Cemiplimab + Ziv-Aflibercept for Uveal Melanoma

Recruiting at 3 trial locations

Overseen By Malik Hall

Age: 18+

Sex: Any

Trial Phase: Phase 2

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 All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 3 weeks per cycle

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether the combination of Cemiplimab (an immunotherapy drug) and Ziv-Aflibercept is safe and effective for treating metastatic uveal melanoma, a type of eye cancer that has spread to other parts of the body. Researchers seek to determine if these drugs can shrink tumors or halt their growth. Suitable candidates for this trial have metastatic uveal melanoma and have previously tried other treatments, such as immunotherapy, without success. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that Cemiplimab plus Ziv-Aflibercept is likely to be safe for humans?

Research has shown that cemiplimab and ziv-aflibercept, studied separately, have yielded promising results in treating different cancers. Cemiplimab is often used for certain skin cancers and is generally well-tolerated. Ziv-aflibercept has been used in other cancer treatments and is considered safe to manage.

Researchers are testing the combination of cemiplimab and ziv-aflibercept for safety in treating metastatic uveal melanoma. While detailed safety information for this combination is still being collected, each treatment alone has been manageable for patients, with side effects common in cancer therapies. This trial is in a phase that examines both safety and effectiveness, indicating some confidence in its potential safety, but more data is needed for firm conclusions. Always consult a healthcare provider to understand the potential risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Cemiplimab and Ziv-Aflibercept for uveal melanoma because they offer a fresh approach compared to current treatments like surgery and radiation. Unlike these standard options, Cemiplimab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells. Ziv-Aflibercept, on the other hand, targets and blocks proteins that promote blood vessel growth in tumors, potentially starving the cancer. This combination could provide a two-pronged attack on the disease, potentially improving outcomes for patients.

What evidence suggests that Cemiplimab plus Ziv-Aflibercept could be effective for metastatic uveal melanoma?

Research has shown that the combination of Cemiplimab and Ziv-Aflibercept, which participants in this trial will receive, may help treat metastatic uveal melanoma, a type of eye cancer that has spread. Early results suggest this treatment can shrink tumors or halt their growth. Cemiplimab boosts the immune system to attack cancer cells, while Ziv-Aflibercept blocks the blood vessels supplying tumors. Together, they aim to strengthen the fight against cancer. Although initial signs are promising, further research is needed to confirm these findings. ^{1 3 5 6 7}

Who Is on the Research Team?

Ahmad Tarhini, MD, PhD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

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.

I am on full-dose anticoagulants and meet specific health criteria.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab
• Ziv-Aflibercept

Trial Overview 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.

How Is the Trial Designed?

Group I: Cemiplimab + Ziv-Aflibercept Experimental Treatment 2 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)

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Regeneron Pharmaceuticals

Industry Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Genzyme, a Sanofi Company

Industry Sponsor

Trials

528

Recruited

186,000+

David Meeker

Genzyme, a Sanofi Company

Chief Executive Officer since 2011

MD from the University of Vermont Medical School, Advanced Management Program at Harvard Business School

Jean-Paul Kress

Genzyme, a Sanofi Company

Chief Medical Officer since 2015

MD from Faculte Necker-Enfants Malades, Paris

Published Research Related to This Trial

In a study of 6 patients with macular edema due to central retinal vein occlusion, treatment with intravitreal ziv-aflibercept led to significant improvements in visual acuity and reductions in central macular thickness over 12 months.

No safety issues were reported, such as uveitis or cataract progression, suggesting that ziv-aflibercept is a safe and effective treatment option, especially in resource-limited settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One-year outcomes of ziv-aflibercept for macular edema in central retinal vein occlusion. Eldeeb, M., Chan, EW., Dedhia, CJ., et al.[2022]

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]

Current adjuvant therapies for uveal melanoma have not been effective in preventing metastasis, highlighting the need for new treatment strategies.

New approaches are focusing on using genetic criteria to tailor immunotherapy and targeted treatments for patients at risk, with ongoing clinical trials exploring these innovative therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant Therapy of Uveal Melanoma: Current Status. Triozzi, PL., Singh, AD.[2022]

Tebentafusp demonstrated a significantly higher median overall survival (mOS) of 22.4 months compared to combined immune checkpoint blockade (ICB) which had an mOS of 15.7 months, based on a systematic review of 55 studies involving 2,682 patients.

While the median progression-free survival (mPFS) was similar across treatment groups, tebentafusp showed a strong advantage in overall survival, with population-adjusted hazard ratios indicating it is more effective than combined ICB in extending patient survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is tebentafusp superior to combined immune checkpoint blockade and other systemic treatments in metastatic uveal melanoma? A comparative efficacy analysis with population adjustment. Petzold, A., Steeb, T., Wessely, A., et al.[2023]

Uveal melanoma, a rare and aggressive form of melanoma, has shown poor responses to traditional immune checkpoint inhibitors, highlighting the need for new treatment strategies.

Tebentafusp, a first-in-class bi-specific fusion protein therapy, has demonstrated a significant overall survival benefit in patients with uveal melanoma compared to standard treatment options, marking a promising advancement in this challenging cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of bi-specific therapies in uveal melanoma. Orloff, M., Seedor, R., Sato, T.[2023]

Ziv-aflibercept is a recombinant fusion protein effective in treating metastatic colorectal carcinoma and shows promise for off-label use in chorioretinal vascular conditions, supported by extensive clinical data.

Studies indicate that ziv-aflibercept is safe and effective, with no significant differences in outcomes between lower and higher doses, making it a cost-effective anti-VEGF treatment option, particularly beneficial for low- and middle-income countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ziv-aflibercept: A cost-effective, off-label, highly potent antagonist of vascular endothelial growth factor. Mansour, AM., Stewart, MW., Farah, ME., et al.[2023]

A study involving 12 patients showed that a single intravitreal injection of ziv-aflibercept for treating choroidal neovascularization due to age-related macular degeneration was safe, with no serious ocular or systemic adverse events reported after 30 days.

While there was only a slight improvement in best-corrected visual acuity after treatment, the absence of significant side effects suggests that ziv-aflibercept could be a viable low-cost alternative for macular disease therapy, especially in resource-limited settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SHORT-TERM SAFETY PROFILE OF INTRAVITREAL ZIV-AFLIBERCEPT. Chhablani, J., Narayanan, R., Mathai, A., et al.[2022]

In a phase 3 trial involving 378 patients with metastatic uveal melanoma, treatment with tebentafusp led to a significant increase in overall survival at 1 year (73%) compared to the control group (59%), demonstrating its efficacy as a new treatment option.

Tebentafusp was associated with manageable treatment-related adverse events, primarily cytokine-mediated and skin-related, which decreased in severity after initial doses, indicating a favorable safety profile with no treatment-related deaths reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. Nathan, P., Hassel, JC., Rutkowski, P., et al.[2022]

Ziv-aflibercept, an analogue of aflibercept, has shown a similar safety profile to existing treatments for neovascular age-related macular degeneration (nAMD), effectively maintaining or improving best-corrected visual acuity (BCVA) and reducing retinal fluid and central foveal thickness (CFT).

Clinical trials indicate that ziv-aflibercept is also effective in treating other neovascular conditions like diabetic macular edema (DME) and retinal vein occlusion (RVO), but further randomized studies are necessary to confirm its efficacy specifically for nAMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal Ziv-Aflibercept: A Comprehensive Review. Barmas-Alamdari, D., D'Souza, HS., Kapoor, KG., et al.[2019]

In a study of 60 patients receiving an average of 8.4 intravitreal injections of ziv-aflibercept over a mean follow-up of 9.2 months, significant improvements in best-corrected visual acuity (BCVA) and reductions in central macular thickness (CMT) were observed, indicating the treatment's efficacy for retinal disease.

The treatment was found to be safe, with no significant increases in intraocular pressure, no progression of lens opacities, and only one case of mild transient iritis, suggesting that repeated injections of ziv-aflibercept are well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of ziv-aflibercept in retinal diseases. Mansour, AM., Ashraf, M., Dedhia, CJ., et al.[2022]

In a study involving 21 eyes from 20 patients, single intravitreal injections of 2 mg ziv-aflibercept were found to be safe, with no reports of worsening vision, pain, or intraocular inflammation after the procedure.

While there were no significant changes in best-corrected visual acuity, the treatment led to a significant reduction in central subfield thickness of the macula, indicating potential efficacy in managing choroidal neovascular membranes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SHORT-TERM SAFETY OF 2 MG INTRAVITREAL ZIV-AFLIBERCEPT. Chhablani, J., Dedhia, CJ., Peguda, HK., et al.[2022]

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]

Citations

1. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT06121180/

Trial | NCT06121180 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 ...

2. clinicaltrials.cedars-sinai.edu clinicaltrials.cedars-sinai.edu/view/MCC21341

Cemiplimab plus Ziv-Aflibercept in Metastatic Uveal Melanoma The purpose of this phase II study for advanced melanoma is to evaluate the safety (side effects profile) and effectiveness (tumor shrinkage) of cemiplimab and ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11979469/

How we treat patients with metastatic uveal melanoma - PMC Recently presented preliminary data show signs of efficacy ... Study of Cemiplimab Plus Ziv-Aflibercept for Subjects With Metastatic Uveal ...

4. cancer.gov cancer.gov/clinicaltrials/NCI-2023-09609

Cemiplimab in Combination with Ziv-Aflibercept for the ... This phase II trial tests the safety and effectiveness of cemiplimab in combination with ziv-aflibercept in treating patients with melanoma that that has ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12295115/

Advances and Challenges in Immunotherapy for Metastatic ... Prognostic factors and outcomes in metastatic uveal melanoma treated with programmed cell death-1 or combined PD-1/cytotoxic T-lymphocyte ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06121180?cond=%22Uveal+Neoplasms%22

NCT06121180 | Study of Cemiplimab Plus Ziv-Aflibercept ... 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. Official ...

7. investor.regeneron.com investor.regeneron.com/news-releases/news-release-details/libtayor-cemiplimab-rwlc-approved-us-first-and-only

Libtayo® (cemiplimab-rwlc) Approved in the U.S. as First ... Approval based on pivotal Phase 3 C-POST trial showing Libtayo significantly reduced the risk of disease recurrence or death by 68% compared ...