Table 2.
Oncolytic HSVs tested in current clinical trials.
| Oncolytic HSV | TumorSelectivity | Route of Administration | Combination | Indication | Phases | NCT Number | Sponsor/Collaborator | Status |
|---|---|---|---|---|---|---|---|---|
|
Talimogene Laherparepvec1
(T-VEC, IMLYGIC) |
- γ134.5 deletion -ICP 47 gene deletion |
Intratumoral Injection |
None | Cutaneous Squamous Cell Cancer | Phase 2 | NCT03714828 | -University of Arizona -Amgen |
Recruiting |
| Intratumoral Injection |
Hypofractionated Radiotherapy | -Melanoma -Merkel Cell Carcinoma -Other Solid Tumors |
Phase 2 | NCT02819843 | -Memorial Sloan Kettering Cancer Center -Amgen |
Active, not recruiting | ||
| Intratumoral Injection |
Nivolumab | -Refractory Lymphomas -Advanced or Refractory Non-melanoma Skin Cancers |
Phase 2 | NCT02978625 | -National Cancer Institute | Recruiting | ||
| N/A | -Nivolumab - Trabectedin |
Sarcoma | Phase 2 | NCT03886311 | -Sarcoma Oncology Research Center, LLC | Recruiting | ||
| Intratumoral Injection | Pembrolizumab | Melanoma | Phase 2 | NCT02965716 | -National Cancer Institute | Active, not recruiting | ||
| Intratumoral Injection |
Pembrolizumab | Metastatic or advanced sarcoma | Phase 2 | NCT03069378 | -Memorial Sloan Kettering Cancer Center -Amgen -Merck Sharp & Dohme LLC |
Recruiting | ||
| Intratumoral Injection |
None | Angiosarcoma of Skin | Phase 2 | NCT03921073 | H. Lee Moffitt Cancer Center and Research Institute | Active, not recruiting | ||
| Intratumora Injection l |
Nivolumab | Melanoma | Phase 2 | NCT04330430 | -The Netherlands Cancer Institute -Amgen |
Recruiting | ||
| Intratumoral Injection |
Radiation | Soft tissue sarcoma | Phase 2 | NCT02923778 | -National Cancer Institute | Recruiting | ||
| Intratumoral Injection |
None | Melanoma | Phase 2 | NCT04427306 | -University of California, Davis -Amgen |
Recruiting | ||
| Intratumoral Injection |
Pembrolizumab | Cutaneous Melanoma | Phase 2 | NCT03842943 | University of Louisville | Recruiting | ||
| Intratumoral Injection |
Pembrolizumab | Anti-PD-1 therapy refractory melanoma | Phase 2 | NCT04068181 | -Amgen -Merck Sharp & Dohme LLC |
Active, not recruiting | ||
| Intratumoral Injection |
None | Kaposi Sarcoma | Phase 2 | NCT04065152 | Assistance Publique - Hôpitaux de Paris | Recruiting | ||
|
TBI-1401
(HF10, Canerpaturev, C-REV) |
Unknown2 | Intratumoral Injection |
None | Solid Tumor | Phase 1 | NCT02428036 | Takara Bio Inc. | Completed |
| Intratumoral Injection |
None | Refractory Head and Neck Cancer, Solid Tumors With Cutaneous and/or Superficial Lesions | Phase 1 | NCT01017185 | Takara Bio Inc. | Completed | ||
| Intratumoral Injection |
Gemcitabine, Nab-paclitaxel, TS-1 | Unresectable Pancreatic Cancer | Phase 1 | NCT03252808 | Takara Bio Inc. | Active, not recruiting | ||
| Intratumoral Injection |
Ipilimumab | Unresectable or Metastatic Melanoma | Phase 2 | NCT03153085 | - Takara Bio Inc. | Completed | ||
| Intratumoral Injection |
Ipilimumab | Malignant Melanoma | Phase 2 | NCT02272855 | -Takara Bio Inc. -Theradex |
Completed | ||
| Intratumoral Injection |
Nivolumab | Resectable Melanoma | Phase 2 | NCT03259425 | - Takara Bio Inc. -Bristol-Myers Squibb -University of Utah |
Terminated | ||
| HSV1716 | - γ134.5 deletion | Intreapleural Injection | none | Malignant Pleural Mesothelioma | Phase 1/2 | NCT01721018 | Virttu Biologics Limited | Completed |
| Intratumoral Injection or Intravenous Injection |
none | Non-CNS Solid Tumors | Phase 1 | NCT00931931 | -Timothy Cripe -Nationwide Children's Hospital |
Completed | ||
| Injection into resection cavity | dexamethasone | Refractory or Recurrent High Grade Glioma | Phase 1 | NCT02031965 | -Pediatric Brain Tumor Consortium -National Cancer Institute (NCI) | Terminated | ||
| G207 | - γ134.5 deletion -UL39 substitution with LacZ gene |
Intratumoral & tumor bed at the resection site |
None | Recurrent Brain Cancer | Phase 1/2 | NCT00028158 | MediGene | Completed |
| Intratumoral Injection |
None | Recurrent or Refractory Cerebellar Brain Tumors in Children | Phase 1 | NCT03911388 | University of Alabama at Birmingham | Recruiting | ||
| Intratumoral Injection |
Radiation | Progressive or Recurrent Supratentorial Brain Tumors in Children | Phase 1 | NCT02457845 | University of Alabama at Birmingham | Recruiting | ||
| Intratumoral Injection |
Radiation | Glioma | Phase 1 | NCT00157703 | - MediGene --National Cancer Institute |
Completed | ||
| Intratumoral Injection |
Radiation | Recurrent glioma in children | Phase 2 | NCT04482933 | - University of Alabama at Birmingham - Treovir, LLC |
Not yet recruiting | ||
| NV1020 | -deletion of a 15-kb region at the UL/S junction containing one copy of the α0, α4, and γ134.5 -deletion to one copy of UL56 gene |
Intrahepatic arterial injection | None | Colorectal cancer metastatic to the liver | Phase 1 | NCT00012155 | -Memorial Sloan Kettering Cancer Center -National Cancer Institute |
Completed |
| Intrahepatic arterial injection | None | Colorectal cancer metastatic to the liver | Phase 1/2 | NCT00149396 | MediGene | Completed | ||
|
OH2
(rHSV2hGM-CSF) |
-Mutation of ICP6 gene - γ134.5 deletion |
Intratumoral Injection |
-irinotecan, -HX008 (PD-1 ICI) |
Solid Tumor | Phase 1/2 | NCT03866525 | Wuhan Binhui Biotechnology | Recruiting |
| Intravesical Injection |
None | Non-muscle-invasive Bladder Cancer | Phase 1/2 | NCT05232136 | Wuhan Binhui Biotechnology | Recruiting | ||
| Intravesical Injection |
None | Pancreatic Cancer | Phase 1/2 | NCT04637698 | Wuhan Binhui Biotechnology | Recruiting | ||
| Intratumoral Injection |
None | Central Nervous System Tumors | Phase 1/2 | NCT05235074 | Wuhan Binhui Biotechnology | Recruiting | ||
| N/A | pembrolizumab | Solid Tumor | NCT04386967 | Wuhan Binhui Biotechnology | Recruiting | |||
| Intratumoral Injection |
None | Advanced Bladder Carcinoma | Phase 2 | NCT05248789 | Wuhan Binhui Biotechnology | Not yet recruiting | ||
| Intratumoral Injection |
-LP002 (PD-L1 ICI) -Cisplatin -Fluorouracil |
Cancer of digestive track | Phase 1 | NCT04755543 | Taizhou HoudeAoke Biomedical Co., Ltd. | Recruiting | ||
| N/A | -HX008 (PD-1 ICI) |
Melanoma | Phase 1/2 | NCT04616443 | Wuhan Binhui Biotechnology | Recruiting | ||
| Intratumoral Injection | -HX008 (PD-1 ICI) -Radiation |
Melanoma with liver metastasis | Phase 1 | NCT05068453 | Beijing Cancer Hospital | Not yet recruiting | ||
| Intratumoral Injection |
-HX008 (PD-1 ICI) -Axitinib |
Melanoma with liver metastasis | Phase 1 | NCT05070221 | Beijing Cancer Hospital | Not yet recruiting | ||
| rQNestin34.5v.2 | - γ134.5 deletion -UL39 deletion -Nestin promoter driven expression of single γ134.5 gene |
N/A | Cyclophosphamide | Recurrent Malignant Glioma | Phase 1 | NCT03152318 | -Dana-Farber Cancer Institute -National Institutes of Health -Candel Therapeutics, Inc. |
Recruiting |
| C134 | - γ134.5 deletion -Expression of human cytomegalovirus protein kinase R evasion protein IRS1 |
Intratumoral Injection |
none | Recurrent glioblastoma | Phase 1 | NCT03657576 | -University of Alabama -National Cancer Institute |
Recruiting |
|
M032
(NSC 733972) |
Substitution of γ134.5 and ORF P gene with α27-tk |
Intratumoral Injection |
none | Brain Cancer | Phase 1 | NCT02062827 | University of Alabama at Birmingham | Active, not recruiting |
| Intratumoral Injection |
Pembrolizumab | Brain Cancer | Phase 1/2 | NCT05084430 | Active, not recruiting | |||
| OrienX010 | Not available | Intratumoral Injection |
none | Melanoma, Liver, Pancreatic, and Lung Cancer |
Phase 1 | NCT01935453 | -OrienGene Biotechnology -START Shanghai -Beijing Bozhiyin T&S Co., Ltd. |
Completed |
| Intratumoral Injection |
JS001 (PD-1 ICI) |
Melanoma | Phase 1 | NCT04206358 | Beijing Cancer Hospital | Recruiting | ||
| Intratumoral Injection |
Toripalimab (PD-1 ICI) |
Melanoma | Phase 1 | NCT04197882 | Beijing Cancer Hospital | Active, not recruiting | ||
| Intratumoral Injection |
Dacarbazine | Melanoma | Phase 2 | NCT04200040 | OrienGene Biotechnology | Recruiting | ||
| RP1 | - γ134.5 deletion -ICP 47 gene deletion |
Intratumoral Injection |
None | Advanced cutaneous cancer | Phase 1/2 | NCT04349436 | Replimune Inc | Recruiting |
| Intratumoral Injection |
Nivolumab | Solid tumors | Phase 2 | NCT03767348 | Replimune Inc | Recruiting | ||
| Intratumoral Injection |
Cemiplimab | Advanced squamous skin cancer | Phase 2 | NCT04050436 | -Replimune Inc -Regeneron Pharmaceuticals |
Recruiting | ||
| RP2 | Intratumoral Injection |
Nivolumab | Solid tumors | Phase 1 | NCT04336241 | Replimune Inc | Recruiting | |
| RP3 | Intratumoral Injection |
Nivolumab | Solid tumors | Phase 1 | NCT04735978 | -Replimune Inc -Bristol-Myers Squibb |
Recruiting | |
| VG161 | - γ134.5 deletion | Intratumoral Injection |
None | Liver cancer | Phase 1 | NCT04806464 | CNBG-Virogin Biotech (Shanghai) Ltd. | Recruiting |
| Intratumoral Injection |
None | Solid Tumor | Phase 1 | NCT04758897 | CNBG-Virogin Biotech (Shanghai) Ltd | Recruiting | ||
| Intratumoral Injection |
Nivolumab | Advanced pancreatic cancer | Phase 1/2 | NCT05162118 | Zhejiang University | Recruiting | ||
| Intratumoral Injection |
None | Hepatocellular Carcinoma or Intrahepatic Cholangiocarcinoma | Phase 2 | NCT05223816 | -Virogin Biotech Canada Ltd -Virogin Biotech Ltd. |
Not yet recruiting | ||
| VG2025 | -Tumor-specific CEA promoter driven ICP27 gene expression | Intratumoral Injection |
None | Solid Tumor | Phase 1 | NCT05266612 | -Virogin Biotech Canada Ltd -Virogin Biotech Ltd |
Not yet recruiting |
| rRp450 | -replacement of UL39 gene encoding ICP6 with rat Cyp2b1 gene | Hepatic artery infusion | None | Liver metastases and liver cancer | Phase 1 | NCT01071941 | Recruiting | |
|
T3011
(MVR-T3011) |
Unknown | Intravenous | Pembrolizumab | Advanced or metastatic solid tumors | Phase 1/2 | NCT04780217 | ImmVira Pharma Co. Ltd | Recruiting |
|
T3011
(MVR-T3011) C5252 (MVR-C5252) |
Unknown | Intratumoral | Pembrolizumab | Advanced or metastatic solid tumors | Phase 1/2 | NCT04370587 | ImmVira Pharma Co. Ltd | Recruiting |
| Intratumoral | None | Recurrent or progressive glioblastoma | Phase 1 | NCT05095441 | ImmVira Pharma Co. Ltd | Recruiting |
1. Only “Active” or “Recruiting” phase II or higher clinical trials using talimogene laherparepvec have been listed in the table due to the largest number of clinical trials being performed to date for a single OV product. 2. HF10 does not express several UL genes, but retains g134.5. Precise mechanism of HF10’s cancer specificity has not been elucidated at present. Detailed discussion of mutations in HF10 gene can be found in REFS (56, 57).