Fianlimab + Cemiplimab for Melanoma

Recruiting at 60 trial locations

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Regeneron Pharmaceuticals

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Uveal melanoma, Autoimmune 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: Unknown

Duration: Up to 1 year

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new combination of drugs, fianlimab and cemiplimab (an immunotherapy drug), is more effective at treating melanoma than cemiplimab alone. The trial targets individuals with high-risk melanoma that can be completely removed by surgery. It will assess side effects, measure drug levels in the blood, and evaluate the treatment's impact on quality of life. Candidates may be suitable if they have stage III or IV melanoma that can be fully removed by surgery. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use immunosuppressive doses of corticosteroids within 14 days of starting the study medication.

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

Research has shown that fianlimab, when combined with cemiplimab, yields promising results in treating melanoma, a type of skin cancer. This combination performs as well as other known immunotherapy treatments. Early studies have examined the tolerance of fianlimab, and results suggest it is generally well-received when used with cemiplimab.

Cemiplimab alone has an established safety record. Common side effects include muscle and joint pain, tiredness, skin rash, and diarrhea, while serious side effects are less common. Many patients with skin-related side effects improved after treatment adjustments.

Both fianlimab and cemiplimab belong to a group of treatments called immune checkpoint inhibitors, which enhance the immune system's ability to fight cancer. Although there is always a risk of side effects, studies so far suggest that fianlimab and cemiplimab can be used safely in many patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Fianlimab and Cemiplimab for treating melanoma because these drugs work together to target the immune system in a unique way. Most standard treatments for melanoma, like Pembrolizumab, focus on boosting the body’s immune response to attack cancer cells. Fianlimab, however, targets a protein called LAG-3, which acts as a brake on the immune system, potentially unleashing a stronger attack on cancer cells. When combined with Cemiplimab, which blocks another immune checkpoint called PD-1, this duo may offer a more powerful and comprehensive approach to fighting melanoma. This innovative combination could potentially enhance effectiveness and provide new hope for patients.

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

Research shows that the combination of the drugs fianlimab and cemiplimab, which participants in this trial may receive, may help treat melanoma, a type of skin cancer. Studies have found that these drugs work together to boost the immune system's ability to attack cancer cells. In patients with advanced melanoma, this combination demonstrated strong and lasting effects against the cancer. The drugs target specific proteins on immune cells, helping the body better recognize and fight the tumor. Overall, early evidence suggests this pair could be an effective option for treating melanoma. ^{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?

This trial is for adults with resectable Stage 3 or 4 melanoma. Candidates must be able to have surgery to remove all cancer with clear margins and have undergone recent full disease staging. Any level of LAG-3 expression is allowed, and participants should have an ECOG performance status of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory.

Inclusion Criteria

You must be able to have surgery to remove the cancer completely, and the doctor must have a plan for the surgery before the study starts.

Before joining the study, you need to have a thorough check-up, including scans of your neck, chest, abdomen, pelvis, and any areas where the cancer was removed before, as well as a scan of your brain.

You need to have a specific test for the LAG-3 protein to be eligible for the study, and the results can range from 0% to 100%.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive peri-operative therapy with fianlimab and cemiplimab or pembrolizumab

Up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 4 years

Long-term follow-up

Participants are monitored for long-term outcomes such as event-free survival and overall survival

Up to 4 years

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab
• Fianlimab
• Pembrolizumab

Trial Overview The study compares the safety and effectiveness of two drugs: fianlimab combined with cemiplimab versus pembrolizumab alone. These medications are immune checkpoint inhibitors that may help the body's immune system fight cancer. The trial will also assess drug levels in blood, potential antibody development against the drugs, and impact on quality of life.

How Is the Trial Designed?

Group I: Arm C Experimental Treatment 1 Intervention

As described in the protocol

Group II: Arm B Experimental Treatment 1 Intervention

As described in the protocol

Group III: Arm A Active Control 2 Interventions

As described in the protocol

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

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]

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]

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]

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]

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]

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 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]

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]

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 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]

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]

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]

Citations

1. 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 ...

2. 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, ...

3. 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 ...

4. 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.

5. 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, ...

6. libtayohcp.com libtayohcp.com/cscc/safety

Safety profile - LIBTAYO® (cemiplimab-rwlc) Immune-mediated dermatologic adverse reactions resolved in 71% of the 24 patients. Of the 17 patients in whom LIBTAYO was withheld for dermatologic adverse ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/761097s014lbl.pdf

LIBTAYO® (cemiplimab-rwlc) injection, for intravenous use In this pooled safety population, the most common adverse reactions (≥15%) were musculoskeletal pain, fatigue, rash, and diarrhea. The most common Grade 3-4 ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11083599/

Efficacy and Safety of Cemiplimab for the Management of Non ... Cemiplimab has a durable and significant effect for the management of BCC and CSCC, with a favorable safety profile. Different specialists ...

9. 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 ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9421083/

Cemiplimab and Cutaneous Squamous Cell Carcinoma with longer follow-up efficacy and safety data. This study enrolled 26 patients and again showed an overall response rate of 50% and that the duration of ...