Sarilumab + Immunotherapy for Melanoma
Recruiting in Palo Alto (17 mi)
+5 other locations
Overseen byJanice 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.
12345What 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.
23467What 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.
458910Eligibility 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.
+5 more
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.
+1 more
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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Study GroupExperimental Treatment3 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)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Angeles Clinic at Cedars SinaiLos Angeles, CA
Dana Farber Cancer InstituteBoston, MA
NYU Langone HealthNew York, NY
The Angeles Clinic at Cedars SinaiLos Angeles, CA
More Trial Locations
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Who Is Running the Clinical Trial?
NYU Langone HealthLead Sponsor
References
New-onset mediastinal and central nervous system sarcoidosis in a patient with metastatic melanoma undergoing CTLA4 monoclonal antibody treatment. [2020]Ipilimumab, a cytotoxic monoclonal antibody that inhibits cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), has been established as an effective therapy in the management of advanced melanoma. Immune-mediated adverse events are a common side effect.
Ipilimumab: first global approval. [2021]Ipilimumab (Yervoy®) is an anti-cytotoxic T-lymphocyte antigen (CTLA)-4 monoclonal antibody that has been approved in the US for the first- or second-line treatment of patients with malignant melanoma. In the EU, it is awaiting approval as second-line therapy for melanoma. Ipilimumab blocks the effects of the negative T-cell regulator CTLA-4, which may in turn augment T-cell responses to tumour cells. Preclinical studies have indicated that antibody blocking of CTLA-4 can lead to potent immune responses. Ipilimumab is also in development as first- and second-line therapy for prostate cancer where it has progressed to phase III clinical trials worldwide, and it is in phase II development for non-small cell lung cancer. Ipilimumab was originated by the University of California, Berkeley, in the US and subsequently licensed to Medarex, which was later acquired by Bristol-Myers Squibb. This article summarizes the milestones in the development of intravenous ipilimumab leading to this first approval. This profile has been extracted from Wolters Kluwer's R&D Insight drug pipeline database. R&D Insight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch.
Ipilimumab: a guide to its use in advanced melanoma. [2017]Ipilimumab (Yervoy™), a recombinant monoclonal antibody targeted at cytotoxic T-lymphocyte-associated antigen 4, is approved for the treatment of advanced melanoma. In a placebo-controlled trial in previously treated patients with advanced melanoma, ipilimumab, without or with an investigational glycoprotein (gp) 100 peptide vaccine, was associated with significantly longer median overall survival than gp100 peptide vaccine monotherapy. The risk of death relative to the gp100 peptide vaccine was reduced by 34% with ipilimumab monotherapy and by 32% with ipilimumab plus gp100 peptide vaccine. Overall survival did not differ significantly between treatment with ipilimumab monotherapy and ipilimumab plus gp100 peptide vaccine. Novel immune-related events that are not typical of other anticancer agents, most commonly dermatologic and gastrointestinal disorders, can occur with ipilimumab, necessitating specific monitoring and management protocols.
Measuring Toxic Effects and Time to Treatment Failure for Nivolumab Plus Ipilimumab in Melanoma. [2023]Nivolumab plus ipilimumab (nivo + ipi) is a standard treatment of advanced melanoma. Two randomized trials describe high objective response rates by Response Evaluation Criteria in Solid Tumors. The trials assessed toxic effects using the Common Terminology Criteria for Adverse Events (CTCAE), which may underestimate incidence of clinically significant immune-related adverse events (AEs).
Ipilimumab and cancer immunotherapy: a new hope for advanced stage melanoma. [2023]Metastatic melanoma remains one of the most lethal and poorly treated forms of human cancer. Its incidence is on the rise, but no therapies offering improved survival rates have been developed over the last 40 years. This has changed with the recent Food and Drug Administration (FDA) approval of the CTLA-4 function blocking antibody Ipilimumab (Yervoy), proven to extend life in patients with previously treated or untreated metastatic melanoma [39,40]. CTLA-4 is a receptor that normally functions to inhibit inappropriate or prolonged activation of T-cells. This review presents the history of initial research into the function of the CTLA-4 receptor, the pre-clinical evidence for CTLA-4 blockade's utility in cancer treatment, and the recent human clinical trials that have proven its efficacy in advanced stage melanoma. Ipilimumab represents one of a growing class of cancer immunotherapies currently under development and highlights both the promise and relative infancy of these agents in the clinical setting.
Serious haematological toxicity during and after ipilimumab treatment: a case series. [2021]Immunotherapy with the anti-cytotoxic T-lymphocyte antigen-4 monoclonal antibody ipilimumab has been shown to improve overall survival in previously treated and treatment-naïve patients with unresectable stage III or IV melanoma. Consistent with its proposed immunomodulating mechanism of action, the most common toxicities associated with ipilimumab therapy are immune-related in nature and include those related to the skin and gastrointestinal tract, with endocrine and hepatic events also frequent. Other rare adverse events, including haematological aberrations, may also occur and can have serious consequences if unrecognised. Here we describe three patients who developed serious haematological adverse events during or after treatment with ipilimumab.
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]Nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (NIVO1+IPI3) is approved for first-line treatment of patients with advanced melanoma in several countries. We conducted a phase IIIb/IV study (CheckMate 511) to determine if nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (NIVO3+IPI1) improves the safety profile of the combination.
Blood mRNA expression profiling predicts survival in patients treated with tremelimumab. [2022]Tremelimumab (ticilimumab, Pfizer), is a monoclonal antibody (mAb) targeting cytotoxic T lymphocyte-associated antigen-4 (CTLA-4). Ipilimumab (Yervoy, BMS), another anti-CTLA-4 antibody, is approved by the U.S. Federal Drug Administration (FDA). Biomarkers are needed to identify the subset of patients who will achieve tumor control with CTLA-4 blockade.
[Not Available]. [2018]ANTI-PD1 ROLE IN TREATMENT OF CUTANEOUS MELANOMA: The treatment of metastatic melanoma dramatically changed over the last years. Two therapeutic revolutions emerged in parallel, targeted anti-BRAF and anti-MEK therapies, for patients BRAFV600 mutated and immunotherapy with immune checkpoint blockers using anti-CTLA-4 then anti-PD1 monoclonal antibodies. Indeed, melanoma immunotherapy was a golden objective for many years but in spite of important efforts using cytokines (interferon, interleukin) and different vaccine approaches no objective improvement of patients 'prognosis was obtained. Ipilimumab, authorized in 2011, was the first drug which showed a benefit of overall survival in patients with metastatic melanoma in spite a low response rate (10-15) and the occurrence of about 25% of serious toxicity. Anti-PD1 appear as a new generation of immune checkpoint blockade with response rates between 30 to 40% of the patients, a proven overall survival benefit as compared with chemotherapy or ipilimumab and less toxicity than ipilimumab. Two molecules, pembrolizumab and nivolumab were recently approved in monotherapy, for metastatic melanoma. Several questions remain unresolved: the respective indications of anti-PD1 and targeted therapies in first line therapy in patients with BRAF mutant melanoma, the benefit of combining immunotherapy with radiotherapy or with targeted therapies, the optimal treatment duration, and the benefit of the anti-PD1 in the adjuvant setting. The combination of ipilimumab and nivolumab, recently approved by the FDA but not yet in Europ, shows an improvement of the objective response rates (50-57%) and progression free survival compared with nivolumab but is associated with an higer incidence of serious adverse events (more than 50%).
Toripalimab for the treatment of melanoma. [2021]Immune therapies have dramatically changed the treatment landscape for melanoma in the past decade. Ipilimumab, nivolumab, and pembrolizumab have been approved by U.S. Food and Drug Administration for the treatment of metastatic melanoma sequentially. Toripalimab, a humanized IgG4 monoclonal antibody against programmed cell death protein-1 (PD-1), was approved by National Medical Product Administration in China in 2018 as second-line therapy for metastatic melanoma.