HSV-1 Oncolytic Viruses from Bench to Bedside: An Overview of Current Clinical Trials
Abstract
:Simple Summary
Abstract
1. Introduction
2. HSV-1-Derived Oncolytic Viruses in Clinical Trials
2.1. HSV-1716
2.2. G207
2.3. HF10
2.4. NV1020
2.5. Talimogene Laherparepvec
3. Future Directions for Next Generation oHSVs
3.1. G47Δ
3.2. rQNestin34.5
3.3. M032
3.4. ONCR-177
3.5. C134
3.6. RP1/2
3.7. Rrp450
4. Conclusions
Funding
Conflicts of Interest
References
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Virus Strain | Modifications | Aim |
---|---|---|
G207 | insertion of the Escherichia coli lacZ sequence at ICP6/UL39 | reducing ribonucleotide reductase activity [14] |
deletion of γ34.5/RL1 | reducing neurovirulence [15] | |
1716 | deletion of γ34.5/RL1 | reducing neurovirulence [15] |
HF10 | deletion in the Bam HI-B fragment | unknown |
two incomplete UL56 copies without promoter | possibly reducing neurovirulence [16] | |
reduced expression of UL43, UL49.5, UL55, LAT | possible influence on immunogenicity (UL43), unknown (UL49.5), reduced virus reactivation (LAT) [17] | |
increased expression of UL53 and UL54 | reduced viral shedding (UL53) [17] | |
NV1020 | deletion of one allele of α0, α4, γ34.5 and UL56 | reducing infectivity, viral replication and neuroinvasiveness [18] |
Talimogene laherparepvec (T-Vec) | deletion of ICP34.5 | reducing neurovirulence [15] |
deletion of ICP47 | augment immune response [19] | |
insertion of GM-CSF gene | augment immune response [19] |
Virus | Study Title | Study Type | Disease Type | Study Aim | Status | NCT/UMIN # |
---|---|---|---|---|---|---|
HF10 | A study of TBI-1401(HF10) in patients with solid tumors with superficial lesions | phase I | solid tumors | safety and tolerability of repeated intratumoral injections | completed | NCT02428036 |
Phase I Study of TBI-1401(HF10) plus chemotherapy in patients with unresectable pancreatic cancer | phase I | stage III/IV unresectable pancreatic cancer | dose determination of combined treatment of HF10 with Gemcitabine+Nab-paclitaxel or TS-1 | active, not recruiting | NCT03252808 | |
Study of HF10 in patients with refractory head and neck cancer or solid tumors with cutaneous and/or superficial lesions | phase I | refractory head and neck cancer, squamous cell carcinoma, skin carcinoma of the breast, malignant melanoma | dose escalation study for single and repeated intratumoral injections, assessment of local tumor response | completed | NCT01017185 | |
A study of combination with TBI-1401(HF10) and ipilimumab in Japanese patients with unresectable or metastatic melanoma | phase II | stage IIIB, IIIC, or IV unresectable or metastatic malignant melanoma | safety and efficacy of repeated administration of intratumoral injections of HF10 in combination with ipilimumab, best overall response rate | completed | NCT03153085 | |
A study of combination treatment with HF10 and ipilimumab in patients with unresectable or metastatic melanoma | phase II | stage IIIB, IIIC, or IV unresectable or metastatic melanoma | efficacy of the combination of HF10 with ipilimumab, best overall response rate | completed | NCT02272855 | |
G207 | HSV G207 alone or with a single radiation dose in children with progressive or recurrent supratentorial brain tumors | phase I | recurrent or progressive supratentorial neoplasms, malignant glioma, glioblastoma, anaplastic astrocytoma, PNET, cerebral primitive neuroectodermal tumor, embryonal tumor | safety and tolerability of intratumoral injection, also in combination with a single low dose of radiation | active, not recruiting | NCT02457845 |
HSV G207 in children with recurrent or refractory cerebellar brain tumors | phase I | recurrent or refractory medulloblastoma, glioblastoma multiforme, giant cell glioblastoma, anaplastic astrocytoma, primitive neuroectodermal tumor, ependymoma, atypical teratoid/rhabdoid tumor, germ cell tumor, other high-grade malignant tumor | safety and tolerability of intratumoral injection, also in combination with a single low dose of radiation | recruiting | NCT03911388 | |
HSV G207 with a single radiation dose in children with recurrent high-grade glioma | phase II | recurrent/progressive high grade glioma including glioblastoma multiforme, giant cell glioblastoma, anaplastic astrocytoma, midline diffuse glioma | efficacy and safety of intratumoral inoculation of G207 combined with a single radiation dose | not yet recruiting | NCT04482933 | |
G47Δ | A clinical study of G47delta oncolytic virus therapy for progressive glioblastoma | phase I/II | recurrent/progressive glioblastoma | safety and efficacy of intratumoral inoculation of G47Δ | completed | UMIN000002661 |
A clinical study of an oncolytic HSV-1 G47delta for patients with castration resistant prostate cancer | phase I | castration resistant prostate cancer | safety and efficacy of intratumoral inoculation of G47Δ | completed | UMIN000010463 | |
A clinical study of G47delta oncolytic virus therapy for progressive olfactory neuroblastoma | n/a | recurrent olfactory neuroblastoma | safety and efficacy of intratumoral inoculation of G47Δ | recruiting | UMIN000011636 | |
A clinical study of G47delta oncolytic virus therapy for progressive malignant pleural mesothelioma | phase I | inoperable/recurrent/progressive malignant pleural mesothelioma | safety and efficacy of inoculation of G47Δ into the pleural cavity | recruiting | UMIN000034063 | |
Talimogene laherparepvec | Talimogene laherparepvec in combination with neoadjuvant chemotherapy in triple negative breast cancer | phase I/II | triple negative breast carcinoma | determination of the maximum tolerated dose of talimogene laherparepvec administered with paclitaxel- doxorubicin/cyclophosphamide, pathological complete response rate | active, not recruiting | NCT02779855 |
T-VEC in non-melanoma skin cancer | phase I | locally advanced squamous cell carcinoma, basal cell, carcinoma, Merkel cell carcinoma or cutaneous T cell lymphoma | detection of local immune effects after talimogene laherparepvec injection | recruiting | NCT03458117 | |
Ipilimumab, nivolumab, and talimogene laherparepvec before surgery in treating participants with localized, triple- negative or estrogen receptor positive, HER2 negative breast cancer | phase I | triple negative or ER positive HER2 negative infiltrating ductal breast cancer | safety of combined treatment of talimogene laherparepvec with nivolumab and ipilimumab | recruiting | NCT04185311 | |
Talimogene laherparepvec in treating patients with recurrent breast cancer that cannot be removed by surgery | phase II | recurrent stage IV breast cancer | determination of talimogene laherparepvec efficacy with overall response rate (ORR) | active, not yet recruiting | NCT02658812 | |
Talimogene laherparepvec and nivolumab in treating patients with refractory lymphomas or advanced or refractory non-melanoma skin cancers | phase II | T cell and NK cell lymphomas, Merkel cell carcinoma, Squamous cell carcinoma of the skin, Other non-melanoma skin cancers | response rate to talimogene laherparepvec, also in combination with nivolumab | recruiting | NCT02978625 | |
Talimogene laherparepvec and pembrolizumab in treating patients with stage III-IV melanoma | phase II | stage IV or unresectable stage III melanoma | response rate to talimogene laherparepvec in combination with pembrolizumab | recruiting | NCT02965716 | |
Talimogene laherparepvec, chemotherapy, and radiation therapy before surgery in treating patients with locally advanced or metastatic rectal cancer | phase I | stage III/IV rectal adenocarcinoma | dose determination and toxicity of talimogene laherparepvec in combination with capecitabibe, 5-fluoruracil, leucovorin, oxaliplatin, radiation | recruiting | NCT03300544 | |
Talimogene laherparepvec with chemotherapy or endocrine therapy in treating participants with metastatic, unresectable, or recurrent HER2- negative breast cancer | phase Ib | HER2-negative, estrogen receptor positive stage III/IV breast carcinoma | safety and tolerability of talimogene laherparepvec in combination with either chemotherapy (paclitaxel, nab-paclitaxel, or gemcitabine/carboplatin) or endocrine therapy | recruiting | NCT03554044 | |
Talimogene laherparepvec and panitumumab for the treatment of locally advanced or metastatic squamous cell carcinoma of the skin | phase I | locally advanced or metastatic squamous cell carcinoma of the skin | safety and efficacy of combined talimogene laherparepvec and panitumumab | recruiting | NCT04163952 | |
Talimogene laherparepvec and radiation therapy in treating patients with newly diagnosed soft tissue sarcoma that can be removed by surgery | phase II | liposarcoma, leiomyosarcoma, undifferentiated pleomorphic sarcoma (UPS)/ malignant fibrous histiosarcoma (MFH) | evaluation of the pathologic complete necrosis rate and safety following neoadjuvant treatment with talimogene laherparepvec and radiation | recruiting | NCT02923778 | |
A Phase 1, multi-center, open-label, dose de-escalation study to evaluate the safety and efficacy of Talimogene laherparepvec in pediatric subjects with advanced non-CNS tumors that are amenable to direct injection | phase I | recurring non-CNS solid tumor | safety and efficacy | recruiting | NCT02756845 | |
ONCR-177 | Study of ONCR-177 alone and in combination with PD-1 blockade in adult subjects with advanced and/or refractory cutaneous, subcutaneous or metastatic nodal solid tumors | phase I | advanced or metastatic solid tumors | determination of the maximum tolerated dose as well as preliminary efficacy of ONCR-177 in combination with pembrolizumab | recruiting | NCT04348916 |
RP2 | Study of RP2 monotherapy and RP2 in combination with nivolumab in patients with solid tumors | phase I | advanced or metastatic non-neurological solid tumors | safety and tolerability of RP2, also in combination with nivolumab | recruiting | NCT04336241 |
RP1 | Study evaluating cemiplimab alone and combined with RP1 in treating advanced squamous skin cancer | phase II | locally advanced or metastatic cutaneous squamous cell carcinoma | determination of the clinical response rate/overall response rate of cemiplimab monotherapy versus combination with RP1 | recruiting | NCT04050436 |
Study of RP1 monotherapy and RP1 in combination with nivolumab | phase I/II | advanced and/or refractory solid tumors | determination of the maximum tolerated dose as well as preliminary efficacy of RP1 in combination with nivolumab | recruiting | NCT03767348 | |
A Phase 1b study of RP1 in transplant patients with advanced cutaneous squamous cell carcinoma | phase I | recurrent, locally advanced or metastatic cutaneous squamous cell carcinoma | safety and tolerability | recruiting | NCT04349436 | |
rQNestin | A study of the treatment of recurrent malignant glioma with rQNestin34.5v.2 | phase I | astrocytoma, malignant astrocytoma, oligodendroglioma, anaplastic oligodendroglioma, mixed oligo-astrocytoma | safety and dose determination of rQNestin with or without previous immunomodulation with cyclophosphamide | recruiting | NCT03152318 |
M032 | Genetically engineered HSV-1 Phase 1 study for the treatment of recurrent malignant glioma | phase I | recurrent or progressive glioblastoma multiforme, anaplastic astrocytoma, gliosarcoma | safety and tolerability | recruiting | NCT02062827 |
C134 | Trial of C134 in patients with recurrent GBM | phase I | recurrent or progressive glioblastoma multiforme, anaplastic astrocytoma, gliosarcoma | safety and tolerability | recruiting | NCT03657576 |
Rrp450 | rRp450-Phase I trial in liver metastases and primary liver tumors | phase I | liver metastases or primary liver cancer | safety and tolerability | recruiting | NCT01071941 |
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Koch, M.S.; Lawler, S.E.; Chiocca, E.A. HSV-1 Oncolytic Viruses from Bench to Bedside: An Overview of Current Clinical Trials. Cancers 2020, 12, 3514. https://doi.org/10.3390/cancers12123514
Koch MS, Lawler SE, Chiocca EA. HSV-1 Oncolytic Viruses from Bench to Bedside: An Overview of Current Clinical Trials. Cancers. 2020; 12(12):3514. https://doi.org/10.3390/cancers12123514
Chicago/Turabian StyleKoch, Marilin S., Sean E. Lawler, and E. Antonio Chiocca. 2020. "HSV-1 Oncolytic Viruses from Bench to Bedside: An Overview of Current Clinical Trials" Cancers 12, no. 12: 3514. https://doi.org/10.3390/cancers12123514