What is the mechanism of action of this treatment?

Tocilizumab, an IL-6 receptor antagonist, reduces inflammation and modulates immune response. Ipilimumab, a CTLA-4 inhibitor, enhances T cell activation by blocking CTLA-4, promoting an immune attack on melanoma cells. Nivolumab, a PD-1 inhibitor, prevents PD-1 from binding to PD-L1, allowing T cells to recognize and destroy cancer cells. These treatments boost the immune system's ability to fight melanoma, potentially improving disease control and survival for patients.

What side effects are associated with this type of intervention?

The most common treatments for melanoma, such as tocilizumab, ipilimumab, and nivolumab, are associated with a range of side effects. Tocilizumab, an IL-6 receptor antagonist, can cause elevated liver enzymes and increased risk of infections. Ipilimumab, a CTLA-4 inhibitor, is known for immune-related adverse events including enterocolitis, dermatitis, thyroiditis, hepatitis, and hypophysitis. Nivolumab, a PD-1 inhibitor, commonly causes skin reactions, endocrine events, and can lead to serious adverse reactions like pneumonia, diarrhea, and acute kidney injury. These treatments, while effective, require careful monitoring for these potential side effects.

What prior FDA approvals exist?

The treatment landscape for melanoma has significantly evolved with several FDA approvals. In 2011, Ipilimumab, a CTLA-4 inhibitor, was approved for metastatic melanoma. Nivolumab, a PD-1 inhibitor, received FDA approval for melanoma treatment and has shown superiority over chemotherapy and Ipilimumab in various settings. Additionally, other agents like Pembrolizumab (another PD-1 inhibitor) have been approved, further expanding the immunotherapy options for melanoma. These approvals have paved the way for combination therapies, such as the ongoing study of Tocilizumab (an IL-6 receptor antagonist) with Ipilimumab and Nivolumab, aiming to enhance treatment efficacy for advanced melanoma.

What other types of research exist?

Promising novel alternatives for melanoma treatment in 2024 include: 1) Relatlimab (LAG-3 inhibitor) in combination with Nivolumab, which has shown efficacy in untreated advanced melanoma. 2) Chemically modified DNA aptamers targeting IL-6, which inhibit signaling by blocking its interaction with the IL-6 receptor. 3) Pembrolizumab (another PD-1 inhibitor) in combination with other checkpoint inhibitors or anticancer agents, which is being evaluated in various clinical trials.

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Monoclonal Antibodies

Triple Drug Therapy for Melanoma

Phase 2

Waitlist Available

Led By Janice Mehnert, MD

Research Sponsored by NYU Langone Health

Eligibility Criteria Checklist

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

Must have

Prior surgery that required general anesthesia must be completed at least 4 weeks before study drug administration

Tumor tissue from the resected site of disease must be provided for biomarker analyses

Must not have

Corrected QT interval using Fridericia's formula value > 480 msec at screening; family or personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy at screening; previous history of drug induced QTc prolongation or the need for treatment with medications known or suspected of producing prolonged QTc intervals on electrocardiogram (ECG)

Any serious or uncontrolled medical disorder or active infection

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from start of treatment until the date of death from any cause (up to 5 years)

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of three drugs to treat melanoma. The drugs will be given for different lengths of time depending on whether the patient is in the induction or maintenance phase of the trial. The trial will assess the safety and tolerability of the combination and the pharmacodynamic activity of one of the drugs.

Who is the study for?

This trial is for adults with advanced melanoma that can't be removed by surgery. Participants must have a good performance status, meaning they're fairly active and able to care for themselves. They should not have had certain previous cancer treatments or serious health conditions like heart failure or uncontrolled disorders. Women who can become pregnant and men with partners of childbearing potential must agree to use contraception.

What is being tested?

The study tests Tocilizumab combined with Ipilimumab and Nivolumab in patients with stage III or IV melanoma. It's an open-label, single-arm Phase II trial where everyone gets the same treatment: Tocilizumab every 6 weeks for five doses plus four induction doses of the other two drugs until week 12, followed by maintenance Nivolumab alone up to one year.

What are the potential side effects?

Possible side effects include immune system reactions affecting organs, infusion-related symptoms (like fever or chills), fatigue, increased risk of infections due to weakened immunity, liver function changes, skin reactions at injection sites, and potentially others as this combination is still under investigation.

Eligibility Criteria

Inclusion Criteria

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

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I had surgery with general anesthesia over 4 weeks ago.

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I can provide a sample of my tumor tissue for testing.

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I have signed the required consent form for this study.

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My brain metastases have been treated and show no signs of returning for at least 4 weeks.

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I am fully active or have some restrictions but can still care for myself.

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My melanoma is at Stage IIIb/c/d or IV and cannot be removed with surgery.

Exclusion Criteria

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

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I don't have a history of heart rhythm problems or need drugs that affect heart rhythm.

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I do not have any serious or uncontrolled health issues or infections.

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I have severe heart failure or had a recent heart attack.

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I have cancer in the lining of my brain or a history of eye melanoma.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from start of treatment until the date of death from any cause (up to 5 years)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from start of treatment until the date of death from any cause (up to 5 years)

This trial's timeline: 3 weeks for screening, Varies for treatment, and from start of treatment until the date of death from any cause (up to 5 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)

Percentage of Participants With Grades 3-5 Treatment Related Immune Related Adverse Events (irAEs)

Secondary study objectives

Disease Control Rate (DCR)

Duration of Disease Control

Duration of Immune-related Disease Control

+7 more

Side effects data

From 2017 Phase 4 trial • 59 Patients • NCT02034474

11%

Low ANC

nausea

agranulocytosis

Inpatient admission

fatigue

100%

80%

60%

40%

20%

Study treatment Arm

Placebo

Tocilizumab

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: Induction Phase, Maintenance PhaseExperimental Treatment3 Interventions

Induction Phase: 2 induction treatment cycles of 42 days (6 weeks) each, of which the first cycle of 6 weeks is the dose-limiting toxicity (DLT) period. Maintenance Phase: Consists of treatment cycles of 84 days (12 weeks) each, and may extend up to 1 year.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ipilimumab

2015

Completed Phase 3

~3420

Nivolumab

2015

Completed Phase 3

~4010

Tocilizumab

2012

Completed Phase 4

~1840

0 / 10Eligibility 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

Tocilizumab, an IL-6 receptor antagonist, reduces inflammation and modulates immune response. Ipilimumab, a CTLA-4 inhibitor, enhances T cell activation by blocking CTLA-4, promoting an immune attack on melanoma cells. Nivolumab, a PD-1 inhibitor, prevents PD-1 from binding to PD-L1, allowing T cells to recognize and destroy cancer cells. These treatments boost the immune system's ability to fight melanoma, potentially improving disease control and survival for patients.

The Clinical Trial Landscape for Melanoma Therapies.Cancer immunology and melanoma immunotherapy.Combination immune checkpoint blockade with ipilimumab and nivolumab in the management of advanced melanoma.