Cemiplimab + Ziv-Aflibercept for Uveal Melanoma
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
Must not be taking: Corticosteroids, Immunosuppressants
Disqualifiers: Pregnancy, Autoimmune disorders, Heart disease, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?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.
Do I need to stop my current medications for the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on systemic corticosteroids or other immunosuppressants, and you must not have had another investigational drug or systemic intervention for uveal melanoma within 4 weeks of starting the study drugs.
What data supports the effectiveness of the drug combination Cemiplimab and Ziv-Aflibercept for uveal melanoma?
The research does not provide direct evidence for the effectiveness of Cemiplimab and Ziv-Aflibercept in treating uveal melanoma. However, it mentions that new therapies are being developed for uveal melanoma, and the use of immune system-targeting treatments like tebentafusp has shown some success in improving survival.
12345Is the combination of Cemiplimab and Ziv-Aflibercept safe for humans?
Ziv-Aflibercept has been studied for safety in eye conditions, showing it is generally safe when injected into the eye for conditions like age-related macular degeneration and retinal diseases. However, this information is specific to eye treatments and may not fully apply to other uses or combinations with Cemiplimab.
678910What makes the drug combination of Cemiplimab and Ziv-Aflibercept unique for treating uveal melanoma?
This drug combination is unique because it combines Cemiplimab, an immune checkpoint inhibitor, with Ziv-Aflibercept, a VEGF inhibitor, to target both the immune system and blood vessel growth in uveal melanoma, a cancer that typically responds poorly to immune therapies alone.
2681112Eligibility Criteria
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.Inclusion Criteria
Patients must have a disease that can be measured using specific guidelines.
I am fully active or can carry out light work.
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
+12 more
Exclusion Criteria
You have had a solid organ transplant, except for corneal transplants.
I have had lung inflammation due to immune response in the last 5 years.
I have undergone invasive medical procedures.
+25 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive Cemiplimab 350 mg IV every 3 weeks and Ziv-Aflibercept 4 mg/kg IV every 2 weeks for metastatic uveal melanoma
3 weeks per cycle
1 visit every 2 weeks (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
5 years
Participant Groups
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.
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.
Cemiplimab is already approved in European Union, United States, Canada, Brazil for the following indications:
🇪🇺 Approved in European Union as Libtayo for:
- Cutaneous squamous cell carcinoma (CSCC)
- Non-small cell lung cancer (NSCLC)
🇺🇸 Approved in United States as Libtayo for:
- Cutaneous squamous cell carcinoma (CSCC)
- Basal cell carcinoma (BCC)
- Non-small cell lung cancer (NSCLC)
🇨🇦 Approved in Canada as Libtayo for:
- Cutaneous squamous cell carcinoma (CSCC)
- Non-small cell lung cancer (NSCLC)
🇧🇷 Approved in Brazil as Libtayo for:
- Cutaneous squamous cell carcinoma (CSCC)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Moffitt Cancer CenterTampa, FL
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Who Is Running the Clinical Trial?
H. Lee Moffitt Cancer Center and Research InstituteLead Sponsor
Regeneron PharmaceuticalsIndustry Sponsor
Genzyme, a Sanofi CompanyIndustry Sponsor
References
Combined immune checkpoint blockade for metastatic uveal melanoma: a retrospective, multi-center study. [2023]Uveal melanoma (UM) is highly refractory to treatment with dismal prognosis in advanced stages. The value of the combined checkpoint blockade with CTLA-4 and PD-1 inhibition in metastatic UM is currently unclear.
Review of bi-specific therapies in uveal melanoma. [2023]Uveal melanoma is a rare subtype of melanoma that once metastatic portends a poor prognosis. Likely due to the distinct differences in biology, metastatic potential, and immunologic profile as compared to cutaneous melanoma, uveal melanoma's response to immune checkpoint inhibition has been disappointing. Bi-specific fusion protein therapies (T cell engagers) are a novel strategy to forcibly bridge the immune system with a target on a cancer cell. This approach has been explored in a number of cancer types and has recently demonstrated success in uveal melanoma. Tebentafusp, a first in class ImmTAC (Immune-mobilizing monoclonal TCRs against cancer), has now shown an overall survival benefit when compared to investigator's choice. This review aims to summarize the experience with this first in class bi-specific T cell engager as well as highlight bi-specifics as a novel treatment strategy in uveal melanoma.
Adjuvant Therapy of Uveal Melanoma: Current Status. [2022]The survival of patients with uveal melanoma remains poor because of the development of metastatic disease. Adjuvant therapy after treatment of the primary tumor has been tested but has not been shown to prevent the development of metastasis. Several new approaches are being developed. Cytotoxic and immunotherapeutic regimens are being more rationally applied using tumor genetic criteria to better identify patients at risk. Trials in the adjuvant setting of novel immunotherapeutic and targeted agents active in the metastatic setting are being developed, as are approaches to promote cellular differentiation and dormancy. The rarity and biology of uveal melanoma present challenges. Participation in well-designed, scientifically sound clinical trials is critical.
New therapeutic agents in uveal melanoma. [2012]Uveal melanoma is the most common primary intraocular malignant tumour in adults. Five, ten and fifteen years after primary tumour treatment, up to 25%, 34% and 50% of patients may develop metastases, respectively. There are only a few systemic therapies that have been approved for uveal melanoma, all with doubtful efficacy. As the molecular knowledge over cancer has improved, new therapies are being developed. Several drugs, such as bortezomib, celecoxib, dacarbazine, anti-angiogenic agents (such as bevacizumab, sorafenib and sunitinib), temsirolimus, mitogen-activated protein kinase kinase (MEK) inhibitors, ipilimumab and AEB071 are candidate drugs, and studies are underway to determine the therapeutic effects of these drugs in uveal melanoma.
Is tebentafusp superior to combined immune checkpoint blockade and other systemic treatments in metastatic uveal melanoma? A comparative efficacy analysis with population adjustment. [2023]Distinct systemic treatments exist for metastatic uveal melanoma. Tebentafusp and combined immune checkpoint blockade (ICB) with ipilimumab plus anti-PD-1 antibodies are the most commonly used treatment options but their comparative efficacy is unclear. The aim of this study is to compare currently available systemic treatments regarding overall survival (OS) and progression-free survival (PFS) with a focus on the comparison of tebentafusp versus combined ICB.
SHORT-TERM SAFETY PROFILE OF INTRAVITREAL ZIV-AFLIBERCEPT. [2022]To evaluate the safety of intravitreal ziv-aflibercept (Zaltrap) in the treatment choroidal neovascularization secondary to age-related macular degeneration.
Long-term safety and efficacy of ziv-aflibercept in retinal diseases. [2022]To investigate the long-term safety of intravitreal ziv-aflibercept in eyes receiving six or more intravitreal injections of ziv-aflibercept, an off-label substitute to the approved aflibercept.
Ziv-aflibercept: A cost-effective, off-label, highly potent antagonist of vascular endothelial growth factor. [2023]Ziv-aflibercept (Zaltrap® ), a recombinant fusion protein that binds diffusible vascular endothelial growth factor (VEGF), is approved for the treatment of metastatic colorectal carcinoma. Its molecular structure is the same as aflibercept (Eylea® ), thus making it an attractive option for the off-label treatment of chorioretinal vascular conditions. Ziv-aflibercept is distributed in 4 and 8 ml vials for intravenous use, and its cost after compounding is similar to bevacizumab. Studies with retinal pigment epithelium cytotoxicity, animal histologic sections and electroretinography have demonstrated its safety, and mathematical modelling combined with over four dozen clinical publications from different ophthalmic centres throughout the world attest to its efficacy. No appreciable differences in visual or anatomic outcomes between 1.25 mg (0.05 ml) and 2.5 mg (1.0 ml) doses have been noted. The long duration of action combined with the low cost make ziv-aflibercept an attractive anti-VEGF treatment option, especially in low- and middle-income countries where its popularity is increasing.
SHORT-TERM SAFETY OF 2 MG INTRAVITREAL ZIV-AFLIBERCEPT. [2022]To evaluate the safety of single intravitreal 2 mg ziv-aflibercept (0.08 mL) injections for the treatment of choroidal neovascular membranes (CNVM).
One-year outcomes of ziv-aflibercept for macular edema in central retinal vein occlusion. [2022]To report the 12-month efficacy and safety outcomes of intravitreal ziv-aflibercept in macular edema secondary to central retinal vein occlusion (CRVO).
Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. [2022]Uveal melanoma is a disease that is distinct from cutaneous melanoma, with a low tumor mutational burden and a 1-year overall survival of approximately 50% in patients with metastatic uveal melanoma. Data showing a proven overall survival benefit with a systemic treatment are lacking. Tebentafusp is a bispecific protein consisting of an affinity-enhanced T-cell receptor fused to an anti-CD3 effector that can redirect T cells to target glycoprotein 100-positive cells.
Intravitreal Ziv-Aflibercept: A Comprehensive Review. [2019]Background: Age-related macular degeneration is the leading cause of blindness in adults over the age of 50 in the United States of America. Neovascular age-related macular degeneration (nAMD) is sight-threatening, but can be treated by three currently utilized, intravitreally administered drugs: aflibercept, bevacizumab, and ranibizumab. Ziv-aflibercept is an analogue of aflibercept, containing the same active molecule in a different buffer solution, and its recent availability has prompted numerous pre-clinical and clinical trials addressing its viability for intraocular use, summarized herein. Results: Trial outcomes demonstrate that ziv-aflibercept has a similar safety profile to other indicated drugs with effective maintenance or improvement of best-corrected visual acuity (BCVA) and reduction of retinal fluid or central foveal thickness (CFT). Clinical trials of ziv-aflibercept in other neovascular disorders such as diabetic macular edema (DME) and retinal vein occlusion (RVO) have shown similar results. Conclusion: Further prospective, randomized studies of ziv-aflibercept are needed, particularly in eyes with nAMD.