Adding Anakinra and Tocilizumab to Nivolumab and Ipilimumab for the Treatment of Melanoma Patients 50 Years of Age or Older

NCT07838974 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: 10M-26-3NCI-2026-06741HS-26-00490P30CA014089
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects of adding anakinra and tocilizumab to standard treatment with nivolumab and ipilimumab and to see how well it works in treating melanoma patients who are 50 years of age or older. Anakinra and tocilizumab are used to decrease the body's immune response and lower side effects. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Researchers think that anakinra and tocilizumab may reduce the side effects experienced from standard treatment with nivolumab and ipilimumab while also preserving their anti-cancer effects. Adding anakinra and tocilizumab to standard treatment with nivolumab and ipilimumab may be safe, tolerable, and/or effective in treating melanoma patients who are 50 years of age or older.

Conditions

Melanoma

Outcome Measures

Primary Outcomes (1)

• Tolerated dose of the combination of anakinra and tocilizumab that can be used in conjunction with nivolumab and ipilimumab in patients 50 years or older

  Up to 12 weeks

Secondary Outcomes (4)

• Incidence of discontinuation of immune checkpoint inhibitor therapy due to grade 3 or higher immune-related adverse events

  Up to 12 weeks

• Objective response rate

  Up to 2 years

• Overall survival

  From first dose of treatment to death due to any cause, assessed up to 2 years

• Progression free survival (PFS)

  From start of treatment to time of progression or death whichever comes first, assessed up to 2 years

Study Arms (1)

Treatment (anakinra, tocilizumab, nivolumab, ipilimumab)

EXPERIMENTAL

Patients receive anakinra SC QD on days 1-21 of each cycle, once every other day of each cycle, or once every 3 days of each cycle. Patients also receive tocilizumab IV, nivolumab IV, and ipilimumab IV on day 1 of each cycle. Cycles repeat every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo MRI and CT or PET/CT during screening and as clinically indicated as well as blood sample collection throughout the study.

Biological: Anakinra; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Other: Electronic Health Record Review; Biological: Ipilimumab; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab; Procedure: Positron Emission Tomography; Biological: Tocilizumab

Interventions

Anakinra BIOLOGICAL

Given SC

Also known as: Kinaret, Kineret, rIL-1ra, rIL1RN

Treatment (anakinra, tocilizumab, nivolumab, ipilimumab)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Treatment (anakinra, tocilizumab, nivolumab, ipilimumab)

Computed Tomography PROCEDURE

Undergo CT or PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (anakinra, tocilizumab, nivolumab, ipilimumab)

Electronic Health Record Review OTHER

Ancillary studies

Treatment (anakinra, tocilizumab, nivolumab, ipilimumab)

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS 734016, BMS-734016, BMS734016, Ipilimumab Biosimilar CS1002, MDX 010, MDX-010, MDX-CTLA4, MDX010, Yervoy

Treatment (anakinra, tocilizumab, nivolumab, ipilimumab)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (anakinra, tocilizumab, nivolumab, ipilimumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: ABP 206, BCD-263, BMS 936558, BMS-936558, BMS936558, CMAB819, MDX 1106, MDX-1106, MDX1106, NIVO, Nivolumab Biosimilar ABP 206, Nivolumab Biosimilar BCD-263, Nivolumab Biosimilar CMAB819, ONO 4538, ONO-4538, ONO4538, Opdivo

Treatment (anakinra, tocilizumab, nivolumab, ipilimumab)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Treatment (anakinra, tocilizumab, nivolumab, ipilimumab)

Tocilizumab BIOLOGICAL

Given IV

Also known as: Actemra, Avtozma, IL-6 receptor monoclonal antibodies: tocilizumab, Immunoglobulin G1, Anti-(Human Interleukin 6 Receptor) (Human-Mouse Monoclonal MRA Heavy Chain), Disulfide with Human-Mouse Monoclonal MRA Kappa-Chain, Dimer, MRA, R-1569, RoActemra, Tocilizumab-aazg, Tocilizumab-anoh, Tyenne

Treatment (anakinra, tocilizumab, nivolumab, ipilimumab)

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 50 years old
• Patients with melanoma, who are going to be treated with ipilimumab 1mg/Kg and nivolumab 3mg/Kg as a standard of care (SOC)
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• Platelets ≥ 50 000/µL
• Hemoglobin ≥ 8.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1500/μL
• Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) ≤ 3.0 X institutional ULN (up to 5 X institutional ULN if patient has liver metastases)
• Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3.0 X institutional ULN (up to 5 X institutional ULN if patient has liver metastases)
• Creatinine \< 2.0 ULN
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Willingness to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol

You may not qualify if:

• Patients must not be receiving other concomitant biologic therapy, targeted therapy, chemotherapy, other anti-cancer therapy or any other investigational agents while on this protocol
• Immunosuppressive systemic corticosteroids equivalent to prednisone 10 mg or greater in the 14 days prior to the first cycle
• Active autoimmune disease requiring systemic treatment in the past 2 years (i.e. use of disease modifying agents or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) is not considered a form of systemic treatment
• Uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness / social situations that would limit compliance with study requirements
• Positive pregnancy test, active pregnancy or nursing / breast-feeding, due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants
• History of solid organ or bone marrow transplantation
• Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug

Sponsors & Collaborators

• University of Southern California: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Interleukin 1 Receptor Antagonist Protein; Receptors, Interleukin-6; Specimen Handling; Ipilimumab; CTLA-4 Antigen; Magnetic Resonance Spectroscopy; Nivolumab; tocilizumab; Immunoglobulin G; Disulfides

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)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Receptors, Interleukin; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biomarkers; Spectrum Analysis; Chemistry Techniques, Analytical; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals

Study Officials

• Fumito Ito

  University of Southern California

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2026
• First Posted: September 24, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): November 1, 2029
• Study Completion (Estimated): November 1, 2030
• Last Updated: September 24, 2026

Record last verified: 2026-09

Locations

US (1)