SUPPLEMENT.
Classification of the DR agonists being tested in clinical trials
| Disease | Phase/Adjunct therapy | Patients | Clinical efficacy |
Reference |
|---|---|---|---|---|
| Lexatumumab fully IgG1-kappa human monoclonal agonistic antibody directed against DR5 | ||||
| Solid cancer tumors | I | 24 | Low | [53] |
| I | 32 | Low | [70] | |
| Ib/gemcitabine, pemetrexed, doxorubicin, or FOLFIRI |
41 | No data | ||
| Mapatumumab fully IgG1-kappa human monoclonal agonistic antibody directed against DR4 | ||||
| Solid cancer tumors | I | 49 | Yes | |
| I | 41 | No | [71] | |
| I/paclitaxel, carboplatin | 27 | No | [72] | |
| NHL | Ib/II | 40 | Low | [57] |
| CRC | II | 38 | Low | [58] |
| Cervical cancer | Ib/II/cisplatin, gemcitabine | 49 | Yes | |
| NSCLC | II | 32 | Low | |
| II/paclitaxel, carboplatin | 100 | No | [60] | |
| HCC | II/sorafenib | 101 | In progress | [73] |
| MM | II/bortezomib (velcade) | 105 | No data | |
| Conatumumab (AMG 655) fully IgG1-kappa human monoclonal agonistic antibody directed against DR5 | ||||
| Solid cancer tumors | I | 37 | Yes | [74] |
| I/increased dose | 18 | [47] | ||
| Ib/AMG 479 (IGF-IR antagonist) | 108 | |||
| NSCLC | II/paclitaxel, carboplatin | 150 | No | [59] |
| Lymphoma | II/bortezomib, vorinostat | 20 | No | |
| Soft tissue sarcoma | I/doxorubicin | 6 | [75] | |
| II/doxorubicin | 120 | Low | ||
| II/FOLFOX6, bevacizumab, ganitumab | In progress | |||
| CRC | II/FOLFIRI, ganitumab | 155 | Yes | [61] |
| II/mFOLFOX, bevacizumab | 180 | No | [76] | |
| I, II/panitumumab | 53 | No | ||
| Pancreatic cancer | II/gemcitabine | 125 | Low | [77] |
| Tigatuzumab (CS-1008) fully IgG1-kappa human monoclonal agonistic antibody directed against DR5 | ||||
| Carcinoma | I | 17 | No | [78] |
| NSCLC | II/paclitaxel, carboplatin | 97 | No | [54] |
| Pancreatic cancer | II/gemcitabine | 62 | No | [62] |
| Breast cancer | II/paclitaxel | 64 | Low | [79] |
| HCC | II/sorafenib | 163 | No | [80] |
| CRC | I | 19 | Low | [81] |
| Metastatic breast cancer | II/abraxane | In progress | ||
| Drozitumab fully IgG1-kappa human monoclonal agonistic antibody directed against DR5 | ||||
| Metastatic colorectal cancer | I/mFOLFOX, bevacizumab | Low | [82] | |
| Dulanermin (rhApo2L/TRAIL) pro-apoptotic receptor agonist | ||||
| Solid cancer tumors | I | 58 | Low | [63] |
| NSCLC | Ib/paclitaxel, carboplatin+bevacizumab | 24 | [83] | |
| II/paclitaxel, carboplatin+bevacizumab | 213 | No | [84] | |
| CRC | Ib/FOLFOX6+bevacizumab | 23 | Yes | [85] |
| II/FOLFOX6+bevacizumab | In progress | |||
| NHL | Ib/rituximab | 7 | Yes | [86] |
| II/rituximab | 132 | In progress | ||
|
PRO95780 fully IgG1-kappa human monoclonal agonistic antibody directed against DR5 | ||||
| Solid cancer tumors | I | 50 | No | [87] |
| CRC | I/FOLFOX, bevacizumab | 6 | ||
| NHL | I/rituximab | 49 | No data | |
| CRC | I/bevacizumab, cetuximab, FOLFIRI, irinotecan |
23 | No data | |
| Chondrosarcoma | II | In progress | ||
| NSCLC | II/paclitaxel, carboplatin, bevacizumab | 128 | No data | |
| NSCLC – non-small cell lung cancer; NHL – non-Hodgkin lymphoma; CRC – colorectal cancer; HCC – hepatocellular carcinoma; MM – multiple myeloma | ||||
#The structure was solved by NMR in contrast to the other structures solved by X-ray crystallography.