Table 1. IL-15 clinical trials in... | Rockefeller University Press

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. for 12 d consecutively	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 had disappearance of lung lesions)	Conlon et al., 2015
E. coli rhIL-15	2 µg/kg/d CIV for 10 d	27 patients with metastatic solid tumors	Two 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., 2019
E. coli rhIL-15	2 µg/kg/d s.c. on days 1–5 and 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., 2018
ALT-803	10 µg/kg i.v. or s.c. weekly for 4 wk	33 patients with hematological malignancies	Two 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., 2018
ALT-803	20 µg/kg s.c. for 4 wk consecutively every 6 wk	24 patients (11 i.v., 13 s.c.) 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 al., 2018
ALT-803 + nivolumab	20 µg/kg ALT-803 s.c. combination with i.v. nivolumab every 2 wk	21 patients with metastatic non-small cell lung cancer	Grade 3 myocardial infarction; injection site reaction	3	NA	Minor response	6 PR, 10 SD	Wrangle et al., 2018

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. for 12 d consecutively	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 had disappearance of lung lesions)	Conlon et al., 2015
E. coli rhIL-15	2 µg/kg/d CIV for 10 d	27 patients with metastatic solid tumors	Two 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., 2019
E. coli rhIL-15	2 µg/kg/d s.c. on days 1–5 and 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., 2018
ALT-803	10 µg/kg i.v. or s.c. weekly for 4 wk	33 patients with hematological malignancies	Two 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., 2018
ALT-803	20 µg/kg s.c. for 4 wk consecutively every 6 wk	24 patients (11 i.v., 13 s.c.) 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 al., 2018
ALT-803 + nivolumab	20 µg/kg ALT-803 s.c. combination with i.v. nivolumab every 2 wk	21 patients with metastatic non-small cell lung cancer	Grade 3 myocardial infarction; injection site reaction	3	NA	Minor response	6 PR, 10 SD	Wrangle et al., 2018

CR, complete response; NA, not available; PR, partial response; SD, stable disease.