Siltuximab for the Prevention of Severe Immune-Related Adverse Events During Immune Checkpoint Inhibitor Rechallenge in Patients With Advanced Cancer, CIRES Trial
NCT Number: NCT06470971
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Advanced Malignant Solid Neoplasm|Hematopoietic and Lymphatic System Neoplasm
Interventions: BIOLOGICAL: Anti-PD-L1 Monoclonal Antibody|BIOLOGICAL: Anti-PD1 Monoclonal Antibody|PROCEDURE: Biopsy|PROCEDURE: Biospecimen Collection|PROCEDURE: Bone Scan|PROCEDURE: Computed Tomography|PROCEDURE: Magnetic Resonance Imaging|OTHER: Quality-of-Life Assessment|BIOLOGICAL: Siltuximab
Sponsor: Yuanquan Yang
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 40
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-07-31
Completion Date: 2025-12-31
Locations: Ohio State University Comprehensive Cancer Center, Columbus, Ohio, 43210, United States

Summary:
This phase II trial studies how well giving siltuximab during the reintroduction (rechallenge) of immune checkpoint inhibitor (ICI) therapy works in preventing severe immune-related adverse events (irAEs) in patients with cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Immune checkpoint inhibitors, such as anti-PD1 and anti-PD-L1 monoclonal antibodies, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The use of ICI therapy may lead to severe irAEs that can affect essentially any organ system in the body. Severe irAEs may lead to the early stopping of life saving treatment. Most patients that stop ICI therapy early will eventually progress and require additional treatment. Sometimes the decision is made to rechallenge with ICI therapy. Many patients who developed severe irAEs during initial ICI therapy are at risk for developing severe irAEs again during the rechallenge. Siltuximab is a monoclonal antibody that binds to receptors for a protein called interleukin-6 (IL-6). This may help lower the body's immune response and reduce inflammation. Giving siltuximab during ICI rechallenge may help prevent severe irAEs in patients with advanced cancer.

Primary Outcome Measures: Incidence of severe immune-related adverse event (irAE), Will be assessed per National Cancer Institute Common Terminology Criteria for Adverse Events version (v) 5.0. irAEs are defined as AEs of immune nature (i.e., inflammatory) in the absence of a clear alternative etiology. The investigators will determine if an AE should be classified as irAE (yes/no). Will be defined as ≥ grade 2 requiring treatment discontinuation and prednisone \> 0.5 milligrams/kilogram/day or equivalent followed by a taper ≥ 4 weeks) within 24 weeks of ICI rechallenge., Within 24 weeks of immune checkpoint inhibitor (ICI) rechallenge
Secondary Outcome Measures: Overall response rate, Will be determined per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Will be calculated as the percentage of patients achieving complete response or partial response. The exact binomial 95% confidence interval (CI) will be provided., Up to 5 years|Median progression-free survival, Will be determined per RECIST v1.1. Survival will be analyzed using Kaplan-Meier methods, resulting in median survival times with 95% CI., Initiation of therapy to time of progression or death, whichever occurs first, assessed up to 5 years|Overall survival, Will be determined per RECIST v1.1. Survival will be analyzed using Kaplan-Meier methods, resulting in median survival times with 95% CI., Initiation of therapy to death, assessed up to 5 years