What side effects are associated with this type of intervention?

The most common treatments for melanoma using immune checkpoint inhibitors, such as Nivolumab (PD-1 inhibitor) and Relatlimab (LAG-3 inhibitor), can cause a range of side effects. Common side effects include skin reactions (rash, pruritus), endocrine events (thyroid dysfunction), and gastrointestinal issues (diarrhea, colitis). Severe side effects may include pneumonitis, hepatitis, and nephritis. These treatments can also lead to immune-related adverse events affecting various organs, which may require immunosuppressive therapy. The combination of these drugs can increase the frequency and severity of these side effects.

What prior FDA approvals exist?

The FDA has approved several immune checkpoint inhibitors for the treatment of melanoma. Nivolumab (Opdivo) and pembrolizumab (Keytruda) are PD-1 inhibitors that have shown significant efficacy in treating advanced melanoma. Ipilimumab (Yervoy), a CTLA-4 inhibitor, has also been approved and is often used in combination with nivolumab for enhanced effectiveness. Recently, relatlimab, which targets the LAG-3 pathway, has been studied in combination with nivolumab to improve outcomes in melanoma patients. These treatments work by enhancing the body's immune response against melanoma cells.

What other types of research exist?

Promising novel alternatives to Relatlimab and Nivolumab for melanoma patients include: 1) Ipilimumab (CTLA-4 inhibitor) in combination with Nivolumab, which has shown improved treatment-free survival in advanced melanoma. 2) Pembrolizumab (PD-1 inhibitor) combined with Talimogene Laherparepvec (T-VEC), an oncolytic virus therapy, which has demonstrated efficacy in advanced melanoma. 3) Investigational agents in clinical trials targeting other immune checkpoints or molecular pathways, such as TIGIT inhibitors or personalized cancer vaccines, which are being evaluated for their potential benefits in melanoma treatment.

← Back to Search

Checkpoint Inhibitor

Relatlimab + Nivolumab for Advanced Melanoma (RELATIVITY-047 Trial)

Phase 2 & 3

Waitlist Available

Research Sponsored by Bristol-Myers Squibb

Eligibility Criteria Checklist

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

Must have

Participants must have histologically confirmed Stage III (unresectable) or Stage IV melanoma, per the AJCC staging system

Participants must not have had prior systemic anticancer therapy for unresectable or metastatic melanoma

Must not have

Participants must not have active brain metastases or leptomeningeal metastases

Participants must not have uveal melanoma

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from randomization up to approximately 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing if using two medications together (relatlimab and nivolumab) is better than using just one (nivolumab) for treating a type of skin cancer that can't be removed by surgery or has spread. The drugs help the immune system to better recognize and attack cancer cells.

Who is the study for?

This trial is for individuals with advanced melanoma that can't be removed by surgery or has spread, and who haven't had previous systemic cancer treatments. They must have a confirmed diagnosis of Stage III (unresectable) or Stage IV melanoma and provide tumor tissue for analysis. People with active brain metastases, uveal melanoma, or autoimmune diseases cannot participate.

What is being tested?

The study is testing the effectiveness of combining two drugs: Relatlimab and Nivolumab versus using Nivolumab alone in treating advanced melanoma. The goal is to see if the combination works better than just one drug on its own.

What are the potential side effects?

Potential side effects from Relatlimab and Nivolumab may include immune-related reactions such as inflammation in various organs, skin rash, hormone gland problems, infusion-related reactions, fatigue, and flu-like symptoms.

Eligibility Criteria

Inclusion Criteria

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

Select...

My melanoma is at an advanced stage and cannot be surgically removed.

Select...

I have not received systemic anticancer therapy for my advanced melanoma.

Select...

I can provide a tissue sample from my cancer that cannot be surgically removed.

Exclusion Criteria

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

Select...

I do not have cancer that has spread to my brain or its coverings.

Select...

I do not have eye melanoma.

Select...

I do not have any known autoimmune diseases.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from randomization up to approximately 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from randomization up to approximately 3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and from randomization up to approximately 3 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

Progression Free Survival (PFS)

Secondary study objectives

Overall Response Rate (ORR)

Overall Survival (OS)

Other study objectives

The Number of Participant Deaths in the Study

The Number of Participants Experiencing Adverse Events (AEs)

The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation

+3 more

Side effects data

From 2023 Phase 1 & 2 trial • 62 Patients • NCT03310619

43%

Neutrophil count decreased

29%

Anaemia

29%

White blood cell count decreased

14%

Blood uric acid increased

14%

Erythema

14%

Back pain

14%

COVID-19

14%

Headache

14%

Neurotoxicity

14%

Neutropenia

14%

Palpitations

14%

Dry eye

14%

Diarrhoea

14%

Dyspepsia

14%

Chills

14%

Oedema peripheral

14%

Cytokine release syndrome

14%

Pneumonia

14%

Aspartate aminotransferase increased

14%

International normalised ratio increased

14%

Lymphocyte count decreased

14%

Platelet count decreased

14%

Dehydration

14%

Hypokalaemia

14%

Hypomagnesaemia

14%

Bone pain

14%

Myalgia

14%

Pain in jaw

14%

Dizziness

14%

Nystagmus

14%

Confusional state

14%

Cough

14%

Dyspnoea

14%

Tachypnoea

14%

Alopecia

14%

Rash maculo-papular

14%

Embolism

100%

80%

60%

40%

20%

Study treatment Arm

Arm F: Cohort 1A Cohort 1A and 1D JCAR017 Plus CC-99282 (Post-JCAR017 Infusion)

Arm D: Cohort 1A JCAR017 Plus Ibrutinib (Pre- and Post-JCAR017 Infusion)

Arm A: Cohort 1A JCAR017 Plus Durvalumab (Post-JCAR017 Infusion)

Arm A: Cohort 1B JCAR017 Plus Durvalumab (Post-JCAR017 Infusion)

Arm B: Cohort 1A JCAR017 Plus CC-122 (Post-JCAR017 Infusion)

Arm C: Cohort 1A JCAR017 Plus CC-220 (Iberdomide) (Post-JCAR017 Infusion)

Arm E: Cohort 1C JCAR017 Plus Relatlimab and/or Nivolumab (Post-JCAR017 Infusion)

Arm F: Cohort 1D Cohort 1A and 1D JCAR017 Plus CC-99282 (Post-JCAR017 Infusion)

Awards & Highlights

No Placebo-Only Group

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

Trial Design

2Treatment groups

Experimental Treatment

Group I: Arm B: NivolumabExperimental Treatment1 Intervention

Monotherapy

Group II: Arm A: Relatlimab + NivolumabExperimental Treatment2 Interventions

Combination

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 / 6Eligibility 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 Relatlimab and Nivolumab, are pivotal in treating melanoma by targeting specific pathways that regulate the immune system. Nivolumab blocks the PD-1 pathway, which normally acts as a brake on T-cells, preventing them from attacking cancer cells. By inhibiting PD-1, Nivolumab enhances the immune response against melanoma. Relatlimab targets the LAG-3 pathway, another checkpoint that dampens T-cell activity. Blocking LAG-3 further boosts the immune system's ability to fight melanoma. These mechanisms are crucial for melanoma patients as they can lead to more effective and sustained anti-tumor responses, offering hope for better outcomes in advanced or unresectable cases.