Fianlimab + Cemiplimab vs Pembrolizumab for Melanoma

Not currently recruiting at 430 trial locations

Overseen By Clinical Trials Administrator

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Regeneron Pharmaceuticals

Disqualifiers: Uveal melanoma, Autoimmune disease, HIV, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of fianlimab (an experimental treatment) and cemiplimab against the approved drug pembrolizumab for individuals who have undergone surgery for melanoma but remain at high risk of recurrence. Researchers aim to determine if this new combination is more effective, while also assessing side effects and the impact on quality of life. They will measure the body's response to the drugs, such as the production of antibodies that might affect the treatment. The study seeks participants who had early to advanced stages of melanoma, have had their cancer surgically removed, and show no signs of the disease post-surgery. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, since the trial involves experimental drugs, it's possible that some medications might need to be adjusted. Please consult with the trial coordinators for specific guidance.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of fianlimab and cemiplimab has a safety profile similar to other treatments targeting PD-1, a protein that regulates the immune system. In some studies, 47% of patients experienced serious side effects, classified as grade 3 or higher. Specifically, 36% of patients had serious side effects, and 13% experienced immune-related side effects, where the immune system mistakenly attacks the body. These figures provide insight into the treatment's safety.

Pembrolizumab has already received approval for treating melanoma in some countries, indicating thorough review and safety for this use. When considering joining a trial, it is important to review these safety details and discuss them with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Fianlimab combined with Cemiplimab for treating melanoma because it represents a fresh approach to boosting the immune system's response to cancer. Unlike the standard treatments, which often involve Pembrolizumab, this combination uses Fianlimab, a novel antibody that targets LAG-3, a protein that can suppress immune activity. By combining this with Cemiplimab, which blocks another protein called PD-1, the treatment aims to unleash a more powerful attack on melanoma cells. This dual mechanism could potentially enhance the effectiveness of the treatment compared to existing options.

What evidence suggests that this trial's treatments could be effective for melanoma?

Research shows that the combination of fianlimab and cemiplimab, which participants in this trial may receive, holds promise for treating advanced melanoma. Studies have found that this combination has a response rate of over 60%, meaning more than half of the patients experienced positive effects. The treatment has demonstrated significant and lasting benefits, with effects continuing over time. This combination targets specific proteins that control the immune system, helping the body fight cancer more effectively. Importantly, patients have experienced manageable side effects, which is encouraging for those considering this treatment. Overall, evidence suggests that the fianlimab and cemiplimab combination could be a strong option against melanoma. Meanwhile, another group in this trial will receive pembrolizumab, serving as an active comparator. ^{2 3 5 6 7}

Who Is on the Research Team?

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for adults who've had melanoma surgically removed recently and are disease-free. They must have been stage IIC, III, or IV at diagnosis per AJCC 8th edition criteria. Excluded are those with uveal melanoma, any remaining disease post-surgery, significant autoimmune diseases in the past 2 years needing immunosuppressants, adolescents under 40 kg, and uncontrolled HIV/HBV/HCV infections.

Inclusion Criteria

My melanoma is stage IIB to IV and has been fully removed by surgery.

I had surgery to remove my cancer and healed well within the last 12 weeks.

My recent tests show no signs of cancer.

Exclusion Criteria

I still have signs of cancer after surgery.

I have been treated for an autoimmune disease in the last 2 years.

I have had myocarditis in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either the combination of fianlimab and cemiplimab or pembrolizumab after melanoma removal surgery

Up to 5 years

Follow-up

Participants are monitored for safety, effectiveness, and quality of life after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab
• Fianlimab
• Pembrolizumab

Trial Overview The study aims to see if fianlimab combined with cemiplimab increases the time patients remain free from melanoma relapse compared to pembrolizumab alone. It will also compare overall survival rates, specific survival rates for melanoma, effects on metastasis-free survival after surgery, quality of life impacts and safety between the two treatments.

How Is the Trial Designed?

Group I: Fianlimab LD + Cemiplimab Experimental Treatment 2 Interventions

Patients will be administered one combination dose of fianlimab low dose (LD) and cemiplimab

Group II: Fianlimab HD + Cemiplimab Experimental Treatment 2 Interventions

Patients will be administered one combination dose of fianlimab high dose (HD) and cemiplimab

Group III: Pembrolizumab Active Control 2 Interventions

Patients will be administered one dose of pembrolizumab co-infused with saline/dextrose placebo

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?

Regeneron Pharmaceuticals

Lead 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

Published Research Related to This Trial

In a real-world study of 42 patients with advanced melanoma treated with pembrolizumab, the median overall survival was 5.5 months, indicating its potential effectiveness in this setting.

A significant number of patients (33%) experienced immune-related adverse events, with 7% discontinuing treatment due to these side effects, highlighting the importance of monitoring for safety in clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the treatment of advanced/metastatic melanoma: a single-center institution experience. Cimminiello, C., Indini, A., Di Guardo, L., et al.[2019]

In a study of 123 patients with advanced melanoma treated with nivolumab or pembrolizumab, the real-world time to treatment discontinuation (rwTTD) was found to be 11.67 months, indicating a significant duration of treatment effectiveness.

Patients who temporarily suspended treatment for more than 45 days had a median rwTTD of 26.4 months, which is three times longer than those who stopped permanently, highlighting the importance of managing treatment-related toxicities to allow for resumption of therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy with nivolumab and pembrolizumab in unresectable or metastatic advanced melanoma: real-life observational study of drug use.] Musicco, F., Fulgenzio, C., La Malfa, A., et al.[2022]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

In a study of 400 advanced melanoma patients, those with poorer health status (Eastern Cooperative Oncology Group score of 2-4) were 6.6 times more likely to be treated with pembrolizumab (PEMBRO) compared to ipilimumab + nivolumab (IPI+NIVO).

Patients who were PD-L1 positive or had BRAF wild-type tumors were also more likely to receive PEMBRO, with odds ratios of 4.5 and 2.2 respectively, highlighting the importance of individual patient characteristics in treatment selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors associated with immunotherapy selection in patients with advanced melanoma. Joseph, RW., Shillington, AC., Macahilig, C., et al.[2019]

In a study of 29 patients with resected stage III melanoma treated with adjuvant pembrolizumab, the median recurrence-free survival (RFS) was not reached, indicating potential effectiveness, but it was not significantly different from the 25 months RFS observed in 27 patients treated with interferon α-2b (IFN-α-2b).

Pembrolizumab was associated with a lower rate of grade 3-4 adverse events (6.90%) compared to IFN-α-2b (22.22%), suggesting a better safety profile for pembrolizumab in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant pembrolizumab versus high-dose interferon α-2b for Chinese patients with resected stage III melanoma: a retrospective cohort study. Li, T., Jia, DD., Teng, LS.[2022]

In a study of 88 advanced melanoma patients treated with pembrolizumab, 81.8% experienced any-grade toxicities, with skin and gastrointestinal issues being the most common side effects.

Despite the high incidence of side effects, pembrolizumab was found to be well tolerated in real-world settings, and severe toxicities were manageable with systemic steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK. So, AC., Board, RE.[2022]

In a study of 103 Chinese patients with advanced melanoma, pembrolizumab demonstrated a 16.7% objective response rate, indicating its effectiveness as a second-line treatment, particularly in aggressive melanoma subtypes.

The treatment was well tolerated, with 84.5% of patients experiencing treatment-related adverse events, but only a small percentage (8.7%) had severe side effects, and no treatment-related deaths occurred.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib Study of Pembrolizumab as Second-Line Therapy for Chinese Patients With Advanced or Metastatic Melanoma (KEYNOTE-151). Si, L., Zhang, X., Shu, Y., et al.[2020]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

In a randomized trial comparing FDA-approved immune checkpoint inhibitors for advanced melanoma, pembrolizumab showed significantly better treatment outcomes than ipilimumab.

This study is notable as it is the first to directly compare these two therapies as first-line treatments, highlighting pembrolizumab's potential as a more effective option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab superior to ipilimumab in melanoma. [2017]

Pembrolizumab (Keytruda) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[2021]

This study presents the first known case of a patient with metastatic melanoma who was successfully treated with pembrolizumab while undergoing hemodialysis, highlighting its potential efficacy in patients with end-stage renal disease.

Pembrolizumab, an FDA-approved monoclonal antibody for metastatic melanoma and non-small cell lung cancer, shows promise for use in patients with renal complications, although specific dosing guidelines for such patients are still lacking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of pembrolizumab in a patient with advanced melanoma on haemodialysis. Chang, R., Shirai, K.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38900987/

Phase I Study of Fianlimab, a Human Lymphocyte ... Conclusion: The current results show a promising benefit-risk profile of fianlimab/cemiplimab combination for patients with advanced melanoma, ...

2. onclive.com onclive.com/view/fianlimab-cemiplimab-demonstrates-persistent-activity-in-advanced-melanoma-independent-of-lag-3-and-pd-l1-status

Fianlimab/Cemiplimab Demonstrates Persistent Activity in ... Fianlimab plus cemiplimab demonstrated persistent and significant clinical activity in patients with advanced melanoma.

3. investor.regeneron.com investor.regeneron.com/news-releases/news-release-details/fianlimab-lag-3-inhibitor-combined-libtayor-cemiplimab

Fianlimab (LAG-3 Inhibitor) Combined with Libtayo® ... Our LAG-3 inhibitor fianlimab combined with Libtayo demonstrated greater than 60% response rates. Notably, the safety profile for this combination appears in ...

4. curemelanoma.org curemelanoma.org/blog/clinical-trials-testing-combination-immunotherapy-for-high-risk-and-advanced-melanoma-regenerons-lag-3-program

Clinical Trials Testing Combination Immunotherapy for ... The phase 3 Harmony Melanoma trial (NCT05352672) is assessing how well the combination of fianlimab + cemiplimab works compared to pembrolizumab ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.02172

Phase I Study of Fianlimab, a Human Lymphocyte ... In advanced melanoma, fianlimab/cemiplimab yielded the highest LAG-3/PD-1 efficacy and durability possibly related to increased LAG-3 exposure, ...

6. investor.regeneron.com investor.regeneron.com/news-releases/news-release-details/fianlimab-lag-3-inhibitor-combined-libtayor-cemiplimab-shows

Fianlimab (LAG-3 inhibitor) Combined with Libtayo® ... Data demonstrate objective response rates from 56% to 63% across three independent cohorts of advanced melanoma patients.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06246916

NCT06246916 | A Study With Combinations of Anti-LAG-3 ... The aim of the study is to see how safe and effective the combination of fianlimab and cemiplimab is in treating melanoma, in comparison with the combination of ...