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

Inclusion Criteria

• •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