Nivolumab + Relatlimab for Uveal Melanoma

Overseen By Edda Bisbal-Loubriel

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Jose Lutzky, MD

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Immunodeficiency, Active tuberculosis, Autoimmune, 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

Compensation: Varies

Number of Visits: 1

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of two immunotherapy drugs, nivolumab and relatlimab, to determine if they can reduce tumors in individuals with metastatic uveal melanoma, a rare eye cancer that has spread. The goal is to assess whether these drugs can work together to stop or shrink the cancer. Participants should have metastatic uveal melanoma that hasn't been treated with certain prior therapies. This trial may suit those with this specific cancer type who wish to explore new treatment options. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must not be on systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before starting the trial treatment, unless it's a replacement dose or pre-medication for imaging contrast allergy.

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

Research has shown that the combination of nivolumab and relatlimab, known as Opdualag, is generally safe for people with melanoma. Studies conducted over four years did not reveal any new or unexpected safety issues with this treatment. More than 15% of patients experienced common side effects, which were anticipated and manageable.

Another study on patients with metastatic uveal melanoma found that nivolumab and relatlimab were safe, although the treatment was not very effective at shrinking tumors. These findings suggest that while the treatment is well-tolerated, its effectiveness in reducing tumors may vary. ^{1 2 3 4 5}

Why are researchers excited about this possible treatment for uveal melanoma?

Researchers are excited about Nivolumab and Relatlimab for uveal melanoma because these drugs offer a fresh approach to treatment. Unlike traditional therapies that often focus on targeting tumors directly, this combination enhances the immune system's ability to fight cancer. Nivolumab is a checkpoint inhibitor that blocks the PD-1 protein, helping the immune system recognize and attack cancer cells. Relatlimab targets the LAG-3 protein, another checkpoint that can slow down immune responses. Together, they potentially offer a more powerful and comprehensive way to tackle uveal melanoma by unleashing the full power of the immune system.

What evidence suggests that this treatment might be an effective treatment for uveal melanoma?

Research shows that using nivolumab and relatlimab together holds promise for treating melanoma, a type of skin cancer. Studies have found that this combination can shrink tumors and keep them smaller for longer. In patients with advanced melanoma, it demonstrated strong effects against tumors. This trial will evaluate the combination of nivolumab and relatlimab for uveal melanoma, a rare eye cancer, to determine if it can similarly help the immune system fight cancer by targeting proteins that typically allow cancer to evade immune cells. ^{2 5 6 7 8}

Who Is on the Research Team?

Jose Lutzky, MD

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

If a female of childbearing potential, be willing to use an adequate method of contraception as outlined in Section 5.8 Contraception, for the course of the study through 24 weeks after the last dose of study medication. Must abstain from ova donation for a minimum of 5 months after the end of treatment

If a female of childbearing potential, have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

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

Exclusion Criteria

I have had myocarditis in the past.

Have a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator

I am not on steroids or immunosuppressants, except for low-dose or allergy-prevention steroids.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Nivolumab and Relatlimab administered together every 4 weeks until disease progression or intolerable toxicity for up to 24 months

24 months

1 visit every 4 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

Up to 4 years

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab
• Relatlimab

Trial Overview 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.

How Is the Trial Designed?

Group I: Nivolumab Plus Relatlimab Group Experimental Treatment 2 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.

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?

Jose Lutzky, MD

Lead Sponsor

Trials

1

Recruited

30+

Bristol-Myers Squibb

Industry 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

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

In a retrospective review of 15 patients with metastatic uveal melanoma treated with anti-PD-1 antibodies (pembrolizumab or nivolumab), the best response observed was stable disease in four patients, indicating limited efficacy as no objective responses were recorded.

The treatment was generally well tolerated, with manageable toxicity, and the median progression-free survival was 3 months, while the overall survival was 5 months, suggesting that while the therapy may not be highly effective, it can be safely administered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-PD-1 antibodies in metastatic uveal melanoma: a treatment option? Bender, C., Enk, A., Gutzmer, R., et al.[2021]

Uveal melanoma, the most common eye cancer in adults, has a significant risk of metastasis, with up to 50% of patients developing metastases within 15 years after treatment of the primary tumor.

Current systemic therapies for uveal melanoma have limited efficacy, but ongoing research is exploring new candidate drugs, including bortezomib and MEK inhibitors, to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New therapeutic agents in uveal melanoma. Velho, TR., Kapiteijn, E., Jager, MJ.[2012]

Nivolumab, a monoclonal antibody targeting the programmed death receptor-1, has shown promising efficacy in treating advanced malignant melanoma, with nearly 25% of patients achieving a partial tumor response in a phase II trial involving previously treated stage III/IV patients.

The treatment demonstrated a durable clinical benefit, with a median progression-free survival of 172 days and an acceptable safety profile, as less than 18% of patients experienced severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: a review of its use in patients with malignant melanoma. Deeks, ED.[2021]

A rare case of panuveitis occurred in a patient receiving Nivolumab and Ipilimumab for recurrent Small Cell Lung Cancer, highlighting the potential for serious immune-related ocular toxicities from checkpoint inhibitors.

The patient successfully managed the panuveitis with an Ozurdex injection, leading to resolution of inflammation and improved vision, allowing her to continue Nivolumab treatment without recurrence of the eye condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Panuveitis in patient on ipilimumab/nivolumab combination for small-cell lung cancer treated with an intravitreal dexamethasone implant. L Hefler, J., M Bailey, L., El Rahi, C., et al.[2021]

In a phase II trial involving 52 patients with metastatic uveal melanoma, the combination of nivolumab and ipilimumab resulted in a 12-month overall survival rate of 51.9%, indicating a modest improvement compared to historical chemotherapy benchmarks.

The treatment demonstrated a manageable safety profile, with stable disease being the most common outcome (51.9%), and the median overall survival was 12.7 months, suggesting that this combination therapy could be a viable first-line option for patients not eligible for liver resection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Plus Ipilimumab for Treatment-Naïve Metastatic Uveal Melanoma: An Open-Label, Multicenter, Phase II Trial by the Spanish Multidisciplinary Melanoma Group (GEM-1402). Piulats, JM., Espinosa, E., de la Cruz Merino, L., et al.[2021]

In a study of 64 patients with metastatic uveal melanoma treated with a combination of CTLA-4 and PD-1 inhibitors, the overall response rate was 15.6%, with a median overall survival of 16.1 months, indicating that this combination therapy may be the most effective option currently available for this difficult-to-treat cancer.

Despite a significant number of patients experiencing severe treatment-related adverse events (39.1%), the tolerability of this combined therapy appears to be better than that seen in trials for cutaneous melanoma, suggesting a potentially safer profile for patients with uveal melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined immune checkpoint blockade for metastatic uveal melanoma: a retrospective, multi-center study. Heppt, MV., Amaral, T., Kähler, KC., et al.[2023]

Nivolumab plus relatlimab is a combination immunotherapy that targets immune checkpoints, specifically PD-1 and LAG-3, and has been approved for treating unresectable or metastatic melanoma in adults and adolescents weighing at least 40 kg.

This combination therapy represents a significant advancement in cancer treatment, as it utilizes two different mechanisms to enhance the immune response against cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Plus Relatlimab: First Approval. Paik, J.[2022]

In a nationwide study of patients with metastatic uveal melanoma (UM), the introduction of immune checkpoint inhibitors (ICI) as first-line treatment significantly improved overall survival rates, increasing from 25.0% to 41.9% one year after treatment.

Despite relatively low response rates (7% for anti-PD-1 monotherapy and 21% for combined therapy), median overall survival improved from 7.8 months to 10.0 months, indicating that ICI therapy offers a meaningful benefit for patients with metastatic UM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Impact of Immune Checkpoint Inhibitors in Metastatic Uveal Melanoma. Bol, KF., Ellebaek, E., Hoejberg, L., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10164023/

The Latest Option: Nivolumab and Relatlimab in Advanced ... This article reports the updated survival data of the combination of relatlimab plus nivolumab in untreated patients with advanced melanoma. 34. Grob JJ ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2109970

Relatlimab and Nivolumab versus Nivolumab in Untreated ... The combination of relatlimab and nivolumab, a PD-1 inhibitor, showed antitumor activity, including durable objective responses in patients with melanoma that ...

3. opdualaghcp.com opdualaghcp.com/efficacy/melanoma/relativity-047

Efficacy | Opdualag® (nivolumab and relatlimab-rmbw) for HCPs ... OPDIVO. 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.

4. news.bms.com news.bms.com/news/details/2025/Bristol-Myers-Squibb-Provides-Update-on-Phase-3-RELATIVITY-098-Trial/default.aspx

Bristol Myers Squibb Provides Update on Phase 3 ... RELATIVITY-098 is a randomized Phase 3, double-blind study evaluating adjuvant immunotherapy with Opdualag, the fixed-dose combination of nivolumab and ...

5. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK602507/

Nivolumab and Relatlimab (Opdualag) - NCBI Bookshelf - NIH CADTH recommends that Opdualag be reimbursed for the treatment of adult and pediatric patients 12 years of age or older with unresectable or metastatic melanoma ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK604840/

Clinical Review - Nivolumab and Relatlimab (Opdualag) - NCBI Safety data reported in this review were based on a median follow-up of 25.3 months. Efficacy Results. Based on the final analysis after a median follow-up of ...

7. opdualaghcp.com opdualaghcp.com/safety/melanoma/relativity-047

Safety Profile - Opdualag® (nivolumab and relatlimab-rmbw) Adverse reactions occurring in ≥15% of patients in the Opdualag or nivolumab monotherapy arm1. No new or unexpected safety events with 4-year data3.

8. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02713-3/fulltext

1126P A phase II study of nivolumab/relatlimab in ... 1126P A phase II study of nivolumab/relatlimab in metastatic uveal melanoma ... Nivolumab + relatlimab is safe but is associated with a low response rate in MUM.