In the CORE1 study, which was a single-arm open-label study using a combination of CG0070, which is an oncolytic adenovirus, along with pembrolizumab in the treatment of patients with BCG unresponsive non-muscle invasive bladder cancer with a carcinoma in situ component.  The rationale for this study really was based off of the data that we had previously generated using the oncolytic virus by itself in a monotherapy trial in BCG refractory patients in which we have seen about 46% response rates and just under 30% complete response sustained at one year, along with the well-publicised data from the KEYNOTE-057 trial using pembrolizumab as a monotherapy in this patient population. We hypothesised that there is mechanistic synergism between the two agents and launched this trial to test whether or not we can achieve even better complete response rates.

To date we have completed accrual with 35 patients and the primary endpoint for the study was to look at the 12-month complete response rate. For that time of data cut-off there were about 15 patients or so. There we’re seeing a better than 70% complete response at 12 months. Overall there was 88% complete response that was seen at month 3 and that’s compared to 41% seen with pembrolizumab in the same patient cohort in the KEYNOTE-057 trial. So we’re definitely seeing that there is added benefit with the oncolytic virus added to pembrolizumab and there seems to be a synergistic efficacy between the two agents.

How can these study results impact treatment of bladder cancer?

BCG unresponsive non-muscle invasive bladder cancer remains a really difficult disease to treat. It often occurs in patients who are older and frail, such that they cannot tolerate the standard of treatment which is radical cystectomy or surgical removal of the bladder. For decades there has been this unmet need for bladder sparing therapies which have been brought on with the approval of pembrolizumab as well as more recently with nadofaragene firadenovec, which is an intravesical agent also using an adenovirus gene therapy strategy. 

So with this clinical trial we are aiming to bring an alternative bladder sparing therapy that’s even more efficacious than pembrolizumab and nadofaragene that has been shown in the past. It seems that we’re well on our way to achieve that.

Anything else to add?

One final point regarding the adverse events that we’re observing on this clinical trial. One concern was that in addition to the synergistic efficacy there could be increased toxicity from the combination. In reality we’re not really seeing any added toxicity from the combo. So there weren’t any surprises in terms of immune-related adverse events; the rate of immune-related adverse events seems to be on a par with what has been observed with pembrolizumab monotherapy in this patient population previously. Even though there were some that were incurred during the trial, they were, for the most part, transient and were self-limiting after the therapy was stopped short. In addition, most of the adverse events that we observed on trial were bladder-related symptoms that had to do with the intravesical oncolytic virus therapy. So, overall, the toxicity profile for this combination is also very favourable.

We’re very excited about the preliminary results from this clinical trial and look forward to launching a future trial in a randomised controlled fashion to compare the combination against pembrolizumab monotherapy and very much look forward to launching that trial in the near future.