Fianlimab + Cemiplimab for Melanoma

Recruiting at 31 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: Regeneron Pharmaceuticals

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Uveal melanoma, Autoimmune disease, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This study is researching an experimental drug called REGN3767, also known as fianlimab (R3767), when combined with another medication called cemiplimab (each individually called a "study drug" or called "study drugs" when combined) compared with an approved medication called pembrolizumab. These types of study drugs are collectively known as immune checkpoint inhibitors. The study is focused on participants with a type of skin cancer known as melanoma. The objective of this study is to see if the combination of fianlimab and cemiplimab is an effective treatment compared to pembrolizumab as peri-operative therapy in participants with high-risk melanoma. The study is looking at several other research questions, including: * What side effects may happen from receiving the study drug(s). * How much study drug(s) is in the blood at different times. * Whether the body makes antibodies against the study drug(s) (which could make the drug less effective or could lead to side effects). Antibodies are proteins that are naturally found in the blood stream that fight infections. * How administering the study drugs might improve quality of life.

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.

What data supports the effectiveness of the drug combination Fianlimab + Cemiplimab for treating melanoma?

Research shows that pembrolizumab, a drug similar to cemiplimab, has been effective in treating melanoma by helping the immune system attack cancer cells. This suggests that cemiplimab, when combined with other drugs like Fianlimab, might also be effective. ^{1 2 3 4 5}

Is the combination of Fianlimab and Cemiplimab generally safe for humans?

Pembrolizumab, a similar treatment, is generally well tolerated and has a favorable safety profile in treating melanoma. Common side effects include fatigue, rash, itching, and diarrhea, while less common ones include thyroid issues, colitis (inflammation of the colon), hepatitis (liver inflammation), and pneumonitis (lung inflammation). ^{6 7 8 9 10}

What makes the drug combination of Fianlimab and Cemiplimab unique for treating melanoma?

The combination of Fianlimab and Cemiplimab is unique because it involves two immune checkpoint inhibitors that work together to enhance the body's immune response against melanoma. Cemiplimab targets the PD-1 pathway, which helps the immune system recognize and attack cancer cells, while Fianlimab may target a different pathway, potentially offering a more comprehensive approach to treatment. ^{2 11 12 13 14}

Research Team

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Eligibility Criteria

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%.

Trial Timeline

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

Treatment Details

Interventions

• Cemiplimab (Checkpoint Inhibitor)
• Fianlimab (Checkpoint Inhibitor)
• Pembrolizumab (Checkpoint Inhibitor)

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.

Participant Groups

Group I: cemiplimab+fianlimab LD Experimental Treatment 2 Interventions

Phase 2 fianlimab LD Randomized 1:1:1 Phase 3 fianlimab (if LD chosen for Phase 3) Randomized 1:1

Group II: cemiplimab+fianlimab HD Experimental Treatment 2 Interventions

Phase 2 fianlimab HD Randomized 1:1:1 Phase 3 fianlimab ((if HD chosen for phase 3) Randomized 1:1

Group III: cemiplimab Active Control 1 Intervention

Phase 2 Randomized 1:1:1

Group IV: pembrolizumab Active Control 1 Intervention

Phase 3 Randomized 1:1

Cemiplimab is already approved in Canada, Brazil for the following indications:

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

Findings from Research

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]

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]

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]

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]

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 (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]

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]

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]

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]

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 (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 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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Current advances and perspectives in the treatment of advanced melanoma. [2018]

2. England 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. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab superior to ipilimumab in melanoma. [2017]

4. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]

5. England pubmed.ncbi.nlm.nih.gov

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

6. United States 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). [2020]

7. England pubmed.ncbi.nlm.nih.gov

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

8. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Multifunctional Nanoparticle Approach for Targeting Melanoma. [2019]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Cemiplimab: First Global Approval. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma. [2019]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Treatment of Unresectable Cutaneous Squamous Cell Carcinoma with Cemiplimab in a Patient on Dialysis. [2023]

14. United States 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. [2022]