Interleukin-6 Receptor Inhibitor Sarilumab in Combination With Ipilimumab, Nivolumab and Relatlimab in Patients With Unresectable Stage III or Stage IV Melanoma

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to 100 Years
• SexAll
• Healthy volunteersNo

You may be able to join if

• Patients must have signed and dated an Institutional Review Board/Independent Ethics Committee -approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal patient care
• Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, tumor biopsies, and other requirements of the study.
• All patients must be either Stage IIIb/c/d or Stage IV according to the American Joint Committee on Cancer (AJCC) (8th edition) and have histologically-confirmed melanoma that is felt to be surgically unresectable in order to be eligible. Please refer to the AJCC Cancer Staging Manual, 8th edition for a description of tumor, lymph node, metastasis and staging.
• All melanomas, except ocular/uveal melanoma, regardless of primary site of disease will be allowed; mucosal melanomas are eligible.
• Patients must not have received prior anticancer treatment for metastatic disease (for example, but not limited to, systemic, local, radiation, radiopharmaceutical).
• oExceptions: Surgery for melanoma and/or post-resection brain radiotherapy (RT) if central nervous system (CNS) metastases and local radiation for locoregional disease and/or prior treatment with adjuvant nivolumab, dabrafenib and trametinib, pembrolizumab, interferon (IFN) or ipilimumab (IPI) (as described in Exclusion Criterion 8,4 full protocol below).
• All patients must have their disease status documented by a complete physical examination and imaging studies within 4 weeks prior to the first dose of study drug. Imaging studies must include computerized tomography (CT) scan of chest, abdomen, pelvis, and all known sites of resected disease in the setting of Stage IIIb/c/d or Stage IV disease, and brain magnetic resonance imaging ([MRI]; brain CT is allowable if MRI is contraindicated).
• Disease must be measurable by RECIST 1.1
• The complete set of baseline radiographic images must be available before treatment initiation.

You cannot join if

• Patients with untreated brain metastases, carcinomatosis meningitis or current ocular/uveal melanoma are excluded.
• Patients with previous non-melanoma malignancies are excluded unless a complete resection or remission was achieved at least 2 years prior to study entry and no additional therapy is required or anticipated to be required during the study period (exceptions include, but are not limited to, non-melanoma skin cancers, in situ bladder cancer, in situ gastric cancer or gastrointestinal stromal tumor, in situ colon cancers, in situ cervical cancers/dysplasia, or breast carcinoma in situ).
• Patients with active, known, or suspected autoimmune disease. Patients with type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, or skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll. For any cases of uncertainty, it is recommended that the Principal Investigator be consulted prior to signing informed consent.
• Patients with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids are permitted in the absence of active autoimmune disease

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

sarilumab. A recombinant, human immunoglobulin (IgG) monoclonal antibody targeting the interleukin 6 receptor (IL-6R), with potential anti-inflammatory activity. Upon intravenous administration of sarilumab, this agent targets and binds to both soluble IL-6 receptor (sIL-6R) and membrane-bound IL-6 receptor (mIL-6R). This inhibits the binding of the pro-inflammatory cytokine IL-6 to the IL-6 receptor (IL-6R), which results in the blockade of the IL-6/IL-6R-mediated signal transduction pathway. This may inhibit IL-6/IL-6R-mediated inflammation. NCI Drug Dictionary

ipilimumab. A recombinant human immunoglobulin (Ig) G1 monoclonal antibody directed against the human T-cell receptor cytotoxic T-lymphocyte-associated antigen 4 (CTLA4), with immune checkpoint inhibitory and antineoplastic activities. Ipilimumab binds to CTLA4 expressed on T cells and inhibits the CTLA4-mediated downregulation of T-cell activation. This leads to a cytotoxic T-lymphocyte (CTL)-mediated immune response against cancer cells. CTLA4, an inhibitory receptor and member of the immunoglobulin superfamily, plays a key role in the downregulation of the immune system. NCI Drug Dictionary

nivolumab. A fully human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed death-1 (PD-1, PCD-1) with immune checkpoint inhibitory and antineoplastic activities. Upon administration, nivolumab binds to and blocks the activation of PD-1, an immunoglobulin superfamily (IgSF) transmembrane protein, by its ligands programmed cell death ligand 1 (PD-L1), which is overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on antigen-presenting cells (APCs). This results in the activation of T cells and cell-mediated immune responses against tumor cells. Activated PD-1 negatively regulates T-cell activation and plays a key role in tumor evasion from host immunity. NCI Drug Dictionary

Treatments listed in the registry

• Sarilumab (Drug): Injectable solutions of sarilumab are formulated in 2 mL of aqueous solution in a 5 mL vial containing 175 mg/ml of sarilumab arginine (8.94 mg), histidine (3.71 mg), polysorbate 20 (2.28 mg), sucrose (57 mg) and Water for Injection USP.Patients will be administered sarilumab at a dose of 150 mg subcutaneously in combination with ipilimumab, nivolumab and relatlimab given intravenously, with nivolumab/relatlimab given intravenously, or sarilumab at a dose of 150 mg subcutaneously given alone.
• Ipilimumab Injection (Drug): Ipilimumab injection is a sterile, nonpyrogenic, clear to slightly opalescent, colorless to pale yellow solution, single-use, preservative-free, isotonic aqueous solution that may contain particles. It is formulated at a concentration of 5 mg/mL ipilimumab in TRIS hydrochloride (also known as 2-amino-2-hydroxymethyl-1,3-propanediol hydrochloride), sodium chloride, mannitol, pentetic acid (also known as diethylenetriaminepentaacetic acid or DTPA), polysorbate 80, and water at pH 7.0. Sodium hydroxide and/or hydrochloric acid may be used to adjust the pH of the solution. Ipilimumab Injection 200 mg/40 mL (5 mg/mL) is packaged in a 50-cc Type I flint molded glass vials.
• Nivolumab/Relatlimab (Drug): The FDC drug product, referred to as nivolumab/relatlimab, contains relatlimab and nivolumab in a single vial in a kit of 2 vials. The product is a sterile, non-pyrogenic, single-use, isotonic aqueous solution for IV infusion. It is formulated at a total protein concentration of 16 mg/mL (4 mg/mL relatlimab and 12 mg/mL nivolumab) and is packaged in a 20-cc glass vial in a kit of two vials. Each vial contains 80 mg of relatlimab and 240 mg of nivolumab.

Randomized · Single Group · masking: None

Main goals

• Number of Grades 3-5 Treatment-Related Immune-Related Adverse Events (irAE) per NCI CTCAE v 5.0 Criteria (week 24 (+/- 7 days))
• Response Evaluation Criteria in Solid Tumors (RECIST 1.1) Category (week 24 (+/- 7 days))

Other goals

• Progression-free survival (PFS)
• Overall survival (OS)
• Best overall response (iBOR)
• Disease Control Rate (DCR)
• Duration of Overall Response
• Duration of disease control
• Immune-related Response Rate (irRR) per irRC criteria
• Immune-related Response Rate (irRR) per irRC criteria
• Immune-related Disease Control Rate per irRC criteria
• Immune-related Progression-Free Survival (irPFS)
• Duration of Immune-related Overall Response
• Duration of Immune-related Disease Control

Planned enrollment: 105 (estimated).

• The Angeles Clinic at Cedars Sinai, Los Angeles, California
• Massachusetts General Hospital, Boston, Massachusetts
• Dana Farber Cancer Institute, Boston, Massachusetts
• NYU Langone Health, New York, New York

Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT05428007
• NCI Drug Dictionary: C152302
• NCI Drug Dictionary: C2654
• NCI Drug Dictionary: C186440

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Oct 27, 2026. Public record; not medical advice.