Table 3.
Selected trials of therapeutic agents tested in glioma.
| Class of drugs | Setting | Trial Description | Target | Phase | NCT | Response rate | OS (months) | Toxicity |
|---|---|---|---|---|---|---|---|---|
| Immunotherapy | ||||||||
| Nivolumab (67) | Neoadjuvant | Neoadjuvant Nivolumab in Glioblastoma | PD-1 | II | NCT02550249 | No clinical benefit was substantiated following salvage surgery | NR | |
| (n = 30) | ||||||||
| (68) | ||||||||
| Pembrolizumab (69) | Neoadjuvant | Neoadjuvant anti-PD-1 immunotherapy in recurrent glioblastoma | PD-1 | Pilot | – | 13.7 | 10 patients (67%) in the neoadjuvant group experienced grade 3-4 adverse events likely attributable pembrolizumab | |
| (n= 35) | ||||||||
| Autologous lymphoid effector cells specific against tumor cells (ALECSAT) (70) | Recurrent | Assess the tolerability and efficacy of ALECSAT in GBM patients (ALECSAT-GBM) | I | NCT01588769 | DCR 50%* | NR | 5/23 (22%) experienced grade 4/5 toxicity including: pneumonia, respiratory insufficiency, cerebral vascular lesion and general physical health deterioration | |
| (n = 25) | ||||||||
| CART-cell therapy (71) | Recurrent | Anti- interleukin-13 receptor alpha 2 chimeric antigen receptor (CAR) T-cells | IL13Rα2 | I | NCT00730613 | NR | ||
| (NR) | ||||||||
| CART-cell therapy (72) | Recurrent | CMV-specific cytotoxic T lymphocytes expressing CAR targeting HER2 (HERT-GBM) | HER2 | I | NCT01109095 | DCR 50% | 11.1 | TRAEs were grade 1-2 and included 3 patients with headache and seizures. No ≥ grade 3 TRAEs reported. No DLT observed |
| (n = 17)± | ||||||||
| IMA950 multi-peptide vaccine + poly-ICLC (73) | New diagnosis | Trial of IMA950 Multi-peptide Vaccine Plus Poly-ICLC | Human leukocyte antigen (HLA)-A2 restricted peptides | I/II | NCT01920191 | DCR 42% | 19 | Grade 1-2 TRAEs: inflammatory reactions at injection sites (53%), headache (37%), fatigue (63%), and flu-like syndrome (21%) |
| (n = 19 16 GBM and 3 grade III astrocytoma) | 1 x Grade 4 - interstitial pneumonia due to pneumocystic infection | |||||||
| Monoclonal antibodies | ||||||||
| Onartuzumab (74) | Recurrent | Onartuzumab in Combination With Bevacizumab Compared to Bevacizumab Alone or Onartuzumab Monotherapy | c-MET | II | NCT01632228 | 8.8 (Onartuzumab + Bevacizumab) vs 12.6 (Bevacizumab) | Grade ≥ 3 TRAEs: 38.5% (experimental arm) vs 35.9% (bevacizumab) | |
| (n = 129) | Experimental arm had higher rates of drug withdrawal + drug interruptions | |||||||
| Tanibirumab (75) | Recurrent | Trial to Evaluate the Safety of TTAC-0001(Tanibirumab) | VEGFR-2 | II | NCT03033524 | NR | NR | No dose limiting toxicities |
| (n = 10) | Cutaneous hemangiomas (83%) - ≤ grade 2 No drug-related G3 or 4 AEs | |||||||
| Nanoparticles | ||||||||
| DNX-2401 (tasadenoturev) (76) | Recurrent | DNX-2401 for Recurrent Malignant Gliomas | Oncolytic adenovirus | I | NCT00805376 | Group A (n = 25): 20% of patients survived > 3 years | NR | |
| (n = 37) | Group A (n = 25) - single intratumoral injection of DNX-2401 into biopsy of confirmed recurrent tumor | Group B (n = 12) – NR | ||||||
| Group B (n = 12) - intratumoral injection post resection | ||||||||
*10 of the 25 recruited patients were evaluable.
±17 patients included 10 adults and 7 children.
CAR-T cells, Chimeric Antigen Receptor (CAR) T-Cell Therapy; DLT, Dose limiting toxicity; GSC, glioma stem cells; NR, not reported; ORR, Overall response rate; TRAE, treatment related adverse event; VEGFR, vascular endothelial growth factor receptor.