Table 2.
Clinical trials of oncolytic Ad.
| Cancer | Phase | Ad type | Genetic change | Route | Combination therapy | Response | Ref. |
|---|---|---|---|---|---|---|---|
| Advanced Pancreatic cancer | I | Ad-SPAM1 (VCN-01) | Expressing SPAM1 | IT | Gemcitabine | [45] | |
| Solid tumors | I | IV | Gemcitabine | ||||
| Recurrent GBM | I | Ad-Δ24 (DNX-2401) | Replication only in cells with alterations of the RB1 signaling pathway | CED | Temozolomide ± surgery | [19,45,52] | |
| Recurrent Glioblastoma/Gliosarcoma | I/II | Ad-Δ24-RGD (ICOVIR®) | IT | IFN-γ | |||
| Glioblastoma at first recurrence | I | Ad-Δ24-RGD (ICOVIR®) | IT | Temozolomide | |||
| Advanced Melanoma | I | ICOVIR-5 | IV | – | |||
| Solid tumors | I/II | ICOVIR-5 | IP (via MSC) | – | |||
| Advanced solid tumors | I | Ad5/3-D24-GMCSF (CGTG-102) | Drive the local expression of GM-CSF | IT, IV | cyclophosphamide | [40,46] | |
| I | IT | – | |||||
| Chemotherapy-refractory Melanoma | III | Ad5/3-D24-GMCSF | Armed with GM-CSF coding | – | SD, MR, PD | [47] | |
| Intermediate-risk Prostate cancer | II/III | Ad5-yCD/mutTKSR39rep-ADP | 2 cytotoxic gene systems; CD/5-FC and HSV-1 TK/vGCV | IT | Intensity modulated RTx | Reduction in positive biopsy results at 2 yrs | [51,53–55] |
| Recurrent Ovarian cancer | I | Ad5/3-Δ24 | Selective replication within RB-p16-deficient tumor cells | IP | SD, PD | [56] | |
| Small cell Lung cancer | I/II | Ad.p53-DC (INGN-225) | p53-modified Ad-transduced dendritic cell vaccine | – | [50] | ||
| Refractory Head & Neck cancer | III | Ad5CMV-p53 (INGN-201), Advexin® | Ad-mediated p53 gene therapy | IT | ±CTx ±RTx |
†survival, delayed progression | [57,58] |
| Hormone-refractory metastatic Prostate cancer | I/II | Ad5-OC/TK plus VAL | Osteocalcin promoter-driven HSV thymidine kinase gene | IT | Docetaxel, estramustine | [48,49] | |
| Bladder cancer-failed BCG-based immunotherapy | II, III | Ad-GMCSF (CG0070) | Armed with GM-CSF Preferential replication in RB-deficient tumors |
IV | – | [40,45,59] | |
| Locally recurrent Prostate cancer | I | CG7060 (CV706) | Ad with PSA promoter–enhancer element to control E1A expression | IT | RTx | PR; PSA control | [5,43,60] |
| Metastatic, hormone-refractory Prostate cancer | I | CG7870 (CV787) | Rat probasin-E1A hPSA-E1B E3+ |
IV | – | No PR, CR | [5,43,44,61] |
| Recurrent Head & Neck cancer | Approved (China) | ONYX-015, Oncorine® (H101) | E1B-55 kDa gene deleted, target p53 deficient cancer cells | IT | Cisplatin, 5-FU | [59,62–64] | |
| Hepatobiliary tumor | II | ONYX-015 | Ad5/2, E1B-55 kDa gene deleted | IT | – | [65] | |
| Metastatic colorectal cancer | I/II | IV | – | SD, PR | [61] | ||
| Liver metastasis | I, II | IV | – | [61] |
BCG; Bacillus Calmette–Guérin, CED; convection enhanced delivery, CTx; chemotherapy, DC; dendritic cell, 5-FU; 5-fluorouracil, GBM; glioblastoma multiforme, GM-CSF; granulocyte-macrophage colony-stimulating factor, IP; intraperitoneal, IPleu; intrapleural, IT; intratumoral injection, IV; intravenous, IVe; intravesicular, MSC; mesenchymal stem cell, MR; minimal response, PD; progressive disease, PR; partial response, RB; retinoblastoma signaling pathway, RTx; radiation therapy, SD; stable disease.