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

Overview

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.

PRIMARY OBJECTIVES: I. To establish the tolerated dose of the combination of anakinra and tocilizumab that can be used in conjunction with nivolumab and ipilimumab for further evaluation in patients 50 years of age or older at the start of treatment. SECONDARY OBJECTIVES: I. To evaluate the safety of the combination based on Common Terminology Criteria for Adverse Events (CTCAE) version (v) 6.0. II. To evaluate the incidence of discontinuation of immune checkpoint inhibitor (ICI) therapy due to grade 3 or higher immune-related adverse events (irAEs). III. To evaluate objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) (v1.1) by investigator assessment (objective response rate \[ORR\] will be reported separately for patients treated neoadjuvant therapy versus \[vs.\] others). IV. To evaluate overall survival (OS). V. To assess progression-free survival (PFS). EXPLORATORY OBJECTIVES: I. To evaluate change in serum cytokine/chemokine profile. II. To profile peripheral blood (PB) immune subsets. OUTLINE: This is a dose de-escalation study of anakinra in combination with tocilizumab, nivolumab, and ipilimumab. Patients receive anakinra subcutaneously (SC) once daily (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 intravenously (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 magnetic resonance imaging (MRI) and computed tomography (CT) or positron emission tomography (PET)/CT during screening and as clinically indicated as well as blood sample collection throughout the study. After completion of study treatment, patients are followed up at 1 week and then every 6 months for up to 2 years.