Table 2 Important ongoing clinical trials combining oncolytic vectors and checkpoint inhibitors
From: Oncolytic viruses and checkpoint inhibitors: combination therapy in clinical trials
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 |