Siltuximab for the Prevention of Severe Immune-Related Adverse Events During Immune Checkpoint Inhibitor Rechallenge in Patients With Advanced Cancer, CIRES Trial

NCT06470971 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: OSU-23393NCI-2024-04853
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Advanced Malignant Solid Neoplasm; Hematopoietic and Lymphatic System Neoplasm

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Overall response rate

  Up to 5 years

• Median progression-free survival

  Initiation of therapy to time of progression or death, whichever occurs first, assessed up to 5 years

• Overall survival

  Initiation of therapy to death, assessed up to 5 years

Study Arms (1)

Treatment (PD1 antibody, PD-L1 antibody, Siltuximab)

EXPERIMENTAL

Patients receive anti-PD1 or anti-PD-L1 monoclonal antibody therapy either every 3 or 6 weeks, or every 2 or 4 weeks per physicians choice. Patients also receive siltuximab IV over 1 hour on day 1 of each cycle prior to the administration of anti-PD1 or anti-PD-L1 therapy. Treatment repeats either every 3 weeks for up to 8 doses or every 4 weeks for up to 6 doses in the absence of disease progression or unacceptable toxicity. Patients may undergo biopsy and bone scan on study, as well as blood sample collection and CT or MRI throughout the study.

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

Interventions

Anti-PD-L1 Monoclonal Antibody BIOLOGICAL

Receive anti-PD-L1 monoclonal antibody therapy

Treatment (PD1 antibody, PD-L1 antibody, Siltuximab)

Anti-PD1 Monoclonal Antibody BIOLOGICAL

Receive anti-PD1 monoclonal antibody therapy

Also known as: Anti-PD-1 Monoclonal Antibody

Treatment (PD1 antibody, PD-L1 antibody, Siltuximab)

Biopsy PROCEDURE

Undergo biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (PD1 antibody, PD-L1 antibody, Siltuximab)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

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

Treatment (PD1 antibody, PD-L1 antibody, Siltuximab)

Bone Scan PROCEDURE

Undergo bone scan

Also known as: Bone Scintigraphy

Treatment (PD1 antibody, PD-L1 antibody, Siltuximab)

Computed Tomography PROCEDURE

Undergo 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, tomography

Treatment (PD1 antibody, PD-L1 antibody, Siltuximab)

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 (PD1 antibody, PD-L1 antibody, Siltuximab)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (PD1 antibody, PD-L1 antibody, Siltuximab)

Siltuximab BIOLOGICAL

Given IV

Also known as: Anti-IL-6 Chimeric Monoclonal Antibody, cCLB8, CNTO 328, CNTO-328, Sylvant

Treatment (PD1 antibody, PD-L1 antibody, Siltuximab)

Eligibility Criteria

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

You may qualify if:

• 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)
• Recovery from prior irAEs to ≤ grade 1
• Patients who are on prednisone ≤ 10 mg/day (d) or equivalent are allowed
• Hemoglobin \> 7 g/dL and \< 17 g/dL
• Absolute neutrophil count (ANC) ≥ 1000 per mm\^3
• Platelet count ≥ 75 × 10\^9/L
• Serum bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 × institutional ULN or ≤ 5 × ULN for patients with liver metastases
• Measured or calculated creatinine clearance (CL) ≥ 30 mL/min except patients with end-stage renal disease on hemodialysis
• Cycle 1 day 1 of the study treatment should be at least 2 weeks since prior systemic therapy, radiotherapy, or surgery
• Estimated life expectancy, in the judgment of the investigator, of at least 12 weeks
• Subjects of childbearing potential must have a negative serum pregnancy test at screening

You may not qualify if:

• 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
• Other concurrent anticancer therapy except for palliative radiation and hormone therapy
• Has a known history of HIV-1/2 with detectable viral load and/or CD4 (cluster of differentiation 4) count \< 300/mL within the previous 3 months
• Has detectable hepatitis B virus (HBV) or hepatitis C virus (HCV) viral load polymerase chain reaction (PCR) if there is a known history of active hepatitis B or hepatitis C
• High risk for bowel perforation per the investigator's judgment, such as history of severe diverticulitis or active ulcers or extensive gastrointestinal (GI) involvement by the tumor
• Presence of a transplanted solid organ (with the exception of a corneal transplant more than 3 months prior to screening) or having received an allogeneic bone marrow transplant or an allogeneic peripheral blood stem cell transplant
• Uncontrolled concomitant illness including, but not limited to, symptomatic congestive heart failure (New York Heart Association \[NYHA\] class III or IV), unstable angina pectoris, myocardial infarction within 1 month prior to enrollment, uncontrolled cardiac arrhythmias, uncontrolled seizures, or severe noncompensated hypertension (systolic blood pressure \> 180mmHg or diastolic blood pressure \> 120mmHg)
• Patients with a current severe infection
• Known unmanageable allergies, hypersensitivity, intolerance to monoclonal antibodies, to murine, chimeric, human proteins or their excipients
• Prior failure of interleukin-6 or interleukin-6 receptor targeted therapies. Prior IL-6 or IL-6 receptor-targeted therapies are permitted if the response was favorable
• Received any investigational drug within 30 days

Sponsors & Collaborators

• Yuanquan Yang: lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Related Links

• The Jamesline

MeSH Terms

Interventions

spartalizumab; Biopsy; Specimen Handling; Magnetic Resonance Spectroscopy; siltuximab

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Yuanquan Yang, MD, PhD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

The Ohio State University Comprehensive Cancer Cener

CONTACT

800-293-5066; OSUCCCClinicaltrials@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 17, 2024
• First Posted: June 24, 2024
• Study Start: July 9, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2030
• Last Updated: January 20, 2026

Record last verified: 2026-01

Locations

US (1)