Study of Cemiplimab Plus Ziv-Aflibercept for Subjects With Metastatic Uveal Melanoma

NCT06121180 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: MCC-21341R2810-ONC-2128
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 4

Brief 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. 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

Outcome Measures

Primary Outcomes (1)

• 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.

  5 years

Secondary Outcomes (2)

• Progression free survival (PFS)

  5 years

• Overall survival (OS)

  5 years

Study Arms (1)

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.

Drug: ZIV-Aflibercept; Drug: Cemiplimab

Interventions

ZIV-Aflibercept DRUG

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.

Also known as: Zaltrap, Eylea

Cemiplimab + Ziv-Aflibercept

Cemiplimab DRUG

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.

Also known as: Libtayo

Cemiplimab + Ziv-Aflibercept

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• Genzyme, a Sanofi Company: collaborator
• H. Lee Moffitt Cancer Center and Research Institute: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (4)

The Angeles Clinic and Research Institute

Los Angeles, California, 90025, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

RECRUITING

Northwell Health Center for Advanced Medicine

New Hyde Park, New York, 11042, United States

RECRUITING

Related Links

• Moffitt Cancer Center Clinical Trials Website

MeSH Terms

Conditions

Uveal Melanoma

Interventions

aflibercept; cemiplimab

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases

Study Officials

• Ahmad Tarhini, MD, PHD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Indra Herron

CONTACT

813-745-4482; Indra.Herron@moffitt.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2023
• First Posted: November 7, 2023
• Study Start: November 4, 2024
• Primary Completion (Estimated): October 31, 2030
• Study Completion (Estimated): October 31, 2030
• Last Updated: December 4, 2025

Record last verified: 2025-12

Locations

US (4)