Table 1.
Completed clinical trials of agents that target the TRAIL core apoptotic pathway
| Therapeutic agents | In combination with | Trial type and tumor | Enrollment | Primary endpoint | Therapy effect | Reference |
|---|---|---|---|---|---|---|
| CPT | Thalidomide+ Dexamethasone |
Phase 2; myeloma | 71 | ORR | Benefit | ChiCTR-TRC-11001625 [135] |
| CPT | Thalidomide | Phase 2; myeloma | 43 | Safety | 2 CR, 7 PR | ChiCTR-ONC-1200206 [136] |
| Dulanermin | Rituximab | Phase 1b/2; lymphoma | 72 | Safety | No benefit | NCT00400764 [137] |
| Dulanermin | mFOLFOX6+ Bevacizumab |
Phase 1b; colorectal cancer | 23 | Safety | 13 PR, 7 SD | NCT00873756 [138] |
| Dulanermin | Phase 1a; cancer | 72 | Biomarkers | NR | [139] | |
| Dulanermin | Paclitaxel Carboplatin Bevacizumab |
Phase 2; NSCLC | 213 | ORR | 1 CR, 13 PR | NCT00508625 [140] |
| Dulanermin | Paclitaxel Carboplatin Bevacizumab |
Phase 1b; NSCLC | 24 | Safety | NR | NCT00508625 [141] |
| Dulanermin | Phase 1; cancer | 71 | Safety | NR | [142] | |
| Dulanermin | Camptosar/Erbitux Folfiri Bevacizumab |
Phase 1b; coloretal cancer | 42 | Safety | NR | NCT00671372 |
| Tigatuzumab | Phase 1; coloretal cancer | 19 | Distribution | 1 PR, 8 SD | NCT01220999 [143] | |
| Tigatuzumab | Sorafenib | Phase 2; liver cancer | 163 | Efficacy | No benefit | NCT01033240 [144] |
| Tigatuzumab | Paclitaxel | Phase 2; TNBC | 64 | ORR | 3 CR, 8 PR, 11SD | NCT01307891 [76] |
| Tigatuzumab | Gemcitabine | Phase 2; pancreatic cancer | 62 | Efficacy | Benefit | [145] |
| Tigatuzumab | Carboplatin/paclitaxel | Phase 2; NSCLC | 97 | Efficacy | No benefit | NCT00991796 [146] |
| Tigatuzumab | Phase 1; cancer | 17 | MTD | 7 SD | [147] | |
| Mapatumumab | Sorafenib | Phase 2; liver cancer | 101 | Efficacy | No benefit | NCT01258608 [148] |
| Mapatumumab | Paclitaxel Carboplatin |
Phase 2; NSCLC | 109 | Efficacy | No benefit | NCT00583830 [149] |
| Mapatumumab | Phase 1b/2; NHL | 40 | Efficacy | 2 CR, 1 PR | NCT00094848 [150] | |
| Mapatumumab | Phase 2; colorectal cancer | 38 | Efficacy | 12 SD | [151] | |
| Mapatumumab | Gemcitabine Cisplatin |
Phase 1; solid tumor | 49 | Safety | 12 PR, 25 SD | NCT01088347 [152] |
| Mapatumumab | Phase 1; solid tumor | 41 | MTD | 12 SD | [153] | |
| Mapatumumab | Paclitaxel Carboplatin |
Phase 1; solid tumor | 27 | Safety | 5 PR, 12 SD | [154] |
| Mapatumumab | Phase 2; NSCLC | 32 | Efficacy | 9 SD | NCT00092924 [155] | |
| Mapatumumab | Phase 1; solid tumor | 49 | Safety | 19 SD | [156] | |
| Mapatumumab | Bortezomib | Phase 2; Myeloma | 105 | Safety | NR | NCT00315757 |
| Mapatumumab | Sorafenib | Phase 1b; Liver cancer | 23 | Safety | NR | NCT00712855 |
| Mapatumumab | Cisplatin+ Radiotherapy |
Phase 1b/2; Cervical cancer | 9 | Safety | NR | NCT01088347 |
| Conatumumab | Paclitaxel Carboplatin |
Phase 2; NSCLC | 172 | PFS | No benefit | NCT00534027 [157] |
| Conatumumab/Ganitumab | FOLFIRI | Phase 2; colorectal cancer | 155 | PFS | Benefit | NCT00813605 [158] |
| Conatumumab | mFOLFOX6+ Bevacizumab |
Phase 1b/2; colorectal cancer | 202 | PFS | No benefit | NCT00625651 [159] |
| Conatumumab/Ganitumab | Gemcitabine | Phase 2; pancreatic cancer | 125 | OS | Benefit | NCT00630552 [160] |
| Conatumumab | Doxorubicin | Phase 1b/2; soft tissue sarcoma | 134 | PFS | No benefit | NCT00626704 [161] |
| Conatumumab | Phase 1; solid tumor | 18 | DLT | 2 SD | [162] | |
| Conatumumab | Phase 1; solid tumor | 37 | Safety | 1 PR, 15 SD | [163] | |
| Conatumumab | Panitumumab | Phase 1b/2; Colorectal cancer | 53 | Safety | NR | NCT00630786 |
| Conatumumab | Birinapant | Phase 1b; Ovarian cancer | 27 | Safety | NR | NCT01940172 |
| TAS266 | Phase 1; solid tumor | 4 | Safety | NR | [164] | |
| ONC201 | Phase 2; glioblastoma | 17 | Efficacy | Benefit | [130] | |
| ONC201 | Phase 1; solid tumor | 28 | Safety | Benefit | [129] |
Abbreviations: CPT, Circularly permuted TRAIL; NR, not reported; MTD, maximum tolerated dose; ORR, objective response rate; DLT, dose limiting toxicity; TNBC, triple-negative breast cancer; NHL, Non-Hodgkin’s lymphoma; NSCLC, non-small cell lung cancer; CR, complete response; PR, partial response; SD, stable disease.