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

27 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a combination of two drugs, nivolumab and relatlimab, to see if they can shrink tumors in patients with metastatic uveal melanoma. These patients have a type of eye cancer that has spread and haven't received certain immune therapies before. The drugs work by helping the immune system better recognize and attack the cancer cells. Nivolumab is an immune checkpoint inhibitor that targets PD-1 and has been approved for use in multiple cancers, including melanoma.

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.

What data supports the effectiveness of the drug Nivolumab + Relatlimab for Uveal Melanoma?

Research shows that immune checkpoint inhibitors, like Nivolumab, have improved survival rates in patients with metastatic uveal melanoma, even though the response rates are lower compared to other types of melanoma. The introduction of these drugs has increased the one-year overall survival rate from 25% to 41.9%. ^{1 2 3 4 5}

Is the combination of Nivolumab and Relatlimab safe for humans?

Nivolumab, used in combination with other drugs, has been associated with rare but serious eye-related side effects, such as uveitis (eye inflammation), which can affect vision. These side effects require prompt medical attention and can be managed with treatments like steroid therapy. ^{2 6 7 8 9}

How is the drug Nivolumab + Relatlimab unique for treating uveal melanoma?

Nivolumab + Relatlimab is unique because it combines two immunotherapy drugs that target different immune checkpoints, PD-1 and LAG-3, potentially offering a novel approach for treating uveal melanoma, a cancer with limited effective treatments. ^{2 3 10 11 12}

Research Team

Jose Lutzky, MD

Principal Investigator

University of Miami

Eligibility Criteria

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

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 have had myocarditis in the past.

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Clinical activity and safety of Pembrolizumab in Ipilimumab pre-treated patients with uveal melanoma. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Combined immune checkpoint blockade for metastatic uveal melanoma: a retrospective, multi-center study. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Anti-PD-1 antibodies in metastatic uveal melanoma: a treatment option? [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Response to Anti-PD-1 in Uveal Melanoma Without High-Volume Liver Metastasis. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Real-World Impact of Immune Checkpoint Inhibitors in Metastatic Uveal Melanoma. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Clinical outcomes in metastatic uveal melanoma treated with PD-1 and PD-L1 antibodies. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Panuveitis in patient on ipilimumab/nivolumab combination for small-cell lung cancer treated with an intravitreal dexamethasone implant. [2021]

8. Greece pubmed.ncbi.nlm.nih.gov

New therapeutic agents in uveal melanoma. [2012]

9. United States pubmed.ncbi.nlm.nih.gov

Unilateral Posterior Uveitis in a Patient Receiving Nivolumab for Malignant Melanoma. [2023]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Nivolumab Plus Relatlimab: First Approval. [2022]

11. United States 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). [2021]

12. New Zealand pubmed.ncbi.nlm.nih.gov

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