What side effects are associated with this type of intervention?

The most common treatments for Uveal Melanoma, particularly immune checkpoint inhibitors like Nivolumab (PD-1 inhibitor) and Relatlimab (LAG-3 inhibitor), are associated with several side effects. These can include immune-related adverse events such as inflammation of various organs, including the eyes (episcleritis, conjunctivitis, uveitis, and orbital inflammation), which can manifest as photophobia, pain, dryness, and blurred vision. Other potential side effects include fatigue, diarrhea, and infusion-related reactions. These treatments can also lead to more severe conditions like hemophagocytic lymphohistiocytosis (HLH), a rare but potentially fatal syndrome of excessive immune activation.

What prior FDA approvals exist?

As of now, there are no specific FDA-approved treatments for Uveal Melanoma that target PD-1 and LAG-3, such as Nivolumab and Relatlimab. However, immune checkpoint inhibitors like Nivolumab (a PD-1 inhibitor) have shown promise in treating various types of metastatic melanoma, including Uveal Melanoma, in clinical trials. The combination of Nivolumab and Relatlimab is currently being studied for its efficacy in reducing tumors in patients with metastatic Uveal Melanoma.

What other types of research exist?

Promising novel alternatives to Nivolumab and Relatlimab for Uveal Melanoma patients include Pembrolizumab (an anti-PD-1 therapy) and combination therapies involving BRAF/MEK inhibitors. Pembrolizumab has been evaluated for its efficacy in UM, and BRAF/MEK inhibitors have shown potential in managing melanoma with specific genetic mutations. These alternatives offer different mechanisms of action and may provide additional options for patients in 2024.

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Checkpoint Inhibitor

Nivolumab + Relatlimab for Uveal Melanoma

Phase 2

Waitlist Available

Research Sponsored by Jose Lutzky, MD

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be ≥ 18 years of age on day of signing informed consent

Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale

Must not have

Have a history of myocarditis, regardless of etiology

Have a known history of active tuberculosis (Bacillus Tuberculosis)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 4 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of two drugs, nivolumab and relatlimab, to see if they can shrink tumors in patients with metastatic uveal melanoma. These patients have a type of eye cancer that has spread and haven't received certain immune therapies before. The drugs work by helping the immune system better recognize and attack the cancer cells. Nivolumab is an immune checkpoint inhibitor that targets PD-1 and has been approved for use in multiple cancers, including melanoma.

Who is the study for?

This trial is for adults with metastatic uveal melanoma who haven't been treated with certain immune-blocking drugs. They must not be pregnant, agree to contraception, and have tumors that can be measured and biopsied. Participants need proper organ function, no active infections or severe psychiatric disorders, and cannot have had recent treatments that could affect the trial.

What is being tested?

The study tests if combining nivolumab with relatlimab reduces tumor size in patients with advanced eye melanoma. It's for those who haven't used similar drugs before. The treatment's effectiveness will be monitored by measuring changes in tumor size.

What are the potential side effects?

Potential side effects include immune-related reactions such as inflammation of organs, infusion reactions like fever or chills during drug administration, fatigue, possible infection risk increase due to immune system suppression, and allergic responses to the medication components.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 18 years old or older.

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I can take care of myself and am up and about more than half of my waking hours.

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I have untreated metastatic uveal melanoma and haven't received specific immune therapies.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had myocarditis in the past.

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I have a history of active tuberculosis.

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I have difficulty making decisions due to my health condition.

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I haven't had cancer treatment in the last 3 weeks or still have side effects.

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I have an autoimmune disease treated with medication in the last 2 years.

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I have not received a live vaccine in the last 30 days.

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I have a history of or currently have non-infectious lung inflammation.

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I have brain metastases or a history of significant brain bleeding.

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I am currently being treated for an infection with medication.

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I have been treated with drugs targeting PD-1 or LAG-3.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 4 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 4 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 4 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Objective Response Rate (ORR)

Secondary study objectives

Disease Control Rate (DCR)

Duration of Response (DOR)

Overall Survival (OS)

+2 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Nivolumab Plus Relatlimab GroupExperimental Treatment2 Interventions

Participants in this group will receive Nivolumab and Relatlimab administered together on Day 1 of every 4 week cycle. Both drugs will be administered until disease progression or intolerable toxicity for up to 24 months.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Nivolumab

2015

Completed Phase 3

~4010

Relatlimab

2019

Completed Phase 2

~1150

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Immune checkpoint inhibitors, such as Nivolumab (targeting PD-1) and Relatlimab (targeting LAG-3), work by blocking proteins that inhibit the immune system's ability to attack cancer cells. PD-1 is a protein on T cells that, when engaged, reduces the immune response. By inhibiting PD-1, Nivolumab enhances the body's immune response against tumor cells. Similarly, LAG-3 is another checkpoint that regulates T cell function, and blocking it with Relatlimab can further boost the immune response. For Uveal Melanoma patients, these treatments are significant because they can potentially overcome the immune evasion mechanisms of the tumor, leading to better control and reduction of the cancer.

Targeted Therapy and Checkpoint Immunotherapy Combinations for the Treatment of Cancer.