Table 1.
Clinical trials for glioblastoma with combination immunotherapy and anti-angiogenic therapy.
| Year | Immunotherapy | Antiangiogenic Therapy | Phase | Status | Results | ClinicalTrials.gov identifier |
|---|---|---|---|---|---|---|
| Vaccine Therapies | ||||||
| 2011 | Rindopepimut EGFRvIII Peptide Vaccine with GM-CSF | Bevacizumab | II | Completed | Primary Endpoint: Objective but nonsignificant increase in six-month progression-free survival in experimental group (28%) compared to control group (16%). Statistically significant increase in overall survival (HR 0.53%; CI 0.32-0.88, p=0.001) Discontinuation of steroids after six months was 33% in experimental group and 0% in control group. |
NCT01498328 (145) |
| 2013 | Heat shock protein peptide complex 96 (HSPPC-96) autologous vaccine | Bevacizumab | II | Active, not recruiting | Primary Endpoint: Statistically significant worse median overall survival in experimental group (7.5 months) compared to control group (10.7 months). HR 2.06%; CI 1.18-3.60; p=0.03 This study was terminated after above interim results. Final publication of data is pending. |
NCT01814813 (146) |
| 2013 | ERC1671 (gliovac) autologous/allogeniec vaccine with GM-CSF | Bevacizumab | II | Active, not recruiting | Primary endpoint: 12-month overall survival. Interim results demonstrate increased median overall survival of 12 months in experimental group compared to 7.5 months in control group. | NCT01903330 (147) |
| 2014 | SL-701 multivalent synthetic TAA vaccine (interleukin-13 receptor alpha-2, ephrinA2, survivin) | Bevacizumab | I/II | Completed | Primary endpoints: objective response rate and 12-month overall survival. Full results not published. |
NCT02078648 (40) |
| 2016 | Synthetic TAA vaccine (EGFRvIII, iL13Ralpha, ephA2, her2/neu, YKL-40), with poly-ICLC (Toll-like Receptor Agonist) and montanide ISA-51 VG (secondary adjuvant) | Bevacizumab | II | Withdrawn | n/a | NCT02754362 |
| 2017 | DSP-7888 dosing emulsion (WT1 peptides) | Bevacizumab | III | Recruiting | Ongoing | NCT03149003 |
| 2019 | Autologous DCs pulsed with genetically modified tumor cells or TAA | Bevacizumab | I | Enrolling by invitation | Ongoing | NCT03914768 |
| 2019 | (EO2401) trivalent synthetic TAA vaccine with and without Nivolumab (anti-PD-1) |
Bevacizumab | I/II | Recruiting | Ongoing | NCT04116658 |
| 2020 | Autologous DCs pulsed with TAA | Bevacizumab | I/II | Recruiting | Ongoing | NCT04277221 |
| Checkpoint Inhibitors | ||||||
| 2012 | Camrelizumab (anti-PD-1) | Bevacizumab | II | Recruiting | Ongoing | NCT04952571 |
| 2015 | Pembrolizumab (anti-PD-1) | Bevacizumab | II | Completed | Primary endpoint: No significant differences in six-month progression-free survival or median overall survival in experimental group vs control group. In experimental group, worse overall survival correlated with baseline dexamethasone use and increased posttherapy plasma VEGF. |
NCT02337491 (148) |
| 2015 | Durvalumab (anti-PD-L1) | Bevacizumab | II | Completed | Primary endpoint: 12-month overall survival. Preliminary analysis demonstrated 60% 12-month survival in MGMT-unmethylated GBM compared to 50% in an historical benchmark. Full results are pending. | NCT02336165 (43) |
| 2018 | Pembrolizumab (anti-PD-1) | Bevacizumab | II | Active, not recruiting | Ongoing | NCT03661723 |
| 2018 | Nivolumab (anti-PD-1) | Bevacizumab | II | Active, not recruiting | Ongoing | NCT03452579 |
| 2018 | Retifanlimab (anti-PD-1) with and without epacadostat (indoleamine 2,3-dioxygenase inhibitor) | Bevacizumab | II | Recruiting | Ongoing | NCT03532295 |
| 2019 | Nivolumab (anti-PD-1) | Bevacizumab | II | Recruiting | Ongoing | NCT03890952 |