Metastatic Uveal MelanomaPhase 2NCT06121180
Study of Cemiplimab Plus Ziv-Aflibercept for Subjects With Metastatic Uveal Melanoma
A Phase 2 study testing ZIV-Aflibercept and Cemiplimab in people with Metastatic Uveal Melanoma, run by H. Lee Moffitt Cancer Center and Research Institute at 4 sites in United States.
Trial summary
The goal of this clinical research study is to find out if Cemiplimab plus Ziv-Aflibercept is safe and effective in treating your condition of metastatic (spread to other parts of your body) uveal melanoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Uveal Melanoma
- What is being tested?
- ZIV-Aflibercept and Cemiplimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 4 sitesUnited States
- Study dates
- 4 Nov 2024to 31 Oct 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of signed and dated informed consent form.
- Male or female, aged >/= 18 years old.
- Life expectancy of greater than 3 months in the opinion of the investigator.
- Must be willing and able to provide informed consent signed by study patient or legally acceptable representative, as specified by health authorities and institutional guidelines.
- Patients must have metastatic uveal melanoma, either initial presentation or recurrent, that is histologically diagnosed.
- Patients with histologically or cytologically confirmed metastatic melanoma or cutaneous, mucosal or unknown primary origin are also eligible. This includes AJCC stage IV or advanced/inoperable stage III. This also includes patients with a history of lower stage melanoma and subsequent recurrent metastatic disease that is either locally/regionally advanced/inoperable disease or distant metastases. These patients must have previously received anti-PD1 immunotherapy (nivolumab or pembrolizumab) as monotherapy or in combination and later experienced disease progression. Patients with BRAF V600 mutant melanoma must have previously received BRAF targeted therapy for metastatic melanoma and later experienced disease progression. Patients who refuse or decline to receive BRAF targeted therapy or prefer to delay or were intolerant of BRAF targeted therapy are eligible
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- Patients must have ECOG performance status of 0-1.
- Patients must have measurable disease, according to RECIST version 1.1.
- Patients must have normal organ and marrow function as defined in protocol.
- Urine protein should be screened by urinalysis for Urine Protein Creatinine Ratio (UPCR). For UPCR > 1, a 24-hour urine protein should be obtained, and the level should be <500 mg.
- An echocardiogram should be performed at baseline in all patients. Ejection fraction (EF) from baseline echocardiogram must be within the institutional limits of normal as determined by the reading cardiologist.
- Patients on full-dose anticoagulants (e.g., warfarin) with PT INR >1.5 are eligible provided that both of the following criteria are met:
- The patient has an in-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin.
- The patient has no active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices).
- A patient may be treatment naïve. However, prior systemic treatments for metastatic uveal melanoma are allowed. There is no limit on the number of prior regimens for metastatic uveal melanoma. However, no prior therapy with bevacizumab, aflibercept or cemiplimab.
- Patients must be free of active brain metastasis by contrast-enhanced CT/MRI scans within 4 weeks prior to enrollment. If known to have prior brain metastases, these must have been adequately managed with standard of care radiation therapy, stereotactic radiosurgery or surgery prior to registration on the study.
- For Women of childbearing potential: use of highly effective contraception for at least 2 or more menstrual cycles prior to screening and agreement to use such a method during study participation and for at least 180 days after the end of study drugs administration.
- For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner For at least 1 month prior to screening and agreement to use such a method during study participation and for at least 180 days after the end of study drugs administration.
Who cannot join
- Pregnancy or lactation.
- Treatment with another investigational drug or other systemic intervention for uveal melanoma within 4 weeks of initiation of study drugs. Patients must not have radiotherapy within the preceding 4 weeks.
- Patients must have recovered from adverse events due to agents administered more than 4 weeks earlier.
- Patients must be at least 4 weeks from major surgery and have fully recovered from any effects of surgery and be free of significant detectable infection.
- Patients must not have autoimmune disorders or conditions of immunosuppression that require current ongoing treatment with systemic corticosteroids (or other systemic immunosuppressants), including oral steroids (i.e., prednisone, dexamethasone) or continuous use of topical steroid creams or ointments or ophthalmologic steroids. A history of occasional (but not continuous) use of steroid inhalers is allowed.
- Replacement doses of steroids for patients with adrenal insufficiency are allowed. Patients who discontinue use of these classes of medication for at least 2 weeks prior to enrollment are eligible if, in the judgment of the treating physician investigator, the patient is not likely to require resumption of treatment with these classes of drugs during the study.
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- 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).
- Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of cemiplimab/placebo. NOTE: Patients who require brief course of steroids (eg, prophylaxis for imaging assessments due to hypersensitivity to contrast agents) are not excluded. People taking steroids for physiologic replacement (ie, adrenal insufficiency) are NOT excluded.
- Prior allogeneic stem cell transplantation, or autologous stem cell transplantation.
- Patients who have permanently discontinued anti-cancer immune modulating therapies due to drug related toxicity.
- Encephalitis, meningitis, or uncontrolled seizures in the year prior to screening/enrollment.
- History of immune related pneumonitis within the last 5 years.
- History of interstitial lung disease (eg, idiopathic pulmonary fibrosis, organizing pneumonia) or active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management. A history of radiation pneumonitis in the radiation field is permitted as long as pneumonitis resolved ≥6 months prior to the enrollment date.
- Patients with a history of solid organ transplant (patients with prior corneal transplant(s) are not excluded).
- Patients with autoimmune hypothyroid disease or type I diabetes on replacement treatment are eligible.
- Patients must not have a history of inflammatory bowel disease or diverticulitis (history of diverticulosis is allowed).
- Patients must not have other significant medical, surgical, or psychiatric conditions or require any medication or treatment that in the opinion of the investigator may interfere with compliance, make the administration of cemiplimab hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea.
- Patients must not have an active infection requiring current treatment with parenteral antibiotics.
- Cardiac: No evidence of congestive heart failure, symptoms of coronary artery disease, myocardial infarction less than 6 months prior to entry, serious cardiac arrhythmias, or unstable angina.
- Central nervous system: No history of cerebrovascular accident or transient ischemic attacks within the past 6 months.
- Serious or non-healing wound, ulcer, or bone fracture.
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks of initiating study treatment.
- Patients with the following invasive procedures:
- Major surgical procedure, open biopsy or significant traumatic injury within 4 weeks of Day 1 of study therapy.
- Anticipation of need for major surgical procedures during the course of the study.
- Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to Day 1 of study therapy. Central venous catheter placements are permitted to be completed 7 or more days prior to Day 1 of study therapy. However, peripherally inserted central catheter (PICC or PIC line) may be placed at any time prior to or during study therapy.
- Patients with clinically significant cardiovascular or cerebrovascular disease:
- History of cerebrovascular accident or transient ischemic attack within past 6 months
- Uncontrolled hypertension, defined as blood pressure >150/100 mm Hg or systolic BP >180 mm Hg if diastolic blood pressure <90 mm Hg, on at least 2 repeated determinations on separate days within past 3 months.
- Myocardial infarction, coronary artery bypass grafting (CABG) or unstable angina within the past 6 Months.
- New York Heart Association grade III or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris within past 6 months.
- Clinically significant peripheral vascular disease within past 6 months.
- Pulmonary embolism, deep vein thrombosis (DVT), or other thromboembolic event within past 6 months.
- History of tumor-related or other serious hemorrhage, bleeding diathesis, or underlying coagulopathy.
- PT INR >1.5 unless the patient is on full-dose warfarin.
- Patients who have other current malignancies are not eligible. Patients with other malignancies are eligible if they have been continuously disease free for > 3 years prior to the time of enrollment. Patients with prior history at any time of any in situ cancer, lobular carcinoma of the breast in situ, cervical cancer in situ, atypical melanocytic hyperplasia or melanoma in situ are eligible. Patients with prior history of basal or squamous skin cancer are eligible. Patients who have had multiple primary melanomas are eligible.
- Receipt of a live vaccine within 28 days of the enrollment date.
- Women of childbearing potential or sexually active men, who are unwilling to practice highly effective contraception for at least 2 or more menstrual cycles (women) or 1 month (men) prior to screening, during the study, and for at least 180 days after the last dose of study drug(s).
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States4 sites, 4 recruiting
- Recruiting
University of Chicago Medical Center
Chicago, Illinois, 60637
Daniel Olson, MD
- Recruiting
The Angeles Clinic and Research Institute
Los Angeles, California, 90025
Inderjit Mehmi, MD
- Recruiting
Northwell Health Center for Advanced Medicine
New Hyde Park, New York, 11042
Shaheer Khan, DO
- Recruiting
Moffitt Cancer Center
Tampa, Florida, 33612
Indra Herron, 813-745-4482, Indra.Herron@moffitt.org
Ahmad Tarhini, MD, PHD
About this study
Official title: A Phase II Study of Cemiplimab Plus Ziv-Aflibercept for Subjects With Metastatic Uveal Melanoma
The goal of this clinical research study is to find out if Cemiplimab plus Ziv-Aflibercept is safe and effective in treating your condition of metastatic (spread to other parts of your body) uveal melanoma. This research study will test the study drugs to see if the combination of Cemiplimab plus Ziv-Aflibercept can make tumors shrink or stop growing.
- Conditions
- Metastatic Uveal Melanoma
- Being tested
- ZIV-Aflibercept, Cemiplimab
- Medical subject headings
- Uveal Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZIV-AfliberceptDrug
Also called Zaltrap, Eylea
Ziv-Aflibercept is an investigational or experimental anti-cancer agent inactivates vascular endothelial growth factor (VEGF) from functioning and scientific experiments have shown that when VEGF is prevented from working, new blood vessels don't form in tumors and these tumors do not grow. In addition, VEGF has been shown to have a negative effect on the immune response and blocking it may help the immune response against cancer.
CemiplimabDrug
Also called Libtayo
Cemiplimab is a human monoclonal anti-PD-1 antibody that works by blocking the programmed death-1 (PD-1), a cell receptor on immune cells that is involved in preventing immune cells from destroying other cells.
Blocking the receptor is expected to help immune cells attack cancer cells.
| Study group | Role | What they receive |
|---|---|---|
| Cemiplimab + Ziv-Aflibercept | Experimental | 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. Receives: Drug: ZIV-Aflibercept; Drug: Cemiplimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
objective response rate (ORR)
objective response rate as defined by Complete response (CR) plus partial response (PR) as assessed by RECIST criteria version 1.1.
Measured: 5 years
Secondary outcomes (2)
Progression free survival (PFS)
Progression free survival (PFS) will be measured from the initial date of treatment to the date of documented progression, or the date of death (in the absence of progression).
Measured: 5 years
Overall survival (OS)
Overall survival (OS) will be measured from the initial date of treatment to the recorded date of death.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2023
- Study start4 Nov 2024
- Primary completion31 Oct 2030 (estimated)
- Study completion31 Oct 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Uveal MelanomaStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Genzyme, a Sanofi Company, Regeneron Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Ahmad Tarhini, MD, PHD, Principal investigator, Moffitt Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06121180
- Sponsor's protocol ID
- MCC-21341
- Other IDs
- R2810-ONC-2128
- Status last verified
- Dec 2025
- First submitted
- 2 Nov 2023
- Last updated
- 4 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Cemiplimab Plus Ziv-Aflibercept for Subjects With Metastatic Uveal Melanoma
- ClinicalTrials.gov ID
- NCT06121180
- Acronym / sponsor ID
- MCC-21341
- Conditions
- Metastatic Uveal Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Genzyme, a Sanofi Company, Regeneron Pharmaceuticals
- Study start
- 4 Nov 2024 (actual)
- Primary completion
- 31 Oct 2030 (estimated)
- Study completion
- 31 Oct 2030 (estimated)
- First posted
- 7 Nov 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical research study is to find out if Cemiplimab plus Ziv-Aflibercept is safe and effective in treating your condition of metastatic (spread to other parts of your body) uveal melanoma. This research study will test the study drugs to see if the combination of Cemiplimab plus Ziv-Aflibercept can make tumors shrink or stop growing.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cemiplimab + Ziv-Aflibercept | Experimental | Drug: ZIV-Aflibercept, Drug: CemiplimabOne 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Provision of signed and dated informed consent form.
- Male or female, aged >/= 18 years old.
- Life expectancy of greater than 3 months in the opinion of the investigator.
- Must be willing and able to provide informed consent signed by study patient or legally acceptable representative, as specified by health authorities and institutional guidelines.
- Patients must have metastatic uveal melanoma, either initial presentation or recurrent, that is histologically diagnosed.
Key exclusion criteria (38 listed)
- Pregnancy or lactation.
- Treatment with another investigational drug or other systemic intervention for uveal melanoma within 4 weeks of initiation of study drugs. Patients must not have radiotherapy within the preceding 4 weeks.
- Patients must have recovered from adverse events due to agents administered more than 4 weeks earlier.
- Patients must be at least 4 weeks from major surgery and have fully recovered from any effects of surgery and be free of significant detectable infection.
- Patients must not have autoimmune disorders or conditions of immunosuppression that require current ongoing treatment with systemic corticosteroids (or other systemic immunosuppressants), including oral steroids (i.e., prednisone, dexamethasone) or continuous use of topical steroid creams or ointments or ophthalmologic steroids. A history of occasional (but not continuous) use of steroid inhalers is allowed.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZIV-AfliberceptAlso: Zaltrap, EyleaZiv-Aflibercept is an investigational or experimental anti-cancer agent inactivates vascular endothelial growth factor (VEGF) from functioning and scientific experiments have shown that when VEGF is prevented from working, new blood vessels don't form in tumors and these tumors do not grow. In addition, VEGF has been shown to have a negative effect on the immune response and blocking it may help the immune response against cancer. | Drug | Cemiplimab + Ziv-Aflibercept |
| CemiplimabAlso: LibtayoCemiplimab is a human monoclonal anti-PD-1 antibody that works by blocking the programmed death-1 (PD-1), a cell receptor on immune cells that is involved in preventing immune cells from destroying other cells. Blocking the receptor is expected to help immune cells attack cancer cells. | Drug | Cemiplimab + Ziv-Aflibercept |
Primary outcome
objective response rate (ORR)
Time frame: 5 years
objective response rate as defined by Complete response (CR) plus partial response (PR) as assessed by RECIST criteria version 1.1.
2 secondary outcomes
Progression free survival (PFS)
Time frame: 5 years
Overall survival (OS)
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2025.
- Individual participant dataSharing planned: Undecided
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Immune Response to Percutaneous Hepatic Perfusion With Melphalan for Ocular Melanoma Metastatic to the Liver
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Sunitinib Malate or Valproic Acid in Preventing Metastasis in Patients With High-Risk Uveal Melanoma
Ciliary Body and Choroid Melanoma, Medium/Large Size, Ciliary Body and Choroid Melanoma, Small Size
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Safety and Efficacy Study in Adults With Advanced Solid Tumors Receiving REGN13089-M404-M2980, an Antibody-drug Conjugate That Targets MET Protein on Tumors
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Different Doses of BI-1607 in Combination With Pembrolizumab and Ipilimumab, in Participants With Unresectable or Metastatic Melanoma
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ahmad Tarhini, MD, PHD principal investigator
Moffitt Cancer Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ZIV-Aflibercept and Cemiplimab in people with Metastatic Uveal Melanoma, run by H. Lee Moffitt Cancer Center and Research Institute at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Indra Herron (813-745-4482, Indra.Herron@moffitt.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
objective response rate (ORR) (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2025.