Selected drug clinical trials in patients with HGG
| Therapy | Intervention | Phase | Tumor type | Summary of results/status | Year | Reference | Trial number |
| Chemotherapy | CCNU vs. CCNU + bevacizumab | III | Progressive GBM | Median PFS 1.5 months vs. 3.8 months | 2017 | 3 | NCT01290939 |
| Irinotecan + bevacizumab | II | Recurrent HGG | For patients with GBM: median PFS 20 weeks; median OS 40 weeks | 2007 | 4 | NCT00268359 | |
| Immunotherapy | 2 pembrolizumab doses before surgery and every 3 weeks afterward | II | Recurrent (operable) GBM | Median PFS 4.5 months; median OS 20 months | 2020 | 5 | NCT02337686 |
| Neoadjuvant nivolumab and ipilimumab | I | Recurrent GBM | Median OS 38 weeks | 2021 | 7 | NCT03233152 | |
| Ipilimumab and nivolumab | II | Recurrent WHO grade 4 glioma | Recruiting | N/A | N/A | NCT04145115 | |
| Ipilimumab and nivolumab vs. TMZ | II/III | Newly diagnosed MGMT unmethylated GBM | Active, not recruiting | N/A | N/A | NCT04396860 | |
| Oncolytic HSV-1 G207 | I | Pediatric progressive/recurrent HGG | For 12 patients, median OS 12.2 months | 2021 | 8 | NCT02457845 | |
| G47Δ | I/II | Recurrent GBM | Median OS 7.3 months | 2022 | 12 | UMIN000015995 | |
| DNX-2401 OV | I | Recurrent HGG | For 37 patients including 33 with GBM: median OS 13.0 months | 2018 | 14 | NCT00805376 | |
| Intratumoral delivery of DNX-2401 OV followed by pembrolizumab | I/II | Recurrent GBM | For 49 patients including 48 with GBM: median OS 12.5 months, ORR 10.4% | 2023 | 15 | NCT02798406 | |
| OH2 OV | I | Recurrent CNS malignant tumors | Recruiting | N/A | N/A | NCT05235074 | |
| DCVax-L + TMZ (as SOC) vs. placebo (unmanipulated peripheral blood mononuclear cells) + TMZ (as SOC) | III | Newly diagnosed and recurrent GBM | For 232 patients with newly diagnosed GBM receiving DCVax-L: median OS 22.4 months (compared with 19.3 months); for 64 patients with recurrent GBM receiving DCVax-L: 42% relative risk reduction in the likelihood of death at any point | 2023 | 20 | NCT00045968 | |
| Intramuscular CGA injection | I | Recurrent HGG | For 17 patients with WHO 4 glioma (including 15 GBM): median OS 9.5 months | 2023 | 23 | CTR20160113 NCT02728349 | |
| Intramuscular CGA injection | II | Recurrent GBM | Recruiting | N/A | N/A | NCT03758014 | |
| Targeted therapy | Orally administered PAC-1 on days 1–21, with TMZ 150 mg/m2/5 days, per 28-day cycle | I | Recurrent HGG | Confirmed PR in 2 of 13 patients with GBM | 2023 | 25 | NCT03332355 |
| CDK4/6 inhibitor (auceliciclib) with TMZ | I | GBM | Recruiting | N/A | N/A | ACTRN12621000479808 | |
| Regorafenib (160 mg once daily for the first 3 weeks of each 4-week cycle) or CCNU (110 mg/m2 every 6 weeks) | II | Recurrent GBM | For patients receiving regorafenib: median OS 7.4 months; for patients in the lomustine group: median OS 5.6 months | 2019 | 29 | NCT02926222 | |
| Regorafenib | II/III | Newly diagnosed and recurrent GBM | Recruiting | N/A | N/A | NCT03970447 | |
| Dabrafenib (150 mg orally twice daily) and oral trametinib (2 mg orally once daily) | II | Recurrent or progressive BRAFV600E mutant glioma | In the GBM cohort: ORR 32%; median OS 13.7 months | 2022 | 31 | NCT02034110 | |
| Cohort 1: buparlisib before re-surgery; cohort 2: buparlisib only | II | PI3K pathway-activated GBM at first or second recurrence | Median follow-up 15.6 months in cohort 1 vs. 9.8 months in cohort 2 | 2019 | 35 | NCT01339052 | |
| Cohort 1: buparlisib (80/100 mg once daily) plus carboplatin (every 3 weeks); cohort 2: buparlisib (60 mg once daily) plus CCNU (every 6 weeks) | Ib/II | Recurrent GBM | Median PFS 1.4 months in cohort 1 vs. 1.3 months in cohort 2, indicating insufficient antitumor activity of buparlisib | 2020 | 36 | NCT01934361 |
CCNU, lomustine; GBM, glioblastoma; PFS, progression-free survival; OS, overall survival; ORR, overall response rate; HGG, high-grade gliomas; TMZ, temozolomide; OV, oncolytic viruses; DC, dendritic cell; SOC, standard of care; CGA, 5-caffeoylquinic acid; PR, partial response; PFS-6, PFS at 6 months.