PK and PD of recombinant human IL-18 (rhIL-18) administered IV in repeated cycles to patients with solid tumors

2535 Background: rhIL-18, a potent immunomodulatory cytokine, has demonstrated anti-tumor activity in a variety of preclinical models. Clinical safety and biological activity were examined in a previous study of rhIL-18 administered in a single cycle at IV doses ranging from 3 - 1000 mcg/kg/day for 5 days. The current study examined the effects of administering repeated cycles, and the resulting PK exposure and PD biomarker response data, which are described below. Methods: Three cohorts of 3 patients each were enrolled (6 with melanoma and 3 with metastatic renal cell carcinoma), and received 100, 500, or 1000 mcg/kg doses of rhIL-18 (SB485232) administered as 2h infusions daily for 5 consecutive days every 28 days in repeated cycles (up to 6). Assessments included tolerability, immunogenicity, anti-tumor activity, PK, and biomarkers of immunomodulatory activity. PK and PD measurements were made on Days 1 and 5 of Cycles 1 and 2. Plasma drug concentrations were measured by ELISA. Cytokine/protein biomark...