乌鸦传媒

TAR-200, an investigational intravesical delivery system designed to provide sustained local release of gemcitabine into the bladder, produced high rates of complete response (CR) in bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer, according to data from the ongoing phase IIb SunRISe-1 study presented at the American Urological Association (AUA) annual meeting.

乌鸦传媒 brought together three expert leaders in the field. Moderator Alexander Kutikov, MD, is joined by Adam Reese, MD, and Laura Bukavina, MD, MPH, all part of the , for a virtual roundtable discussion. This third of four exclusive episodes covers their reactions to results from this study.

Following is a transcript of their remarks:

Kutikov: So, Laura, why don't you tell us a little bit, let's switch gears and talk about . So this is the TAR-200 gemcitabine-eluding pretzel.

Bukavina: Yeah. So this is great. This is the phase IIb TAR-200 study that many of us know as the pretzel, because it literally looks like a pretzel. And this is with TAR-200 alone, with or without cetrelimab, which is a PD-1 blocker. The study is small. There were 50 patients in each arm and 100 patients in the arm that was not reported.

Overall, in terms of the TAR-200, of how it's performed in clinic, it's a cystoscopic insertion of this pretzel, which looks like a rod, and then within the bladder becomes pretzel-like. Within the pretzel, there's small beads of gemcitabine-coded little beads that over a week, so it takes about a week to dissolve, and then this pretzel is removed every 3 weeks, and a new pretzel is reinserted.

So the study reported on just a second and a third arm. They did not report anything in terms of the first arm, which included combination therapies that they looked at response rate in non-muscle BCG-refractory disease in the TAR-200-alone [arm] versus cetrelimab alone. So, we'll go to the PD-1 blocker first, which they reported a 38.1% CR rate at 12 months. And then if you look at TAR-200 alone, they reported a 72.7% 12-month CR rate.

So it's pretty impressive, I think, overall. And even if we have to look at the small number of patients, 50 patients in each arm -- a) I think 38% alone is pretty high if you look at pembrolizumab [Keytruda] alone at 12 months. And then if you look at combination with TAR-200, I wonder how high that number's going to be. Are we going to be able to get pretty high to 90s in terms of the CR rate on the line? But none of these numbers have been reported yet.

The side effect profile for TAR-200, as many of us probably assumed, a lot of dysuria, a lot of frequency, which is common with intravesical chemotherapy, and very similar grade 3 side effect profile for a PD-1 blocker.

So, very exciting. I think TAR-200 results are probably one of the most exciting things that were presented at AUA.

Kutikov: Adam, thoughts on this? Are you excited about this?

Reese: Yeah, I agree. I mean, these are preliminary results. So I don't want to get overly excited, but I think preliminarily they're quite promising -- 73% initial complete response rate in the TAR-200 arm is impressive, I think comparable to what we just discussed in the CORE1 trial. It's just important to keep in the back of our mind, these are preliminary results of a relatively small study with limited follow-up. So in the TAR-200 cohort, I think there were 22 patients, the median follow-up was about 10.7 months. So the long-term durability of this agent, I think is still sort of up for question.

I am interested in seeing the results of their cohort one, which is the combination of the TAR-200 with the cetrelimab. I guess those results were not mature at the time of reporting, but it would be interesting to see what that combination therapy can do.

Bukavina: Mm-hmm.

Kutikov: Perfect.

Bukavina: Yeah, and I think unlike other potential therapies, it's feasible in terms of production. Gemcitabine until recently has been widely available, at least until recently. And I think the production in terms of capabilities is feasible on the wide scale.

Kutikov: Laura, thoughts about the use of this IO [immunotherapy] agent cetrelimab, which is, clearly the community is not as familiar with it, and there's not as much data. Thoughts about using this particular agent in this trial?

Bukavina: I think this is a great study for introduction of this new therapy and tagging it along with additional therapy. So I think because of pembrolizumab and the approval, a lot of pharmaceutical companies are fighting for a chance to have a seat at the table in terms of immunotherapy for BCG-refractory disease. And I think having this added-on therapy to the TAR-200 was probably the only way that this could be introduced and urologists could be excited about it, more so than pembrolizumab. I'll say this in the most politically correct possible way.

Kutikov: That was very diplomatic, Laura. But I do have to say that taking things in and out of bladders, that gets all urologists excited. This is a very urologic drug, so to speak. And my understanding is that, you know, there is enthusiasm to try different agents in this delivery strategy.

Bukavina: Yeah, I think there was a poster presented on EV [enfortumab vedotin], so EV beads within the pretzel as well. So there's potentially multiple different drug combinations that you could put -- you could put gem/doce [gemcitabine/docetaxel] perhaps instead of a single-agent gemcitabine down the line. So there is a lot of potential.

I think the conundrum is going to be when the results are released, and the CR rate in combination therapy is something like 84%, right? So you're dealing with 75% versus 84%, but the addition of those side effects. And so that's going to be a challenging question for a lot of urologists, is that, do you go with combination therapy or do you just do the TAR-200? Is TAR-200 alone going to be available, or do you have to always combine it with cetrelimab? And those are the questions that I think we're going to have to deal with once the new data comes up.

Kutikov: Perfect.

Watch episode one: Anti-PD-1 in BCG-Unresponsive Papillary Bladder Tumors

Watch episode two: Immunotherapy Combo Shows Promise in Tough-to-Treat, Early Bladder Cancer

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