Table 2.
Timing of oncolytic virotherapy and immune checkpoint inhibitor combinations in selected clinical trials
| Virus family | Virus | Indication | Combination drug | Virus RoA | Dosing schedule | Timing comment | ClinicalTrials.gov identifier |
|---|---|---|---|---|---|---|---|
| Adenovirus | Ad-p53 | HNSCC | Nivolumab | IT |
3 × virus (week 1), nivolumab day 5 Combination repeats on week 1 of each cycle q4w |
Delayed ICI (4 days) | NCT03544723 |
| DNX-2401 | GBM, gliosarcoma | Pembrolizumab | IT |
Virus day 1 Pembrolizumab day ~ 8, q3w |
Delayed ICI (1 week) | NCT02798406 | |
| Enadenotucirev | Advanced epithelial tumors | Nivolumab | IV |
Unknown virus schedule Unknown nivolumab schedule |
Unknown | NCT02636036 | |
| ONCOS-102 | Anti-PD1-refractory metastatic melanoma |
Cyclophosphamide Pembrolizumab |
IT |
Cyclophosphamide day – 1 Virus days 1, 4, 8 Pembrolizumab day 22, q3w |
Delayed ICI (3 weeks) | NCT03003676 | |
| VCN-01 | R/M HNSCC | Durvalumab | IV |
Arm 1: virus IV day 1, durvalumab IV day 1, q4w Arm 2: virus IV day 1, durvalumab IV day 15, q4w |
Simultaneous ICI or delayed ICI (2 weeks) | NCT03799744 | |
| CVA21 | Cavatak | Uveal melanoma with liver metastases | Ipilimumab | IV |
Virus days 1, 3, 8, q3w (up to 19 ×) Ipilimumab day 8, q3w (up to 4 ×) |
Delayed ICI (1 week) | NCT03408587 |
| Cavatak | Advanced melanoma | Pembrolizumab | IT |
Virus days 1, 3, 8, q3w (up to 19 ×) Pembrolizumab day 8, q3w (up to 2 years) |
Delayed ICI (1 week) | NCT02565992 | |
| Cavatak | NSCLC | Pembrolizumab | IV |
Virus days 1, 3, 8, q3w (up to 8 ×) Pembrolizumab q3w (up to 24 months) |
Uncertain | NCT02824965 | |
| HSV1 | HF-10 | Resectable advanced melanoma | Nivolumab | IT neoadjuvant |
9 × virus (5 × virus q1w then 4 × virus q2w) Nivolumab q2w × 7, surgery, nivolumab q4w up to 1 year |
Uncertain | NCT03259425 |
| T-VEC | Early breast cancer | Atezolizumab | Unknown |
Virus days 1, 21, q2w Atezolizumab day 21, q2w |
Delayed ICI | NCT03802604 | |
| T-VEC | TNBC, CRC with liver metastases | Atezolizumab | IT |
Virus day 1, q3w Atezolizumab day 1, q3w |
Simultaneous ICI | NCT03256344 | |
| T-VEC |
Refractory lymphoma Advanced or refractory non-melanoma skin cancer |
Nivolumab | IT |
Virus days 1, 21, q2w Nivolumab day 21, q2w |
Delayed ICI (3 weeks) | NCT02978625 | |
| T-VEC | Malignant pleural effusion | Nivolumab | Intrapleural | Virus (unknown schedule) ± nivolumab (same day as virus) | Simultaneous ICI | NCT03597009 | |
| T-VEC | Advanced melanoma | Pembrolizumab | IT |
Virus day 1, q3w Pembrolizumab day 1, q3w |
Simultaneous ICI | NCT02965716 | |
| T-VEC | Unresected melanoma | Pembrolizumab | IT |
Virus days 1, 21, q2w Pembrolizumab week 5, q3w |
Delayed ICI (5 weeks) | NCT02263508 | |
| RP1 | Melanoma, bladder, skin, MSI-high solid | Nivolumab | IT |
3 × virus in escalating doses q2w Unknown nivolumab schedule |
Unknown | NCT03767348 | |
| Maraba | MG1-E6/E7 | HPV-associated cancer |
Ad-E6/E7 Atezolizumab |
IV or IT + IV |
Prime IM Ad-E6/E7 (– 14 days) 4 × IV MG1-E6/E7 (spread over 2 weeks) OR IV MG1-E6/E7 day 1, IT MG1-E6/E7 days 4,14 Atezolizumab day 43, q3w |
Delayed ICI (6 weeks) | NCT03618953 |
| MG1-MAGEA3 | Metastatic melanoma, CSCC |
Ad-MAGEA3 Pembrolizumab Cyclophosphamide |
IV or IT + IV |
Ad-MAGEA3 IM day 1 ± CPA day – 3 Virus IV days 15,18, or IV day 15, IT days 22, 29, 36 (+ day 43, q3w IT boosters) Pembrolizumab q3w (start either day 1 or week 6) |
Pre-virus ICI (– 2 weeks) or delayed ICI (4 weeks) | NCT03773744 | |
| Reovirus | Reolysin | Advanced pancreatic adenocarcinoma |
Chemotherapy Pembrolizumab |
IV |
Virus days 1, 2 q3w Chemotherapy combination day 1 q3w Pembrolizumab day 8 q3w |
Delayed ICI (1 week) | NCT02620423 |
| Reolysin | Advanced pancreatic cancer | Pembrolizumab | IV |
Virus days 1, 2, 3, 8 + days 1, 8 q3w (up to 24 months) Pembrolizumab day 1, q3w |
Simultaneous ICI | NCT03723915 | |
| Vaccinia | PexaVec | Unresectable RCC | Cemiplimab | IV or IT |
3 × virus IT q2w or 4 × virus IV q1w, cemiplimab q3w Cemiplimab q3w: @PD, 3 × virus IT q2w |
Uncertain | NCT03294083 |
| PexaVec | Refractory CRC |
Durvaumab Tremelimumab |
IV |
Virus days 2, 12, 16 cycle 1, day 2 cycle 2 Durvalumab day 1 each cycle Tremelimumab day 1 cycles 1–4 |
Simultaneous ICI | NCT03206073 | |
| PexaVec | Advanced solid tumors | Ipilimumab | IT |
Virus up to 5 × (weeks 1, 3, 5, 9, + week 12 if PD) Ipilimumab up to 4 × IT (weeks 3, 5, 9, + week 12 if PD) |
Delayed ICI (3 weeks) | NCT02977156 | |
| PexaVec | HCC | Nivolumab | IT |
Virus days 1, 15, 29 Nivolumab day 15 q2w |
Delayed ICI (2 weeks) | NCT03071094 | |
| VSV | VSV-IFNβ-NIS | Solid Tumors | Avelumab | IV | Virus day 1, avelumab day 1, q3w | Simultaneous ICI | NCT02923466 |
| VSV-IFNβ-NIS | HNSCC, NSCLC | Pembrolizumab | IV | Virus day 1, pembrolizumab day 1, q3w | Simultaneous ICI | NCT03647163 |
CPA cyclophosphamide, CRC colorectal cancer, CSCC cutaneous squamous cell carcinoma, CVA21 coxsackievirus A21, GBM glioblastoma, HCC hepatocellular carcinoma, HNSCC head and neck squamous cell carcinoma, HPV human papillomavirus, HSV1 herpes simplex virus 1, ICI immune checkpoint inhibitor, IM intramuscular, IT intratumoral, IV intravenous, MAGEA3 melanoma-associated antigen 3, MSI microsatellite instability, NSCLC non-small cell lung carcinoma, PD progressive disease, PD1 programmed death 1, qxw every x weeks, RCC renal cell carcinoma, R/M recurrent/metastatic, RoA route of administration, TNBC triple-negative breast cancer, T-VEC talimogene laherparepvec, VSV-IFNβ-NIS vesicular stomatitis virus expressing both interferon β and sodium iodide symporter genes