Table 1.
Combination of immunotherapy with radiation therapy in clinical development for glioblastoma.
| Target | Agent | New or Recurrent | Phase | Clinical Trial ID | Radiation regimen | Status | Notes |
|---|---|---|---|---|---|---|---|
| PD-1 | Nivolumab | Newly diagnosed | III | NCT02617589 | Standard fractionation | Active, not recruiting | Unmethylated MGMT; comparison anti-PD-1 versus TMZ each in combination with RT |
| PD-1 | Nivolumab | Newly diagnosed | III | NCT02667587 | Standard fractionation | Active, not recruiting | Methylated MGMT; TMZ plus RT combined with anti-PD-1 |
| PD-1 | Nivolumab | Newly diagnosed | I | NCT03576612 | Standard fractionation | Recruiting | Neoadjuvant onclolytic adenovirus (GMCI) + TMZ |
| PD-1 | Nivolumab | Recurrent | II | NCT03743662 | Hypofractionated | Recruiting | Re-irradiation (6Gy x 5) +/- anti-PD-1 +/- Bevacizumab |
| PD-1 | Nivolumab | Newly diagnosed | II | NCT04195139 | Standard fractionation | Recruiting | Elderly patients; comparison RT+anti-PD-1 + TMZ versus standard treatment (RT+TMZ) |
| PD-1 | Pembrolizumab | Newly diagnosed | II | NCT03018288 | Standard fractionation | Recruiting | TMZ +/- heat shock protein (HSPPC-96) |
| PD-1 | Pembrolizumab | Newly diagnosed | II | NCT03197506 | Standard fractionation | Recruiting | Standard therapy (RT+TMZ) +/- anti-PD-1 |
| PD-1 | Pembrolizumab | Recurrent | I | NCT02313272 | Standard fractionation | Active, not recruiting | Bevacizumab and RT (6Gy x 5) +/- anti-PD-1 |
| PD-1 | Pembrolizumab | Newly diagnosed | II | NCT03899857 | Standard fractionation | Recruiting | standard treatment (RT+TMZ) + anti-PD-1 |
| PD-1 | Pembrolizumab | Newly diagnosed | I | NCT02287428 | Standard fractionation | Recruiting | Unmethylated MGMT; RT+anti-PD-1+NeoAntigen Vaccine |
| PD-1 | Pembrolizumab | Newly diagnosed | I | NCT03426891 | Standard fractionation | Recruiting | Standard therapy (RT+TMZ) +/- HDAC inhibitor (Vorinostat) +/- anti-PD-1 |
| PD-1 | Pembrolizumab | Recurrent | II | NCT03661723 | Hypofractionated | Recruiting | Re-irradiation (7Gy x 5) per week for 2 weeks +/- Bevacizumab |
| PD-1 and CTLA-4 | Nivolumab and Ipilimumab | Newly diagnosed | II | NCT03367715 | Hypofractionated | Recruiting | Unmethylated MGMT; RT (6Gy x 5) + anti-PD-1 + anti-CTLA4 |
| PD-1 and CTLA-4 | Nivolumab and Ipilimumab | Newly diagnosed | II/III | NCT04396860 | Standard fractionation | Recruiting | Unmethylated MGMT; comparison standard treatment (RT+TMZ) versus RT+anti-PD-1+anti-CTLA-4 |
| PD-1 and IDO | Nivolumab and BMS-986205 | Newly diagnosed | I | NCT04047706 | Standard fractionation | Recruiting | Standard treatment (RT+TMZ) +/- anti-PD-1 +/- IDO inhibitor |
| PD-L1 | Durvalumab | Newly diagnosed and recurrent | II | NCT02336165 | Standard fractionation | Active, not recruiting | Bevacizumab |
| PD-L1 | Durvalumab | Recurrent | I/II | NCT02866747 | Hypofractionated | Recruiting | RT (8Gy x 3) |
| PD-L1 | Atezolizumab | Newly diagnosed | I/II | NCT03174197 | Standard fractionation | Active, not recruiting | Standard treatment (RT+TMZ) +/− anti-PD-L1 |
| PD-L1 | Avelumab | Newly diagnosed | II | NCT02968940 | Hypofractionated | Completed | IDH mutant; RT (6Gy x 5) |
| PD-L1 | Avelumab | Newly diagnosed | II | NCT03047473 | Standard fractionation | Active, not recruiting | Standard treatment (RT+TMZ) +/− anti-PD-L1 |
| PD-L1 | Avelumab | Recurrent | II | NCT03291314 | Standard fractionation | Completed | Standard treatment (RT+TMZ) + anti-PD-L1 + tyrosine kinase inhibitor (axitinib) |
| GM-CSF | Sargranostim | Newly diagnosed | II | NCT02663440 | Hypofractionated | Unknown | RT (regimen not specified) + TMZ + GM-CSF |
| GM-CSF and poly I:C | Sargranostim and Hiltonol | Recurrent | I | NCT03392545 | Not specified | Recruiting | RT + GM-CSF and poly I:C |
| GM-CSF and tetanus-diphtheria toxoid (Td) | GM-CSF and Td | Newly diagnosed | II | NCT03927222 | Standard fractionation | Recruiting | Unmethylated MGMT; Standard treatment (RT+TMZ) + Td + GM-CSF |
| TGF-β | Galunisertib | Newly diagnosed | I/II | NCT01220271 | Standard fractionation | Completed | Standard treatment (RT+TMZ) +/− anti-TGF-β |
| IDO | Indoximod | Newly diagnosed | I/II | NCT02052648 | Hypofractionated | Completed | TMZ +/− bevacizumab +/− IDO inhibitor +/− RT (5.5 × 5 Gy) |
| CXCR4 | Plexirafor | Newly diagnosed | I/II | NCT01977677 | Standard fractionation | Completed | Standard treatment (RT+TMZ) +/− CXCR4 inhibitor |
| CSF1R | Pexidartinib | Newly diagnosed | I/II | NCT01790503 | Standard fractionation | Completed | Standard treatment (RT+TMZ) +/− CSF1R inhibitor |
| IGF-1R | IGV-001 | Newly diagnosed | Iib | NCT04485949 | Standard fractionation | Not yet recruiting | Standard treatment (RT+TMZ) +/− IGV-001 cell immunotherapy |
| PD-L1 | Atezolizumab | Recurrent | II | NCT04729959 | Hypofractionated | Not yet recruiting | IDH1 wild type; PD-L1 inhibitor; tocilizumab; RT |