Roger Li, MD, on Bladder Cancer: Boosting Immune Checkpoint Blockade With an Oncolytic Adenovirus

The purpose of our study was to look at the efficacy of combination CG0070, which is an oncolytic adenovirus, along with immune checkpoint blockade, in the setting of BCG-unresponsive CIS-containing non-muscle invasive bladder cancer. The BCG-unresponsive space has been well described, but it's a very difficult to treat disease in which the standard of care is surgical removal of the bladder. Because the disease takes place in a cohort of patients who are older and frail, it's unfit. That procedure is unfit, unfortunately, for many of the patients, because it's fraught with a lot of complications. Hence, there is a critical, unmet need for efficacious bladder-sparing therapies. We hypothesized that the combination of CG0070, along with immune checkpoint, can engender an efficacious anti-tumor immunogenic response that can help patients preserve their bladders, and set out to test this hypothesis. In the study, we enrolled 35 patients and out of the first 32 evaluable patients, we looked at the primary endpoint, which is the 12-month complete response rate. And of the first 15 patients who had reached that endpoint, we're seeing a 73% complete response rate at one year. In the entire cohort, there were just under 90% of the patients who had reached the complete response by the three-month mark. And those numbers compared to pembro alone were much better. Whereas the pembro alone cohort had achieved only a 40% complete response at three months and 20% complete response by one year. So we're seeing a really synergistic effect between the virus and pembrolizumab together, and in addition to that, we're also seeing a tolerable toxicity profile where the combination really didn't have any surprises in terms of toxicity, with essentially just added toxicity from the two agents put together. As a next step, we're really looking forward to launching a randomized control trial where we're testing the combination of the two agents against pembrolizumab alone in this disease setting to really show that it's more efficacious than the monotherapy agent.