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Medicine Matters oncology

SARMAD SADEGHI: This was a clinical trial for a combination of two immunotherapy drugs. One is pembrolizumab. It is standard of care in urothelial carcinoma. In the metastatic setting, the expected response rate is about 21%. So we have an experimental agent that was developed by one of our scientists, Dr. Parkash Gill and this experimental agent interrupts the interactions between EphB4 and Ephrin B2 in tumor cells.

Once interrupted, we think that the flow of immune cells into the tumor microenvironment is improved, cell viability is decreased, and cancer cells can die, and then it also affects the vasculature in the tumor microenvironment. So with all of these combined, we thought that there could be some synergy between pembrolizumab and sEphB4 or soluble B4, which is the experimental agent.

This trial was set up for urothelial carcinoma patients that have had platinum-based chemotherapy and have had progression of disease. Once that happens, they were enrolled in the study, and they received the treatment, which is pembrolizumab, every three weeks and the experimental agent weekly. We found that the response rate for all 70 patients that enrolled in this trial was 37%. This was higher than the 21% expected from pembrolizumab alone. And among these we had, again, a higher than expected complete response rate. It was 15.7.

Interestingly, when we looked at Ephrin B2, which is a target of this drug, and analyzed the data, we realized that, first of all, we have 46 patients that had the expression of Ephrin B2, and among these the response rate was over 50%. It was 52.2%, and we had a CR or complete response rate of 23.9%. This was a very interesting finding and points out that we may be looking at a novel biomarker in urothelial carcinoma, which is something we haven't had-- well, we haven't had a successful one to date.

Based on these results, the FDA has granted breakthrough designation for this combination among urothelial cancer patients whose tumors express Ephrin B2. The next step for this would be to pursue accelerated approval to try and bring this drug to the patients a little bit earlier. This may require expansion cohorts on the phase two, which are in the works.

And then, of course, for this drug to get a full approval from the FDA, we have to have a phase three in a randomized setting confirming the findings that we see on this study. Once that happens, we can ask the FDA to grant full approval. But those are quite a while from today. It's going to take some time to get to that point.

So in the short run, this is something that may be coming. Hopefully we can get to the next steps in a timely fashion and make it available to patients in clinic.