What side effects are associated with this type of intervention?

The combination of Ipilimumab and Nivolumab, used in the treatment of malignant melanoma, is associated with a range of immune-related adverse events. Common side effects include fatigue, rash, diarrhea, and pruritus. More severe toxicities can involve colitis, hepatitis, endocrinopathies (such as hypothyroidism or adrenal insufficiency), and pneumonitis. These side effects result from the immune system's heightened activity against normal tissues, necessitating careful monitoring and management, often with immunosuppressive therapies like corticosteroids.

What prior FDA approvals exist?

The FDA has approved several treatments for malignant melanoma, including the combination of nivolumab (a PD-1 inhibitor) and ipilimumab (a CTLA-4 inhibitor). This combination has shown significant efficacy in clinical trials, improving progression-free survival (PFS) and overall survival (OS) in patients with advanced melanoma. Other approved treatments include single-agent therapies such as pembrolizumab and nivolumab, which have also demonstrated substantial benefits in treating melanoma. These approvals provide multiple therapeutic options for patients, particularly those with advanced or metastatic disease.

What other types of research exist?

Promising novel alternatives to Ipilimumab + Nivolumab for malignant melanoma patients include: 1) Relatlimab + Nivolumab, which targets LAG-3 and PD-1, showing improved outcomes in the RELATIVITY-047 trial. 2) Pembrolizumab (anti-PD-1) combined with other agents like epacadostat (an IDO inhibitor), although further validation is needed. 3) Talimogene laherparepvec (T-VEC) combined with Pembrolizumab, which has shown efficacy in the MASTERKEY-265 trial. These alternatives may offer different mechanisms of action and potentially improved safety profiles.

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Checkpoint Inhibitor

Neoadjuvant Ipilimumab + Nivolumab for Melanoma (NADINA Trial)

Phase 3

Waitlist Available

Research Sponsored by The Netherlands Cancer Institute

Eligibility Criteria Checklist

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

Must have

No other malignancies, except adequately treated and with a cancer-related life-expectancy of more than 5 years

No prior immunotherapy targeting CTLA-4, PD-1 or PD-L1

Must not have

Prior radiotherapy

Women who are pregnant or breastfeeding

Timeline

Screening 3 weeks

Treatment Varies

Follow Up analysis will be performed after 132 events, though not later than after 2 years follow-up of all patients.

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing two treatment plans for patients with stage III melanoma. One plan uses two drugs before surgery, while the other uses surgery first followed by one of the drugs. The goal is to see which plan works better at stopping the cancer from coming back. These drugs have been shown to improve survival rates in patients with advanced melanoma.

Who is the study for?

This trial is for adults and teens (16+) with stage III melanoma that can be surgically removed. Participants must not have used immunosuppressive drugs in the last 6 months, should have good health status, no history of certain cancers or treatments targeting BRAF/MEK or CTLA-4/PD-1/PD-L1, and no active infections or autoimmune diseases. Women who can bear children and sexually active men must use contraception.

What is being tested?

The study compares two approaches: one group receives neoadjuvant ipilimumab + nivolumab before surgery followed by adjuvant nivolumab; the other has standard surgery first then adjuvant nivolumab. Some may get additional treatment if they don't respond well initially. The goal is to see which method works better for preventing cancer progression.

What are the potential side effects?

Possible side effects include immune-related reactions affecting various organs, infusion reactions similar to allergic responses, fatigue, skin issues like rash or itching, digestive problems such as diarrhea or colitis, liver inflammation known as hepatitis, hormone gland problems like thyroid disorders.

Eligibility Criteria

Inclusion Criteria

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

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I have no other cancers, or if I do, they are under control and not expected to affect my life expectancy significantly.

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I have not had immunotherapy targeting CTLA-4, PD-1, or PD-L1.

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My melanoma is at stage III and can be surgically removed.

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I am fully active or able to carry out light work.

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I have not had treatments targeting BRAF or MEK.

Exclusion Criteria

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

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I have undergone radiotherapy before.

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I am not pregnant or breastfeeding.

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I am taking medication that weakens my immune system.

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I have an active autoimmune disease or a history of one.

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My melanoma is in the eye or mucous membranes.

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My melanoma has spread to distant parts of my body.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ analysis will be performed after 132 events, though not later than after 2 years follow-up of all patients.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~analysis will be performed after 132 events, though not later than after 2 years follow-up of all patients.

This trial's timeline: 3 weeks for screening, Varies for treatment, and analysis will be performed after 132 events, though not later than after 2 years follow-up of all patients. for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Comparison of event-free survival (EFS) in the neoadjuvant and adjuvant group.

Secondary study objectives

Description of surgical morbidity

Description of type of immune-related adverse events

Neoplasm Metastasis

+7 more

Awards & Highlights

No Placebo-Only Group

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

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: A: NeoadjuvantExperimental Treatment1 Intervention

2 cycles of neoadjuvant ipilimumab (80mg) + nivolumab (240mg) every 3 weeks followed by a total lymph node dissection (TLND) and if applicable, resection of in-transit metastases. Patients with a pathologic partial or non-response in arm A will also receive adjuvant nivolumab 480 mg every 4 weeks 11 cycles. In case of BRAF V600E/K mutation-positivity, patients will be treated with adjuvant dabrafenib plus trametinib for 46 weeks instead.

Group II: B: AdjuvantActive Control1 Intervention

Standard upfront total lymph node dissection (TLND) and if applicable, resection of in-transit metastases followed by 12 cycles adjuvant nivolumab 480 mg every 4 weeks

0 / 11Eligibility 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

The combination of Ipilimumab (a CTLA-4 inhibitor) and Nivolumab (a PD-1 inhibitor) represents a powerful approach in the treatment of malignant melanoma. Ipilimumab works by blocking CTLA-4, a checkpoint protein on T cells that downregulates immune responses. By inhibiting CTLA-4, Ipilimumab enhances the immune system's ability to attack melanoma cells. Nivolumab, on the other hand, blocks PD-1, another checkpoint protein that normally helps keep immune responses in check. By inhibiting PD-1, Nivolumab further boosts the immune response against melanoma cells. This dual blockade of CTLA-4 and PD-1 pathways leads to a more robust and sustained immune attack on melanoma, which is crucial for improving patient outcomes and potentially achieving long-term remission.

Immunotherapy for the Treatment of Uveal Melanoma: Current Status and Emerging Therapies.