Table 3.

Clinical trials of IL-15 in combination immunotherapy of cancer.

IL-15 and combination agent	MTD or expansion dose/dosing schedule	Study population	Serious and notable adverse event	Maximum fold increase of NK cells	Best clinical response	References
ALT-803 + nivolumab	20 μg/kg ALT-803 sc combination with IV nivolumab every 2 weeks	21 patients with metastatic non-small cell lung cancer	Grade 3 myocardial infarction. Injection site reaction.	3	6 PR, 10 SD	Wrangle et al. (74) Medical University of South Carolina, Health Hollings Cancer Center
E. coli rhIL-15 with haploidentical NK cell infusion	IL-15, 1.0 mcg/kg for 12 consecutive days IV with haploidentical NK cell infusion 2.0 mcg sc for 10 doses	42 patients: 26 IV and 16 sc with refractory acute myeloid leukemia	One patient died with cerebral infarct intracranial aspergilloma. 9 of 16 sc patients had CRS including fever, hypotension and in 5 of 9 concurrent neurotoxicity including one Grade 5.	NA	Of 15 IV patients: 6 CR and 2 Cri.	Cooley et al. (75) Masonic Cancer Center, University of Minnesota
E. coli rhIL-15 alemtuzumab	IL-15 sc Mon-Fri 0.5, 1.0, 2.0 mcg/kg/day for 2 weeks, followed by alemtuzumab 3, 10, 30 mcg/kg/day	8 patients with mature T cell malignancy	None	15	PR, CR elimination of leukemic T cells in each of 7 patients studied with leukemia	Miljkovic et al. (76)National Cancer Institute, NIH

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.