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

Description

PRIMARY OBJECTIVE:

I. To determine whether siltuximab prophylaxis reduces rates of de novo or recurrent severe irAE within 24 weeks of anti-PD-1/PD-L1 therapy rechallenge.

SECONDARY OBJECTIVE:

I. To assess the preliminary anti-tumor activity of this combination including overall response rate (ORR), progression-free survival (PFS) and overall survival (OS).

EXPLORATORY OBJECTIVES:

I. To evaluate potential predictive biomarkers such as baseline serum IL-6 level, C-reactive protein (CRP) suppression level, tissue IL-6 expression, stool microbiome, and antibody clearance rate.

II. To assess changes in immune cell infiltration of irAE site pre- and post-treatment by multiomics profiling.

III. To assess patient-reported outcomes by Patient-Reported Outcomes Measurement Information System (PROMIS) instruments.

IV. To correlate circulating tumor deoxyribonucleic acid (ctDNA) levels with treatment responses.

OUTLINE:

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 intravenously (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 computed tomography (CT) or magnetic resonance imaging (MRI) throughout the study.

After completion of study treatment, patients are followed up at day 28, every 12 weeks for up to 2 years, and then every 6 months until 5 years following registration.