Table 1.

IL-15 Clinical trials in patients with metastatic malignancy.

IL-15 agent	MTD or expansion dose/dosing schedule	Study population	Serious and notable adverse events	Maximum fold increase in total NK cells at MTD	Maximum fold increase in CD56 bright NK cells	Maximum fold increase in CD8 T cells	Best clinical Response	References
E. coli rhIL-15	0.3 μg/kg/d bolus i.v. 12 consecutive days	18 patients with malignant melanoma or renal cell cancer	Grade 3 hypotension Grade 3 thrombocytopenia Grade 3 ALT, AST elevations	2–3	3–4	3	Stable disease (5 patients had 10–30% decrease in marker lesions and 2 disappearance of lung lesions)	Conlon et al. (43) National Cancer Institute, NIH
E. coli rhIL-15	2 μg/kg/d CIV for 10 days	27 patients with metastatic solid tumors	2 deaths (one due to gastrointestinal ischemia and one due to disease progression) Grade 3 bleeding Grade 3 papilledema Grade 3 uveitis Grade 3 hepatic encephalopathy	38	358	5.8	Stable disease	Conlon et al. (45) National Cancer Institute, NIH
E. coli rhIL-15	2 μg/kg/d SC days 1–5, 8–12	19 patients with advanced solid tumors	Grade 2 pancreatitis Grade 3 cardiac/chest pain	10.8	39.7	3.3	Stable disease	Miller et al. (44) Minnesota Cancer Center
ALT-803	10 μg/kg IV or SC weekly for 4 weeks	33 patients with hematological malignancies	2 deaths (one due to sepsis, one due to intracranial hemorrhage) Grade 4 sepsis Grade 2 pemphigus	8	8	2	1 CR, 1 PR, 3 SD	Romee et al. (46) Minnesota Cancer Center
ALT-803	20 μg/kg SC 4 consecutive weeks every 6 weeks	21 patients 11 IV, 13 SC with solid tumors	Grade 4 congestive heart failure Grade 4 neutropenia Injection site reaction	3.3	6.3	6.3	No PR or CR	Margolin et al. (47) Fred Hutchinson Cancer Center

CIV, continuous intravenous infusion; d, day; IL-15, interleukin 15; IV, intravenous; Kg, kilogram; NA, not available; SC, subcutaneous; CR, complete response; PR, partial response; SD, stable disease; CRS, cytokine release syndrome.