Table 1.
Clinical trials combining chemotherapy with reovirus and immune parameters
| PMID | Cancers | Phase | Reovirus Dose | Anti-cancer agent | Results | Immune parameters |
|---|---|---|---|---|---|---|
| 32156785 | Refractory metastatic colorectal cancer | I | 1×1010 TCID50-3×1010 TCID50 | FOLFIRI-bevacizumab + reovirus | PR: 3/6 (50%) | Dendritic cell maturation: 48 hours, 4.5%-18.6% (P=000016) |
| Median PFS: 65.6 weeks | CD4-count increase: 3.5-fold (P=0.00015) | |||||
| Median OS: 25.1 months | CD8-count increase: 2.4-fold (P=0.00015) | |||||
| 18323793 | Advanced solid cancers | I | 1×108 TCID50-3×1010 TCID50 | None | N/A | CD4+: 10/21 (47.6%) |
| CD8+: 7/21 (33%) | ||||||
| NK: 6/21 (28.6%) | ||||||
| Increase in IL-5, IL-8, IL-6, IL-2, IL-12p40 | ||||||
| NARA: increase in 250-fold | ||||||
| 29653857 | Metastatic colorectal cancer, 1st line | II | 3×1010 TCID50 | FOLFOX-6-bevacizumab ± reovirus | Median PFS: 7 vs. 9 months, HR 1.59 (P=0.046) | N/A |
| Median OS: HR 1.22; (P=0.38) | ||||||
| ORR: 2.52 (P=0.03) | ||||||
| 20926400 | Advanced solid cancers | I | 3×1010 TCID50 | Docetaxel + reovirus | ORR: 14/16 | NARA: increase in 729-fold at peak |
| PR: 4/16 in breast, stomach, gastroesophageal, ocular melanoma | ||||||
| Minor response: 3/16 in mesothelioma, prostate, head and neck | ||||||
| SD: 7/16 in prostate, melanoma, esophagus, pancreas, unknown | ||||||
| 26709987 | KRAS or EGFR mutant metastatic NSCLC | II | 3×1010 TCID50 | Carboplatin, paclitaxel + reovirus | PR: 11/37 | N/A |
| SD: 20/37 | ||||||
| PD: 4/37 | ||||||
| Not evaluable: 2/37 | ||||||
| Median PFS: 4 months | ||||||
| Median OS: 13.1 months | ||||||
| 27039845 | Metastatic pancreatic adenocarcinoma | II | 3×1010 TCID50 | Carboplatin, paclitaxel ± reovirus | PFS: 4.9 vs. 5.2 (P=0.6) | Reovirus arm with increased pro-inflammatory markers, including fractalkine, IL-10, RANTES, SDF-1, VEGF-A |
| Reovirus arm with increase in CD8+ expressing CD71, CD95, CD45RO | ||||||
| 22316603 | Relapsed/metastatic Head and Neck Cancer | I | 3×1010 TCID50 | Carboplatin, paclitaxel + reovirus | CR: 1/31 (3.8%) | NARA: increase by 27-729-fold |
| PR: 6/31 (23.1%) | ||||||
| SD: 9/31 (34.6%) | ||||||
| PD: 8/31 (30.8%) | ||||||
| Duration of response: 6 months | ||||||
| Median OS: 7.1 months | ||||||
| 29748010 | NSCLC | II | 4.5×1010 TCID50 | Pemetrexed or docetaxel ± reovirus | PFS: 3.0 vs. 2.8 months (P=0.53) | N/A |
| STK11 (HR 0.29) and PIK3CA (HR 0.45) mutations with improved PFS | ||||||
| 29799479 | Advanced pancreatic adenocarcinoma, 1st line | II | 1×1010 TCID50 | Gemcitabine + reovirus | PR: 1/34 | Upregulation of PD-L1 on immunohistochemistry |
| SD: 23/34 | ||||||
| PD: 5/34 | ||||||
| Median OS: 10.2 months | ||||||
| 29027598 | Metastatic breast cancer | II | 3×1010 TCID50 | Paclitaxel ± reovirus | PFS: 3.78 months vs. 3.38 months (P=0.87) | N/A |
| OS: 17.4 months vs. 10.4 months (P=0.1) | ||||||
| 31694832 | Advanced pancreatic adenocarcinoma | Ib | 4.5×1010 TCID50 | Reovirus and pembrolizumab + 5-fluorouracil, gemcitabine, or irinotecan | Disease control in 3 of 10 patients | Creation of new T-cell clones observed |
| PR: 1/10 for 17.4 months | ||||||
| SD: 2/10 for 9 months and 4 months |
PR: partial response, SD: stable disease, PFS: progression free survival, OS: overall survival, ORR: overall response rate, NARA: neutralizing anti-reoviral antibodies, NSCLC: non-small cell lung cancer.