Table 2.
Dendritic cell vaccine trials for glioblastoma.
| Trial name ClinicalTrial.gov identifier | Phase | Immune targets | Associated treatments in active arm | Control | Sample size | T cell response (CD4/CD8 response details) | Humoral response | Median PFS (months) | Median OS (months) | Primary endpoint | Results |
|---|---|---|---|---|---|---|---|---|---|---|---|
| PERCELLVAC NCT02709616 NCT02808364 (121) |
I | Personalized TAA | None | None | 5 | Yes (CD4 and CD8 response in 80% patients: up to 3.5% specific CD8) |
NA | NA | 19 | Safety | Positive |
| ATTAC NCT00639639 (122, 123) |
I | CMV pp65 | None | None | 11 | Yes (up to 4.5% specific CD8 in 55% patients) |
NA | 25.3 | 41.1 | Safety and feasibility | Safe vaccine |
| NCT03615404 | I | CMV RNA | Td + GM-CSF + DI-TMZ | None | 10 | Ongoing | Ongoing | Ongoing | Ongoing | Safety and feasibility | Ongoing |
| NCT00612001 (124) | I | Autologous glioma lysate vs. GAA peptides |
None | None | 34 | NA | NA | 9.6 | 34.4 for lysate-DC, 14.4 for GAA-DC | Safety and feasibility | Safe vaccine |
| NCT00068510 (125) | I | Autologous glioma lysate | None | None | 12 | Yes (CTL response in 50% patients) |
NA | 15.5 | 23.4 | Safety and feasibility | Safe vaccine |
| Rudnick 2020 (126) | I | Autologous glioma lysate | Gliadel | None | 28 | Yes (CD8 response in 25% patients, no details in %specific CD8) |
NA | 3.6 | 32 for nd-GBM, 16.3 for r-GBM | Safety and clinical outcome | Positive |
| MC1272 NCT01957956 (127) |
I | Autologous glioma lysate | Temozolomide | None | 20 | Results pending | Results pending | Results pending (interim results: 9.7) | Results pending (interim results: 20.5) | Safety and feasibility | Safe vaccine |
| NCT02010606 (128) | I | Autologous glioma stem like lysate | Temozolomide for nd-GBM Bevacizumab for r-GBM |
None | 38 | Results pending | Results pending | Results pending (interim results: 8.6 For nd-GBM; 3.14 For r-GBM) |
Results pending (interim results: 21.1 for nd-GBM; 12.0 For r-GBM) |
Safety | Safe vaccine |
| ICT-107 (129) | I | AIM-2, MAGE1, TRP-2, gp100, HER2, IL-13Ra2 | None | None | 16 | Yes (specific CD8 increase in 31% patients) |
NA | 16.9 | 38.4 | Immunological response | Positive (trend) |
| NCT01808820 | I | Autologous glioma lysate | Imiquimod | None | 20 | Results pending | Results pending | Results pending | Results pending | Safety | Results pending |
| NCT03360708 | I | Autologous glioma lysate | None | None | 20 | Ongoing | Ongoing | Ongoing | Ongoing | Safety | Ongoing |
| ATL-DC NCT04201873 |
I | Autologous glioma lysate | Pembrolizumab | ATL-DC plus poly ICLC plus placebo | 40 | Ongoing | Ongoing | Ongoing | Ongoing | Safety and immunological response | Ongoing |
| NCT03360708 | I | Autologous glioma lysate | None | None | 20 | Ongoing | Ongoing | Ongoing | Ongoing | Safety and toxicity | Ongoing |
| NCT00890032 | I | BTSC mRNA | None | None | 50 | Ongoing | Ongoing | Ongoing | Ongoing | Safety, Feasibility and immune response | Ongoing |
| NCT03914768 | I | Genetically modified tumour cells and neoantigens | Cyclophosphamide + Bevacizumab | None | 10 | Ongoing | Ongoing | Ongoing | Ongoing | Safety, feasibility and OS12 | Ongoing |
| NCT01171469 (130) | I | Allogenic BTSCs | Imiquimod | None | 8 | Increase in IL-17 expressing CD4 (Th17) cells in stable patients compared to non-stable patients | None | NA | NA | MTD and immune response | Vaccine well tolerated with not MTD reached |
| DENDR-STEM NCT02820584 | I | Allogenic BTSC | None | None | 20 | Ongoing | Ongoing | Ongoing | Ongoing | Safety and Immune response | Ongoing |
| ICT-121 NCT02049489 (131) |
I | CD133 | None | None | 20 | Immune response detected to CD133 epitopes) | NA | NA | NA | Safety and Feasibility | Vaccine was safe and well tolerated |
| NCT00846456 (132) | I/II | Autologous glioma stem cells lysate | None | None | 7 | Yes (100% patients, defined via proliferation assay) |
NA | 23.1 | 25.3 | Safety | Safe vaccine |
| 16-184-4412 (133) | I/II | Autologous glioma cells | None | None | 32 | Yes (CD8 response in 13% patients: up to 5.5% specific CD8 of total CD8 T cells) |
NA | 10.3 (r-GMB) 18.3 (nd-GBM) |
18.0 (r-GMB) 30.5 (nd-GBM) |
Safety, feasibility, immunological response | Positive for safety and feasibility |
| NCT04388033 | I/II | Autologous glioma cells | Temozolomide | None | 10 | Ongoing | Ongoing | Ongoing | Ongoing | Safety and PFS6 | Ongoing |
| DEN-STEM NCT03548571 |
II/III | Autologous glioma stem cells | Temozolomide | TMZ | 60 | Ongoing | Ongoing | Ongoing | Ongoing | PFS | Ongoing |
| ADDIT-GLIO NCT02649582 (134) |
I/II | WT1 | Temozolomide | None | 20 | Ongoing (interim results: CD4 response correlated with OS) |
Results pending | Results pending | Results pending (interim results: 43.7) |
OS | Ongoing |
| NCT03879512 | I/II | Autologous tumor lysate | Metronomic cyclophosphamide | None | 25 | Ongoing | Ongoing | Ongoing | Ongoing | Safety and Feasibility | Ongoing |
| ICT-107 NCT01280552 (135) |
II | AIM-2, MAGE1, TRP-2, gp100, HER2 and IL-13Ra2 | Temozolomide | TMZ | 81 (vs. control 43) |
Yes (CD8 response in 50% patients) |
NA | 11.2 | 17.0 | OS | Positive (trend for OS and significant for PFS) |
| ICT-107 NCT01006044 (136) |
II | AIM-2, MAGE1, TRP-2, gp100, HER2 and IL-13Ra2 | Radiotherapy-Temozolimide + fluorescence-guided surgery |
None | 27 | Yes (11/27 patients displayed tumor specific responses with increased serum cytokine levels) | NA | 12.7 | 23.4 | PFS | Safe vaccine |
| DENDR1 EUDRACT N° 2008-005035-15 (137) |
II | Autologous tumor lysate | Radiotherapy-Temozolimide | None | 22 | No | NA | 10.5 | 20.1 | PFS12 | Positive (PFS12 = 41%) |
| Audencel NCT01213407 (138, 139) | II | Autologous tumor-derived peptides | Temozolomide | TMZ | 34 (vs. control 42) | NA | NA | 6.8 | 18.8 | PFS12 | Negative |
| NCT00323115 (140) | II | Autologous glioma lysate | None | None | 10 | Trends (CD8 and CD4) | NA | 9.5 | 28 | Immunological response | Positive trend |
| NCT01567202 (141) | II | Autologous glioma stem-like lysate | None | Placebo | 22 (vs. control 21) | NA | NA | 7.7 | 13.7 | OS and PFS | Positive (trend for PFS) (Second phase of trial in IDH1wt TERTmt subgroups of GBM patients ongoing) |
| NCT01204684 | II | Autologous glioma lysate | None | None | 60 | Results pending | Results pending | Results pending | Results pending | Immunological response | Results pending |
| AV-GBM-1 NCT03400917 |
II | Autologous glioma cells | TAA-pulsed DC vaccine plus GM-CSF | None | 55 | Results pending | Results pending | Results pending | Results pending | OS | Results pending |
| ELEVATE NCT02366728 |
II | CMV pp65 | +-/Basiliximab | None | 100 | Results pending | Results pending | Results pending | Results pending | OS and DC migration | Results pending |
| I-ATTAC NCT03927222 |
II | CMV pp65 | Temozolomide | None | 48 | Ongoing | Ongoing | Ongoing | Ongoing | OS | Ongoing |
| ATTAC-II NCT02465268 |
II | CMV pp65 | Temozolomide | Unpulsed PBMC and saline | 120 | Ongoing | Ongoing | Ongoing | Ongoing | OS | Ongoing |
| DERIVe NCT03688178 |
II | CMV pp65 | Varlilumab plus Temozolomide |
Unpulsed DCs | 112 | Ongoing | Ongoing | Ongoing | Ongoing | OS, Safety and T reg depletion | Ongoing |
| GlioVax NCT03395587 (142) |
II | Autologous glioma lysate | DC vaccine plus TMZ | TMZ | 136 | Ongoing | Ongoing | Ongoing | Ongoing | OS | Ongoing |
| ADCV01 NCT04115761 |
II | Autologous glioma lysate | Temozolomide | TMZ | 24 | Ongoing | Ongoing | Ongoing | Ongoing | PFS12 | Ongoing |
| NCT00576537 | II | Autologous tumor lysate | None | None | 50 | Ongoing | Ongoing | Ongoing | Ongoing | Safety and feasibility | Ongoing |
| ADCTA-G NCT02772094 (143) |
II | Autologous tumor lysate | TMZ + Radiotherapy | None | 42 | NA | NA | NA | 22.9 (median for this trial and Taiwan DOH/MA0910072504) | OS and safety | Positive |
| Combi G-Vax NCT04523688 |
II | Autologous tumour lysate | TMZ + radiotherapy | None | 28 | Ongoing | Ongoing | Ongoing | Ongoing | PFS | Ongoing |
| STING (ICT-107) NCT02546102 |
III | AIM-2, MAGE1, TRP-2, gp100, HER2 and IL-13Ra2 | None | Autologous PBMCs | Estimated 414 but suspended | NA | NA | NA | NA | Overall survival | Suspended |
| DCVax-L NCT00045968 (144) |
III | Autologous tumor lysate | None | Autologous PBMC | 331 | NA | Results pending | NA | Results pending (interim results: 23.1) | PFS | Results pending |
| NCT04277221 | III | Autologous tumor lysate | Bevacizumab | Bevacizumab | 118 | Ongoing | Ongoing | Ongoing | Ongoing | OS | Ongoing |
KLH, keyhole limpet haemocyanin, TTF, Tumor Treating Fields; nd-GBM, newly diagnosed glioblastoma; r-GBM, recurrent glioblastoma; TAA, Tumor Associated Antigen; PFS, progression free survival; OS, overall survival; Td, Tetanus toxoid; GM-CSF, Granulocyte Macrophage-Colony Stimulating Factor; DI-TMZ, Dose-Intensified Temozolomide; BTSC, Brain Tumor Stem Cells; CMV, Cytomegalovirus; MTD, maximum tolerated dose.