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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, as always, to be joined by Dr. Sarah Psutka, who is a urologic oncologist at the University of Washington. Today, we're going to be discussing a presentation presented at SUO 2024, looking at the expanded access program for cretostimogene. Sarah, as always, thanks so much for your time. And thank you for joining us on Uro Today.

Sarah Psutka: Hey, Zach, it's great to see you. Thank you so much for highlighting this poster. What I'm going to detail here is a protocol that is being rolled out to evaluate cretostimogene in patients with high-risk, non-high-risk BCG-unresponsive non-muscle invasive bladder cancer with carcinoma in situ. This is a different type of research trial. It's an expanded access program. And I'll explain to you what that means.

But I think one of the highlights I would definitely point people to review is the data that was presented at the SUO, where Mark Tyson presented the top-level results of the BOND III trial. So this is the trial that actually established the efficacy of this drug that led to the FDA Fast Track application status and also the breakthrough indication.

But let's just take a step back. So what is cretostimogene? This is an oncolytic immunotherapy. It works two different ways. I think the way that I explain it to patients is that it essentially turns bladder cancer cells into bioreactors. The drug is selectively replicated within bladder cancer cells, and when it kills the cell, it both releases more drug into the environment, which is directly toxic to bladder cancer cells, as well as then can promote further uptake and replication. So it sort of creates this really powerful, amplified immune response and efficacy.

The data that was presented at the SUO showed that, importantly, there was a 74% complete response rate in patients with BCG-unresponsive non-muscle invasive bladder cancer. What's really interesting is the duration of response. So, at the time of the presentation that Mark gave, they have not yet reached the median duration of response, but it's greater than 27 months, which in this patient population is a really excellent oncologic result.

And then the other big point is it's really well-tolerated. There were no grade 3 AEs, so that's exciting. However, while we're waiting for what will hopefully be the successful application with the FDA and approval of this drug, there's a couple of important points that remain to be discovered. I think one of the things in the original trial that was presented at the SUO, the patient population was very similar to what is often seen in clinical trials in bladder cancer. So this was an overwhelmingly male and Caucasian patient population.

So if anyone had the pleasure of attending the clinical trials workshop that was put on by NYU and the SUO, there was a great talk by Dr. Sheryl Lee on the absolute imperative of representative enrollment to clinical trials and the importance of understanding how these agents that are being approved in cancer care act in unresponsive patient populations. And if you don't have diverse enrollment, then you can't actually fully understand how this drug is going to work in the real world. So that's where the EAP comes in. This is a protocol that is essentially a registration study. The expanded access program, when opened at, hopefully, diverse sites across the United States, will permit active enrollment of real-world populations. It has incredibly broad eligibility criteria.

So these are patients who wouldn't get on a clinical trial for BCG-unresponsive non-muscle invasive bladder cancer, which obviously the actual trials that are out there of novel therapies have very stringent eligibility criteria. Here, performance status can basically be anywhere up to an ECOG of three. Essentially, you just have to have BCG-unresponsive disease. And then the idea is that the sponsor provides the drug.

So one of the real reasons is why would you put somebody on the EAP when there are FDA-approved therapies for BCG-unresponsive non-muscle invasive bladder cancer? Well, as we all know, many of those drugs are quite expensive, and there are access issues to the FDA-approved options. The only alternative is radical cystectomy, which is obviously not an option for a lot of patients with BCG-unresponsive non-muscle invasive bladder cancer, either because the patient is prioritizing maintaining their bladder or they are not a candidate for radical cystectomy.

So here is an opportunity to get a patient a drug that is efficacious and safe, and well-tolerated, that will hopefully have FDA approval within the next one to two years. And ideally, we'll be able to roll it out to folks who might have access issues and also to ensure diverse data collection in the real world. And then the objective is really to track that data. So by opening this program at your institution and enrolling patients onto this study, we can actually see how the drug performs in a real-world population. So that's the summary at a very high level. And the actual protocol is detailed on the poster in terms of the administration of the drug.

Zachary Klaassen: Outstanding, that's great, Sarah. Thanks so much. So a couple of discussion points. And I think you've really highlighted what the meaning of an expanded access program is. But just from your experience with this program, what has it meant to you as a clinician and also to your patients to have early access to not only a drug that's well-tolerated, but a drug that works in this BCG-unresponsive disease space?

Sarah Psutka: Yeah, well, I'll be open. I'll be quite honest. We're working on actually getting this open right now. This study is actively enrolling and is opening across the country. And that's why we're actually really promoting the protocol here at the SUO, because we're excited about it and we want to ensure that people are aware that this is an option. We're hoping to open this not only at big academic centers like mine, but at lots of community sites, because diverse enrollment needs to reflect the whole bladder cancer world.

So obviously—and I spoke with the folks at CG Oncology, who are sponsoring this study—one of the key points that we talked about was, I asked, how are you ensuring that you're getting diverse enrollment? And so they're really targeting opening this study not only to academic programs and community sites, but also, for example, the VA system, to really ensure that folks have early access to this drug that is well-tolerated, allows us to preserve the bladder, and has a very, very strong safety signal and an excellent early efficacy signal.

Zachary Klaassen: Yeah, absolutely. And I think, to go on that point more, because I think it's important, we know that minorities are underrepresented in clinical trials. We know that bladder cancer is very common in the Caucasian population. But where I practice, probably one third of my patients are African American in the bladder cancer population. So, again, just to give us data for what we may not have applicability with the clinical trial, just speak from a clinician standpoint and your statistical background, how this is important, and how we roll this out to these other populations.

Sarah Psutka: Well, I think the biggest kind of assumption that we make when we jump from clinical trial to real-world practice is that what we're going to see in the real world is going to reflect the results that were achieved in the clinical trial. We often know that when you look at a quote-unquote "Phase IV study," which is what happens in a real-world patient population, the results sometimes can be fairly disparate from what was presented in the phase III clinical trial that led to the registration of that agent.

So collecting this data prospectively, early, while the agent is going through regulatory approval, is actually really powerful and important. Because at the end of the day, the results of this study will help me determine how I might really integrate this drug into my practice in the sea of other novel agents that have recently been or are in the process of being approved.

I think that—here's the tricky bit, right? So BCG-unresponsive non-muscle invasive bladder cancer, we actually have this embarrassment of riches right now, which is so exciting, as someone who takes care of a lot of these patients, to have options. But the new options are expensive. Not everybody is going to have access to them. I don't know how they perform against one another. I don't know how to sequence them.

And then one other thing that I just want to really highlight about this protocol is the fact that they're collecting a lot of really patient-centric PRO and quality of life data that will help us to understand the impact of the treatment on the patient as well as the cancer. So having that data, I think, is really powerful.

Zachary Klaassen: It's awesome. Any other aspects of an EAP that we should highlight just in general? I mean, this is such a great initiative by CG Oncology in certainly giving us access to the drug. And you're right, I mean, the sequencing situation is the Wild West. So any other important things we can maybe learn from this program?

Sarah Psutka: No, I think it's just really—it makes me really happy to see a company that is working hard to actually track real-world data like this, and to think about how you can actually see how a novel biologic performs in a pragmatic patient cohort. So the fact that you're not limiting patients, you have as expansive eligibility criteria as literally as possible, and it's a pretty easy study to run. It's also not—it's patient-friendly and it's investigator-friendly. That's really important.

The co-primary endpoints for the study are safety and CR. And we'll see how it maps to what was seen in the original BOND III study. And then, I do think that these exploratory endpoints that are looking at PROs and health-related quality of life are just really important, because ultimately, as we start to think about how you start selecting amongst all of these different therapies, you need to have some idea of generalizability of results to the person who's sitting in front of you. And then you need to have some way to talk to patients about that concept of treatment burden, which you and I have talked about before, and what the experience of a drug is going to look like and how that's going to play out in the patient's lived experience and going through treatment.

Zachary Klaassen: Yeah, and I think, too, I mean, just to delve into prostate cancer for one second. I mean, a lot of the real-world stuff in prostate cancer is retrospective after it's been approved. It's database from claims database. But this is truly prospective collection, which I think is really cool.

Sarah Psutka: Yeah, I think so. And so it's exciting to think about how to really ensure diverse recruitment, and then to take that data and really transparently transmit that and disseminate it, because I think that's a lot of foresight to see how this is actually going to perform in a real-world population.

Zachary Klaassen: For sure. Sarah, great to have you back on Uro Today. As always, thanks for your time and expertise. And we appreciate you joining us.

Sarah Psutka: Thank you so much for the opportunity. See you soon.