Table 1.
Anti-IL-6 or anti-IL-6-receptor antibodies in clinical trials
| Inhibitor (type of agent) | Indication | Study phase | NCT identifier | Trial results | Refs |
|---|---|---|---|---|---|
| Siltuximab (anti-IL-6 mAb) | Multiple myeloma, B cell non-Hodgkin lymphoma, Castleman disease | I | NCT00412321 | No DLTs observed; recommended dose for future studies determined | 154 |
| Multiple myeloma (smoldering or indolent) | I | NCT01219010 | 10% M-protein response, 30% minor M-protein response; acceptable safety profile | NA | |
| Multiple myeloma | I | NCT01309412 | Study terminated owing to safety concerns | 156 | |
| Multiple myeloma | I/II | NCT01531998 | 90.9% ORR (PR) in combination with RVD; MTD determined | 160 | |
| Multiple myeloma | II | NCT00401843 | No increase in PFS or OS compared with bortezomib alone | 157 | |
| Multiple myeloma (high-risk smoldering) | II | NCT01484275 | NA | NA | |
| Multiple myeloma | II | NCT00402181 | No response to single-agent siltuximab; 17% ORR in combination with dexamethasone in patients with dexamethasone-refractory disease | 158 | |
| Multiple myeloma | II | NCT00911859 | Addition of siltuximab to VMP did not improve the number of patients having a CR, PFS, or OS but did improve the number of patients with a VGPR | 159 | |
| Myelodysplastic syndromes | II | NCT01513317 | Study terminated owing to a lack of efficacy | NA | |
| Prostate cancer | I | 2047 SN:218/4.2 (Innsbruck Medical University) | No siltuximab-related adverse events observed | 164 | |
| Metastatic, hormone-refractory prostate cancer | I | NCT00401765 | 62.2% of patients had a PSA-defined response; 89.7% of patients discontinued treatment prior to completion of all 14 cycles | NA | |
| Metastatic, hormone-refractory prostate cancer | II | NCT00385827 | Study terminated owing to a lack of efficacy; well tolerated in combination with MP | 166 | |
| Metastatic, hormone-refractory prostate cancer | II | NCT00433446 | Minimal clinical activity despite evidence of a reduction in IL-6 levels (decrease in serum CRP levels) | 165 | |
| Solid tumours | I/II | NCT00841191 | No clinical activity observed but well tolerated as monotherapy; recommended phase II dose determined | 168 | |
| Metastatic renal cell carcinoma | I/II | NCT00265135 | SD in >50% of patients; no DLTs observed | 167 | |
| Tocilizumab (anti-IL-6 receptor mAb) | B cell chronic lymphocytic leukaemia | I | NCT02336048 | NA | NA |
| Metastatic HER2+ breast cancer | I | NCT03135171 | NA | NA | |
| Ovarian cancer | I/II | NCT01637532 | Immunological changes consistent with decreased levels of immunosuppression; no DLTs observed | 174 | |
| Pancreatic cancer | II | NCT02767557 | NA | NA |
CR, complete response; CRP, C-reactive protein; DLT, dose-limiting toxicity; mAb, monoclonal antibody; MP, mitoxantrone plus prednisone; MTD, maximum-tolerated dose; NA, not available; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; PSA, prostate-specific antigen; RVD, lenalidomide plus bortezomib and dexamethasone; SD, stable disease; VGPR, very good partial response; VMP, bortezomib plus melphalan and prednisone.