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Zachary Klaassen: Hi, my name is Zach Klaassen. I'm a urologic oncologist at the Georgia Cancer Center in Augusta, Georgia. I'm delighted to be joined on UroToday by Dr. Sia Daneshmand, who is a urologic oncologist at University of Southern California. Sia, thanks so much for joining us today.

Sia Daneshmand: Thanks, Zach.

Zachary Klaassen: So we're going to discuss some SUO presentations that you did in terms of the SunRISe-1 trial. And I'd love for you to share the slides that you presented at SUO.

Sia Daneshmand: Sure. A lot of excitement with these SunRISe trials. And this is one of the iterations. So basically, this was looking at the complications or zooming in on the safety and tolerability of this. Obviously, a global effort here.

So just an introduction, the TAR-200, as many of you know, is a targeted releasing system. And it basically provides a sustained release of gemcitabine into the bladder. The device is placed, and it sits there for about three weeks, and the drug is eluted into the lower urinary tract over those three weeks.

And the SunRISe-1 trial is a Phase IIb study looking at three different arms. I have another slide that shows this a little bit better, but this was looking at the additional results on safety and tolerability as we move further in the trial and have more patients on it. So there's very promising results so far, and they will be providing an update soon.

So here's the SunRISe study. Basically, the BCG-refractory or unresponsive non-muscle invasive bladder cancer, standard definitions. Then patients were randomized into three cohorts initially—the cohort 1, which was TAR-200 plus cetrelimab. Cetrelimab is a PD-1 inhibitor. The second cohort was TAR-200 monotherapy, so just the device in the bladder alone.

And then the third arm was cetrelimab monotherapy. Now, that arm was closed early. There were only 28 patients. The same safety profile as we've seen before, and same efficacy profile that we've seen before with other checkpoint inhibitors.

So really we're concentrating on the TAR-200 alone arm here. Again, the dosing was Q3 weeks now for the first 24 months, and then after that, every quarter. And the primary endpoint was overall CR rates, with the secondary endpoints being the usual duration of response, overall survival, safety and tolerability.

There was a cohort 4 that opened somewhere along the way, and that was TAR-200 monotherapy for patients with papillary disease only. So that was just a limited number of 52 patients that we're not reporting on. So we're just reporting on the monotherapy arm here. Again, these were patients with BCG-refractory plus/minus papillary disease, so you had to have some CIS presence, and then the other basic inclusion criteria that we have for most of the trials. Again, the primary endpoint was CR rate at any time, with the secondary endpoints being duration of response, safety and tolerability.

So the characteristics are the same as usual—mostly males, 70 years old, and most of them are smokers. ECOG performance status was zero in most of the patients. There were, of note, CIS only in 57 patients, which is 67% of the patients, and then CIS plus papillary disease in a third of the patients. Total doses of prior BCG was on average 12, and time from last BCG to CIS diagnosis was 3.4 months.

So here are the results of the 85 patients. This is as of May 13, 2024, when the last data cut was established. Eighty-five patients with CIS median age as we went through received the TAR-200. CR rate was 83.5%—I'll show you the figure—and the insertion success rate was essentially close to 100%. I think they had maybe one patient that they were unable to place the device for unclear reasons.

And then median indwelling duration was 22 days, as I showed you before, the device is supposed to stay in for three weeks. So that's good. Most of the patients were able to tolerate that.

Here's the overall CR rate, and then the patients with both centrally-assessed as well as investigator-assessed. These are numbers we have not seen for BCG-unresponsive trials. This is, again, CR rate at any time. Obviously, there's some decline of this by the time you get to one year. And we're beginning to get longer-term follow-up for these patients, but highly efficacious.

And the focus of this abstract was not really to go through these results. Again, these will be presented, hopefully, at the next meetings coming up with longer-term follow-up for these patients. But really, the point of this abstract and poster was to look at the treatment-related adverse events.

So most of the patients, as expected in this disease state, will report some form of TRAE, but the majority of them are grade 1 to 2. Most common ones are the ones we know about, the severe urinary tract infection, urgency, frequency, hematuria. If you look at BCG or any other intravesical therapy, they're very, very similar. And again, most of them are grade 1 to 2.

So no unique side effects that are showing up with a device that is fairly well tolerated. Eight patients did have grade 3 to 4. I'll go through those in a bit. And five patients had serious treatment-related adverse events and had the device removed early. Obviously, no deaths. That would be terrible.

So these five patients that led to treatment discontinuation included non-infective cystitis. One patient with grade 1 to 2 within very early to within three months of starting treatment of pollakiuria, 1.7 months after starting treatment. And there was one patient with urinary retention, 4.8 months after starting treatment. Again, these are side effects that we see with any kind of, I think, intravesical therapy. Nothing specific or unique to this device or drug, so I'm not too surprised by these numbers.

And here are the serious side effects. Any—I'm sorry, these are any grade. And you can see, again, in table format what I just described with urinary tract pain, bladder pain, bladder spasm, and things like that. And, of course, we use anticholinergics and medicines to try to control these symptoms. But here are the grade 3s and higher. Urinary tract pain was one of them, bladder pain—I don't know what the difference between the two of those are—but dysuria, renal impairment, urinary retention, UTI, and urosepsis in one patient. Again, nothing very specific to this therapy.

So really the key takeaways are these are well tolerated. There's a high CR rate associated with it, supports continued investigation. And we'll see again the ongoing results for this.

One of the questions I get asked often is, how well is it tolerated? The patients have this device in place, and many patients have stent-related discomfort, and pain, and frequency. They want us to remove stents ASAP. But what I remind folks is that this device is floating in the bladder. It's not static. It's not sitting at the trigone like a stent is. And so, as the urine fills the bladder up, this device is just floating around. So when you look in there, you don't see that inflammation that you see or edema, the bolus edema that you see with indwelling stents, indwelling catheters, and things like that.

Zachary Klaassen: Great. Great presentation, Sia. Thanks so much for updating the SunRISe-1 trial. I think to go off your point about the three-week insertion and removal—just from your standpoint as a urologist and maybe the patient standpoint—is this cumbersome? Does it get into routine? How does it fit into the practice workflow? What are the patients telling you?

Sia Daneshmand: Yeah, very good question. I think as we get more and more therapies becoming available to us for management, these questions become very relevant. I can tell you it's very well tolerated in terms of the procedure. And the reason is because these patients are very used to having catheters inserted in and out for BCG treatment, for other forms of treatment, intravesical treatments.

So essentially, it's almost the same thing. You're putting a scope in and looking at the bladder, but this insertion of the TAR-200 is done with a special catheter. So whether you're putting a solution in, you're putting a device in, that part of the discomfort is essentially the same. And one could argue, look, instead of every week of doing this, you're actually doing it every three weeks for the first six months.

So I think most of the patients, if they live close by, that's been probably the biggest impediment is patients who live far away and not being able to come in every three weeks for the first six months. But other than that, I think patient acceptance of this has been quite high.

Zachary Klaassen: Excellent. And I know you mentioned the CR rate of 83.5%, phenomenal results. Just maybe give our listeners some context into what some of the other agents and what those CR rates look like in this BCG-unresponsive state?

Sia Daneshmand: Yeah, I mean these are exciting times, Zach. As you know, we're getting readouts from multiple different drugs in this space, particularly with one-year results and two-year results. Look, these are all above 50%. We're used to the old Valrubicin being 11% at one year. Adstiladrin monotherapy being 25%, and now we're looking into the 57, 58%.

At the SUO, as I'm sure you've covered, the greatest imaging made a big splash with their results. That was excellent CR rates in the high 70's at any time, and then it was durable. And many of the patients are now getting beyond the two years.

A lot of these are estimates of the responses, Kaplan-Meier estimates, as we don't have too many patients in there. But to me, the most informative are those swimmer plots. You can see exactly all the patients. And you can see where they are. And you can see many of them are beyond that two years. So I'm really encouraged to see that.

So I would say, look, these are all neck-to-neck in terms of response. They're all doing very well in that one year time period of being above 57% and 58%. And often, in the patients who've completed more than two years of therapy, many of them are sustaining that response. So time will tell. It's still early. The primary objective of most of these trials has been that CR at any time, and that's acceptable because we want to know that these drugs work before we move them further along.

Zachary Klaassen: Yeah, as you said, very exciting times. This disease space having options coming down the pipeline, tolerable options with excellent response rates. So it's going to be great for our patients as we continue to follow these forward. And I think, just a couple take-home messages for UroToday listeners, if you could?

Sia Daneshmand: Yeah, I think the take home is stay tuned, and learn these new drugs because they're coming to your offices very soon. Both [INAUDIBLE] and the TAR-200 device have fast track designation by the FDA. So hopefully, almost by—I'm hoping by next year, late 2025—we'll actually have these drugs in our armamentarium for treatment. So it behooves anyone who treats bladder cancer to know about these drugs and when and where to use them and what the indications are.

So it is exciting times. We finally have more drugs available to us for these BCG refractory unresponsive patients. And the next set of questions I think we need to answer is the sequencing.

Zachary Klaassen: Sure.

Sia Daneshmand: And what do we do from one to the other? Fortunately, the mechanism of action is very different for all of these. So right now, there's no rationale to use one before the other. And really you can use any one of them. It's going to be a discussion with the patient—what makes sense for them? And the practitioner—what's good for their office and workflow?

Zachary Klaassen: Wonderful. Great discussion as always, Sia. Thanks so much for your time and expertise on UroToday.

Sia Daneshmand: Thanks so much, Zach.