What side effects are associated with this type of intervention?

Common treatments for uveal melanoma, particularly those involving PD-1 inhibitors like Cemiplimab and VEGF inhibitors like Ziv-Aflibercept, are associated with a range of side effects. PD-1 inhibitors can lead to immune-related adverse events such as fatigue, rash, diarrhea, and various endocrinopathies. VEGF inhibitors often cause hypertension, proteinuria, and gastrointestinal perforations. Patients undergoing these treatments should be closely monitored for these potential side effects.

What prior FDA approvals exist?

Uveal melanoma has limited FDA-approved treatments, particularly in the context of immunotherapy and anti-VEGF therapies. While there are no specific FDA approvals for the combination of a PD-1 inhibitor like Cemiplimab and a VEGF inhibitor like Ziv-Aflibercept for uveal melanoma, similar drugs have been explored in clinical trials. Immunotherapy agents such as pembrolizumab (another PD-1 inhibitor) have shown promise in treating various cancers, including melanoma. VEGF inhibitors like bevacizumab have also been used in ocular conditions, though not specifically approved for uveal melanoma. The combination of these therapeutic classes is being actively studied to improve outcomes in metastatic uveal melanoma.

What other types of research exist?

Promising novel alternatives for Uveal Melanoma treatment in 2024 may include combination therapies involving other immune checkpoint inhibitors like Pembrolizumab or Nivolumab, potentially paired with novel VEGF inhibitors or other angiogenesis inhibitors. Additionally, emerging therapies targeting different pathways, such as HIF-2 inhibitors or bispecific antibodies targeting multiple angiogenic pathways, could also be considered.

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Checkpoint Inhibitor

Cemiplimab + Ziv-Aflibercept for Uveal Melanoma

Phase 2

Recruiting

Led By Ahmad Tarhini, MD, PHD

Research Sponsored by H. Lee Moffitt Cancer Center and Research Institute

Eligibility Criteria Checklist

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

Must have

Patients must have ECOG performance status of 0-1

Patients must have metastatic uveal melanoma, either initial presentation or recurrent, that is histologically diagnosed

Must not have

Exclusion from this study also includes patients with a history of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, Sjögren's syndrome, autoimmune vasculitis [e.g., Wegener's granulomatosis]); motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre Syndrome and Myasthenia Gravis); other central nervous system autoimmune disease (e.g., poliomyelitis, Multiple sclerosis)

Patients who have permanently discontinued anti-cancer immune modulating therapies due to drug related toxicity

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of two drugs, Cemiplimab and Ziv-Aflibercept, to treat patients with metastatic uveal melanoma. Cemiplimab helps the immune system fight cancer, while Ziv-Aflibercept stops tumors from getting the blood they need to grow. The goal is to see if this combination can shrink or stop the growth of tumors.

Who is the study for?

Adults with metastatic uveal melanoma can join this trial. They should have a life expectancy over 3 months, an ECOG performance status of 0-1 (fully active or restricted in physically strenuous activity but ambulatory), measurable disease, and normal organ/marrow function. Women must use effective contraception, as must men who agree to use condoms. Prior treatments for melanoma are allowed except for bevacizumab, aflibercept, or cemiplimab.

What is being tested?

The study is testing the safety and effectiveness of combining Cemiplimab with Ziv-Aflibercept to see if they can shrink tumors or halt their growth in patients with metastatic uveal melanoma.

What are the potential side effects?

Potential side effects may include immune-related reactions that could affect various organs, infusion-related symptoms like fever or chills during drug administration, fatigue, digestive issues such as diarrhea or constipation, skin reactions at injection sites and increased risk of infections.

Eligibility Criteria

Inclusion Criteria

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

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I am fully active or can carry out light work.

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I have been diagnosed with metastatic uveal melanoma.

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My organ and bone marrow functions are normal.

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My heart's pumping ability is within the normal range according to my recent echocardiogram.

Exclusion Criteria

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

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I do not have any autoimmune diseases like rheumatoid arthritis or multiple sclerosis.

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I stopped taking cancer immunotherapy because of its side effects.

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I have had lung inflammation due to immune response in the last 5 years.

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I have autoimmune thyroid disease or type 1 diabetes and am on replacement therapy.

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I am not currently on IV antibiotics for an infection.

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I have a serious or non-healing wound, ulcer, or bone fracture.

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My blood clotting time is longer than normal, but I am on warfarin.

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I had major surgery over 4 weeks ago and have fully recovered without any significant infections.

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I have never had inflammatory bowel disease or diverticulitis.

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I have a serious heart or brain blood vessel condition.

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I have a history of serious bleeding related to my tumor or a bleeding disorder.

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I haven't had encephalitis, meningitis, or uncontrolled seizures in the last year.

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I am willing to use effective birth control during and after the study for the required time.

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I have had a stem cell transplant from a donor or myself.

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My heart is healthy with no recent major issues.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 5 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

objective response rate (ORR)

Secondary study objectives

Overall survival (OS)

Progression free survival (PFS)

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Cemiplimab + Ziv-AfliberceptExperimental Treatment2 Interventions

One cycle consists of 3 weeks during which: Cemiplimab 350 mg administered IV every 3 weeks given with Ziv-Aflibercept 4 mg/kg administered IV every 2 weeks.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cemiplimab

2015

Completed Phase 3

~1470

0 / 19Eligibility 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

Cemiplimab, a PD-1 inhibitor, works by blocking the PD-1 pathway, thereby activating T-cells to recognize and attack cancer cells. Ziv-Aflibercept, a VEGF inhibitor, targets VEGF to reduce the blood supply to the tumor, inhibiting its growth. These mechanisms are crucial for Uveal Melanoma patients as they address immune evasion and tumor angiogenesis, two key processes that allow the cancer to grow and spread.

Real-world cost-effectiveness of anti-VEGF monotherapy and combination therapy for the treatment of polypoidal choroidal vasculopathy.Switching to aflibercept versus continuing bevacizumab for treatment-resistant neovascular age-related macular degeneration: a one-year comparative observational study.Month 24 Outcomes After Treatment Initiation With Anti-Vascular Endothelial Growth Factor Therapy for Macular Edema Due to Central Retinal or Hemiretinal Vein Occlusion: SCORE2 Report 10: A Secondary Analysis of the SCORE2 Randomized Clinical Trial.