Table 1.
Recent clinical studies with immune-checkpoint inhibitors and some combinational therapies targeting glioblastoma.
| Therapeutic Approach | Immune Targets | Type of Glioma | Type of Study | Number of Subjects | Overall Survival (OS) | Progression Free Survival (PFS) | Clinical Trial Identifier | Ref No. |
|---|---|---|---|---|---|---|---|---|
| Immune-Checkpoint Inhibitors and Combinational Therapies | ||||||||
| Nivolumab vs. Bevacizumab | PD-1 | Recurrent glioblastoma | Phase III | 369 | 9.8 vs. 10.0 months | 1.5 vs. 3.5 months | NCT02017717 | [44] |
| Neoadjuvant Nivolumab | PD-1 | Primary and recurrent glioblastoma | Phase II | 30 | 7.3 months | 4.1 months | NCT02550249 | [45] |
| Nivolumab + Radiation + Bevacizumab | PD-1 | Recurrent glioblastoma | Phase II | 94 (recruiting) | N/A | N/A | NCT03743662 | [46] |
| Pembrolizumab | PD-1 | Refractory high grade glioma | Retrospective study | 25 | 4 months | 1.4 months | N/A | [47] |
| Nivolumab + Temozolomide | PD-1 | Glioblastoma | Phase II | 102 (recruiting) | N/A | N/A | NCT04195139 | [48] |
| CAR T Cells ± Nivolumab and Ipilimumab | PD-1, IL13Ralpha2, CTLA4 | Recurrent or refractory glioblastoma | Phase I | 60 (recruiting) | N/A | N/A | NCT04003649 | [49] |
| Ipilimumab + Nivolumab | PD-1 and CTLA4 | Glioblastoma | Phase I | 6 | N/A | N/A | NCT03233152 | [50] |
| Ipilimumab + Nivolumab | PD-1 and CTLA4 | Recurrent and secondary glioblastoma | Phase II | 37 (not yet recruiting) | N/A | N/A | NCT04145115 | [51] |
| DC vaccines + Nivolumab | CTLA 4 | Recurrent glioblastoma | Phase I | 6 | 15.3 months with surgery | 6.3 months with surgery | NCT02529072 | [52] |
| Oncolytic adenovirus (DNX-2401) + Pembrolizumab | PD-L1 | Recurrent glioblastoma or gliosarcoma | Phase II | 49 (not yet recruiting) | N/A | N/A | NCT02798406 | [53] |
| Stereotactic radiosurgery (SRS) + Spartalizumab + MBG453 | TIM3 + PD-1 + SRS | Recurrent glioblastoma | Phase I | 15 (recruiting) | N/A | N/A | NCT03961971 | [54] |
| Nivolumab + BMS-986205 + Radiotherapy + Temozolomide | IDO + PD-1 | Glioblastoma | Phase I | 30 (recruiting) | N/A | N/A | NCT04047706 | [55] |
| Indoximod + Radiation + Temozolomide | IDO | Pediatric glioblastoma | Phase I | 29 | N/A | 6.2 months | NCT02502708 | [56] |
| Oncolytic Viruses | ||||||||
| Oncolytic virus TG6002 + 5-flucytosine | N/A | Recurrent glioblastoma | Phase I/Phase II | 78 (recruiting) | N/A | N/A | NCT03294486 | [57] |
| Engineered herpes virus G207 | N/A | Recurrent glioblastoma | Phase Ib | 6 | 6.6 months | N/A | NCT00028158 | [58] |
| DNX-2401 + Interferon gamma (IFN-γ) | N/A | Recurrent glioblastoma | Phase Ib | 27 | N/A | N/A | NCT02197169 | [59] |
| Polio/Rhinovirus recombinant (PVSRIPO) | N/A | Recurrent glioblastoma | Phase Ib | 61 | 12.5 months | N/A | NCT01491893 | [60,61] |
| DC Vaccines | ||||||||
| Pembrolizumab + DC vaccine (ATL-DC) | N/A | Recurrent glioblastoma | Phase I | 40 (recruiting) | N/A | N/A | NCT04201873 | [62] |
| Pp65-DCs + Temozolomide | N/A | Glioblastoma | Phase II | 100 (ongoing) | N/A | N/A | NCT02366728 | [63] |
| CAR T Therapy | ||||||||
| Anti-EGFRvIII CAR T cells + Cyclophosphamide | EGFRvIII | Recurrent glioblastoma | Pilot trial | 20 (estimated) | N/A | N/A | NCT02844062 | [64] |
| IL13Ralpha2-specific CAR | IL13Ra2 | Recurrent glioblastoma or refractory high grade glioma | Pilot trial | 3 | 11 months (mean survival) | N/A | NCT00730613 | [65] |
| HER2-CAR VSTs | HER2 | Progressive HER2+ glioblastoma | Phase I | 17 | 11.1 months | N/A | NCT01109095 | [66] |
PD-1, Programmed cell death 1; PD-L1, Programmed cell death ligand 1; CTLA-4, Cytotoxic T lymphocyte protein 4; IDO, Idolamine 2, 3-dioxygenase; CAR T Cells, Chimeric antigen receptors T cells; SRS, Stereotactic radiosurgery; DC vaccines, Dendritic cell vaccines; IFN-γ, Interferon gamma. PVSRIPO, Polio/Rhinovirus Recombinant; ATL-DC, Autologous tumor lysate-pulsed dendritic cell vaccine; Pp65-DCs, Pp65-dendritic cells; Anti-EGFRvIII CAR, anti-epidermal growth factor receptor variant III chimeric antigen receptors; IL13Ralpha2-specific CAR, Interleukin-13 receptor subunit alpha2-specific chimeric antigen receptors. 5-FC, 5-flucytosine; HER2-CAR VSTs, Human epidermal growth factor receptor 2- chimeric antigen receptors virus-specific T cells. OS and PFS were depicted from the time of inoculation. Data taken from https://clinicaltrials.gov/.