Clinically Explored Virus-Based Therapies for the Treatment of Recurrent High-Grade Glioma in Adults
Abstract
:1. Introduction
1.1. Background
1.2. Historical Context
1.3. Mechanism of Antitumor Effect of Oncolytic Viruses
2. Clinical Experiences with Virotherapy in High-Grade Glioma
2.1. Herpesviridae
2.1.1. Talimogene Laherparepvec (TVEC, OncoVexGM-CSF, or IMLYGIC)
2.1.2. HSV G207
2.1.3. HSV1716
2.1.4. rQNestin34.5v.2
2.1.5. M032
2.1.6. C134
2.2. Adenoviridae
2.2.1. Aglatimagene Besadenovec (AdV-tk)
2.2.2. DNX-2401 (Tasadenoturev, Formerly Delta-24-RGD)
2.2.3. ONYX-015
2.2.4. CRAd-S-pk7
2.3. Retroviridae
Vocimagene Amiretrorepvec + (5-fluorocytosine(6-amino-5fluoro-1H-pyrimidin-2-one)) − (Toca 511 + Toca FC)
2.4. Picornoviridae
PVSRIPO
2.5. Reoviridae
Pelareorep (REOLYSIN)
2.6. Paramyxoviridae
MV-CEA
2.7. Parvoviridae
Parvovirus H-1 (H-1PV, Parv-Oryx)
2.8. Summary of Clinical Experiences Using OVs in High-Grade Glioma
3. Summary of Preclinical Experiences with Combinatory Virotherapy in Glioblastoma
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
WHO | World Health Organization |
HGG | high-grade glioma |
CNS | central nervous system |
BBB | blood–brain barrier |
OV | oncolytic virus |
Treg | regulatory T cell |
MDSC | myeloid-derived suppressor cell |
NK | natural killer |
PAMP | pathogen-associated molecular pattern |
PRR | pattern recognition receptor |
DAMP | damage-associated molecular patterns |
GM-CSF | granulocyte macrophage colony-stimulating factor |
CTLA-4 | cytotoxic T-lymphocyte associated protein 4 |
PD-1 | programmed cell death protein-1 |
HSV | herpes simplex virus |
FDA | Food and Drug Administration (of the United States) |
CPA | cyclophosphamide |
TMZ | temozolomide |
CD | cytosine deaminase |
5-FU | 5-fluorouracil |
CEA | carcinoembryogenic antigen |
ECM | extracellular matrix |
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Agent | NCT | Study Phase | Published Results | n | Study Population | Outcomes |
---|---|---|---|---|---|---|
G207 | NCT00157703 | Phase I | Markert et al. 2014 | 9 | Recurrent malignant glioma | Safety demonstrated (AEs) Median survival from inoculation = 7.5 months mPFS = 2.5 months |
NCT00028158 | Phase Ib/II | Markert et al. 2000 | 21 | Recurrent malignant glioma | Safety demonstrated (AEs) Mean TTP = 3.5 months Mean OS = 15.9 (glioblastoma) and 40.5 (anaplastic astrocytoma) | |
HSV1716 | (UK) | Phase I | Rampling et al. 2000 | 9 | Recurrent malignant glioma | Safety demonstrated (AEs) |
(UK) | Phase I | Papanastassiou et al. 2002 | 12 | Malignant glioma | Safety demonstrated (AEs) | |
(UK) | Phase I | Harrow et al. 2004 | 12 | Recurrent or newly diagnosed high grade glioma | Safety demonstrated (AEs) | |
AdV-tk | NCT00589875 | Phase II | Wheeler et al. 2016 | 48 | Newly diagnosed glioblastoma | Safety demonstrated (AEs, DLTs) mOS = 17.1 months mPFS = 8.1 months Surival at 1, 2, 3 years = 67%, 35%, 19% |
DNX-2401 | NCT00805376 | Phase I | Lang et al. 2018 | 37 | Recurrent malignant glioma | Safety demonstrated (AEs, DLTs) Study arm A (single injection)- Tumor reduction in 72% of patients mOS = 9.5 months Study arm B (infusion and resection) mOS = 13 months |
NCT02197169 (TARGET-1) | Phase Ib | Lang et al. 2017 | 27 | Recurrent glioblastoma | Tolerability of DNX-2401 as monotherapy (compared to combination with IFN-gamma) demonstrated (AEs) OS-12 (33%) OS-18 (22%) | |
NCT01956734 (Spain) | Phase I | Alonso et al. 2017 | 31 | Glioblastoma at first recurrence | Safety demonstrated when combined with TMZ (AEs), efficacy endpoints not yet reported | |
NCT02798406 (CAPTIVE/KEYNOTE-192) | Phase II | Zadeh et al. 2020 | 49 | Recurrent glioblastoma | Safety demonstrated when combined with pembrolizumab (AEs) mOS = 12.5 months OS12 = 54.5%, OS18 = 20.8% | |
ONYX-015 | - | Phase I | Chiocca et al. 2004 | 24 | Recurrent malignant glioma | Safety demonstrated (AEs, DLTs) Median survival = 6.2 months (4.9 months for glioblastoma patients, 11.4 in AA/AO) |
Toca511 + TocaFC | NCT01470794 | Phase I | Cloughesy et al. 2016 | 43 | Recurrent high grade glioma | Safety (AEs, DLTs) OS (HGG) = 13.6 months OS (glioblastoma) = 11.6 months For all evaluable patients: OS6 (87.9%), OS9 (72.4%), OS12 (52.5%), OS24 (29.1%) PFS = 3.2 months, PFS6 = 16.3% |
NCT01156584 | Phase I | - | 54 | Recurrent high grade glioma | - | |
NCT01985256 | Phase I | - | 17 | Recurrent or progressive high grade glioma | - | |
NCT02414165 (Toca 5) | Phase II/III | Cloughesy et al. 2020 | 201 | Recurrent glioblastoma/anaplastic astrocytoma | Safety (AEs) mOS = 11.1 months Efficacy was not demonstrated over control arm | |
PVSRIPO | NCT01491893 | Phase I | Desjardins et al. 2018 | 61 | Recurrent glioblastoma | mOS = 12.5 months OS 24 M and 36 M = 21% |
REOLYSIN | NCT00528684 | Phase I/II | Forsyth et al. 2008 | 12 | Recurrent malignant glioma | mOS = 21 weeks (range 6–234) mTTP 4.3 weeks (range 2.6–39) MTD not reached |
NCT00528684 | Phase I/II | Kickielinski et al. 2014 | 15 | Recurrent malignant glioma | mOS = 140 days mTTP = 61 days |
Agent | NCT | Study Phase | n | Trial Design/Population | Outcomes (Safety, Efficacy) |
---|---|---|---|---|---|
G207 | NCT02457845 | Phase I | 12 | Pediatric progressive or recurrent supratentorial tumors | Safety, tolerability (AEs) PFS, OS |
NCT03911388 | Phase I | 15 | Pediatric recurrent or refractory cerebellar tumors | Safety, tolerability (AEs) PFS, OS | |
HSV1716 | NCT02031965 | Phase I Terminated by sponsor | 2 | Pediatric refractory/recurrent high grade glioma | MTD, PFS, and OS up to 15 years |
rQNestin | NCT03152318 | Phase I | 108 | Malignant glioma | MTD |
M032 | NCT02062827 | Phase I | 36 | Recurrent malignant glioma | MTD TTP and survival up to 12 months |
C134 | NCT03657576 | Phase I | 24 | Recurrent glioblastoma | Safety, tolerability (AEs) PFS- 3 d, 28 d, 3 M, 6 M, 12 M, OS up to 12 M |
DNX-2401 | NCT03896568 | Phase I | 36 | Recurrent high-grade glioma | MTD, AEs Tumor response, TTP for 1 year |
CRAd-S-pk7 | NCT03072134 | Phase I | 12 | Newly diagnosed malignant glioma | Neurological side effects, MRIs for progression |
Toca 511 + Toca FC | NCT02598011 (Toca 7) | Phase Ib Terminated by sponsor | 18 | Newly diagnosed high grade glioma | DLTs |
PVSRIPO | NCT03043391 | Phase Ib | 12 | Pediatric recurrent malignant glioma | Toxicity, 24 month OS |
PVSRIPO + atezolizumab | NCT03973879 | Phase Ib/2 Withdrawn, resubmission expected | _ | Recurrent malignant glioma | Safety (AEs), survival at 24 M |
PVSRIPO + lomustine | NCT02986178 | Phase II | 122 | Recurrent malignant glioma | Objective response (iRANO) at 24 and 36 M, duration of ORR, OS at 24 and 36 M, safety (AEs) |
REOLYSIN + GM-CSF | NCT02444546 | Phase I | 6 | Pediatric relapsed/refractory brain tumors | MTD (DLT), AE, mOS, OR, TTP |
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Immidisetti, A.V.; Nwagwu, C.D.; Adamson, D.C.; Patel, N.V.; Carbonell, A.-M. Clinically Explored Virus-Based Therapies for the Treatment of Recurrent High-Grade Glioma in Adults. Biomedicines 2021, 9, 138. https://doi.org/10.3390/biomedicines9020138
Immidisetti AV, Nwagwu CD, Adamson DC, Patel NV, Carbonell A-M. Clinically Explored Virus-Based Therapies for the Treatment of Recurrent High-Grade Glioma in Adults. Biomedicines. 2021; 9(2):138. https://doi.org/10.3390/biomedicines9020138
Chicago/Turabian StyleImmidisetti, Amanda V., Chibueze D. Nwagwu, David C. Adamson, Nitesh V. Patel, and Anne-Marie Carbonell. 2021. "Clinically Explored Virus-Based Therapies for the Treatment of Recurrent High-Grade Glioma in Adults" Biomedicines 9, no. 2: 138. https://doi.org/10.3390/biomedicines9020138