Sarilumab + Immunotherapy for Melanoma

Recruiting at 5 trial locations

Overseen by Janice Mehnert, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: NYU Langone Health

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Untreated brain metastases, Autoimmune disease, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests a combination of drugs, including one usually for arthritis and three for cancer. It targets patients with advanced melanoma that can't be surgically removed. The drugs help the immune system attack the cancer by blocking proteins that help the cancer grow.

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.

What data supports the effectiveness of the drug combination Sarilumab + Immunotherapy for Melanoma?

Ipilimumab, one of the drugs in the combination, has been shown to extend life in patients with advanced melanoma by blocking a receptor that normally inhibits T-cells, allowing the immune system to better attack cancer cells. Additionally, combining Nivolumab with Ipilimumab has shown high response rates in treating advanced melanoma. ^{1 2 3 4 5}

What safety information is available for Sarilumab and immunotherapy treatments like Ipilimumab and Nivolumab in melanoma?

Ipilimumab and Nivolumab, used in melanoma treatment, can cause immune-related side effects, mainly affecting the skin and digestive system, and sometimes serious blood-related issues. Monitoring and managing these side effects is important for patient safety. ^{2 3 4 6 7}

What makes the Sarilumab + Immunotherapy treatment for melanoma unique?

This treatment combines sarilumab, an anti-inflammatory drug, with immunotherapy drugs like ipilimumab and nivolumab, which are known to boost the immune system's ability to fight cancer. The combination aims to enhance the effectiveness of immunotherapy by potentially reducing inflammation-related side effects, offering a novel approach compared to using immunotherapy alone. ^{4 5 8 9 10}

Research Team

Janice Mehnert, MD

Principal Investigator

NYU Langone Health

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Ipilimumab Injection (Monoclonal Antibodies)
• Nivolumab/Relatlimab (Monoclonal Antibodies)
• Sarilumab (Monoclonal Antibodies)

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.

Participant Groups

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.

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Findings from Research

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]

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]

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 (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]

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]

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]

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]

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]

References

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

New-onset mediastinal and central nervous system sarcoidosis in a patient with metastatic melanoma undergoing CTLA4 monoclonal antibody treatment. [2020]

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

Ipilimumab: first global approval. [2021]

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

Ipilimumab: a guide to its use in advanced melanoma. [2017]

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

Measuring Toxic Effects and Time to Treatment Failure for Nivolumab Plus Ipilimumab in Melanoma. [2023]

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

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

6. England pubmed.ncbi.nlm.nih.gov

Serious haematological toxicity during and after ipilimumab treatment: a case series. [2021]

7. United States 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. [2020]

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

Blood mRNA expression profiling predicts survival in patients treated with tremelimumab. [2022]

9. France pubmed.ncbi.nlm.nih.gov

[Not Available]. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Toripalimab for the treatment of melanoma. [2021]