Fianlimab + Cemiplimab for Melanoma

Recruiting in Palo Alto (17 mi)

+219 other locations

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Regeneron Pharmaceuticals

Must not be taking: Immunosuppressants, Corticosteroids

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 two new drugs, fianlimab and cemiplimab, to treat melanoma skin cancer. It examines their effectiveness and how they work in both teenagers and adults. The drugs help the immune system fight cancer cells.

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.

What evidence supports the effectiveness of the drugs Fianlimab and 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. It has shown better outcomes compared to other treatments like ipilimumab, suggesting that similar drugs like cemiplimab could also be effective. ^{1 2 3 4 5}

Is the combination of Fianlimab and Cemiplimab safe for treating melanoma?

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 are related to the immune system, like thyroid issues and 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 by blocking proteins that prevent the immune system from attacking cancer cells, potentially enhancing the body's ability to fight melanoma. This approach is part of a newer class of cancer treatments called immunotherapy, which is becoming more common for treating immune-sensitive tumors like melanoma. ^{1 11 12 13 14}

Research Team

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

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

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.

Participant Groups

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 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 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]

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]

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]

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. 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]

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

Pembrolizumab superior to ipilimumab in melanoma. [2017]

3. Germany pubmed.ncbi.nlm.nih.gov

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

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]