Table 1.
Active trials involving immune checkpoint inhibitors
| NCT | Phase | Intervention | Target population | Location | Sample size | Key outcomes |
|---|---|---|---|---|---|---|
| NCT02337686 | Phase II | Pembrolizumab both pre- and postoperatively | Recurrent glioblastoma | USA | 20 | PFS, OS, ORR, toxicity, cytokine evaluation |
| NCT02617589 | Phase III | Nivolumab/RT vs TMZ/RT | Newly diagnosed MGMT-unmethylated glioblastoma | USA | 560 | OS, PFS, tumor mutational burden comparison |
| NCT02667587 | Phase III | Nivolumab/TMZ/RT vs placebo/TMZ/RT | Newly diagnosed MGMT-methylated glioblastoma | USA | 716 | PFS, OS |
| NCT02852655 | Phase I | Neoadjuvant pembrolizumab vs placebo | Surgically accessible recurrent/progressive glioblastoma | USA | 25 | TIL density, adverse events, PFS |
| NCT02974621 | Phase II | Cediranib/olaparib vs bevacizumab | Recurrent glioblastoma | USA | 70 | PFS, OS, adverse events, cytokine evaluation, tumor genetics |
| NCT03047473 | Phase II | Adjuvant avelumab with TMZ/RT | Newly diagnosed glioblastoma | Canada | 30 | Adverse events, MRI evaluation, biomarker evaluation |
| NCT03158389 | Phase I/II | Matches one of 7 drugs to patients (APG101, alectinib, idasanutlin, atezolizumab, vismodegib, Palbociclib, and temsirolimus) based on molecular markers after surgery, in addition to RT | MGMT-unmethylated glioblastoma | Germany | 350 | PFS, OS, adverse events |
| NCT03174197 | Phase I/II | Atezolizumab/TMZ/RT | Newly diagnosed glioblastoma | USA | 80 | DLT, OS, adverse events, ORR, PFS |
| NCT03197506 | Phase II | Neoadjuvant pembrolizumab and then adjuvant RT/TMZ/pembrolizumab | Newly diagnosed glioblastoma | USA | 50 | DLT, OS, adverse events, PFS, biomarkers |
| NCT03341806 | Phase I | Avelumab (PD-L1 inhibitor) with or without MRI-guided laser interstitial thermal therapy | Recurrent glioblastoma | USA | 13 | DLT, ORR, PFS |
| NCT03426891 | Phase I | Pembrolizumab/vorinostat (histone deacetylase inhibitor)/TMZ/RT in dose escalation | Newly diagnosed glioblastoma | USA | 21 | MTD, OS |
| NCT03493932 | Phase I | Nivolumab with BMS-986016 (anti-Lag-3 antibody), with active monitoring by cerebral microdialysis | Recurrent glioblastoma | USA | 20 | IFN–γ levels, microdialysis safety, drug safety |
| NCT03532295 | Phase II | Epacadostat (IDO-1 inhibitor) + INCMGA00012 (anti-PD1 antibody) given alone or in combination prior to RT/bevacizumab | Recurrent glioblastoma | USA | 55 | OS, PFS, neurological function, safety |
| NCT03718767 | Phase II | Adjuvant nivolumab | IDH mutant glioma with or without hypermutator phenotype | USA | 95 | PFS, HRQOL, neoantigen burden |
| NCT03899857 | Phase II | Study of standard of care with the addition of pembrolizumab for newly diagnosed GBM | Newly diagnosed glioblastoma | Switzerland | 56 | OS, PFS, treatment failure, PD-1 expression levels |
| NCT03925246 | Phase II | Nivolumab in varying doses | Recurrent IDH mutant glioblastoma, prior TMZ/RT | France | 43 | PFS, OS, ORR, safety |
| NCT03961971 | Phase I | MBG453 (anti-Tim3 antibody) and Spartalizumab (anti-PD1 antibody) given 1 week prior to SRS, then in an adjuvant fashion ongoing | Recurrent glioblastoma | USA | 15 | Adverse events, toxicity, PFS, OS, ORR |
| NCT04047706 | Phase I | BMS 986,205 (IDO1 inhibitor) with nivolumab and TMZ/radiation | Newly diagnosed glioblastoma | USA | 30 | Adverse events, OS, PFS, MRI evaluation |
| NCT04145115 | Phase II | Combination therapy with ipilimumab and nivolumab | Somatically hypermutated glioblastoma | USA | 37 | ORR, OS, PFS, adverse events |
| NCT04225039 | Phase II | A Cohort = single priming dose of both drugs prior to RT, then adjuvant schedule for both drugs; B Cohort = neoadjuvant schedule of both drugs, then RT/resection, then adjuvant treatment | Recurrent glioblastoma | USA | 32 | ORR, adverse events, OS, PFS |
| NCT04323046 | Phase I | Neoadjuvant Ipilimumab/nivolumab plus adjuvant nivolumab after surgery, vs placebo | Recurrent/progressive high-grade glioma in children/young adults | USA | 45 | Cell cycle gene changes, adverse events, OS, PFS |
| NCT04396860 | Phase II/III | Phase II = ipilimumab alone; Phase III = ipilimumab and nivolumab; all patients received RT as well; active comparator is TMZ/TTF | Newly diagnosed MGMT-unmethylated glioblastoma, IDH wild type | USA | 485 | PFS, OS, adverse events, HRQOL, MGMT expression |
| NCT04608812 | Phase I | OS2966 (mAb against CD28/b1 integrin) directly infused into the brain tumor and surrounding infiltrated brain | Newly diagnosed glioblastoma that has received resection and standard of care | USA | 24 | DLT, optimal dose, spatial distribution of drug, MRI evaluation |
| NCT04656535 | Phase 0/I | AB154 (anti-TIGIT) and AB122 (anti-PD-1) in various combinations vs placebo control | Recurrent glioblastoma | USA | 46 | Adverse events, RNA sequencing, T cell changes |
| NCT04729959 | Phase II | Tocilizumab ± atezolizumab, combination w/ surgery ± RT | Recurrent glioblastoma | USA | 12 | DLT, MTD, ORR, PFS, OS, adverse events |
| NCT04817254 | Phase II | TMZ/RT and ipilimumab in two different dose regimens | Newly diagnosed glioblastoma or gliosarcoma | USA | 48 | OS, T cell responses, HRQOL |
| NCT04826393 | Phase Ib | Dose escalation trial of ASP8374 (anti-TIGIT antibody) and cemiplimab (anti-PD1 antibody) | Recurrent high-grade glioma | USA | 24 | MTD, TIL, adverse events, PFS, OS |
| NCT04922723 | Phase I/II | Adjuvant TMZ/RT plus daratumumab (anti-CD38) | Newly diagnosed glioblastoma | USA | 16 | DLT, OS, PFS, adverse events |
| NCT04952571 | Phase II | Camrelizumab and bevacizumab | Recurrent glioblastoma | China | 94 | PFS, OS, ORR, control rate, functional outcomes, adverse events |