Fianlimab + Cemiplimab for Melanoma

Recruiting at 282 trial locations

Overseen By Clinical Trials Administrator

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Regeneron Pharmaceuticals

Must not be taking: Immunosuppressants, Corticosteroids

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: 27 months

1535 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new drug combination, fianlimab and cemiplimab, for treating melanoma, a serious type of skin cancer. It compares the effectiveness of these drugs to pembrolizumab, a medication already used for melanoma, and examines differences in effects between adults and adolescents. The trial also investigates side effects, drug levels in the blood, and potential immune responses that might reduce the drugs' effectiveness. Individuals with advanced melanoma that cannot be surgically removed and who have not received prior systemic treatment for this stage of the disease might be suitable candidates. As a Phase 3 trial, this research represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take certain medications like immunosuppressive drugs or other anti-cancer therapies close to the start of the trial. It's best to discuss your specific medications with the trial team.

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

A previous study found that the combination of fianlimab and cemiplimab had no unexpected safety issues, with side effects similar to those in earlier studies. Research has shown that this combination was tested in patients with various cancers, including advanced melanoma, and was generally well-tolerated. The study did not identify any new or surprising side effects when these drugs were used together, suggesting the combination is relatively safe based on current observations. However, side effects can vary from person to person, so participants should discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about fianlimab and cemiplimab for melanoma because these drugs target immune checkpoints in a unique way. Most treatments for melanoma, like pembrolizumab, focus on blocking the PD-1 pathway to help the immune system attack cancer cells. However, fianlimab works by inhibiting LAG-3, another checkpoint that can suppress immune responses, while cemiplimab targets PD-1. This dual approach could potentially enhance the immune system's ability to fight melanoma more effectively than standard treatments.

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

This trial will evaluate different treatment combinations for advanced melanoma. Studies have shown that the combination of fianlimab and cemiplimab, which participants in this trial may receive, appears promising for treating advanced melanoma, with response rates between 56% and 63% in patients. Cemiplimab alone, another treatment option in this trial, has proven very effective, significantly reducing the chance of the disease returning. Additionally, pembrolizumab, part of another treatment arm in this trial, has demonstrated long-term benefits, with 34% of patients living for 10 years and experiencing tumor shrinkage. Overall, these treatments show strong potential for improving outcomes in melanoma patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Are You a Good Fit for This Trial?

Adolescents and adults with advanced melanoma that hasn't spread too much can join this trial. They should be over 12 years old, have a life expectancy of at least 3 months, and not have had previous systemic treatments for their condition. People with certain types of melanoma or those who are immunocompromised can't participate.

Inclusion Criteria

My previously treated cancer spots can only be tracked if they've grown and there are no other spots to track.

I had cancer treatment without worsening for 6+ months and stopped only if side effects were too severe, except fully treated hormone issues.

I have acral or mucosal melanoma.

Exclusion Criteria

Systemic immune suppression: Use of immunosuppressive doses of corticosteroids (>10mg of prednisone per day or equivalent) within 14 days of the first dose of study medication. Physiologic replacement doses are allowed up to and including 10mg of prednisone/day or equivalent. Inhaled or topical steroids are permitted, if they are not for treatment of an autoimmune disorder. Other clinically relevant forms of systemic immune suppression. Treatment with other anti-cancer therapy including immuno- therapy, chemotherapy, major surgery or biological therapy within 21 days prior to the first dose of trial treatment. Adjuvant hormonotherapy used for breast cancer or other hormone-sensitive cancers in long term remission is allowed. History or current evidence of significant (CTCAE Grade ≥2) local or systemic infection (e. g., cellulitis, pneumonia, septicemia) requiring systemic antibiotic treatment within 14 days prior to the first dose of trial medication. Participants with a history of myocarditis

I have been diagnosed with uveal melanoma.

I don't know my cancer's BRAF V600 mutation status.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive fianlimab and cemiplimab or pembrolizumab for melanoma treatment

27 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 90 days post last dose

Long-term follow-up

Participants are monitored for long-term outcomes and quality of life

Approximately 6 years

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab
• Fianlimab
• Pembrolizumab

Trial Overview

The study is testing if combining two drugs, Fianlimab and Cemiplimab, works better than Pembrolizumab alone in stopping the cancer from progressing. It also looks at overall survival rates, response to treatment, safety in young people (12-18), quality of life impacts, and how the body processes the drugs.

How Is the Trial Designed?

Group I: C: cemiplimab+placebo Experimental Treatment 2 Interventions

As defined in Protocol Amendment 5

Group II: B: pembrolizumab+placebo Experimental Treatment 2 Interventions

As defined in Protocol Amendment 5

Group III: A: fianlimab+cemiplimab dose 1 Experimental Treatment 2 Interventions

As defined in Protocol Amendment 5

Group IV: A1: fianlimab+cemiplimab dose 2 Experimental Treatment 2 Interventions

As defined in Protocol Amendment 5

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

Ipilimumab, an anti-CTLA-4 antibody, was the first treatment to show a significant overall survival benefit in melanoma, marking a breakthrough in therapy for this previously resistant cancer.

Vemurafenib, a BRAF-inhibitor, has demonstrated substantial improvements in both progression-free and overall survival for patients with the BRAF(V600E) mutation, highlighting the effectiveness of targeted therapies in melanoma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current advances and perspectives in the treatment of advanced melanoma. Livingstone, E., Zimmer, L., Vaubel, J., et al.[2018]

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 phase 1 study involving 26 patients with advanced hormone-responsive breast cancer, tremelimumab combined with exemestane was found to be tolerable, with the maximum tolerated dose established at 6 mg/kg every 90 days.

The treatment led to immune activation, indicated by an increase in ICOS+ T cells, and resulted in stable disease for at least 12 weeks in 42% of patients, suggesting potential efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tremelimumab in combination with exemestane in patients with advanced breast cancer and treatment-associated modulation of inducible costimulator expression on patient T cells. Vonderheide, RH., LoRusso, PM., Khalil, M., et al.[2022]

In a post hoc analysis of the KEYNOTE-006 study involving 555 patients with advanced melanoma, both ipilimumab and BRAF ± MEK inhibitors showed antitumor activity as subsequent therapies after pembrolizumab, with overall response rates (ORR) of 17.5% for ipilimumab and 30.5% for BRAF ± MEK inhibitors.

Patients who had not previously received BRAF ± MEK inhibitors showed a significantly higher ORR of 43.2% when treated with these agents after pembrolizumab, indicating that prior treatment status may influence the effectiveness of subsequent therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of ipilimumab or BRAF ± MEK inhibition after pembrolizumab treatment in patients with advanced melanoma: analysis from KEYNOTE-006. Long, GV., Arance, A., Mortier, L., 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]

Cemiplimab (Libtayo®), a programmed death-1 inhibitor, is now a standard treatment for advanced cutaneous squamous cell carcinoma (cSCC), but clinical trials typically excluded patients with autoimmune diseases or those on immunosuppressive treatments.

This report highlights a successful case of a patient with locally advanced cSCC who was treated with cemiplimab while on dialysis for renal failure after a transplant, suggesting potential efficacy and safety in a previously excluded patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Unresectable Cutaneous Squamous Cell Carcinoma with Cemiplimab in a Patient on Dialysis. Grace de Lima, S., Hyrcza, MD., Monzon, JG.[2023]

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]

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]

Pembrolizumab, an anti-PD-1 antibody, has shown significant efficacy in treating advanced melanoma, demonstrating superior progression-free survival compared to chemotherapy in Phase II trials and improved overall survival in Phase III trials.

The treatment is generally well tolerated with a favorable safety profile, though common side effects include fatigue and rash, while less frequent but serious immune-related adverse events can occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. Spain, L., Younger, E., Hatipoglu, E., et al.[2020]

Cemiplimab-rwlc (Libtayo) is an FDA-approved immunotherapy for advanced cutaneous squamous cell carcinoma (CSCC) that works by blocking the PD-1 receptor, enhancing the immune system's ability to fight tumors.

Clinical trials have shown that cemiplimab is effective in treating CSCC, although common side effects and safety issues were noted, highlighting the need for ongoing research to improve treatment outcomes and reduce toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma. Ahmed, SR., Petersen, E., Patel, R., et al.[2019]

Cemiplimab is a PD-1 monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, which is crucial for enhancing the immune response against cancer cells.

In September 2018, cemiplimab received FDA approval for treating patients with metastatic or locally advanced cutaneous squamous cell carcinoma who cannot undergo curative surgery or radiation, marking a significant advancement in cancer treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab: First Global Approval. Markham, A., Duggan, S.[2023]

The FDA approved two groundbreaking drugs for malignant melanoma in 2011, marking a significant advancement in treatment after a 13-year gap, specifically ipilimumab for immune checkpoint modulation and targeted therapies like vemurafenib and dabrafenib for BRAF(V600) mutations.

These new therapies have changed the landscape of melanoma treatment, but they also raise important questions about how to best combine and sequence these agents for patients with BRAF mutant melanoma to enhance efficacy and manage resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab, vemurafenib, dabrafenib, and trametinib: synergistic competitors in the clinical management of BRAF mutant malignant melanoma. Luke, JJ., Hodi, FS.[2021]

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]

Recent advancements have led to the FDA approving six new targeted therapies and immunotherapies for metastatic melanoma, significantly improving survival rates for this aggressive skin cancer.

Despite these advancements, challenges remain, such as rapid resistance to BRAF/MEK inhibitors and varying response rates or side effects associated with immune therapies, which may limit their broader use in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multifunctional Nanoparticle Approach for Targeting Melanoma. Li, J., Xie, J., Zhu, J., et al.[2019]

Citations

1.

newsroom.regeneron.com

newsroom.regeneron.com/news-releases/news-release-details/libtayor-cemiplimab-phase-3-data-adjuvant-treatment-post

Libtayo® (cemiplimab) Phase 3 Data in the Adjuvant ...

Libtayo demonstrated a 68% reduction in the risk of disease recurrence or death, the primary endpoint of the trial (p<0.0001).

2.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.9533

CemiplimAb-rwlc survivorship and epidemiology (CASE)

Conclusions: The interim results of this Phase IV study demonstrate robust effectiveness and a generally manageable safety profile of cemiplimab ...

3.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40869427/

Efficacy of Neoadjuvant Cemiplimab Treatment for ...

Neoadjuvant Cemiplimab for cSCC therapy shows high response rates, low recurrence, improved survival, and manageable side effects. The current ...

4.

libtayohcp.com

libtayohcp.com/cscc/efficacy/response-duration

Up to 5 years of Long-term follow-up data

Of the 9 patients in whom LIBTAYO was withheld, 5 reinitiated LIBTAYO after symptom improvement; of these, 1/5 (20%) had recurrence. Immune-mediated ...

5.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40075670/

Effectiveness and Toxicity of Cemiplimab Therapy for ...

Results: Of the 36 patients treated, 22 (61.1%) achieved complete remission, 10 (27.8%) experienced a partial response, 3 (8.3%) had stable ...

6.

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 ...

A phase II trial (NCT06190951) is currently recruiting and testing if the combination of fianlimab + cemiplimab works better than cemiplimab ...

7.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.23.02172

Phase I Study of Fianlimab, a Human Lymphocyte ...

We report results from a first-in-human phase-I study of fianlimab and cemiplimab safety and efficacy in various malignancies including advanced melanoma.

8.

yalemedicine.org

yalemedicine.org/clinical-trials/a-study-with-combinations-of-anti-lag-3-and-anti-pd-1-antibodies-in-adult-participants-with-advanced

R3767-ONC-22122: A Phase 3 Study of Fixed Dose ...

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 ...

9.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05352672

NCT05352672 | Clinical Study of Fianlimab in Combination ...

The aims of the study are to see how effective the combination of fianlimab and cemiplimab are in treating the melanoma skin cancer, in comparison with a ...

10.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11647203/

First-in-Human Dose-Escalation Study of Fianlimab, an ...

There were no unexpected safety signals with fianlimab monotherapy or fianlimab-plus-cemiplimab combination therapy compared with previous reports for ...