relatlimab
* Drug: Nivolumab
* Drug: Relatlimab
* Drug: Nivolumab
* Drug: Relatlimab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Nivolumab and Relatlimab<br>480mg/160mg (co-administered) | Drug: Nivolumab<br>* Patients will receive treatment every 28 days for up to 2 years. Nivolumab will be administered IV on day 1 (28 day cycle).<br>* Other names: anti-PD-1, OPDIVO;Drug: Relatlimab<br>* Patients will receive treatment every 28 days up to 2 years. Relatlimab will be administered IV on day 1 (28 day cycle).<br>* Other names: BMS-986016;|
| Experimental: Cohort 2: Nivolumab and Relatlimab<br>480mg/960mg or 480mg/160mg (sequential administration) | Drug: Nivolumab<br>* Patients will receive treatment every 28 days for up to 2 years. Nivolumab will be administered IV on day 1 (28 day cycle).<br>* Other names: anti-PD-1, OPDIVO;Drug: Relatlimab<br>* Patients will receive treatment every 28 days up to 2 years. Relatlimab will be administered IV on day 1 (28 day cycle).<br>* Other names: BMS-986016;|
| Experimental: Cohort 3: Nivolumab and Relatlimab<br>480mg/480mg (sequential administration) | Drug: Nivolumab<br>* Patients will receive treatment every 28 days for up to 2 years. Nivolumab will be administered IV on day 1 (28 day cycle).<br>* Other names: anti-PD-1, OPDIVO;Drug: Relatlimab<br>* Patients will receive treatment every 28 days up to 2 years. Relatlimab will be administered IV on day 1 (28 day cycle).<br>* Other names: BMS-986016;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) |  | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants experiencing study drug-related toxicities |  | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relatlimab, Nivolumab, Immunotherapy, Anti - PD-1, Anti - LAG-3, Antibodies, MSI, MMR deficient, Microsatellite instability