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Sam Chang: Hi. I'm Sam Chang, a urologist in Nashville, Tennessee, at Vanderbilt University, and we really have the honor of having one of the rising stars in urologic cancer. Specifically, we're fortunate to have Dr. Roger Li. Roger is now an associate member at the Moffitt Cancer Center, did his residency at Loma Linda, and fellowship at MD Anderson. Clearly, he has continued to lead the way when it comes to a variety of clinical trials both here in the US and internationally. We have Dr. Li here with us today to actually present one of the MoonRISe trials, a trial from Johnson and Johnson, looking at a novel agent with a novel targeted release system. So Dr. Li, Roger, thanks so much for spending some time with us, and we look forward to you catching us up on this promising new trial.

Roger Li: Thanks so much again, Sam, for the invitation, and I'm really glad to share the concept behind MoonRISe. The MoonRISe-1 trial was a phase 3 study of TAR-210, which is an erdafitinib intravesical delivery system. The study is to look at the efficacy of TAR-210 versus intravesical chemotherapy in patients with intermediate-risk non-muscle-invasive bladder cancer with susceptible FGFR alterations. Here are my disclosures again. The introduction for this study was made at the recent AUA 2024, and the rationale for this study is that for intermediate-risk disease patients, unfortunately, despite all the available treatment options, these patients still are fraught with a lot of recurrences that are seen in the bladder. At the same time, we know that intermediate-risk non-muscle-invasive bladder cancer has a high incidence rate of FGFR alterations, occurring in up to 80% of the patients.

Erdafitinib, as we all know, is a tyrosine kinase inhibitor that has already been approved in the United States to be used in patients with metastatic or locally-advanced urothelial carcinoma with susceptible FGFR3 alterations following progression or after one line of prior treatment, following the THOR-1 trial. Oral erda has also been tested in the non-muscle-invasive bladder cancer setting, but the challenge there is really, along with systemic toxicity, many of the patients were not able to tolerate the treatment for a long period of time. Hence the rationale for TAR-210, which is, again, a novel intravesical delivery system that is designed to elute erdafitinib within the bladder in a very targeted fashion over a 90-day period.

I should also mention that TAR-210 can be placed within the bladder using a very easy two to three-minute in-office instillation procedure, and it only needs to be exchanged every three months. In a first-in-human study, TAR-210 was looked at in an ablative marker lesion trial and achieved an almost 90% complete response as was reported at the time of ESMO. And so in the MoonRISe-1 trial, patients with intermediate-risk non-muscle-invasive bladder cancer with at least one risk factor per the IBCG criteria, so patients with recurrent disease, or primary disease with multifocality, or greater than three centimeters in size, or have been treated with prior intravesical therapies along with an FGFR2 or 3 alteration, are randomized one-to-one to be treated with TAR-210 every 12 weeks for up to one year without disease recurrence or to investigator's choice of intravesical chemotherapy, whether it's mitomycin C or gemcitabine for a four to six weekly induction course followed by a maintenance course of six months to one year given at a monthly rate.

Furthermore, the study is going to be stratified according to the anticipated choice of intravesical chemotherapy agents used, whether the patient is newly diagnosed versus having recurrent disease, and also the cystoscopic assessment method whether it's white light versus photodynamic diagnostics. The primary endpoint for the study is disease-free survival with the secondary endpoints being time to next treatment, high-grade recurrence-free survival, progression-free survival, the rate of diagnostic and therapeutic urologic interventions, as well as safety and tolerability. As of April 10, 2024, MoonRISe-1 has been opened for enrollment and enrollment is anticipated at 200 sites over four different continents in 20 different countries. And as of the date of the presentation, enrollment has already begun at three different sites in the United States and one additional one in Israel. So with that, I'd like to thank you for your attention and I'd be happy to take any questions.

Sam Chang: Roger, great presentation. Obviously, there's a lot of buzz and excitement about the targeted release system, which has been referred to in the past, and with, I think, more familiarity as the pretzel, that pretzel can be actually impregnated with different agents. So this is different from the SunRISe trials which have gemcitabine, which is placed every three weeks. This is a medication now with erdafitinib that honestly probably most urologists don't know about, but the placement is every three months, correct?

Roger Li: That's right, that's right. So as I understand from talking over with the company, it's really an engineering feat to get this accomplished where the pretzel is used to continuously elute the erdafitinib over a three-month period. And as you know, Sam, this coincides with the rate at which we're performing cystoscopies for these patients, and it becomes very convenient for them to come into the office to get this stent exchange and at the same time to perform a surveillance cystoscopy so we can understand whether the patients are deriving a complete response and to act upon any recurrences accordingly.

Sam Chang: And then when you look at this trial, tell me roughly the total number of patients that are planned to be enrolled in the two randomized arms. Is it about 300 in each or is it more? I couldn't get that.

Roger Li: Yeah, so it's a total of 540 patients in both arms, randomized one to one. And as you know, so the patients will need to be screened positive from a molecular screening test. And the unique thing about screening for patients with bladder cancer is that we can not only use the tissue samples that were taken from the patients from previous biopsies but we could also use a urine sample that's collected prior to their TURBT. And we've had good experience with both approaches now on the first in-human study where we saw that there was complementarity between screening using the tissue samples that the patients have had in the past and the urine. As you know, a lot of these patients will have had very small biopsy samples, these tumors tend to be very small, and thus the next-generation sequencing could be a challenge in some of these patients. And hence the urine test can really come into play here to help enroll all of the patients who are indeed qualified for the study.

Sam Chang: Well, I think when you look at how quickly the other novel target release trials, the SunRISe trials, the other trials, the early first in-human, the enrollment went very quickly and were able to meet targets at the times that the sponsor thought that they would be able to reach target. How do you look at in terms of when this would read out? Because if you think about these patients and if they really do in the comparator arm get, we know, effective chemotherapy agents, and put on maintenance, I think they might take some time to actually read out a difference in recurrence. But I was wondering if you look at the timeline, what's the guesstimated thought of, okay, we're at targeted complete enrollment at what point and then where do we think we're going to actually get our initial readout?

Roger Li: Yeah, great question. And as you know, we're kind of faced with this conundrum in the BCG-naive high risk NMIBC setting where the control arm, BCG, is probably outperforming the anticipated results. And as a result of that, we're having somewhat of a delay of the first readouts of those studies. I think really for MoonRISe-1 we have a good idea of how well the chemo is going to work. And the reason why I say that is because the THOR-2 study has already been completed, albeit the accrual had been very slow because of the toxicity that was seen on the patients who were treated with erda. But nevertheless, despite the non-adherence to the treatment protocol, we did see that there was a 77% complete response rate or lack of recurrence-free survival rate in that patient population at one year versus around 60% for the chemo-treated patients. And that's with a non-continuous treatment with the erda. So certainly I think with this novel intravesical treatment system, we're going to be even seeing better responses in the adjuvant setting than what we-

Sam Chang: With fewer side effects, right?

Roger Li: Absolutely.

Sam Chang: That's something that you've reported actually was with this intravesical delivery avoidance of those side effects associated with the oral erdafitinib. And so as urologists have more and more of these options, the ability to have an intravesical treatment with decreased side effects, I think is something that really appeals. And then the simple point that you made, and it's simple things that actually drives, I think, our practice many times, that ability to have an exchange and evaluation at the three-month mark. It's the first I've actually heard that kind of spelled out so clearly, like it's almost like a eureka moment of, hey, this makes sense, this helps facilitate compliance, helps facilitate actually careful evaluation and then adoption within clinical practice. So we really look forward to actually the completion of enrollment, starting more and more sites. Is Johnson and Johnson still looking for more sites, and if so what's the best way for academic practices, large urology group practices, how can they actually then think about participating in the trial?

Roger Li: Certainly. So if any investigators are interested in the trial, they can contact me directly, or reach out to Johnson and Johnson directly to inquire about the study. We're anticipating having to screen many more than 540 patients in order to get the eligible patients enrolled. So I fully anticipate hopefully getting even more sites up and running as quickly as possible so that we can really see what the efficacy rate is compared to the standard of care in this disease space.

Sam Chang: Well, Roger, thanks so much for all the efforts that you've made, not only for this exciting trial but for all the other kind of different awesome clinical trials and research that you're doing. And we are all, I especially, am so impressed and look so forward to actually future things coming up down the road. And so thanks for spending some time with us and we look forward to getting together again soon.

Roger Li: Absolutely. Thanks so much for highlighting.