Comparison of dosing schedule and toxicity of IL-15 targeted therapies in oncology clinical trials
| Regimen . | Dosing schedule . | Study population . | Adverse events . | Clinical outcome . | Reference . |
|---|---|---|---|---|---|
| rhIL15 | Bolus infusion of 0.3-3 μg/kg for 12 days | Metastatic melanoma and kidney cancer | Hypotension, thrombocytopenia, liver function test abnormalities | Maximum tolerated dose was the lowest dose level, 0.3 μg/kg | 10 |
| rhIL15 | Subcutaneous injection of 0.25-3 μg/kg Monday to Friday for 2 weeks | Metastatic solid tumor | Hypotension, cardiac chest pain, pancreatitis | No clinical responses, and study was stopped early because of chest pain episode | 11 |
| rhIL15 | Continuous infusion of 3-5 μg/kg per day for 5 d | Metastatic solid tumor | Pulmonary capillary leak | No DLT; 4 μg/kg was selected as recommended phase 2 dose | 12 |
| rhIL15 | Continuous infusion of 0.125-4 μg/kg per day for 10 days | Metastatic solid tumor | Bleeding, uveitis, pneumonitis, intestinal ischemia | Recommended phase 2 dose was 4 μg/kg per day | 13 |
| rhIL15 + alemtuzumab | Subcutaneous injection of 0.5-2 μg/kg Monday to Friday for 2 weeks of rhIL15 with fixed dose alemtuzumab | Mature T-cell malignancies | Cytopenias, infusion reaction | No DLT | 16 |
| rhIL15 + avelumab | Continuous infusion of 1-4 μg/kg per day for 5 days of rhIL15 with fixed dose avelumab | Mature T-cell malignancies | Autoimmune hemolytic anemia, infusion reaction | Study terminated early because of slow accrual | 17 |
| rhIL15 + mogamulizumab (current study) | Continuous infusion of 2-4 μg/kg per day for 5 days of rhIL15 with fixed-dose mogamulizumab | Mature T-cell malignancies | Capillary leak, rash, infection | Maximum tolerated dose was 2 μg/kg | NA |
| N-803 (IL-15 receptor agonist) + rituximab | 1-20 μg/kg N-803 weekly for 4 doses with 4 consolidation doses with fixed dose rituximab | Indolent B-cell lymphomas | Infusion reaction, hypertension, lymphopenia | Recommended phase 2 dose 15-20 μg/kg | 61 |
| N-803 + BCG | 100-400 μg N-803 with fixed dose weekly bladder instillations of BCG | Non-muscle invasive bladder cancer | Hypertension, hematuria, fatigue | No DLT | 62 |
| Regimen . | Dosing schedule . | Study population . | Adverse events . | Clinical outcome . | Reference . |
|---|---|---|---|---|---|
| rhIL15 | Bolus infusion of 0.3-3 μg/kg for 12 days | Metastatic melanoma and kidney cancer | Hypotension, thrombocytopenia, liver function test abnormalities | Maximum tolerated dose was the lowest dose level, 0.3 μg/kg | 10 |
| rhIL15 | Subcutaneous injection of 0.25-3 μg/kg Monday to Friday for 2 weeks | Metastatic solid tumor | Hypotension, cardiac chest pain, pancreatitis | No clinical responses, and study was stopped early because of chest pain episode | 11 |
| rhIL15 | Continuous infusion of 3-5 μg/kg per day for 5 d | Metastatic solid tumor | Pulmonary capillary leak | No DLT; 4 μg/kg was selected as recommended phase 2 dose | 12 |
| rhIL15 | Continuous infusion of 0.125-4 μg/kg per day for 10 days | Metastatic solid tumor | Bleeding, uveitis, pneumonitis, intestinal ischemia | Recommended phase 2 dose was 4 μg/kg per day | 13 |
| rhIL15 + alemtuzumab | Subcutaneous injection of 0.5-2 μg/kg Monday to Friday for 2 weeks of rhIL15 with fixed dose alemtuzumab | Mature T-cell malignancies | Cytopenias, infusion reaction | No DLT | 16 |
| rhIL15 + avelumab | Continuous infusion of 1-4 μg/kg per day for 5 days of rhIL15 with fixed dose avelumab | Mature T-cell malignancies | Autoimmune hemolytic anemia, infusion reaction | Study terminated early because of slow accrual | 17 |
| rhIL15 + mogamulizumab (current study) | Continuous infusion of 2-4 μg/kg per day for 5 days of rhIL15 with fixed-dose mogamulizumab | Mature T-cell malignancies | Capillary leak, rash, infection | Maximum tolerated dose was 2 μg/kg | NA |
| N-803 (IL-15 receptor agonist) + rituximab | 1-20 μg/kg N-803 weekly for 4 doses with 4 consolidation doses with fixed dose rituximab | Indolent B-cell lymphomas | Infusion reaction, hypertension, lymphopenia | Recommended phase 2 dose 15-20 μg/kg | 61 |
| N-803 + BCG | 100-400 μg N-803 with fixed dose weekly bladder instillations of BCG | Non-muscle invasive bladder cancer | Hypertension, hematuria, fatigue | No DLT | 62 |
BCG, bacillus calmette-guerin; NA, not applicable.