Table 2.
Clinical trials featuring oncolytic viruses against pancreatic cancer.
Oncolytic Virus Backbone | Oncolytic Virus Name | Brief Description of the Clinical Trial |
---|---|---|
Adenovirus | ONYX-015 (dl1520) | ONYX-015 injection via EUS into pancreatic carcinomas by the transgastric route with prophylactic antibiotics is feasible and generally well tolerated either alone or in combination with gemcitabine [167]. |
ONYX-015 (dl1520) | Intratumoral injection of an E1B-55 kDa region-deleted adenovirus into primary pancreatic tumors was feasible and well-tolerated at doses up to 10(11) PFU (2 x 10(12) particles), but viral replication was not detectable [168]. | |
Ad5-yCD/mutTKSR39rep-ADP | A combination of intratumoral Ad5-DS and gemcitabine is safe and well tolerated in patients with LAPC [169]. | |
Ad5-yCD/mutTKSR39rep-hIL12 | Ongoing clinical trial, no results posted to date. NCT03281382. | |
LOAd703 | Ongoing clinical trial, no results posted to date. NCT02705196. | |
VCN-01 | Ongoing clinical trial, no results posted to date. NCT02045589. | |
VCN-01 | Ongoing clinical trial, no results posted to date. NCT02045602. | |
Herpesvirus | T-VEC | EUS-guided FNI of T-VEC in advanced pancreatic ca, at initial doses of 104 to 106 PFU/mL followed by up to 107 PFU/mL, was feasible and tolerable. Evidence of biologic activity was observed [170]. |
T-VEC | Ongoing clinical trial, no results posted to date. NCT03086642. | |
HF10 | HF10 direct injection under EUS-guidance in combination with erlotinib and gemcitabine was a safe treatment for locally advanced pancreatic cancer [171]. | |
HF10 | Ongoing clinical trial, no results posted to date. NCT03252808. | |
OrienX010 | Ongoing clinical trial, no results posted to date. NCT01935453. | |
Reovirus | Reolysin | Pelareorep was safe but ineffective when administered with carboplatin/paclitaxel, regardless of KRAS mutational status. Immunologic studies suggest that chemotherapy backbone improves immune reconstitution and that targeting remaining immunosuppressive mediators may improve oncolytic virotherapy [172]. |
Reolysin | PD analysis revealed reovirus replication within pancreatic tumor and associated apoptosis. Upregulation of immune checkpoint marker PD-L1 suggests future consideration of combining oncolytic virus therapy with anti-PD-L1 inhibitors [173]. | |
Reolysin | Pelareorep and pembrolizumab added to chemotherapy did not add significant toxicity and showed encouraging efficacy [174]. | |
Reolysin | Ongoing clinical trial, no results posted to date. NCT01280058. | |
Parvovirus | ParvOryx | The drug was safe and well-tolerated and showed a promising profile of anti-tumor effects and signs of clinical efficacy, i.e., prolonged survival. However, the optimum dose as well as the most appropriate route and schedule of administration have to be further investigated [175]. |
PFU = plaque-forming unit.