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Ashish Kamat: Hello, and welcome, Roger, once again to UroToday's Bladder Cancer Center of Excellence. You've been with us many times before, and it's a pleasure to have you here during the AUA.

Roger Li: Thanks so much for having me, Ashish.

Ashish Kamat: So Roger, you're doing a lot of things this year at the conference, right? You obviously have your presentation with the gene therapy with CG, and you're co-hosting, the International Bladder Cancer Bladder Forum. If you could just share with our audience your thoughts on both your abstract and the forum, that'd be great.

Roger Li: Sure. So again, we're very excited to share the updated results from the CORE1 trial combining CG0070, or cretostimogene now, with pembrolizumab in the BCG-unresponsive CIS-containing population. And we're continuing to see very good efficacy results 12 months out from the start of treatment. So at the conference here, we're going to be reporting the 12-month data for the first 25 patients who have reached that time point. And of that 25 patients, 17 actually continue to have a complete response, as you know, as assessed by the bladder biopsy cystoscopy and urine cytology. So 68%, just under 70% complete response at that time point. Really a major step up, I would say, from pembrolizumab monotherapy alone. And hand in hand with that, the toxicity seems to be okay, well tolerated, nothing that was synergistic in terms of toxicity between the two agents, very much in line with what has been reported previously with the PD-1 and PD-L1 inhibitors, monotherapy trials.

Ashish Kamat: Now of course, if this data holds true, in the larger cohort, if you see the same sort of CR rates, it'd be very surprising for most of us if it doesn't get approved. I mean, just frankly. So if it does get approved, and it's available for patients, where do you see it landing in the sequence of therapies that we can offer patients?

Roger Li: Yeah, no, that's a great question, and I think there's going to be a lot to be worked out in that setting. So as you know, pembrolizumab, Adstiladrin, or nadofaragene firadenovec has both been approved. The ImmunityBio N-803 plus BCG is also on the docket. So it'd be interesting to see, out of all of those combinations, which one would be more commonly used by urologists and medical oncologists based on their efficacy and the safety profiles.

But I think ultimately it really will boil down to the efficacy, and more importantly, the long-term efficacy. Because in these patients, as you know, they are really down to the last ditch effort in saving their bladders, and nobody wants to lose their bladders. So the longer that we can help patients keep their bladders, obviously the better, and the more willing that they're to enroll onto the treatments for their disease.

Ashish Kamat: Now you are doing some studies, right, correlative studies to try and predict responses, et cetera. Can you share some of what you're thinking there?

Roger Li: Yeah, so the main effort in the correlative science that we're conducting at Moffitt are centered around a neoadjuvant trial that's using a similar combination with cretostimogene plus nivo. So these are patients who are ineligible for cisplatin chemotherapy and are undergoing six cycles of instillation with CG0070 on a weekly basis. And in addition to that, we're adding on nivolumab at week two and six. So we actually have completed accrual to that trial as of a couple of weeks ago. And out of the 21 patients, we have 19 patients who are valuable. And the PCR rate there is about 50%. So we're really excited about the data there and it really shows and corroborates the CORE1 trial data that there is this synergistic mechanism of action between cretostimogene and immune checkpoint blockade.

We're looking at a few things. So some of the correlates are based on the mechanism of action of the oncolytic virus itself. So the viral promoter, as you know, is based off of the human E2F gene. So we're looking to see, in the original tumors that were treated, whether the expression level of E2F is increased in those patients who ended up responding to therapy. In addition to that, we're also looking at immunogenic biomarkers such as the tertiary lymphoid structures that may appear in the baseline tumors, but also the increase in the number and the density of the TLSs as you continue on treatment for these patients to see whether that correlates with response.

Ashish Kamat: Excellent. I mean, it's really impressive to see the work that you're doing. And like I said, you're doing a lot here at AUA. Just a brief few words on the IBCG forum that you're co-leading this year.

Roger Li: Yeah. No, thank you for the opportunity to talk about that forum. So I participated as a discussant at the Bladder Cancer Forum last year, and that was the inaugural forum that was chaired by yourself. And I really enjoy that experience. It's really a wide array of different topics that are controversial in the treatment of bladder cancer.

So this year, no different. We have a great panel of experts that are taking care of bladder cancers for a living, day in and day out, and we're going to be discussing various topics of controversy in bladder cancer management, ranging from whether it's beneficial to use enhanced blue light cystoscopy to diagnose patients with bladder cancer to the benefit of trimodal therapy versus radical cystectomy to how to manage node positive disease. So really kind of a huge range of topics that I think is going to create a lot of excitement and debate.

Ashish Kamat: Yeah, I think so. And again, UroToday is going to give us the opportunity to host a lot of these debates on the platform, which is really great. So again, thank you again for taking the time, and it's always a pleasure to chat with you.

Roger Li: Absolutely. My pleasure as well.