Ashish Kamat: A warm welcome to all of you from the UroToday studios. I'm Ashish Kamat, Professor of Urologic Oncology at M.D. Anderson Cancer Center in Houston, Texas, and we're live at AUA 2025, in Las Vegas. It's a great pleasure to welcome to the studio, Professor Joe Jacob. Welcome.

Joseph M. Jacob: Thank you. Pleasure to be here.

Ashish Kamat: So you're presented and the data from the SunRISe trial, right. And it was a huge success. So share with us what you presented. What are your insights and where it's headed.

Joseph M. Jacob: Sure, yeah. It was fun to present this. Today, we presented our durability data. So our one year outcomes. So this is in a difficult patient population to treat. It's a BCG unresponsive high-risk non-muscle invasive bladder cancer with carcinoma in situ. In the past these patients have received cystectomy. And so in the last few years, we've actually come up with some intravesical therapies that we've been able to try to salvage these patients with. So this trial is unique because it's a device trial.

And it's a TAR-200 device that's deployed into the bladder, and it's designed for sustained release of gemcitabine. So it's both a drug and a device that urologists have to be a little bit more involved in. Outcomes are impressive if you compare it to what's been published and what's been reported. So the CR rate was 82.4%. And what the new data that we presented today was the 12-month CR and the durability data. But the 12-month CR rate was about 46%.

Ashish Kamat: Yeah, I think that's key. Because anytime you have therapies that are being studied, especially in single arm studies, you're looking at initial CR rates. But is that durable is what the patient's always asking. And in this case, just for the audience talk a little bit more about the statistics because the CR rate is calculated one way. And then of course, you have Kaplan-Meier estimates et cetera. Drill down a little bit more into the data.

Joseph M. Jacob: Yeah, I'm glad you asked that because there's so many numbers that we throw out and you have to move through these presentations pretty quickly. So the 12-month observed complete response rate that we talk about, that's from treatment initiation. And that's all comers. And that's just a proportion. How many patients at the 12-month mark from treatment initiation are in response. And so that's the 46%. So the Kaplan-Meier curves are more of an estimated those give us a signal. But what we really care about are the observed CR rates. So it's very competitive. At 12 months, 46% is almost half of patients that are going to be in response from the treatment initiation.

Now, there's different ways of looking at durability as well. So one thing that we talked about in the study today was not just looking at from when you start treatment. But let's look at patients that had a response and then that response lasted for a year or greater. And so we looked at that number and that was 44%. So very similar number. So bottom line is these patients that are responding a very good number of them, their response is lasting more than a year.

Ashish Kamat: Yeah, no. And I asked you that question for that very specific reason. Because people will often look at the prior reports from other studies that reported a CR say, let's take pembrolizumab, which is 40%, and then 50% of those at 12 months rather than the absolute numbers. And here, I wanted you to emphasize, and I'll just emphasize it again for our audience, that was the absolute number of patients that were free of disease and in response at that time, which is really great because the bar is going up historically, like 8% and 25%, now in the 50%, and it's the number that patients are most critical of. Now, of course, you're well aware of the entire portfolio of the SunRISe studies. So based on this data that you presented, what's your sense as to where the TAR-200 device is going to fit in the overall armamentarium?

Joseph M. Jacob: Yeah, that's a good question. Well, there's a new drug application. And so hopefully this will get approved. There's SunRISe-3 which I think is the key that's in the BCG naive space going head to head against BCG. I think that's a much bigger cohort of patients. And so if that's a positive trial I could see TAR-200 being used in the earlier setting like in the BCG naive setting. But we'll see what the trial shows. But I think it all depends.

One thing to think about is once these trials-- once these treatments and once this device gets into clinics, I think people will use it for the CIS population, but they'll probably use it for the papillary population. So in the real world, it'd be interesting to see, where it fits in with all these other treatment options.

Ashish Kamat: Yeah. And again, just to clarify, the whole BCG unresponsive CIS paradigm definition that was proposed to the FDA. The FDA absorbed was purely for single arm studies. But it doesn't mean that the drug is not effective in the papillary cohort. People often take it to mean that drug XYZ is not going to be effective. It's not that it's not effective. It's just not a regulatory pathway. And if you use it off label as clinicians sometimes do, that's a whole different question. People will often look at data such as what you presented and say that's great. We have that percentage of patients that are disease-free at 12 months. What about toxicity? What about fallout? What about drop off? Shed some light.

Joseph M. Jacob: Sure, yeah. So drop off. So there were only three patients in the cohort. So three patients out of 85 that discontinued due to AEs. And most of the AEs were grade 1 or 2, which you would expect, urinary symptoms mainly. One thing I found that if you could get patients through the first or second treatment, then they usually do pretty well after that, I don't know if you found the same thing. But there's usually the first treatment is a little bit tricky.

The other thing I found is I think we got a little bit better as time went on. It's very different than the intravesical solutions. They have symptoms that day and maybe the day after, but this is a device that's implanted in the bladder for three weeks. And so I think their symptoms build over time. So what we've done is we've just given patients prescriptions. As soon as they get the device put in, we give them everything and say, just start taking it because you'll probably have more symptoms later.

Ashish Kamat: So this is a good practical tip, right. What are some of the agents that you're using.

Joseph M. Jacob: Yeah. So Ditropan, Pyridium, Flomax, the typical things. Gemtesa.

Ashish Kamat: And again, this is one of the efforts that we at the IBCG are working on, which is to develop a bladder specific toxicity tool, because oftentimes you take all these toxicities, you lump them in. And then that's how they're counted in these studies. But if you give these patients prophylactic drugs that should not be counted as a grade one or two, AE because that's what we're doing as clinicians. It's pre-treating like you would with any other chemo, for example, if you know that you need to treat them. So I think that is one of those things that as we learn the side effect profile of all these agents and then we premedicate patients or give them PRN medications, I think that should just be an accepted way to get patients to continue and finish their treatment paradigm. Is that how you look at it as well?

Joseph M. Jacob: I do, yeah, I think that's a great point. And I think the important distinction is it's just that the symptomatology may be a little bit different for this device compared to what we're used to with the BCG and the intravesical therapies. But yeah, I agree.

Ashish Kamat: Great. So great discussion. Just a summary highlight for the audience. Take home message from the presentation.

Joseph M. Jacob: Listen, I think this is practice changing. And I think we're going to start to have to reevaluate, is cystectomy the standard of care in this patient cohort. So I think it's just an exciting time for bladder cancer.

Ashish Kamat: Great. Thank you so much.

Joseph M. Jacob: Yeah, thank you.