So it has a NCT number now:
NCT03206073
A Phase I/II Study of Pexa-Vec Oncolytic Virus in Combination With Immune Checkpoint Inhibition in Refractory Colorectal Cancer
https://clinicaltrials.gov/ct2/show/NCT03206073
It proposes the combination of a therapeutic vaccine with one or two checkpoint inhibitors; one arm is the vaccine plus durva --anti PD-1--, the other is the vaccine plus durva plus tremelimumab --anti CTLA-4. All the agents involved are immunotherapies.
Only at the NIH, in Bethesda, Maryland.
FROM THE INCLUSION CRITERIA:
'Patients must have progressed on, been intolerant of OR REFUSED prior oxaliplatin- and irinotecan-containing, fluorouracil-based, chemotherapeutic regimen and have disease that is not amenable to potentially curative resection. Patients who have a known KRAS wild type tumor must have progressed, been intolerant of OR REFUSED cetuximab or panitumumab-based chemotherapy.'
Background:
-Immune-based approaches in colorectal cancer have unfortunately with the notable exception of immune checkpoint inhibition in microsatellite instable (MSI-hi) disease been largely unsuccessful. The reasons for this are unclear but no doubt relate to the fact that in advanced disease colorectal cancer appears to be less immunogenic, as evidenced by the lack of infiltrating lymphocytes with advancing T stage
-Pexa-Vec (JX-594) is a thymidine kinase gene-inactivated oncolytic vaccinia virus engineered for the expression of transgenes encoding human granulocyte- macrophage Colony-stimulating factor (GM-CSF) and beta-galactosidase. Apart from the direct oncolytic activity, oncolytic viruses such as Pexa-Vec have been shown to mediate tumor cell death via the induction of innate and adaptive immune responses
-Tremelimumab is a fully human monoclonal antibody that binds to CTLA-4 expressed on the surface of activated T lymphocytes and causes inhibition of B7-CTLA-4-mediated downregulation of T-cell activation.
- Durvalumab is a human monoclonal antibody directed against PD-L1.
It is for MSS CRC patients who had not received prior immunotherapy and for MSI-High CRC patients for whom anti PD-1 monotherapy has not worked.
It is listed not open yet; people who have checked were told that is about to start on August, probably.
Pexa Vec (JX-594) has been discussed/ followed in this forum since at least 2013. Pexa-Vec upcoming data in ASCO 2013