Table 3.
Completed phase I–III clinical trials of vaccines for glioblastoma with primary outcomes.
| Investigational Treatment versus Comparator Treatment | N of Patients | Newly Diagnosed/Recurrent | Results for Primary Outcome | ClinicalTrials.gov Identifier | References |
|---|---|---|---|---|---|
| Phase III trials | |||||
| Rindopepimut * plus GM-CSF and TMZ versus KLH plus TMZ | 745 | Newly diagnosed | mOS: 20.1 versus 20.0 months (HR 1.01, 95% CI 0.79–1.30; p = 0.93) | NCT01480479 | [2] |
| Autologous cytokine-induced killer cells plus ST versus ST | 180 | Newly diagnosed | mOS: 22.5 versus 16.9 months (p = 0.5237) mPFS: 8.1 versus 5.4 months (HR 0.693, 90% CI 0.512–0.937, p = 0.0218) |
NA | [25] |
| Autologous DC * vaccine versus autologous PBMC | 331 | Newly diagnosed | Pending | NCT00045968 | [20] |
| Phase II trials | |||||
| Rindopepimut plus GM-CSF and standard or dose-intensified TMZ versus a historical control | 22 | Newly diagnosed | mOS: 23.6 versus 15.0 months (HR = 0.23; 95% CI 0.07–0.79; p = 0.019); mPFS: 15.2 versus 6.3 months (HR = 0.35, 95% CI 0.14–0.87; p = 0.024) |
NCT00643097 | [151] |
| Rindopepimut plus GM-CSF and adjuvant TMZ | 65 | Newly diagnosed | mOS: 21.8 months; mPFS: 9.2 months |
NCT00458601 | [152] |
| Rindopepimut and GM-CSF plus bevacizumab versus KLH plus bevacizumab | 73 | Recurrent | mOS: 11.6 versus 9.3 months (HR = 0.57, 95% CI 0.33–0.98, p = 0.039) | NCT01498328 | [153] |
| ICT-107 * versus unpulsed autologous DC vaccine | 124 | Newly diagnosed | mOS: 18.3 versus 16.7 months (p > 0.05); PFS: 11.2 versus 9.0 months (p = 0.010) |
NCT01280552 | [154] |
| Autologous DC vaccine plus ST versus ST | 76 | Newly diagnosed | mOS: 564 versus 568 days (p = 0.99); PFS: 204 versus 210 days (p = 0.83) |
EudraCT number 2009-015979-27 | [155] |
| Autologous DC vaccine plus ST versus ST | 34 | Newly diagnosed | mOS: 31.9 versus 15.0 months (p < 0.002); mPFS: 8.5 versus 8.0 months (p = 0.075) |
NA | [156] |
| Autologous DC vaccine plus ST | 27 | Newly diagnosed | mOS: 23.4 months; mPFS: 12.7 months |
NCT01006044 | [157] |
| Autologous DC vaccine plus ST versus ST plus placebo | 43 | Newly diagnosed or recurrent | mOS: 13.7 versus 10.7 months (p = 0.05); mPFS: 7.7 versus 6.9 months (p = 0.75) |
NA | [158] |
| HSPPC-96 * plus TMZ | 46 | Newly diagnosed | mOS: 23.8 months; mPFS: 18.0 months |
NCT00905060 | [17] |
| ERC1671 */GM-CSF/cyclophosphamide plus bevacizumab versus placebo plus bevacizumab | 9 | Recurrent | Interim mOS: 12.0 versus 7.5 months | NCT01903330 | [159] |
| LAK cells * | 33 | Newly diagnosed | mOS: 20.5 months | NCT00331526 | [160] |
| Phase I and I/II trials | |||||
| IMA950 * vaccine with poly ICLC plus ST | 16 | Newly diagnosed | mOS: 21.2 months | NCT01920191 | [161] |
| Autologous DC vaccine plus ST | 23 | Newly diagnosed | mOS: 31.4 months | NA | [162] |
| Autologous DC vaccine plus ST versus ST | 25 | Newly diagnosed | mOS: 17.0 versus 10.5 months (p < 0.05) | NA | [163] |
| Autologous DC vaccine plus ST versus a historical control | 11 | Newly diagnosed | mOS: 759 days versus 585 days | NCT00846456 | [164] |
| Autologous DC vaccine plus ST | 77 | Newly diagnosed | mOS: 18.3 months in ITT analysis; mPFS: 10.4 months in the ITT group versus 20.4 months in the PP group |
NA | [165] |
| Autologous DC vaccine versus RT plus nitrosourea | 45 | Recurrent | mOS: 480 versus 400 days (p = 0.010) | NA | [166] |
| Autologous DC vaccine | 56 | Recurrent | mOS: 9.6 months; mPFS: 3 months |
NA | [167] |
| Autologous DC vaccine pulsed with pp65 RNA plus tetanus/diphtheria (Td) toxoid or unpulsed autologous DCs | 12 | Newly diagnosed | mOS: 18.5 months; mPFS: 10.8 months |
NA | [8] |
| Autologous DC vaccine pulsed with pp65 RNA plus GM-CSF and dose-intensified TMZ | 11 | Newly diagnosed | mOS: 41.1 months; mPFS: 25.3 months |
NA | [19] |
| HSPPC-96 vaccine plus ST | 20 | Newly diagnosed | mOS: 31.4 months | NA | [18] |
* DC: dendritic cells; ERC1671 vaccine is composed of primary irradiated/inactivated whole tumor cells and lysates from the patient to be treated and from three other allogeneic and autologous glioblastoma patients; GM-CSF: granulocyte-macrophage colony-stimulating factor; Rindopepimut, or CDX-110-KLH peptide vaccine, presents a 14-amino acid peptide corresponding to the fusion junction of EGFRvIII, which is linked to the keyhole limpet hemocyanin (KLH), a large copper-containing immunogenic carrier glycoprotein; HSPPC-96 peptide vaccine is comprised of autologous antigenic peptides chaperoned by heat shock glycoprotein-96; ICLC: an immunostimulating adjuvant consisting of double-stranded RNAs of polyinosinic-polycytidylic acid stabilized with poly L-lysine in carboxymethylcellulose; ICT-107 vaccine presents an autologous dendritic cell vaccine pulsed with peptides from six glioma-associated antigens (HER2, TRP-2, gp100, MAGE-1, IL13Rα2, and AIM-2); IMA950 peptide vaccine consists of 11 glioma-associated peptides; ITT: intention-to-treat; LAK cells: lymphokine-activated killer cells; mOS: median overall survival; mPFS: median progression-free survival; PP: per protocol; ST: standard therapy; TMZ: temozolomide.