Siltuximab to Prevent Immune Side Effects During Cancer Treatment Rechallenge
This study is testing if giving siltuximab can help prevent severe immune-related side effects (irAEs) when patients with advanced cancer restart (rechallenge) immune checkpoint inhibitor (ICI) therapy. ICI therapies, like anti-PD1 and anti-PD-L1 monoclonal antibodies, help your body's immune system fight cancer, but they can also cause serious side effects. This trial aims to see if siltuximab can reduce these severe irAEs, which sometimes lead to stopping life-saving cancer treatment. You might be able to join if you are 18 or older, have advanced cancer, and previously experienced a severe irAE from ICI therapy. The study will look at how many people experience severe irAEs within 24 weeks of restarting ICI therapy.
- Study design
- This is an interventional study with a planned enrollment of 40 participants. The phase is not specified.
- What's involved
- You would receive anti-PD1 or anti-PD-L1 therapy along with siltuximab given intravenously (IV) on day 1 of each cycle. Treatment cycles repeat every 3 or 4 weeks for up to 6 to 8 doses.
- Compensation
- Not stated in the trial record.
- Follow-up
- The primary endpoint measures severe irAEs within 24 weeks of immune checkpoint inhibitor rechallenge.
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NCT06470971
Siltuximab for the Prevention of Severe Immune-Related Adverse Events During Immune Checkpoint Inhibitor Rechallenge in Patients With Advanced Cancer, CIRES Trial
Recruiting
PHASE2Ages 18+InterventionalTreatmentYuanquan YangInvestigator-initiated
~40 participants
Updated 2026-01-20 on ClinicalTrials.gov
What's tested:Anti-PD-L1 Monoclonal AntibodyAnti-PD1 Monoclonal AntibodyBiopsyBiospecimen CollectionBone ScanComputed Tomography
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Incidence of severe immune-related adverse event (irAE)
Measured over Within 24 weeks of immune checkpoint inhibitor (ICI) rechallenge
Conditions
Where it's being run
1 sites across 1 statesOhio1
Study leadership
- Yuanquan Yang, MD, PhD · PRINCIPAL_INVESTIGATOR · Ohio State University Comprehensive Cancer Center
Who to contact
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Do you actually qualify for this trial?
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Eligibility criteria
Inclusion
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
Subjects of childbearing potential must be willing to completely abstain or agree to use a highly effective method of contraception (i.e., less than 1% failure rate), from the time of signing informed consent and for the duration of study participation through 3 months following the last dose of study drug
Childbearing potential is defined by the following criteria: 1. Subject has not undergone a hysterectomy or bilateral oophorectomy; or 2. has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
Highly effective birth control methods (less than 1% failure rate per year if used consistently and correctly) include but are not limited to: 1. Oral, injected, or implanted hormonal method of contraception; 2. Place of intrauterine device (IUD) or system (IUS); 3. Tubal ligation (tubes tied) or a sterile partner (effective bilateral vasectomy)
Subjects must not breastfeed a child during the study and for 3 months after the last dose of study drug
Ability to understand and willingness to sign the written informed consent document
Exclusion
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
What this trial measures
- Incidence of severe immune-related adverse event (irAE)Within 24 weeks of immune checkpoint inhibitor (ICI) rechallenge
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.