Table 1.
Completed and Ongoing Clinical Trials for Glioblastoma Immunotherapy
| Vaccines | |||||
|---|---|---|---|---|---|
| Clinical Trial Name | Description | No. of Participants | Primary Outcome Measure | Phase | Study Completed |
| NCT01480479 (ACT IV) | Rindopepimut (CDX-110) + TMZ; newly diagnosed EGFRvIII GBM patients | 745 | Overall survival | 3 | Yes |
| NCT02193347 (RESIST) | IDH peptide vaccine (PEPIDH1M) + TMZ; recurrent grade II glioma patients | 24 | % patients with unacceptable (grade 3) toxicity | 1 | No |
| NCT02960230 | H3.3K27M peptide vaccine; children with newly diagnosed DIPG/other gliomas | 29 | % patients with AEs; overall survival at 12 mo | 1 | No |
| NCT01920191 (IMA-950) | IMA950 Multipeptide vaccine + poly-ICLC; newly diagnosed GBM patients | 19 | Tolerability and safety | 2/3 | Yes |
| NCT02924038 | Varlilumab (CDX-1127) + IMA950/poly-ICLC; low-grade glioma patients | 30 | AEs; CD4 + and CD8 + T-cell responses | 1 | No |
| NCT02149225 (GAPVAC) | APVAC 1 and 2 + GM-CSF + poly-iCLC + TMZ; newly diagnosed GBM patients | 16 | AEs | 1 | Yes |
| NCT02287428 (NeoVax) | Neoantigen cancer vaccine (NeoVax) + RT + pembrolizumab MGMT unmethylated; newly diagnosed GBM patients | 46 | AEs; No. of patients with actionable peptides; No. of patients able to receive post-RT vaccine therapy | 1 | No |
| NCT01280552 (ICT-107) | Randomized, double-blind, controlled study of ICT-107 with maintenance TMZ; newly diagnosed GBM following resection | 124 | Overall survival | 2 | Yes |
| NCT00045968 (DCVax-L) | Randomized, double-blind, controlled study of DCVax-L; newly diagnosed GBM following resection | 348 | PFS | 3 | Yes |
| NCT03018288 (HSPPC-96) | Randomized, double-blind study of RT + TMZ and pembrolizumab with and without HSPPC-96; newly diagnosed GBM | 108 | 1-y overall survival | 2 | No |
| Checkpoint Inhibitors | |||||
| Clinical Trial Name | Description | No. of Participants | Primary Outcome Measure | Phase | Study Completed |
| NCT02017717 (CheckMate 143) | Nivolumab alone nivolumab + ipilimumab comparator: bevacizumab; recurrent GBM patients | 626 | Safety and tolerability: Overall survival | 3 | Yes |
| NCT02617589 (CheckMate 498) | Nivolumab + RT comparator: TMZ + RT MGMT unmethylated; newly diagnosed GBM patients | 550 | Overall survival | 3 | No |
| NCT02667587 (CheckMate 548) | Nivolumab + TMZ + RT comparator: TMZ + RT MGMT unmethylated; newly diagnosed GBM patients | 693 | PFS; overall survival | 3 | No |
| NCT02337491 | Pembrolizumab alone pembrolizumab + bevacizumab; recurrent GBM patients | 80 | Pembrolizumab maximum tolerated dose; pembrolizumab dose-limiting toxicity at 6 mo. PFS | 2 | Yes |
| NCT02313272 | Hypofractionated stereotactic irradiation + pemobrolizumab + bevacizumab; recurrent HGG patients | 32 | Pembrolizumab maximum tolerated dose | 1 | No |
| CAR T-cell therapy | |||||
| Clinical Trial Name | Description | No. of Participants | Primary Outcome Measure | Phase | Study Completed |
| NCT02208362 | IL13Rα2-specific CAR T cells; refractory or recurrent malignant glioma patients | 92 | AEs (grade 3 or higher); dose-limiting toxicity; incidence of toxicities (including neurological); | 1 | No |
| NCT02209376 | EGFRvIII CAR T cells; EGFRvIII GBM patients | 11 | No. of AEs (2 y) | 1 | Yes |
| NCT01109095 | HER2 virus-specific CAR T cells | 16 | Dose-limiting toxicity after T-cell infusion | 1 | Yes |
| NCT02442297 | HER2 CAR T cells | 28 | Dose-limiting toxicity after T-cell infusion | 1 | No |
| Oncolytic Viral therapy | |||||
| Clinical Trial Name | Description | No. of Participants | Primary Outcome Measure | Phase | Study Completed |
| NCT00805376 (DNX-2401) | DNX-2401 (conditionally replication-competent adenovirus) ± surgery; recurrent HGG patients | 37 | Maximum tolerated dose | 1 | Yes |
| NCT03896568 (Ad5-DNX-2401) | Ad5-DNX-2401 (oncolytic adenovirus) in bone marrow human mesenchymal stem cells; recurrent HGG patients | 36 | Maximum tolerated dose Incidence adverse events | 1 | No |
| NCT01491893 (PVSRIPO) | Recombinant nonpathogenic polio-rhinovirus chimera (PVSRIPO); recurrent GBM patients | 61 | Maximum tolerated dose; dose-limiting toxicities; recommended phase 2 dose | 1 | No |
| NCT02414165 (Toca 5) | Toca 511 (retroviral replicating vector encoding cytosine deaminase) + Toca FC (flucytosine) comparator: lomustine, TMZ, bevacizumab; recurrent HGG patients | 403 | Overall survival | 2/3 | Yes |
| NCT02457845 (G207) | HSV G207 (first-generation oncolytic HSV-1) + RT; children with recurrent supratentorial brain tumors | 18 | Safety and tolerability (grade 3 or higher AEs) | 1 | Yes |
| NCT03152318 (rQNestin) | rQNestin34.5v0.2 (oncolytic HSV-1) + cyclophosphamide; recurrent malignant glioma patients | 108 | Maximum tolerated dose | 1 | No |
| NCT00390299 | MV-CEA (carcinoembryonic antigen-expressing measles virus); recurrent GBM patients | 23 | Maximum tolerated dose; no. and severity of all AEs; no. and severity of grade 3 + AEs; overall toxicity | 1 | Yes |
| NCT01301430 (ParvOryx01) | H-1PV; progressive primary or recurrent GBM patients | 18 | Safety and tolerability | 1/2a | Yes |
| NCT03714334 (DNX-2440) | DNX-2440 conditionally replication-competent adenovirus armed with OX40 ligand (T-cell stimulator); recurrent GBM patients | 24 | Treatment-emergent AEs | 1 | No |
| NCT02062827 (M032-HSV-1) | M032-HSV-1 (second-generation oncolytic HSV) armed with IL-12 (immune-stimulatory); recurrent progressive/GBM patients | 36 | Maximum tolerated dose | 1 | No |
| Combination Therapies | |||||
| Clinical Trial Name | Description | No. of Participants | Primary Outcome Measure | Phase | Study Completed |
| NCT03726515 | CART-EGFRvIII + pembrolizumab; newly diagnosed EGFRvIII MGMT-unmethylated GBM patients | 7 | No. of patients with treatment-related AEs | 1 | No |
| NCT03422094 | NeoVax + ipilumumab/nivolumab; newly diagnosed unmethylated GBM | 30 | Safety and tolerability; identification of tumor-specific neoantigens | 1 | No |
| NCT02798406 (CAPTIVE) | DNX-2401 + pembrolizumab; recurrent GBM patients | 49 | Objective response rate (tumor size reduction) | 2 | No |
| NCT03665545 (IMA950-106) | Pembrolizumab + IMA950/poly-ICLC; relasping GBM | 24 | Treatment-emergent AEs | 2/3 | No |
All information taken from www.clinicaltrials.gov. Information current as of February 9, 2020.
Abbreviations: AEs, adverse events; DIPG, diffuse intrinsic pontine glioma; EGFRvIII, epidermal growth factor receptor variant III; GBM, glioblastoma; H-1PV, H-1 parvovirus; HGG, high-grade glioma; HSPPC-96, heat-shock protein peptide complex-96; HSV, herpes simplex virus; IDH, isocitrate dehydrogenase; MGMT, O6-methylguanine-DNA methyltransferase; PFS, progression-free survival; RT, radiation therapy; TMZ, temozolomide.