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

NCT05428007 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 22-00325
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 4

Brief Summary

This study will evaluate how safe the study drug is, how well patients tolerate it, how it works in the body, and the disease's response to the drug. The study drug being tested is sarilumab, when given with the combination of ipilimumab, nivolumab, and relatlimab in patients like yourself, with stage III or stage IV melanoma that cannot be removed by surgery. Previous studies have provided a strong rationale for combining sarilumab, with ipilimumab, nivolumab and relatlimab in metastatic melanoma to reduce side effects and potentially work better for your type of cancer. Sarilumab is an FDA-approved inhibitor of the receptor for the cytokine IL-6, currently approved for the treatment of rheumatoid arthritis, but it is not FDA-approved to treat melanoma. This means that the use of Sarilumab to treat melanoma is considered investigational. The other drugs which will be administered in this study, ipilimumab and nivolumab, are also monoclonal antibodies, but they target different proteins. Ipilimumab and nivolumab are both approved by the FDA to treat advanced stage III and IV melanomas. The nivolumab + relatlimab FDC (fixed dose combination) being used in this study is considered investigational, meaning it is not approved by the FDA. The combination of sarilumab, ipilimumab, nivolumab and relatlimab is considered investigational because it has not yet been approved by the FDA. The FDA has given its permission to study the investigational combination of these drugs in this research study.

Conditions

Melanoma; Unresectable Melanoma

Outcome Measures

Primary Outcomes (2)

• Number of Grades 3-5 Treatment-Related Immune-Related Adverse Events (irAE) per NCI CTCAE v 5.0 Criteria

  The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v 5.0) grades adverse events by the following scale: Grade 1 - Mild, Grade 2 - Moderate, Grade 3 - Severe, Grade 4 - Life-threatening, Grade 5 - Death Safety will be measured by physical examinations, vital sign measurements, Eastern Cooperative Oncology Group (ECOG) performance status evaluations, AE assessments, laboratory testing, electrocardiograms (ECGs), oxygen saturation, and concomitant medications.

  week 24 (+/- 7 days)

• Response Evaluation Criteria in Solid Tumors (RECIST 1.1) Category

  Each patient will be assigned one of the following categories: 1. = Complete Response (CR) = Disappearance of all target lesions; 2. = Partial Response (PR) = At least a 30% decrease in the sum of the longest diameter (LD) of target lesions. 3. = Stable Disease (SD) = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD since treatment started. 4. = Progressive Disease (PD) = At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. 5. = Early death from malignant disease 6. = Early death from toxicity 7. = early death because of other cause 9 = Unknown (not assessable, insufficient data)

  week 24 (+/- 7 days)

Secondary Outcomes (12)

• Progression-free survival (PFS)

  Up to Month 31

• Overall survival (OS)

  Up to Month 31

• Best overall response (iBOR)

  week 24 (+/- 7 days)

• Disease Control Rate (DCR)

  Month 31

• Duration of Overall Response

  Month 31

Study Arms (3)

Stage I: sarilumab, ipilimumab, nivolumab and relatlimab

EXPERIMENTAL

Participants with unresectable Stage III/Stage IV melanoma 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.

Drug: Sarilumab; Drug: Ipilimumab Injection; Drug: Nivolumab/Relatlimab

Stage II: ipilimumab, nivolumab and relatlimab

EXPERIMENTAL

Participants with unresectable Stage III/Stage IV melanoma receive 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.

Drug: Ipilimumab Injection; Drug: Nivolumab/Relatlimab

Stage II: sarilumab, ipilimumab, nivolumab and relatlimab

EXPERIMENTAL

Participants with unresectable Stage III/Stage IV melanoma 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.

Drug: Sarilumab; Drug: Ipilimumab Injection; Drug: Nivolumab/Relatlimab

Interventions

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.

Also known as: BMS-986213

Stage I: sarilumab, ipilimumab, nivolumab and relatlimab; Stage II: ipilimumab, nivolumab and relatlimab; Stage II: sarilumab, ipilimumab, nivolumab and relatlimab

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.

Also known as: REGN88

Stage I: sarilumab, ipilimumab, nivolumab and relatlimab; Stage II: sarilumab, ipilimumab, nivolumab and relatlimab

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.

Also known as: BMS-734016, MDX010, MDX-CTLA4

Stage I: sarilumab, ipilimumab, nivolumab and relatlimab; Stage II: ipilimumab, nivolumab and relatlimab; Stage II: sarilumab, ipilimumab, nivolumab and relatlimab

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify 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).
• 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 may not qualify 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

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (4)

The Angeles Clinic at Cedars Sinai

Los Angeles, California, 90025, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

NYU Langone Health

New York, New York, 10016, United States

RECRUITING

MeSH Terms

Conditions

Melanoma

Interventions

sarilumab; Ipilimumab; CTLA-4 Antigen; Nivolumab; relatlimab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers

Study Officials

• Janice Mehnert, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Janice Mehnert, MD

CONTACT

212-731-5431; janice.mehnert@nyulangone.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2022
• First Posted: June 22, 2022
• Study Start: February 2, 2023
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): February 1, 2028
• Last Updated: January 5, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)