| 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 CD56bright 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 CD56bright 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.