The study was a randomised phase II study in patients with advanced metastatic adenocarcinoma of the pancreas, first line – patients were untreated. Patients were randomised to standard of care chemotherapy with gemcitabine and Abraxane versus gemcitabine and Abraxane in combination with VCN-001 which is an oncolytic adenovirus.
What was the study design?
The study was a randomised 1:1 phase II study. So patients were randomly allocated to either standard of care or the combination and overall survival was the primary endpoint.
What were the results of this study?
The study was positive in terms of survival benefit. There was a survival advantage of the combination of the virus versus the standard of care chemotherapy. It was also positive with regards to overall response rate and progression free survival. No subset of patients appears to benefit more than others, the results appear to be similar across different segments, like differences in gender, differences in liver metastases or not.
The other aspect that was important is that in patients who were stable after 14 weeks we administered a second dose of the virus. In that subset of patients, which were about 60 patients or so, the results were clearly much better with the virus as compared to chemotherapy, indicating that a second dose of the virus, which is something that typically we won’t do because of the concern that there may be already an immune response to the virus and being effective, was not the case. The virus in the second dose appears to be also effective and those patients had a significantly better outcome.
What is the importance of these results?
It’s important because, as you know, standard of care in the first-line setting is chemotherapy and we are interested in developing agents such as this one that would make chemotherapy better. This virus has a very pleiotropic mechanism of action – it is oncolytic, kills cancer cells, itself, but also produces an enzyme called laronidase which we think may facilitate the delivery and efficacy of the chemotherapy.
So it’s a positive signal, it’s still a small trial. So the next step will be to take this to a randomised trial properly powered for survival outcome.
What is next for this study?
Next, we submitted the paper for publication. The study is completed and now the idea, as I said, will be to do a randomised trial, phase III trial, a larger trial with a higher power to prove that this signal is sustained and maintained and therefore that the drug offers benefit above chemotherapy. In addition it opens the opportunity to do trials in other segments of pancreatic cancer in combination with other chemotherapy backbones like FOLFIRINOX, also in the second line.
What I think is very interesting and, of course, we would like to explore is what is the efficacy of combining this class of agents with RAS inhibitors that we know are showing very positive results in pancreatic cancer and hopefully will be approved for patient care very soon.
