Fianlimab + Cemiplimab for Melanoma

Recruiting at 79 trial locations

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Regeneron Pharmaceuticals

Must not be taking: Immunosuppressants

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: Up to 72 months

560 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should not have received prior systemic therapy for melanoma and should not be on systemic immune suppression. It's best to discuss your current medications with the trial team.

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

Research shows that similar drugs like nivolumab, when combined with other treatments, have been effective in treating advanced melanoma by enhancing the body's immune response to fight cancer. This suggests that combining Fianlimab and Cemiplimab might also be effective in treating melanoma. ^{1 2 3 4 5}

What safety data exists for Fianlimab + Cemiplimab treatment in humans?

The safety data for treatments similar to Fianlimab + Cemiplimab, such as other immune checkpoint inhibitors, show that they can cause immune-related side effects like skin rashes, fatigue, and inflammation in various body parts. These side effects are often manageable with medications like steroids, and some studies suggest that experiencing these side effects might be linked to better treatment outcomes. ^{6 7 8 9 10}

What makes the drug Fianlimab + Cemiplimab unique for treating melanoma?

Fianlimab + Cemiplimab is unique because it combines two immune checkpoint inhibitors, which work by helping the immune system recognize and attack cancer cells more effectively. This combination aims to enhance the body's immune response against melanoma, potentially offering a novel approach compared to existing treatments that often use single agents or different combinations. ^{1 3 11 12 13}

What is the purpose of this trial?

This study is researching an experimental drug called fianlimab (also known as REGN3767), combined with another medication called cemiplimab (also known as REGN2810), called "study drugs". The study is focused on patients with a type of skin cancer known as melanoma. 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 the combination of two medications, relatlimab and nivolumab, commercialized under the brand name Opdualag™ and approved for the treatment of melanoma in adults and children. The study is looking at several other research questions, including: * What side effects may happen from taking the study drugs. * How much study drug is in the blood at different times. * Whether the body makes antibodies against the study drugs (which could make the drug less effective or could lead to side effects)

Research Team

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Eligibility Criteria

This trial is for adults with advanced or metastatic melanoma who haven't had systemic therapy for this condition. They should have a performance status indicating they can carry out light activity, and their major organs must be functioning well.

Inclusion Criteria

My blood, liver, and kidney tests are normal.

My melanoma is at an advanced stage and cannot be surgically removed.

I have not had systemic therapy for my advanced melanoma.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either fianlimab and cemiplimab or relatlimab and nivolumab to assess safety and effectiveness in treating melanoma

Up to 72 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including incidence of laboratory abnormalities

4-8 weeks

Treatment Details

Interventions

• Cemiplimab
• Fianlimab
• Relatlimab+Nivolumab

Trial Overview The study compares the safety and effectiveness of two treatments: fianlimab combined with cemiplimab versus relatlimab plus nivolumab (Opdualag™). It also examines side effects, drug levels in blood over time, and potential immune responses to the drugs.

Participant Groups

Group I: fianlimab+cemiplimab Experimental Treatment 2 Interventions

Randomized 1:1

Group II: relatlimab+nivolumab Active Control 1 Intervention

Randomized 1:1

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

Findings from Research

The combination of nivolumab and ipilimumab, two immune checkpoint inhibitors, is a promising treatment for advanced melanoma, enhancing the body's immune response against the cancer.

Adding denosumab to this treatment may further improve anti-tumor effects by counteracting the immunosuppressive environment created by CD8+ T cells, as suggested by recent reports.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Treatment of Multiple Metastatic Melanoma with Nivolumab, Ipilimumab plus Denosumab Combined Therapy. Yoshida, S., Fujimura, T., Kambayashi, Y., et al.[2020]

Pembrolizumab and nivolumab are effective PD-1 inhibitors for treating metastatic melanoma, showing objective response rates of 26-38% and 31-40% respectively in patients who did not respond to previous treatments.

Both therapies have an acceptable safety profile, with most treatment-related side effects being mild (grade 1 or 2) and manageable, making them viable options for patients with treatment-refractory melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab and nivolumab: PD-1 inhibitors for advanced melanoma. Ivashko, IN., Kolesar, JM.[2022]

Regorafenib and NU7441 were identified as promising therapies that can enhance T-cell immunotherapy for melanoma by modifying immunomodulatory proteins and increasing melanoma antigens, which may improve treatment outcomes.

In mouse models, regorafenib not only suppressed melanoma progression but also positively influenced T-cell behavior, leading to increased proliferation and cytokine production, suggesting a synergistic effect when combined with other immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Multikinase and DNA-PK Inhibitor Combination Immunomodulates Melanomas, Suppresses Tumor Progression, and Enhances Immunotherapies. Tsai, AK., Khan, AY., Worgo, CE., et al.[2018]

The combination of bempegaldesleukin (BEMPEG) and nivolumab has shown promising clinical activity and good tolerability as a first-line treatment for metastatic melanoma in the Phase I/II PIVOT-02 trial.

The ongoing Phase III PIVOT IO 001 trial aims to compare the effectiveness of this combination therapy against nivolumab alone, focusing on key outcomes like objective response rate and overall survival in patients with untreated metastatic melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bempegaldesleukin plus nivolumab in untreated, unresectable or metastatic melanoma: Phase III PIVOT IO 001 study design. Khushalani, NI., Diab, A., Ascierto, PA., et al.[2021]

In a phase II study involving 41 patients with untreated stage III/IV metastatic melanoma, the combination of bempegaldesleukin (BEMPEG) and nivolumab (NIVO) showed a promising objective response rate of 52.6%, with 34.2% achieving complete responses.

The treatment was well-tolerated, with only 17.1% of patients experiencing grade 3 or 4 adverse events, and it resulted in a median progression-free survival of 30.9 months, indicating its potential as an effective first-line therapy for metastatic melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bempegaldesleukin Plus Nivolumab in First-Line Metastatic Melanoma. Diab, A., Tykodi, SS., Daniels, GA., et al.[2022]

Combining nivolumab and ipilimumab shows improved effectiveness in treating metastatic melanoma compared to using either drug alone, based on a retrospective analysis of approximately 7700 patients.

The combination therapy presents a safety profile that includes immune-related adverse events from both drugs, indicating that while the combination is effective, it also carries a heightened risk of toxicity that needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Side Effect Profiling of the Metastatic Melanoma Combination Therapy Ipilimumab-Nivolumab Using Adverse Event Data. Soldatos, TG., Dimitrakopoulou-Strauss, A., Larribere, L., et al.[2022]

In a study of 249 melanoma patients, immune-related adverse events (irAEs) were observed in 74.6% of patients, with a notable correlation between the occurrence of irAEs and improved treatment outcomes in the non-adjuvant setting.

The frequency of irAEs was high in both treatment settings, but in the adjuvant setting, they did not correlate with disease relapse, suggesting that while irAEs may indicate better efficacy in some cases, they do not universally predict treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frequency, Treatment and Outcome of Immune-Related Toxicities in Patients with Immune-Checkpoint Inhibitors for Advanced Melanoma: Results from an Institutional Database Analysis. Dimitriou, F., Staeger, R., Ak, M., et al.[2021]

In a study of 93 Chinese patients with advanced melanoma treated with PD-1 inhibitors, those who developed immune-related adverse events (irAEs) had significantly higher overall response rates (ORR) and disease control rates (DCR) compared to those without irAEs.

Patients experiencing three or more irAEs showed even better clinical outcomes, including longer progression-free survival and overall survival, suggesting that the presence of irAEs may indicate a more effective immune response to PD-1 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between immune-related adverse events and efficacy of PD-1 inhibitors in Chinese patients with advanced melanoma. Zhao, JJ., Wen, XZ., Ding, Y., et al.[2021]

Ipilimumab, an immune checkpoint inhibitor approved in 2011, has shown the potential to induce deep and durable remissions in up to 20% of metastatic melanoma patients by enhancing T-cell activation against tumors.

While ipilimumab can cause significant immune-related adverse events (irAEs), such as uveitis and nephritis, these can be effectively managed, and patients can still achieve remarkable outcomes, as demonstrated by a case where a patient had a complete response after treatment despite experiencing severe irAEs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Full Spectrum: Efficacy and Toxicity of Immunotherapy in Metastatic Melanoma Zibelman, M., Olszanski, AJ.[2019]

In a study of 747 patients receiving immune checkpoint inhibitor therapy for advanced melanoma, 31.6% developed cutaneous immune-related adverse events (cirAEs), which were linked to improved survival rates overall (HR = 0.76).

Patients with acral melanoma were less likely to develop cirAEs compared to those with nonacral cutaneous melanoma (HR = 0.41), and they exhibited the worst survival outcomes, suggesting that lower cirAE incidence may indicate poorer immunotherapy response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of melanoma type on incidence and downstream implications of cutaneous immune-related adverse events in the setting of immune checkpoint inhibitor therapy. Nguyen, N., Wan, G., Ugwu-Dike, P., et al.[2023]

Interferon (IFN)-alpha-2b has been established as an effective adjuvant therapy for patients with localized melanoma at high risk for relapse, showing improved relapse-free and overall survival in three large randomized trials.

Recombinant interleukin-2 (rIL-2) has been approved for metastatic melanoma, demonstrating a 15-20% overall response rate and the potential for complete remissions in about 6% of patients, although ongoing trials are needed to confirm the benefits of combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving survival in patients with high-risk and metastatic melanoma: immunotherapy leads the way. Agarwala, S.[2018]

In a study of 945 patients with untreated metastatic melanoma, the combination of nivolumab and ipilimumab significantly improved progression-free survival to a median of 11.5 months compared to just 2.9 months with ipilimumab alone.

For patients with PD-L1-negative tumors, the combination therapy was particularly effective, showing a progression-free survival of 11.2 months compared to 5.3 months with nivolumab alone, highlighting the potential of dual checkpoint inhibition in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. Larkin, J., Chiarion-Sileni, V., Gonzalez, R., et al.[2023]

Tremelimumab, a monoclonal antibody, has shown the ability to induce durable tumor regressions in 7% to 10% of patients with metastatic melanoma, with effects lasting up to 8 years, primarily through the activation of cytotoxic T lymphocytes.

While tremelimumab can lead to significant tumor responses, it also carries a risk of severe toxicities (20% to 25% of patients), mainly due to inflammatory or autoimmune reactions from its mechanism of action, which involves inhibiting CTLA-4 to enhance immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical development of the anti-CTLA-4 antibody tremelimumab. Ribas, A.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Successful Treatment of Multiple Metastatic Melanoma with Nivolumab, Ipilimumab plus Denosumab Combined Therapy. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab and nivolumab: PD-1 inhibitors for advanced melanoma. [2022]

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

A Multikinase and DNA-PK Inhibitor Combination Immunomodulates Melanomas, Suppresses Tumor Progression, and Enhances Immunotherapies. [2018]

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

Bempegaldesleukin plus nivolumab in untreated, unresectable or metastatic melanoma: Phase III PIVOT IO 001 study design. [2021]

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

Bempegaldesleukin Plus Nivolumab in First-Line Metastatic Melanoma. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Retrospective Side Effect Profiling of the Metastatic Melanoma Combination Therapy Ipilimumab-Nivolumab Using Adverse Event Data. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Frequency, Treatment and Outcome of Immune-Related Toxicities in Patients with Immune-Checkpoint Inhibitors for Advanced Melanoma: Results from an Institutional Database Analysis. [2021]

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

Association between immune-related adverse events and efficacy of PD-1 inhibitors in Chinese patients with advanced melanoma. [2021]

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

Full Spectrum: Efficacy and Toxicity of Immunotherapy in Metastatic Melanoma [2019]

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

Influence of melanoma type on incidence and downstream implications of cutaneous immune-related adverse events in the setting of immune checkpoint inhibitor therapy. [2023]

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

Improving survival in patients with high-risk and metastatic melanoma: immunotherapy leads the way. [2018]

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

Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. [2023]

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

Clinical development of the anti-CTLA-4 antibody tremelimumab. [2021]