Zachary Klaassen: Hi. My name is Zach Klaassen. We are at AUA 2025 in Las Vegas. I'm a urologic oncologist at the Georgia Cancer Center. Delighted to be joined, as always, on UroToday by Dr. Roger Li, urologic oncologist at the Moffitt Cancer Center. Roger, thanks, as always, for your time.

Roger Li: Thanks so much for having me.

Zachary Klaassen: So we're going to talk about MoonRISe-1. It's a trial-in-progress update you presented at AUA. Before we get into MoonRISe-1, just take us back to what TAR-210 is, the device technology that led to this trial.

Roger Li: Yeah, TAR-210 is actually a very interesting technology. So as you know, there are a number of trials that have been rolling out with the TAR-200 device, which is an intravesical delivery system that delivers gemcitabine on a sustained basis. And TAR-210 is a very similar product where, instead of gemcitabine, it delivers erdafitinib, which is a pan-FGFR inhibitor with local delivery within the bladder. So it limits the systemic toxicity that you see from patients and also makes a lot of sense to be used in the intermediate-risk NMIBC setting because there's a high prevalence of FGFR alterations in this population.

Zachary Klaassen: And intermediate risk has become just a hot space, just like BCG-unresponsive was in the last five years. So just maybe highlight what that frequency of FGFR mutations is in low-grade, even intermediate risk that we're talking about today.

Roger Li: Yeah. So it's really rewarding for me to see how the evolution of the clinical trials has been. We're starting off with the highest risk of NMIBC patients that we're dealing with and we're slowly moving up the line.

And I think intermediate risk is one of those disease types that it's very easy to treat on a per-case basis for the patients. But if you accumulate all of the different TURBTs and the intravesical therapies that the patients undergo throughout the lifespan of their disease, it really adds up, especially for the type of patients that we're seeing with bladder cancer, who tend to be elderly. They're frailer than others.

So all of these different procedures and intravesical therapies will add up in the toxicity. And so I think in that setting, it's perfect to have such a device to be placed within the bladder for the local delivery of erdafitinib.

And just going back to your second question about the prevalence, so it's very, very high in the intermediate-risk disease space, thought to be about 60% to 70% in terms of prevalence. And so, we've actually had quite an easy time in identifying these patients because we used both the archival tissue samples for the traditional genomic sequencing, but we're also taking the urine samples. And as long as the FGFR3 alterations are found within the urine or the tissue, then the patient can be enrolled.

Zachary Klaassen: That's great. So before we get into MoonRISe-1, just lead us up to what happened to get to MoonRISe-1.

Roger Li: It's been a long road.

Zachary Klaassen: Yeah.

Roger Li: And it's been an exciting--

Zachary Klaassen: We talked about it before.

Roger Li: That's right. So in the beginning, obviously, with anything else, it was tested in the metastatic setting and specifically for chemotherapy-treated patients who then have disease progression. And so in the THOR-1 trial, it was tested in these patients who were FGFR-positive and were treated with erdafitinib versus the standard-of-care chemotherapy. And it was found that erdafitinib did confer an overall survival benefit of about four months or so.

So from there, it also was moved to the high-risk NMIBC setting and the THOR-2 study, where oral erdafitinib was actually delivered for patients with intermediate-risk NMIBC with FGFR alterations compared against intravesical chemotherapy. And there, the hazard ratio was fantastic. It was less than 0.3. And that conferred about a 6 or 7-month disease recurrence-free survival benefit.

But despite that, what we found was that oral erdafitinib, as we saw on the systemic treatment trials, did have a lot of systemic toxicity, things like hyperphosphatemia and also retinal issues that came up because of the systemic delivery. So that kind of led to the rationale for developing this intravesical system so that we can deliver it on a sustained basis and limit the toxicity within the bladder.

Zachary Klaassen: It's a great summary. Really well done. I think when we look at the MoonRISe-1 trial, just go through the design and maybe what the outcomes are or what the primary objective is.

Roger Li: Yeah. So MoonRISe-1 really came off of the first-in-human study that we did with the TAR-210 device. And this has been reported multiple times now with very good efficacy. So for patients with marker lesions-- not only marker lesions, but sometimes a lot of different lesions within their bladder not being resected-- there's over 90% complete response at three months and with excellent durability out to more than one year.

So based off of those results, we launched the MoonRISe-1 trial, which is a phase III randomized controlled trial conducted in patients with intermediate-risk NMIBC as per the IBCG definition, stratified by things like whether they had primary or recurrent tumor, whether the patient was anticipated to be treated with gemcitabine versus mitomycin, versus the anticipated modality of cystoscopy, whether it be enhanced cystoscopy versus white-light cystoscopy.

And these patients are randomized one-to-one to receive either TAR-210 for a duration of one year versus intravesical chemotherapy at the dealer's choice, essentially mitomycin or gemcitabine, with an induction course followed by a maintenance course, and with the primary endpoint of recurrence-free survival.

Zachary Klaassen: Yeah. It's a great trial. And I think leading all this discussion up to where is this trial at now, how many patients are enrolled? What are we looking at for MoonRISe-1?

Roger Li: Yeah. So we have been really having an excellent time in terms of enrolling patients. There's so much excitement within the community. So we're definitely way ahead of schedule.

Zachary Klaassen: That's great.

Roger Li: I'm actually waiting for the final update from the team before tomorrow's tip--

Zachary Klaassen: Wow.

Roger Li: --to understand exactly where we're at. We're literally enrolling a few patients every single day onto this trial.

Zachary Klaassen: That's outstanding.

Roger Li: It's been really a rewarding process, seeing how quickly this trial was able to enroll and seeing the enthusiasm, because we, as urologists, we know that this is a huge problem in the community. And if we can save patients like this a lot of procedures in terms of TURBT, and also in terms of intravesical therapies, I think that's a huge win for the patients first and foremost, but also for us as urologists.

Zachary Klaassen: So based on this accelerated enrollment, when do you think it'll be fully enrolled? Just your best estimate.

Roger Li: I would say probably within the end of this year.

Zachary Klaassen: That's great. Fantastic. So we'll book you for AUA 2026 and we'll talk about that.

Roger Li: And hopefully, we'll see some--

Zachary Klaassen: The data. 

Roger Li: That's right.

Zachary Klaassen: No, that's great. As you mentioned, this is such a hot disease space now. Maybe just a couple of quick take-home messages for our listeners.

Roger Li: Yeah. So I think we're at a very exciting time in terms of non-muscle-invasive bladder cancer investigational trials. There's a lot of different exciting agents with different mechanisms of action that are available now to our patients. And most importantly, for me, as an investigator, I like to understand the disease a little bit better so that we can further improve upon the progress that we've already made.

And for our patients, there's going to be so many different options. They can pick and choose between what it is. That's the most important thing for them. And I think it's overall going to make our management for NMIBC just that much better.

Zachary Klaassen: Yeah. Kudos on where it's coming so far. And we're excited for the progress. Just the fact that we're ahead of schedule is great. So thanks again for joining us on here today, Roger.

Roger Li: Absolutely. My pleasure. Thanks so much.