Table 7.
Selected completed trials with immunotherapies (including viral therapies)
| Vaccines | Type | Phase | Trial | Trial Result |
|---|---|---|---|---|
| ICT107 (dendritic cell vaccine against MAGE-1, HER-2, AIM-2, TRP-2, gp100, and IL13Rα2)273 | Newly diagnosed GBM | Randomized placebo controlled phase II | NCT01280552 | • 124 patients randomized • PFS increased by 2.2 months (P = 0.011) • OS increased by 2.0 months (NS) • HLA-A2 subgroup showed increased clinical benefit and immune response |
| Rindopepimut (EGFRvIII peptide vaccine) ACT IV202 | Newly diagnosed GBM with EGFRvIII mutation | Double blind phase III | NCT01480479 | 745 patients randomized • No difference in outcome with addition of rindopepipimut • Median overall survival was 20·1 months (95% CI 18·5–22·1) in the rindopepimut group versus 20·0 months (18·1–21·9) in the control group (HR 1·01, 95% CI 0·79-1·30; P = 0.93) |
| DC Vax (dendritic cell vaccine)256 | Newly diagnosed GBM | Phase III | NCT00045968 | • 331 patients treated • Primary endpoint of PFS not reported • 90% crossover at progression • Median OS was 23.1 months from surgery |
| Checkpoint Inhibitors | Type | Phase | Trial | Trial result |
| Nivolumab versus bevacizumab (CheckMate 143)255 | Recurrent GBM | III | NCT02017717 | • 369 patients randomized • No difference in outcome between the nivolumab or bevacizumab arm • Median OS was 9.8 months with nivolumab and 10.0 months with bevacizumab (NS), and the 12-mo OS rate was 42% in both arms. • Median PFS was 1.5 months for nivuolumab and 3.5 months for bevacizumab ORRs were 8% for nivolumab and 23% for bevacizumab • No steroid use and MGMT promoter methylation were associated with longer OS in the nivolumab arm versus the bevacizumab arm |
| Viral Therapies | Type | Phase | Trial | Trial Result |
| DNX-2401 (Delta-24-RGD) Oncolytic adenovirus257 | Recurrent GBM | I | NCT02197169 | • 37 patients • Fairly well-tolerated • 20% of patients survived > 3 years • 12% response • Evidence of virus replication in tumor • Cases of pseudoprogression |
| Polio virus (PVSRIPO)258 | Recurrent GBM | 1 (convection enhanced delivery) | NCT01491893 | • 61 patients enrolled • Dose level −1 (5.0×107 TCID50) was identified as the phase 2 dose • 19% of the patients had a PVSRIPO-related adverse event of grade 3 or higher • OS reached a plateau of 21% (95% confidence interval, 11 to 33) at 24 months that was sustained at 36 months |
| Ad-RTS-hIL12 (adenovirus producing IL-12) + velidimex259 | Recurrent GBM | 1 | NCT03679754 | • 31 patients • Fairly well tolerated but cytokine syndrome observed in some • Median OS = 12.7 months • Inflammatory responses seen in recurrent tumors • Concurrent corticosteroids negatively affected survival: Patients cumulatively receiving >20 mg versus ≤20 mg of dexamethasone (days 0 to 14), median OS was 6.4 and 16.7 months, respectively |
| Gene mediated cytotoxic immunotherapy (GMCI; AdV-Tk) + valacyclovir + RT and TMZ260 | Newly diagnosed GBM | II | NCT00589875 | • 48 patients • No dose-limiting toxicities • Median OS was 17.1 months for GMCI + SOC versus 13.5 months for SOC alone (P = 0.0417) • Greatest benefit was observed in gross total resection patients: median OS of 25 versus 16.9 months (P = 0.0492) |
| TOCA 511 (replication competent retrovirus which transduces tumor cells with the cytosine deaminase gene) in combination with TOCA FC (5-flucytosine) versus SOC (TOCA 5 Study)261 | Recurrent GBM | II/IIII | NCT02414165 | • 403 patients treated • Fairly well tolerated • No difference in primary endpoint of OS between TOC 511 and lomustine (HR = 1.06 (95% CI: 0.83, 1.35; P-value = 0.6154) • Median OS: Toca 511: 11.07 months • SOC 12.22 months • Durable response rate 2.5% with TOCA 511; 4.5% with SOC (NS) |
GBM; glioblastoma; NS, not significant; SOC, standard of care; Tk, thymidine kinase.