Table 2.
Important ongoing clinical trials combining oncolytic vectors and checkpoint inhibitors
| Trial identifier | Study phase | Virus type | Virus name | Virus dose, schedule | Virus route | Checkpoint inhibitor | Study regimen | cancer type |
|---|---|---|---|---|---|---|---|---|
|
NCT 03004183 STOMP |
II | Adenovirus | ADV/HSV-tk | 5x1011 vp, single injection | IT | Pembrolizumab | Virus (Day 0), Valacyclovir (Day1–15), SBRT (Day 2–16, total 30 Gy), CI (starting day 22) | Metastatic NSCLC Metastatic TNBC |
|
NCT 02798406 CAPTIVE/KEYNOTE-192 |
II | Adenovirus | DNX-2401 | 5x108–5x1010 vp, single injection | IT | Pembrolizumab | Virus (Day 0), CI (starting Day 7–9) | Glioblastoma, gliosarcoma |
| NCT 03003676 | I | Adenovirus | ONCOS-102 | 3 × 1011 vp, multiple injection (× 3) | IT | Pembrolizumab | Cyclophosphadmide priming, Virus (Day 1, 4, 8), CI (starting day 22) | Advanced/Unresectable Melanoma Progressing After PD1 Blockade |
|
NCT 03408587 VLA-024 CLEVER |
Ib | Coxsackie | CAVATAK (CVA21) | 1 × 109 TCID50, multiple doses | IV | Ipilimumab | Virus (Day 1, 3, 5, 8 then repeat cycle every 21 days for up to 8 cycles) + CI (Day 8, 29, 50, 71) | Uveal Melanoma with Liver Metastases |
|
NCT 02565992 VLA-011 CAPRA |
I | Coxsackie | CAVATAK (CVA21) | 4.5 × 106 TCID50/kg, multiple injections | IT | Pembrolizumab | Virus (Day 1, 3, 5, 8, then 3 week intervals), CI (starting day 8) | Advanced Melanoma |
| NCT 02824965 | I, II | Coxsackie | CAVATAK (CVA21) | 1 × 108–1 × 109 TCID50, multiple injections | IT | Pembrolizumab | Virus (Day 1, 3, 5, 8, 29, 50, 71, 92, 113, 134, 155) + CI (starting day 8) | Advanced NSCLC |
| NCT 03153085 | II | HSV | HF10 (TBI-1401) | 1 × 107 TCID50/mL, multiple injections (× 6) | IT | Ipilimumab | Virus (Week 1, 2, 3, 4, 7, 10) + CI (3-week intervals × 4 doses) | Unresectable/Metastatic Melanoma in Japanese Patients |
| NCT 02272855 | II | HSV | HF10 (TBI-1401) | 1 × 107 TCID50/mL, multiple injections (× 6) | IT | Ipilimumab | Virus (Week 1, 2, 3, 4, 7, 10) + CI (3-week intervals × 4 doses) | Unresectable/Metastatic Melanoma |
| NCT 03259425 | II | HSV | HF10 (TBI-1401) | 1 × 107 TCID50/mL, multiple injections | IT | Nivolumab | Virus (Day 0, 7, 14, 21, 28, 42, 56, 70, 84) + CI (starting day 0, every 2 weeks for 7 doses) | Resectable Stage IIIB/C, IV Melanoma |
| NCT 01740297 | Ib, II | HSV | TVEC (Talimogene Laherparepvec) | 106 PFU/mL, multiple injections | IT | Ipilimumab | Virus (Week 1, 4, then every 2 weeks) + CI (Week 1, then every 3 weeks for 4 total doses) | Unresected Stage IIIb/IV melanoma |
|
NCT 02263508 Masterkey 265/KEYNOTE-034 |
Ib, III | HSV | TVEC (Talimogene Laherparepvec) | Multiple injections | IT | Pembrolizumab | Virus (Day 1, then every 2–3 weeks) + CI (starting 2–5 weeks after first viral inoculation) | Unresectable Stage IIIb/IV Melanoma |
|
NCT 02626000 Masterkey 232/Keynote-137 |
Ib, III | HSV | TVEC (Talimogene Laherparepvec) | 106 PFU/mL, multiple injections | IT | Pembrolizumab | Virus (Day 1 and every 3 weeks) + CI (Day 1 and every 3 weeks) | Recurrent/Metastatic HNSCC |
| NCT 02879760 | I, II | Maraba Virus | MG1-MAGEA3 | 1x1010–3x1011 pfu, multiple doses | IV | Pembrolizumab | Ad/MAGEAE priming, MG1-MAGEA3 (Day 15/18), CI starting day 22 | Previously treated NSCLC |
| NCT 02620423 | Ib | Reovirus | Reolysin (Pelareorep) | 4.5 × 1010 TCID50, multiple doses | IV | Pembrolizumab | Virus (Day 1, 2), Chemo: Gemcitabine or Irinotecan or 5-FU/LV (Day 1), CI (starting Day 8) | Pancreatic Adenocarcinoma |
| NCT 03206073 | I, II | Vaccinia | Pexa Vec (Pexastimogene Devacirepvec) | 3 × 108–1 × 109 pfu, multiple doses (× 4) | IV | Durvalumab Tremelimumab |
Virus (Day 1, 2, 16 of cycle 1; Day 2 of cycle 2) + CI (Day 1 of each cycle) | Refractory Colorectal Cancer |
|
NCT 02977156 ISI-JX |
I | Vaccinia | Pexa Vec (Pexastimogene Devacirepvec) | 1 × 109 pfu, multiple injections | IT | Ipilimumab | Virus (Week 1, 3, 5, 9, 12) + CI (Week 3, 5, 9, 12–IT injection) | Metastatic/Advanced Solid Tumors |
| NCT 03071094 | I, IIa | Vaccinia | Pexa Vec (Pexastimogene Devacirepvec) | 1 x 109 pfu, multiple injections | IT | Nivolumab | Virus (Day 1, Day 14, Day 28) + CI (starting day 14) | Advanced HCC |
VP viral particle, pfu plaque forming unit, TCID tissue culture infective dose, IT intratumoral, IV intravenous, SBRT stereotactic body radiotherapy, CI checkpoint inhibitor, NSCLC non small cell lung cancer, TNBC triple negative breast cancer, HNSCC head and neck squamous cell carcinoma, HCC hepatocellular carcinoma