Table 1.
Completed clinical trials using oncolytic virotherapy in high-grade glioma.
| Agent | NCT | Study Phase | Published Results | n | Study Population | Outcomes |
|---|---|---|---|---|---|---|
| G207 | NCT00157703 | Phase I | Markert et al. 2014 | 9 | Recurrent malignant glioma | Safety demonstrated (AEs) Median survival from inoculation = 7.5 months mPFS = 2.5 months |
| NCT00028158 | Phase Ib/II | Markert et al. 2000 | 21 | Recurrent malignant glioma | Safety demonstrated (AEs) Mean TTP = 3.5 months Mean OS = 15.9 (glioblastoma) and 40.5 (anaplastic astrocytoma) |
|
| HSV1716 | (UK) | Phase I | Rampling et al. 2000 | 9 | Recurrent malignant glioma | Safety demonstrated (AEs) |
| (UK) | Phase I | Papanastassiou et al. 2002 | 12 | Malignant glioma | Safety demonstrated (AEs) | |
| (UK) | Phase I | Harrow et al. 2004 | 12 | Recurrent or newly diagnosed high grade glioma | Safety demonstrated (AEs) | |
| AdV-tk | NCT00589875 | Phase II | Wheeler et al. 2016 | 48 | Newly diagnosed glioblastoma | Safety demonstrated (AEs, DLTs) mOS = 17.1 months mPFS = 8.1 months Surival at 1, 2, 3 years = 67%, 35%, 19% |
| DNX-2401 | NCT00805376 | Phase I | Lang et al. 2018 | 37 | Recurrent malignant glioma | Safety demonstrated (AEs, DLTs) Study arm A (single injection)- Tumor reduction in 72% of patients mOS = 9.5 months Study arm B (infusion and resection) mOS = 13 months |
|
NCT02197169 (TARGET-1) |
Phase Ib | Lang et al. 2017 | 27 | Recurrent glioblastoma | Tolerability of DNX-2401 as monotherapy (compared to combination with IFN-gamma) demonstrated (AEs) OS-12 (33%) OS-18 (22%) |
|
|
NCT01956734 (Spain) |
Phase I | Alonso et al. 2017 | 31 | Glioblastoma at first recurrence | Safety demonstrated when combined with TMZ (AEs), efficacy endpoints not yet reported | |
|
NCT02798406 (CAPTIVE/KEYNOTE-192) |
Phase II | Zadeh et al. 2020 | 49 | Recurrent glioblastoma | Safety demonstrated when combined with pembrolizumab (AEs) mOS = 12.5 months OS12 = 54.5%, OS18 = 20.8% |
|
| ONYX-015 | - | Phase I | Chiocca et al. 2004 | 24 | Recurrent malignant glioma | Safety demonstrated (AEs, DLTs) Median survival = 6.2 months (4.9 months for glioblastoma patients, 11.4 in AA/AO) |
| Toca511 + TocaFC | NCT01470794 | Phase I | Cloughesy et al. 2016 | 43 | Recurrent high grade glioma | Safety (AEs, DLTs) OS (HGG) = 13.6 months OS (glioblastoma) = 11.6 months For all evaluable patients: OS6 (87.9%), OS9 (72.4%), OS12 (52.5%), OS24 (29.1%) PFS = 3.2 months, PFS6 = 16.3% |
| NCT01156584 | Phase I | - | 54 | Recurrent high grade glioma | - | |
| NCT01985256 | Phase I | - | 17 | Recurrent or progressive high grade glioma | - | |
|
NCT02414165 (Toca 5) |
Phase II/III | Cloughesy et al. 2020 | 201 | Recurrent glioblastoma/anaplastic astrocytoma | Safety (AEs) mOS = 11.1 months Efficacy was not demonstrated over control arm |
|
| PVSRIPO | NCT01491893 | Phase I | Desjardins et al. 2018 | 61 | Recurrent glioblastoma | mOS = 12.5 months OS 24 M and 36 M = 21% |
| REOLYSIN | NCT00528684 | Phase I/II | Forsyth et al. 2008 | 12 | Recurrent malignant glioma | mOS = 21 weeks (range 6–234) mTTP 4.3 weeks (range 2.6–39) MTD not reached |
| NCT00528684 | Phase I/II | Kickielinski et al. 2014 | 15 | Recurrent malignant glioma | mOS = 140 days mTTP = 61 days |
Abbreviations: AE = adverse events; DLT = dose limiting toxicity; OS = overall survival; mOS = median overall survival; mTTP = median time to progression; mPFS = median progression free survival; PFS6 = progression free survival at 6 months; AA = anaplastic astrocytoma; AO = anaplastic oligodendroglioma; TMZ = temozolomide.