Results

Three patients have been enrolled in each of the 0.25, 0.5, 1.0 and 3.0 mcg/kg dose cohorts and six at 2.0 mcg/kg (N=18). Fourteen patients completed ≥2 cycles, three completed one cycle, and one patient (3 mcg/kg) received only 2 doses due to dose limiting toxicity (DLT). This last patient had NSCLC and developed grade 3 chest pain, hypoxia and dyspnea leading to hospitalization and discontinuation of rhIL-15. One serious adverse event, grade 2 pancreatitis, was observed in a metastatic melanoma patient 3 days after completing Cycle 1 (at 2.0 mcg/kg). Flow cytometric data indicate a consistent increase in the frequency of CD56+CD3-NK cell frequencies peaking at Day 15 of Cycle 1 (3 days after the last dose), with lesser increases in subsequent cycles. The mean fold-increase in circulating NK cells during Cycle 1 was 2.3, 3.3, 4.4, 9.6, and 11.8-fold for the 0.25, 0.5, 1.0, 2.0 and 3.0 mcg/kg dose cohorts respectively, demonstrating dose responsiveness. By contrast, the mean fold-increase in circulating CD8+ T cells was relatively modest at 1.1, 0.9, 1.2, 3.3, and 3.2-fold for the 0.25, 0.5, 1.0, 2.0 and 3.0 mcg/kg dose cohorts respectively.