Fianlimab + Cemiplimab vs Pembrolizumab for Melanoma

Recruiting at 382 trial locations

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Regeneron Pharmaceuticals

Disqualifiers: Uveal melanoma, Autoimmune disease, HIV, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug combination in patients at high risk of melanoma coming back after surgery. The drugs aim to help the immune system fight any remaining cancer cells better than the current treatment.

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.

What data supports the idea that Fianlimab + Cemiplimab vs Pembrolizumab for Melanoma is an effective drug?

The available research does not provide specific data comparing Fianlimab + Cemiplimab directly to Pembrolizumab for melanoma. However, it does show that Pembrolizumab is effective for treating melanoma, as it has been approved for advanced cases and has shown better outcomes than some other treatments like ipilimumab. Pembrolizumab has been associated with longer periods without the cancer returning in some patients and has fewer severe side effects compared to another treatment, IFN-α-2b. This suggests that Pembrolizumab is a strong option for melanoma treatment, but without direct comparison data, we can't conclude how Fianlimab + Cemiplimab measures up against it. ^{1 2 3 4 5}

What safety data exists for Fianlimab + Cemiplimab vs Pembrolizumab in melanoma treatment?

The safety data for pembrolizumab, one of the treatments being compared, shows that it has a favorable safety profile in metastatic melanoma. Common immune-mediated adverse reactions include hypothyroidism, pneumonitis, and hyperthyroidism. Real-world studies also reflect similar safety profiles, with some patients experiencing disease progression. However, specific safety data for the combination of Fianlimab + Cemiplimab is not detailed in the provided research. ^{6 7 8 9 10}

Is the drug Cemiplimab, Fianlimab, Pembrolizumab a promising treatment for melanoma?

Yes, the drug Pembrolizumab, which is part of the treatment, is promising for melanoma. It has shown strong antitumor effects, high response rates, and has been approved for treating melanoma. It is effective even in challenging cases, like patients on dialysis, and has been associated with longer survival without the cancer returning. It also has a lower rate of severe side effects compared to some other treatments. ^{2 3 6 10 11}

Research Team

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Eligibility Criteria

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 am a teenager between 12 and 18 years old and weigh less than 40 kg.

Trial Timeline

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

Treatment Details

Interventions

• Cemiplimab (Monoclonal Antibodies)
• Fianlimab (Monoclonal Antibodies)
• Pembrolizumab (Monoclonal Antibodies)

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.

Participant Groups

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 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

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]

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]

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]

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]

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 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 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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Factors associated with immunotherapy selection in patients with advanced melanoma. [2019]

2. United States 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. [2022]

3. England pubmed.ncbi.nlm.nih.gov

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

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

Pembrolizumab: first global approval. [2021]

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

Pembrolizumab superior to ipilimumab in melanoma. [2017]

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

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

8. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the treatment of advanced/metastatic melanoma: a single-center institution experience. [2019]

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

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

10. Italy pubmed.ncbi.nlm.nih.gov

[Immunotherapy with nivolumab and pembrolizumab in unresectable or metastatic advanced melanoma: real-life observational study of drug use.] [2022]

11. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of pembrolizumab in a patient with advanced melanoma on haemodialysis. [2019]