Zachary Klaassen: Hello, UroToday. My name is Zach Klaassen. I'm a urologic oncologist at the Georgia Cancer Center in Augusta, Georgia. I'm happy to be joined on UroToday by Dr. Wes Kassouf, who is a urologic oncologist at McGill University in Montreal, Canada. Today, we're going to be discussing Dr. Kassouf's Canadian Urological Association presentation, expanded access program of cretostimogene in patients with high-risk BCG-unresponsive non-muscle invasive bladder cancer with CIS. Wes, thanks for taking time out of your busy day to join us on UroToday.

Wassim Kassouf: Thank you, Zach, for having me. It's a real pleasure to be here. Basically, the focus of this is on that poster that we'll be presenting at the Canadian Urological Association in the next couple of weeks, talking about the expanded access program. In Canada, we refer to it, at least Health Canada refers to it, as the special access program, which has pretty much similar goals and benefits, I would imagine, as in the States.

The premise of this is talking about cretostimogene, creto to be short, because these words are quite long and hard to pronounce. But essentially, it's an oncolytic immunotherapy with a dual mechanism of action. It has a cytotoxic aspect but also amplifies the immune response against bladder tumors.

And the trial that led to the expanded access program is actually the BOND-003 trial. And this is a trial in the BCG-unresponsive space, similar to what we've seen in other novel therapeutics with regards to trial design, single-arm study, looking at BCG-unresponsive carcinoma in situ with or without papillary disease.

Where patients got an induction course of creto followed by a maintenance regimen quarterly the first year and then every six months the second year. So a total of two-year duration. What's nice about this trial, it allows for a re-induction. So there's kind of variations across those trials. So it allows for a re-induction in someone who has stable disease.

Now this trial, the most recent update, was presented at AUA a couple of months ago, showing a 75% complete response, median duration of 28 months. And what it means for that patient is if you have a complete response, you can tell that patient you roughly have a 58% chance of being disease-free at two years.

And the tolerability is quite good. There's actually 0% of grade 3 or more treatment-related adverse effects, so quite tolerable from that aspect. And based on these results, it was granted FDA fast track and breakthrough therapy.

And having said that, that expanded access program that's open in the States and soon to be open in Canada this month allows an opportunity to access this novel agent in those patients who want to keep their bladders and fall in that category.

I think it's particularly relevant in Canada because Canada has, as you know, it's somewhat of a socialized medicine program. So we can get approval from Health Canada, but approval doesn't mean reimbursement. So reimbursement comes from another government body, provincial usually.

And sometimes, they don't go together. So in Canada, for example, the only approved drug for BCG-unresponsive carcinoma in situ is pembrolizumab. So that's approved by Health Canada but not reimbursed everywhere. And as such, there's zero uptake in Canada based on that discrepancy between the two.

So that special access program, once it's open, it does give that opportunity to access this drug in those patients and to access them at no cost to the patient, which is quite a big, big benefit to our patients.

What's also different about this, it doesn't have the strict inclusion-exclusion criteria as typical clinical trial settings. So it's a bit more flexible in terms of it accepts ECOG up to 3. It's got an expanded window for prior intravesical BCG. So you don't have to really meet that 6- and 12-month mark. It allows previous investigational therapy permitted as well. And it doesn't mandate biopsies at the end. So I think it's more practical and allows a bit more patients to qualify and get access to this program.

The other thing that's interesting is sometimes, you do have patients who get enrolled on trials, and they get induction or re-induction. And somewhere down the line, they do have disease relapse. So I remember a patient of mine who had this florid carcinoma in situ all over the bladder. And along the line, the bladder looks pristine clean with a very small focal erythematous patch, biopsy-proven carcinoma in situ.

So this kind of program allows what we call those partial responders who you can see they clinically benefited. But on paper, they still had that histologically proven small focus of carcinoma, which is much, much better than what they started with. It allows for continuing therapy in that space as well.

So that program hopefully will roll out soon in Canada. And through CG Oncology, once you have a patient that potentially is eligible to access this program, to contact them, and then we can get that form filled and get that drug accessible through that special access program in Canada.

Zachary Klaassen: That's great, Wes. I think there's so many benefits to an EAP, just from an EAP standpoint in general. We have all these great trials, whether it's in bladder cancer or prostate. What's the benefit of the EAP to get this drug to the patients almost right after the trial's been approved and it's been reported?

Wassim Kassouf: Well, if you look at, I mean, we do know from the literature that many patients who have a strong indication for cystectomy refuse it or are too sick to undergo it. Even in the invasive space, literature after literature, be it in the United States, Canada, Scandinavia, there's roughly 40%, 50% of patients are not getting anything because they're refusing what we have to offer them as what we think is the ideal option.

Now in patients, similarly, in patients with BCG-unresponsive disease, although in the non-muscle invasive bladder cancer setting, at least especially in regions such as Canada where there's really no access to any of the novel therapeutic agents, we're going to be faced with many patients adamantly refusing cystectomy or too sick to undergo it. At least it brings that opportunity to control the disease and be proactive in preserving that bladder in the long run.

Zachary Klaassen: No, it's great. I think we look a little bit more at the Health Canada Special Access Program. I'm excited for you guys and the patients in Canada to have access to some novel therapeutics. We're getting ready to open the EAP at our institution as well.

You said it's rolling out this month. Maybe just maybe just give our listeners an idea of what that conversation will go like with the patients and what their feedback may be, having access to this novel therapeutic. Because as you said, pembro is not being used. There's very limited options at that point, right?

Wassim Kassouf: So you're going to have a patient come into your office, relapsing after BCG therapy, deemed BCG unresponsive. You're going to have that conversation with that patient. Well, listen, right now, what's present is a radical cystectomy. You can try gemcitabine-docetaxel based on some very soft evidence in a retrospective setting.

Or there is an opportunity to tap into a drug that has a higher, stronger evidence of benefit and likely will get approval in the near future based on exciting results. And if you're interested, we can start the process to see if you can access that.

Zachary Klaassen: Yeah. No, it's great. I think when we look at this, it's almost like a phase 4 trial. What us as clinicians will learn from it, the company will learn from it, it's exciting that not only are we going to have access in the US but also in Canada too. Wes, thanks for your time. Anything we haven't hit on, any concluding remarks for our listeners?

Wassim Kassouf: No. I think we covered everything. I think you're right. I think the main people who will actually appreciate it and benefit from it is our patients. And I think that's the most important right now.

Zachary Klaassen: Absolutely. Well said, Wes. Thanks so much for your time. Appreciate you joining us on UroToday.

Wassim Kassouf: Pleasure, Zach. Have a good day.