Relatlimab + Nivolumab for Advanced Melanoma

(RELATIVITY-047 Trial)

Not currently recruiting at 286 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Bristol-Myers Squibb

Disqualifiers: Brain metastases, Uveal melanoma, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 33 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a new combination of drugs, relatlimab (Opdualag) and nivolumab (Opdivo), is more effective than nivolumab alone for treating advanced melanoma that cannot be surgically removed or has spread. Melanoma is a serious skin cancer, and the trial seeks better treatment options. Participants must have a confirmed diagnosis of Stage III or IV melanoma and should not have received prior treatments for their condition. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to potentially groundbreaking advancements in melanoma treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of relatlimab and nivolumab is generally safe for patients with advanced melanoma. One study found that the side effects of this combination mirrored those known for each drug when used alone, making them expected and manageable based on past experiences. Nivolumab alone has long been used to treat melanoma, and studies have demonstrated its general safety. While it can cause side effects, these are typically known and manageable by doctors. Overall, both the combination of relatlimab and nivolumab and nivolumab alone have demonstrated safety based on previous research and use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination treatment of Relatlimab and Nivolumab for advanced melanoma because it offers a novel way to tackle the disease. Unlike traditional treatments like surgery, chemotherapy, or even standalone immunotherapies, this combo leverages both drugs to enhance the immune response against cancer cells. Relatlimab targets the LAG-3 protein, potentially boosting the effectiveness of Nivolumab, which targets the PD-1 protein. This dual approach could lead to more robust and sustained anti-tumor activity, offering new hope for patients who may not respond to existing therapies.

What evidence suggests that this trial's treatments could be effective for advanced melanoma?

This trial will compare the effectiveness of two treatment approaches for advanced melanoma. Arm A will test the combination of relatlimab and nivolumab. Studies have shown this combination can effectively treat melanoma that cannot be surgically removed or has metastasized. Patients receiving this combination have experienced long-lasting benefits, with the treatment working well for an extended period. In some cases, this combination has allowed patients to go longer without needing additional treatment compared to nivolumab alone. Arm B will test nivolumab alone, which has also proven effective in slowing cancer growth and improving survival rates. Both treatments boost the immune system to help fight cancer cells. ^{2 6 7 8 9}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

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

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

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

Exclusion Criteria

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

I do not have eye melanoma.

I do not have any known autoimmune diseases.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Relatlimab combined with Nivolumab or Nivolumab alone

Up to approximately 33 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab
• Relatlimab

Trial Overview 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.

How Is the Trial Designed?

Group I: Arm B: Nivolumab Experimental Treatment 1 Intervention

Monotherapy

Group II: Arm A: Relatlimab + Nivolumab Experimental Treatment 2 Interventions

Combination

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

Bristol-Myers Squibb

Lead Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

Combining nivolumab and ipilimumab shows improved effectiveness in treating metastatic melanoma compared to using either drug alone, based on a retrospective analysis of approximately 7700 patients.

The combination therapy presents a safety profile that includes immune-related adverse events from both drugs, indicating that while the combination is effective, it also carries a heightened risk of toxicity that needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Side Effect Profiling of the Metastatic Melanoma Combination Therapy Ipilimumab-Nivolumab Using Adverse Event Data. Soldatos, TG., Dimitrakopoulou-Strauss, A., Larribere, L., et al.[2022]

Combined immune checkpoint blockade (ICB) using nivolumab and ipilimumab shows significant efficacy in treating advanced melanoma, but it also leads to a higher frequency and severity of adverse drug reactions (ADRs) compared to single-agent therapies, based on pooled safety data from 1551 patients.

Most immune-related ADRs are reversible with glucocorticoids, but due to the increased risk and rapid onset of these toxicities, clinicians must be well-trained to monitor and manage these side effects effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined immune checkpoint blockade (anti-PD-1/anti-CTLA-4): Evaluation and management of adverse drug reactions. Hassel, JC., Heinzerling, L., Aberle, J., et al.[2022]

The combination of nivolumab and relatlimab shows a manageable safety profile for patients with advanced melanoma who have already undergone treatment.

This combination therapy may offer a new option for patients with pretreated melanoma, suggesting potential efficacy in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Plus Relatlimab Is Safe and Efficacious in Pretreated Melanoma. [2023]

In a phase 2 trial involving 142 patients with untreated advanced melanoma, the combination of nivolumab and ipilimumab resulted in a 2-year overall survival rate of 63.8%, compared to 53.6% for those receiving ipilimumab alone, suggesting improved survival outcomes with the combination therapy.

However, the combination treatment was associated with a higher incidence of severe side effects, with 54% of patients experiencing grade 3-4 adverse events compared to 20% in the ipilimumab-only group, indicating a trade-off between efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. Hodi, FS., Chesney, J., Pavlick, AC., et al.[2022]

In a study of 142 patients with advanced melanoma, the combination of nivolumab and ipilimumab resulted in a significantly higher objective response rate of 61% compared to 11% for ipilimumab alone, indicating that the combination therapy is much more effective for treating this type of cancer.

While the combination therapy showed promising efficacy, it also had a higher incidence of severe adverse events (54% vs. 24% for monotherapy), but most of these side effects were manageable with immune-modulating medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. Postow, MA., Chesney, J., Pavlick, AC., et al.[2022]

Combining nivolumab with ipilimumab results in higher response rates in cancer treatment compared to using nivolumab alone, indicating a potentially more effective therapeutic strategy.

This combination therapy may enhance the immune response against cancer, but specific details on the number of subjects or study duration are not provided in the abstract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus Ipilimumab Achieves Responses in dMMR/MSI-H Tumors. [2019]

Nivolumab significantly improved overall survival and progression-free survival in patients with unresectable or metastatic melanoma compared to dacarbazine, with hazard ratios of 0.42 and 0.43 respectively, based on a trial involving 418 patients.

The most common side effects of nivolumab included fatigue, diarrhea, and rash, but it was still considered to have a favorable benefit-risk profile compared to dacarbazine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval of Nivolumab for the First-Line Treatment of Patients with BRAFV600 Wild-Type Unresectable or Metastatic Melanoma. Beaver, JA., Theoret, MR., Mushti, S., et al.[2018]

Nivolumab combined with ipilimumab has been established as a first-line treatment for advanced melanoma, showing significant efficacy based on results from the phase III CheckMate 067 trial.

While this combination therapy is effective, it is also associated with severe immune-related toxicities, highlighting the need to identify patient subgroups, such as those with BRAF mutations or asymptomatic brain metastases, who may benefit most from this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus ipilimumab in metastatic melanoma: a critical appraisal focused on specific subpopulations. Vázquez-Montero, L., de la Gala, MDCÁ., de la Cruz-Merino, L.[2023]

In a study of 129 patients with advanced melanoma treated with nivolumab and relatlimab, those without diabetes had significantly better progression-free survival (PFS) and overall survival (OS) compared to patients with type 2 diabetes, indicating that diabetes negatively impacts treatment efficacy.

Interestingly, patients who developed immune checkpoint inhibitor-induced diabetes (ICI-DM) during treatment had the best outcomes, suggesting that this condition may enhance the effectiveness of the therapy, possibly due to changes in LAG3 expression in tumor tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of diabetes in metastatic melanoma patients treated with nivolumab plus relatlimab. Mallardo, D., Woodford, R., Menzies, AM., et al.[2023]

In a phase 3 trial with patients suffering from advanced melanoma, the combination of nivolumab and ipilimumab resulted in significantly longer overall survival rates (58% at 3 years) compared to ipilimumab alone (34%).

The safety profile of the combination therapy was consistent with previous reports, showing that 59% of patients experienced severe treatment-related adverse events, indicating that while effective, the combination therapy has a higher risk of serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. Wolchok, JD., Chiarion-Sileni, V., Gonzalez, R., et al.[2023]

Citations

1. opdivo.com opdivo.com/melanoma/clinical-trial-results/advanced-immunotherapy-combination

Advanced Melanoma Skin Cancer | Clinical Trial Results In the clinical trial, people given OPDIVO + YERVOY had a 58% lower risk of their cancer spreading, growing, or getting worse than those given YERVOY alone.

2. opdivohcp.com opdivohcp.com/efficacy/melanoma

Efficacy Data for Melanoma | OPDIVO® (nivolumab) In melanoma patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, infusion-related reactions occurred in 2.5% (10/407) of patients. In HCC ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12293425/

A Single-Center Retrospective Study - PMC This retrospective study evaluated Japanese patients with advanced melanoma treated with various nivolumab regimens to assess the impact of ...

4. nejm.org nejm.org/doi/10.1056/NEJMoa2407417

Final, 10-Year Outcomes with Nivolumab plus Ipilimumab ... Among patients who had been alive and progression-free at 3 years, 10-year melanoma-specific survival was 96% with nivolumab plus ipilimumab, 97 ...

5. opdivo.com opdivo.com/melanoma/clinical-trial-results/advanced-immunotherapy

Advanced Melanoma Skin Cancer | Clinical Trial Results 55% of those given OPDIVO® for advanced melanoma survived, versus 37% of. In the clinical trial, people given OPDIVO had a 37% lower risk of dying than those ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12080919/

Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in ... Further, in patients who had progression-free survival at 3-years, 10-year melanoma-specific survival rates were 96% with nivolumab-plus- ...

7. news.bms.com news.bms.com/news/details/2021/Six-and-a-Half-Year-Outcomes-for-Opdivo-nivolumab-in-Combination-with-Yervoy-ipilimumab-Continue-to-Demonstrate-Durable-Long-Term-Survival-Benefits-in-Patients-with-Advanced-Melanoma/default.aspx

Six-and-a-Half-Year Outcomes for Opdivo (nivolumab) in ... With a minimum follow-up of 6.5 years, median overall survival (OS) was 72.1 months with Opdivo plus Yervoy (95% CI: 38.2-NR), the longest ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33428772/

Effectiveness and safety of nivolumab in patients with ... This retrospective observational study aimed to determine the effectiveness, safety and patterns of the use of nivolumab in patients with advanced melanoma

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.24.00400

Pooled Long-Term Outcomes With Nivolumab Plus ... Six-year OS was 52% with NIVO + IPI and 41% with NIVO, with a median OS of 84.6 months (95% CI, 59.5 to not reached [NR]) and 36.9 months (95% ...