A phase 1 trial of recombinant human IL-21 in combination with cetuximab in patients with metastatic colorectal cancer.

Authors: Steele N Anthony A Saunders M Esmarck B Ehrnrooth E Kristjansen PE Nihlén A Hansen LT Cassidy J
Address: CRUK Clinical Trials Unit, Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow G12 0YN, UK. n.steele@nhs.net
Journal:

Publication:

abstract

BACKGROUND:

Pre-clinical data indicate enhanced anti-tumour activity when combining recombinant human interleukin-21 (rIL-21), a class 1 cytokine, with cetuximab, a monoclonal antibody, targeting the epidermal growth factor receptor. This phase 1 trial assessed the safety and tolerability of escalating doses of rIL-21 in combination with cetuximab in chemo-naïve patients with stage IV colorectal cancer.

PATIENTS AND METHODS:

Sequential cohorts of PS 0-1, asymptomatic patients, were treated weekly with cetuximab 250 mg m(-2) intravenously (i.v.) plus escalating i.v. doses of rIL-21 following an initial loading dose of cetuximab 400 mg m(-2). Initial treatment period was 8 weeks, with extension permitted in patients without disease progression.

RESULTS:

In all, 15 patients were included in this study. Adverse events related to rIL-21 or rIL-21 plus cetuximab included lethargy, nausea/vomiting, stomatitis, lymphopenia and pyrexia and were mainly ≤ grade 2. One dose limiting toxicity occurred (grade 3 diarrhoea). Maximum tolerated dose was not determined because of the premature study closure. Maximum administered dose was 100 μg kg(-1) rIL-21 weekly. In all, 60% of the patients had stable disease. Immune activation was confirmed by various T- and NK-cell activation biomarkers, including dose-dependent increases in serum sCD25.

CONCLUSION:

rIL-21 weekly combined with cetuximab is well tolerated at doses up to 100 μg kg(-1) and results in activation of immune response biomarkers.

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