Brian Mazzarella: Exactly.
Sam Chang: Mazz actually rhymes with jazz, so keep that in mind because he's someone that you should actually be looking for in the future when it comes to important clinical trial results. We're lucky enough to have Brian today talk to us about MoonRISe-3. Brian is the vice president of Urology Alliance. He's vice president of clinical research there and actually is a practicing urologist in Austin, Texas, one of my favorite cities.
Brian Mazzarella: Thanks, Sam.
Sam Chang: So, Brian, we're at the AUA 2026 in our nation's capital.
Brian Mazzarella: We are.
Sam Chang: So, tell us a little bit about your presentation on MoonRISe-3 and a little bit about the mechanism of action, but then specifically the cohort of patients looking at another option perhaps for BCG-exposed slash ... I'll let you talk about it specifically.
Brian Mazzarella: Yeah. I mean, you're right to allude to the fact that there's some complexity. MoonRISe-3 is being presented here at the Clinical Trials in Progress session, which has been a really nice session in the past. I'm very excited to participate in that again. So MoonRISe-3 is a study looking at J&J's erdafitinib intravesical drug-releasing system, which I know is a mouthful as a name previously also known as TAR-210 through JNJ or the erdafitinib pretzel.
And so MoonRISe-3 builds on a lot of previous data, but this study looks specifically at patients who have received previous BCG and it breaks into three cohorts like you spoke about. They have pure papillary disease, they've recurred after their previous BCG and they're compared between the Erda intravesical drug-releasing system and intravesical chemotherapy.
Sam Chang: So Brian, this focuses then on patients with papillary disease-
Brian Mazzarella: Pure papillary.
Sam Chang: ... that have been ... Pure papillary, they've been exposed to BCG. In some way exposed, quotation marks.
Brian Mazzarella: Correct.
Sam Chang: And that have the FGFR mutation.
Brian Mazzarella: Correct.
Sam Chang: So tell me a little bit about the rationale behind choosing this cohort of patients. Was there earlier data? Was animal-based data, I'm not really sure, that led to, "Hey, let's focus on these patients"?
Brian Mazzarella: Yeah. So there are a couple of earlier clinical trials that sort of informed MoonRISe-3, both in terms of its efficacy and design. So the first one is the THOR-2 study. And just to back up and explain a little bit about erdafitinib, erdafitinib is FDA approved for metastatic or advanced urothelial cancer that's failed a previous line of therapy and is FGFR-altered. That's obviously a very different disease state.
Sam Chang: Yeah, absolutely.
Brian Mazzarella: There were two used oral erdafitinib, which is the same as the systemic treatment, but it did have a high-risk non-muscle-invasive group, one cohort within that trial. And so it actually similarly to MoonRISe-3 compared erdafitinib to intravesical chemo. And in the erdafitinib group of that trial, the median RFS was not reached compared to 11 months was the median RFS with intravesical chemo. So that was some early data that oral erdafitinib would be effective in non-muscle invasive bladder cancer.
The next study that was looked at was the MoonRISe first-in-human data. And this was actually just updated a few weeks ago at EAU. So that was also very early data, really mostly a dose-finding clinical trial, but it also had a cohort one in that study and some similar data. So at 12 months in MoonRISe-1, the recurrence-free survival in the treatment arm was 82%. So some nice efficacy data led into all of that.
So I think the other answer to your question is why this particular patient population?
Sam Chang: Yes.
Brian Mazzarella: Well, first, FGFR is reasonably prevalent in pure papillary disease, so about a 40% prevalence. And then this group of patients that we're sort of generically going to talk about as having received previous BCG, technically on the trial, there are actually three cohorts. It's officially BCG-unresponsive by the strict definition. It's BCG-exposed having received some BCG, not meeting the unresponsive criteria. And it's BCG-intolerant. So as you know, we've had a whole lot of innovation in the BCG-unresponsive CIS space. We really don't have any new therapies yet that have moved to this pure papillary and sort of more heterogeneous BCG-exposed group.
Sam Chang: Which is very real world.
Brian Mazzarella: Very real world.
Sam Chang: The papillary, the fact that it's difficult to really have all the patients meet that definition of BCG-unresponsive, at least five out of six, at least two out of three, et cetera.
Brian Mazzarella: That's right.
Sam Chang: This is a very real world type of study. Where are we now in terms of enrollment? Because I know this is being presented in the Trials in Progress session, as you mentioned.
Brian Mazzarella: It is.
Sam Chang: So how are we doing and tell me what the primary outcome is for the study.
Brian Mazzarella: So the primary outcome is recurrence-free survival and this is the same endpoint that we see in most pure papillary studies. So that's a little different than what we see in carcinoma in situ where we talk about CR rates.
Sam Chang: Sure. complete response, right.
Brian Mazzarella: Yep, exactly. So that's the primary endpoint of the trial. The enrollment is making nice progress. So it's enrolling around the world. This is a global clinical trial. There are 340 patients consented. Many of these are still in screening at this point and because they have to be FGFR-altered in order to qualify for the trial, that's a pretty rigorous process. Last time I spoke to J&J, there were 51 patients that are actually randomized on the trial. So it takes some work, but it's actually enrolling ahead of schedule at this point.
Sam Chang: So, I mean, the attractiveness of this would be a medication via a device that's given once a quarter, so every three months.
Brian Mazzarella: Correct.
Sam Chang: Avoiding some of the systemic side effects of the oral erdafitinib type medication.
Brian Mazzarella: Exactly right.
Sam Chang: And obviously the endpoint that we're familiar with, with this cohort of papillary-only disease. So I hate to put you on the spot, but any idea regarding, okay, let's get a readout, let's get a ... I know it depends on probably the enrollment. But, what else? Tell me your thoughts about that.
Brian Mazzarella: I think we're a little bit away from a readout. I mean, if we're super optimistic, maybe some early data a year from now in this meeting.
Sam Chang: Sure.
Brian Mazzarella: But I think that may even be a little bit optimistic as well.
Sam Chang: Okay. Well, book a spot here. If you've got early data, we definitely will want to talk to you.
Brian Mazzarella: I'd love to give an update. That'd be great.
Sam Chang: All right, Brian, thanks so much for spending some time with us.
Brian Mazzarella: My pleasure. Thank you, Sam. Appreciate it.