Table 3 |.
Clinical trials in high-g rade glioma: localized immunotherapy
| Study | Treatment | Study type | Patient cohort | Results | Adverse events (number of patients) |
|---|---|---|---|---|---|
| Viral therapy | |||||
| Wheeler et al. (2016)87 | AdvHSV-tk injection in resection cavity wall + ganciclovir with standard of care | Phase II, with historical controls | Primary glioblastoma (n = 48) | 3 × 1011 particles well tolerated; median survival, 17.1 months vs 13.5 months in historical controls; median OS after gross total resection, 25.0 vs 16.9 months | Worsening of existent hemiparesis (1) |
| Ji et al. (2016)88 | Repeated dosing of intra-arterial AdvHSV-tk with BBB disruption and standard of care vs standard of care | Phase II | Recurrent WHO grade III or IV glioma (n = 53) | Median OS, 10.4 months in AdvHSV-tk group vs 3.3 months in controls; median PFS, 6.8 vs 1.9 months; treatment of controls (surgery, chemotherapy or palliative care) not stated | No increased risk of adverse events |
| Chiocca et al. (2019)89 | Ad-RTS-hIL-12 in resection cavity wall + systemic veledimex | Phase I | Recurrent glioblastoma (n = 31) | Maximum tolerated dose of veledimex, 20 mg; median survival, 12 months | Reversible cytokine release syndrome (10 grade 2, 6 grade 3), brain oedema (1), confusion (1), aseptic meningitis (1) |
| Desjardins et al. (2018)96 | Single dose of PVSRIPO via CED | Phase I | Recurrent glioblastoma (n = 61) | Median OS, 12.5 months vs. 11.3 months in historical controls | Haemorrhage leading to hemiparesis (1), peritumoural inflammation requiring bevacizumab (32), requiring surgery (4) |
| Lang et al. (2018)98 | DNX-2401 in resection cavity wall | Phase I | Recurrent glioblastoma (n = 37) | 20% of patients survived >3 years, three showed >95% tumour reduction; OS, 13.0 months | Transient fever, headache and malaise (2) |
| Markert et al. (2014)102 | Single stereotactic injection of G207 combined with radiotherapy | Phase I | Recurrent glioblastoma (n = 9) | Six patients showed stabilization of disease or partial response; median OS, 7.5 months; median PFS, 2.5 months | Seizures and hemiparesis (number of patients unclear) |
| Friedman et al. (2021)104 | Single injection of G207 via CED combined with radiotherapy | Phase I | Paediatric recurrent high-grade glioma (n = 12) | Radiological and/or clinical response in 11 patients; median OS, 12.2 months | No dose-l imiting adverse effects |
| Cytokine and antibody therapy | |||||
| Kunwar et al. Single injection of (2010)50 IL13-Pe38QQR via CED vs carmustine wafers | Phase III | Recurrent glioblastoma (n = 296) | Median OS, 9.1 months in IL13-Pe38QQR group vs 8.8 months in controls | Increased incidence of pulmonary embolism in IL13-Pe38QQR group (16 vs 2 patients) | |
| Immunostimulating oligodeoxynucleotides | |||||
| Carpentier et al. (2010)111 | Single stereotactic injection of CpG-O DN | Phase II | Recurrent glioblastoma (n = 31) | One partial response and three minor responses; median OS, 6.4 months; median PFS, 2.1 months | Transient worsening of neurological deficits (22), death owing to haemorrhage (1) |
| Ursu et al. (2017)112 | CpG-ODN injected into resection cavity wall followed by standard of care vs standard of care only | Phase II | Primary glioblastoma (n = 81) | Median OS, 17 months in CpG-ODN group vs 18 months in controls; median PFS, 9 months in both groups | Increased occurrence of fever and postoperative haemorrhage |
BBB, blood–brain barrier; CED, convection-enhanced delivery; CpG-ODN, oligodeoxynucleotides containing unmethylated cytosine–guanosine motifs; OS, overall survival; PFS, progression-free survival; PVSRIPO, recombinant non-pathogenic polio–rhinovirus chimaera.