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.
Males or females aged ≥ 18 years
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
Patients with any advanced cancer types who would benefit from anti-PD1 or anti-PD-L1 therapy rechallenge at the investigator's discretion
Patients must have had prior severe irAE while on ICI monotherapy or in combination with other anticancer treatment. Severe irAE is defined as any grade 2 or higher irAE requiring treatment discontinuation and prednisone > 0.5 milligrams (mg)/kilogram (kg)/day (or equivalent) followed by a taper ≥ 4 weeks. Patients with history of grade 4 severe irAE need to carefully weigh the risks and benefits and might be eligible on a case-by-case basis after discussion with principal investigator (PI)
Women who are pregnant or breastfeeding
Any ≥ grade 3 irAEs in which the risks outweigh the benefits per investigator's discretion (these may include but are not limited to myocarditis, myasthenia gravis, Guillain-Barré syndrome, encephalitis, myelitis, or other life-threatening events)
Has active autoimmune disease or irAE requiring systemic treatment with steroids (> 10 mg daily doses of prednisone or equivalent) or other immunosuppressive agents or any condition that, in the investigator's judgment, precludes treatment with anti-PD-1/PD-L1 therapy
Cycle 1 day 1 of the study treatment must be at least 2 weeks beyond high dose systemic corticosteroids (prednisone > 0.5 mg/kg/day or equivalent); chronic steroid use up to 10 mg daily prednisone (or equivalent) is permitted
Single group
Anti-PD-L1 Monoclonal Antibody
Biological/VaccineReceive anti-PD-L1 monoclonal antibody therapy
Anti-PD1 Monoclonal Antibody
Biological/VaccineReceive anti-PD1 monoclonal antibody therapy
Biopsy
Procedure/SurgeryUndergo biopsy
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Bone Scan
Procedure/SurgeryUndergo bone scan
Computed Tomography
Procedure/SurgeryUndergo CT
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Quality-of-Life Assessment
Other interventionAncillary studies
Siltuximab
Biological/VaccineGiven IV
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.
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.
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.
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.
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Yuanquan Yang
Lead sponsor
Ohio State University Comprehensive Cancer Center
Sponsor institution
