Sarilumab + Immunotherapy for Melanoma

Recruiting at 5 trial locations

Overseen By Jeffrey Weber, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NYU Langone Health

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Untreated brain metastases, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 6

69 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of treatments for advanced melanoma, a type of skin cancer that cannot be removed with surgery. The researchers are testing the safety and effectiveness of adding sarilumab, an arthritis drug, to a mix of other cancer drugs (ipilimumab, nivolumab, and relatlimab) to see if it reduces side effects and improves outcomes. People with stage III or IV melanoma who haven't received prior treatment for metastatic disease may be suitable candidates. As a Phase 2 trial, this research focuses on measuring how well the treatment works in an initial, smaller group, offering a chance to contribute to important advancements in melanoma care.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or other immunosuppressive medications, you may need to stop them at least 14 days before starting the study drugs.

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

Research has shown that combining sarilumab with ipilimumab, nivolumab, and relatlimab may benefit people with advanced melanoma. In earlier studies, 63.6% of patients responded to this combination after 24 weeks, with their cancer either shrinking or stopping its growth. This indicates that the treatment is effective.

Most patients tolerated the treatment well. While side effects can occur, as with any treatment, most were manageable. Sarilumab is already approved for rheumatoid arthritis, indicating its safety for humans, though it is still under study for melanoma. The drugs ipilimumab and nivolumab are already approved for advanced melanoma, which supports their safety.

Overall, early evidence suggests that this treatment is generally well-tolerated and could be a promising option for patients with advanced melanoma. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment combination for melanoma because it incorporates sarilumab, which is primarily known as an anti-inflammatory drug used for rheumatoid arthritis, making its application in cancer treatment quite novel. Unlike the standard of care for melanoma—which often involves immunotherapies like ipilimumab and nivolumab—this study adds sarilumab to potentially address inflammation-related resistance to immunotherapy. By targeting the interleukin-6 (IL-6) pathway, sarilumab might enhance the effectiveness of existing immunotherapies, offering new hope for patients with advanced melanoma.

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

In this trial, participants will receive a combination of sarilumab with ipilimumab, nivolumab, and relatlimab. Research has shown that this combination yields promising results for treating advanced melanoma. Specifically, earlier studies reported a 63.6% response rate after 24 weeks, with many patients experiencing significant tumor reduction. Additionally, 78.8% of patients experienced overall benefits. Sarilumab works by blocking a protein that causes inflammation, potentially making the cancer less aggressive. Ipilimumab and nivolumab are already approved for advanced melanoma, and adding relatlimab has demonstrated similar effectiveness. This combination aims to enhance the body's immune response against melanoma. ^{1 2 6 7 8}

Who Is on the Research Team?

Janice Mehnert, MD

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

This trial is for adults with advanced melanoma (Stage IIIb/c/d or Stage IV) that can't be surgically removed. Participants must not have had previous treatments for metastatic melanoma, except under certain conditions. They should be able to follow the study plan and provide consent. People with brain metastases, another type of melanoma, other cancers within the last 2 years, or autoimmune diseases are excluded.

Inclusion Criteria

I am willing and able to follow the study's schedule and requirements.

I have signed the consent form for this study.

I haven't had any treatment for cancer that has spread, with some exceptions.

Exclusion Criteria

You have a known autoimmune disease that is currently active or suspected, unless you have specific conditions that are allowed.

I haven't taken high-dose steroids or other immune-weakening drugs in the last 14 days.

I do not have untreated brain metastases, carcinomatosis meningitis, or current ocular/uveal melanoma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive an induction treatment cycle of 8 weeks with ipilimumab, nivolumab, relatlimab, and sarilumab

8 weeks

2 visits (in-person) at 4-week intervals

Maintenance

Participants continue treatment cycles of 56 days (8 weeks) each, with sarilumab administered every 2 weeks for the first 24 weeks

Up to 2 years

Visits every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to Month 31

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab Injection
• Nivolumab/Relatlimab
• Sarilumab

Trial Overview

The trial tests Sarilumab combined with Ipilimumab, Nivolumab, and Relatlimab in patients with unresectable advanced melanoma. While Sarilumab is approved for rheumatoid arthritis but not yet for melanoma, Ipilimumab and Nivolumab are FDA-approved for this cancer stage; however, their combination here is investigational.

How Is the Trial Designed?

Group I: Study Group Experimental Treatment 3 Interventions

Participants receive sarilumab at 150 mg flat dose is administered subcutaneously every 2 weeks for 12 doses from day 1, cycle 1 in combination with a regimen of ipilimumab at 1 mg/kg every 8 weeks and fixed dose nivolumab at 480 mg and relatlimab at 160 mg flat dose every 4 weeks two times during the 8-week induction period, then the same regimen again up to week 16, and up to week 24 in maintenance. After week 24 the regimen will be ipilimumab at 1 mg/kg every 8 weeks and fixed dose nivolumab at 480 mg with relatlimab at 160 mg flat dose every 4 weeks for 8 week cycles for up to a total of 2 years in patients with unresectable Stage III/Stage IV melanoma.

Ipilimumab Injection is already approved in United States, European Union for the following indications:

Approved in United States as Yervoy for:

• Advanced melanoma (Stage III and IV)

Approved in European Union as Yervoy for:

• Advanced melanoma (Stage III and IV)

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Published Research Related to This Trial

In a cohort of 64 adults with advanced melanoma treated with nivolumab and ipilimumab, 91% experienced clinically significant immune-related adverse events (AEs), highlighting the treatment's potential for serious side effects.

Despite the high incidence of AEs, most patients did not complete all 4 doses of the treatment, suggesting that fewer doses may still provide clinical benefits without the need for extensive immunosuppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measuring Toxic Effects and Time to Treatment Failure for Nivolumab Plus Ipilimumab in Melanoma. Shoushtari, AN., Friedman, CF., Navid-Azarbaijani, P., et al.[2023]

Ipilimumab significantly improves overall survival in patients with advanced melanoma compared to the gp100 peptide vaccine, reducing the risk of death by 34% with monotherapy and 32% when combined with the vaccine.

The treatment can cause unique immune-related side effects, particularly affecting the skin and gastrointestinal system, which require careful monitoring and management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab: a guide to its use in advanced melanoma. Lyseng-Williamson, KA., Sanford, M.[2017]

Ipilimumab (Yervoy), a CTLA-4 blocking antibody, has been FDA-approved and shown to significantly extend survival in patients with metastatic melanoma, a cancer that has seen little progress in treatment for over 40 years.

The review discusses the mechanism of CTLA-4, which normally inhibits T-cell activation, and highlights the promising results from recent clinical trials demonstrating the efficacy of CTLA-4 blockade in advanced melanoma, marking a significant advancement in cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab and cancer immunotherapy: a new hope for advanced stage melanoma. Mansh, M.[2023]

A four-gene model (CTSD, PLA2G7, TXNRD1, IRAK3) was identified as a strong predictor of survival in melanoma patients treated with the monoclonal antibody tremelimumab, based on a study of 218 patients.

This gene expression model was validated in a separate group of 260 treatment-naïve melanoma patients, demonstrating its potential to enhance the predictive value of existing clinical indicators for patient outcomes in immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood mRNA expression profiling predicts survival in patients treated with tremelimumab. Saenger, Y., Magidson, J., Liaw, B., et al.[2022]

Anti-PD1 therapies, such as pembrolizumab and nivolumab, have shown response rates of 30-40% in patients with metastatic melanoma, providing a significant overall survival benefit compared to traditional chemotherapy and the earlier drug ipilimumab, which had a lower response rate and higher toxicity.

The combination of ipilimumab and nivolumab has been approved and demonstrates improved response rates of 50-57%, but it also comes with a higher risk of serious adverse events, highlighting the need for careful consideration in treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Not Available]. Mateus, C., Libenciuc, C., Robert, C.[2018]

The CheckMate 511 study found that using nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (NIVO3+IPI1) resulted in a significantly lower incidence of severe treatment-related adverse events (34%) compared to nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (NIVO1+IPI3) which had a 48% incidence (P = .006).

While the efficacy outcomes such as objective response rate (45.6% for NIVO3+IPI1 vs. 50.6% for NIVO1+IPI3) and median progression-free survival (9.9 months vs. 8.9 months) were similar between the two groups, the NIVO3+IPI1 regimen showed a better safety profile without compromising effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Two Dosing Regimens for Nivolumab in Combination With Ipilimumab in Patients With Advanced Melanoma: Results From the Phase IIIb/IV CheckMate 511 Trial. Lebbé, C., Meyer, N., Mortier, L., et al.[2020]

Ipilimumab, an effective treatment for advanced melanoma, can cause immune-mediated adverse events, such as sarcoidosis, which may mimic tumor progression in imaging studies.

In a case study of a 37-year-old male, ipilimumab treatment led to the development of sarcoidosis affecting the mediastinum and pituitary gland, successfully managed with corticosteroids, emphasizing the importance of recognizing potential side effects of immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New-onset mediastinal and central nervous system sarcoidosis in a patient with metastatic melanoma undergoing CTLA4 monoclonal antibody treatment. Murphy, KP., Kennedy, MP., Barry, JE., et al.[2020]

Ipilimumab (Yervoy®) is an approved monoclonal antibody for treating malignant melanoma by blocking the CTLA-4 protein, which enhances T-cell responses against tumor cells, showing its efficacy in cancer immunotherapy.

Currently, ipilimumab is also being tested in phase III trials for prostate cancer and phase II trials for non-small cell lung cancer, indicating its potential for broader applications in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab: first global approval. Cameron, F., Whiteside, G., Perry, C.[2021]

Toripalimab is an effective second-line therapy for metastatic melanoma, showing comparable efficacy to pembrolizumab, which is significant given its approval in China in 2018.

However, toripalimab and other PD-1 inhibitors are less effective in certain melanoma subtypes, such as mucosal and acral melanomas, highlighting the need for further research into biomarkers and mechanisms of resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toripalimab for the treatment of melanoma. Tang, B., Chi, Z., Guo, J.[2021]

Ipilimumab, an immunotherapy for metastatic melanoma, can cause serious but rare haematological adverse events like anaemia and leukopenia in some patients, as seen in three cases presented in the study.

These haematological toxicities, while potentially severe, are manageable and can be effectively treated with corticosteroids, highlighting the importance of prompt recognition and intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious haematological toxicity during and after ipilimumab treatment: a case series. Simeone, E., Grimaldi, AM., Esposito, A., et al.[2021]

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