Table 2.

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
Escherichia coli rhIL-15	0.3 µg/kg/day bolus intravenous 12 consecutive days	18 patients with malignant melanoma or renal cell cancer	Grade 3 hypotension Grade 3 thrombocytopenia Grade 3 ALT and AST elevations	2–3	3–4	3	Stable disease (five patients had 10%–30% decrease in marker lesions and two disappearance of lung lesions)	Conlon et al16
E. coli rhIL-15	2 µg/kg/day subcutaneous days 1–5, 8–12	19 patients with advanced solid tumors	Grade 2 pancreatitis Grade 3 cardiac/chest pain	10.8	37	3.3	Stable disease	Miller et al30
E. coli rhIL-15	2 µg/kg/day CIV for 10 days	27 patients with metastatic solid tumors	2 deaths (1 due to gastrointestinal ischemia and 1 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 al31
E. coli rhIL-15	3–5 µg/kg/day CIV for 5 days	11 patients with advanced solid tumors	None	34	144	3.4	Stable disease	Dubois et al (present study)
ALT-803	10 µg/kg intravenous or subcutaneous weekly for 4 weeks	33 patients with hematological malignancies	2 deaths (1 due to sepsis, 1 due to intracranial hemorrhage) Grade 4 sepsis Grade 2 pemphigus	5	6	2	1 CR, 1 PR, 3 SD	Romee et al34
ALT-803	20 µg/kg subcutaneous, 4 consecutive weeks every 6 weeks	24 patients 11 intravenous, 13 subcutaneous with solid tumors	Grade 4 congestive heart failure Grade 4 neutropenia Injection site reaction	3.3	6.3	1.3	No PR or CR	Margolin et al35

ALT, alanine aminotransferase; CIV, continuous intravenous infusion; CR, complete response; IL, interleukin; MTD, maximum tolerated dose; NK, natural killer; PR, partial response; rhIL-15, recombinant human interleukin-15; SD, stable disease.