SunRISe-1 Data: Benefits of the Pretzel Device and Gemcitabine Monotherapy

Part four of this roundtable series examines the SunRISe-1 trial results for high-risk, non-muscle invasive bladder cancer (NMIBC), with a focus on TAR-200, a sustained-release gemcitabine delivery device. The panelists review the trial’s three arms: TAR-200 with cetrelimab, TAR-200 alone, and cetrelimab alone, highlighting that TAR-200 monotherapy achieved a superior 12-month complete response rate (57%) compared to the combination therapy. The conversation explores the logistical advantages of TAR-200, including its shelf stability, ease of use in clinical settings, and reduced systemic toxicity. They also discuss potential mechanisms for TAR-200’s efficacy, operational considerations for integrating this therapy into practice, and the growing role of advanced practice providers in managing the increasing procedural demands of NMIBC treatments.

Watch part five of this series: Patient ID, Protocol and Procedure in NMIBC

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Dr. Brown:
Thinking about the data itself right now, the Sunrise-1 trial had four arms, right? We’re going to report on three of those arms. The first arm was a combination of the TAR-200 plus cetrelimab. Second arm was the TAR-200 alone, and the third arm was the cetrelimab arm alone. Looking at the 12-month estimated CR rates, we’re seeing approximately 57% CR rate in the TAR-200 alone arm, which is actually slightly superior to that estimated in the combination cetrelimab plus TAR. And the cetrelimab alone arm is roughly about 22% CR rate, which is tracking in line with other IO therapies in some of our patient populations in previously reported trials. So one, what do you think about the data, and two, what do you think about the monotherapy being superior to the combination?

Dr. Richardson:
I was happy with it because I was hopeful that we could potentially get away from systemic therapy for this disease state just because the potential for toxicity is so much different than anything intravesical. So I think it was refreshing to see that we’re on the right track. Something in the bladder is going to work better than something systemically that has the potential to cause much more toxicity.

Dr. Cone:
I was also really excited about it from a logistical standpoint because there are many, many, many more urology practices in the country that are going to be comfortable with an intravesical therapy than with a systemic therapy and with an infusion. And so from a, how do you get the drug to the patient standpoint, one of the nice things about the TAR, comes in a small little package, it’s shelf stable for years. This is something that even far-flung clinics can stack up on a shelf and know that they’re going to use it, whereas if it had been superior with the cetrelimab, that would’ve presented a bit more of a challenge. So I was actually happy about it.

Dr. Pieczonka:
I think the thing that’s interesting to me is that the TAR-200 device gives medicine that is not immunotherapy. But I think for those of us that have been doing this for a while, Bryan and I go way back with the sipuleucel-T days, is there’s a concept of antigen cascade. So in some ways, the chemotherapy becomes immunogenic. So I think that may be one of the reasons that it’s there for a while and that you’re getting this over this period of time that you have such superior results that as the cancer cells are destroyed by the gemcitabine, that you’re provoking some sort of immune response because otherwise you have no way of explaining why it would be more durable and better than the immunotherapy that’s given every couple of weeks. And I second everything else that was said about the tolerability and ease of use of the medicine. Using any type of systemic immunotherapy is something that I really would try and not want to do a lot in my clinic just because I own those patients when they have side effects. This is light years better.

Dr. Brown:
Yeah. And when we look at the CR 12 months, it’s dramatically better than anything that’s in the marketplace right now. And when these trials are designed, a lot of these trials talk about three-month CRs, right? So I’d like to get the group’s thought about what’s the implication of a three-month CR to you guys, if anything, and how important is a 12-month compared to a three-month CR, Gene?

Dr. Cone:
Yeah, so I have a little bit of a soapbox here on this one because this is a fundamentally different disease state than a lot of the oncology spaces where if you have someone who has metastatic disease, they’re incurable, and that’s the mindset that a lot of medical oncologists are bringing to the table. Three months, six months, 12 months, 18 months, those are all very, very important. This is a space where we do have an excellent curative option in cystectomy, but it is a morbid operation, and most patients would rather keep their bladder than undergo a cystectomy. So if we’re kicking the can down the road three months, that’s not clinically meaningful.

Dr. Pieczonka:
Yeah.

Dr. Cone:
If we can potentially get a high complete response rate so that we can tell patients, no, there’s a good chance that you’re going to be keeping your bladder for the long run, not just delaying cystectomy a year or two until you’re older and sicker and maybe not even cystectomy fit, that’s a much bigger win in this space. And so I think that this is one of the first therapies to really clear that bar where you don’t feel like you’re just delaying the cystectomy that they’re probably still going to need with a 20% CR rate at 12 months. And now we’re really entering into territory of are we more durably curing you?

Dr. Mehlhaff:
Yeah, we’ve come a long way. Valrubicin was used really, really very infrequently just because of that. We all were like, why? So incrementally better. Now, I agree, we’re getting to the point where, okay, that’s meaningful. Because the fear is that you’re dinking around with a bladder cancer and then this patient escapes and develops metastatic disease and then we all feel bad.

Dr. Brown:
Yeah, and I think there should be distinction between the status patient population and papillary population with this conversation too.

Dr. Pieczonka:
That’s true.

Dr. Brown:
Because I believe that they’re inherently different disease states and your risk tolerance may be different in those folks. But this was a heavily pre-treated patient population, right? They had far over at least 12 on median or more and a series of intravascular treatments. So they were the appropriate patient to come on the trial in this space. And the results are compelling. They’re paradigm changing. Bryan, what are your thoughts?

Dr. Mehlhaff:
Obviously every patient wants to keep their bladder. And it is a life-changing morbid operations. So I think I’m excited by this data. I want to see more. And then I have yet to participate in the TAR trial, so I would like to take it for a test drive. So I’m still sitting on the sidelines watching.

Dr. Brown:
While Mehlhaff’s kicking the tires, Gene, you’re taking it around the track a little bit. You’ve been on trial with this and I know you’ve had a fair amount of experience. Tolerability seems to be manageable in your practice response, seems to consistent with what was reported at ESMO 2024, in your opinion?

Dr. Cone:
Yeah, I think that that data is consistent with what we’ve seen on the ground and in terms of the test drive, because until you do it, it’s hard to know exactly how it’s going to fit into your clinic. We had a fair amount of trepidation with the first patient that we put a TAR into. And after you do it a couple times, it’s a under 90-second exchange. Scope in, grab it, pull it out, catheter in, put it in, pull it out. We put them in a 20-minute procedure slot just because there’s some MA time and they have to get unchanged and prepped and all of that. But this is something that any clinic that performs cystoscopies can very easily operate.

Dr. Richardson:
Our experience has been the same. They just go into a normal cysto clinic spot as any other cysto would, and it doesn’t really add any extra time.

Dr. Brown:
So let’s drill down on that a little bit operationally. This is something that docs are doing in your practice; mid-levels are going to be doing, and will be surveilling them simultaneously, which is I think one of the benefits here personally to me, one. Two, you’re looking at eight visits over six months. Is that a lot, too much, and eight procedures in that same period of time?

Dr. Pieczonka:
I think this is, the procedure itself is very advanced practice provider friendly, but I think we just have to be cautious because assuming this gets approval, this is going to be in a heavily pre-treated patient population that I still want to have in our group, our docs eyeball on the bladder periodically. And as they get used to using the device. I think that’s the one thing I just have a little bit of concern about. I think the second thing that’s interesting to me is J&J has a lot of experience with devices and I think there’s only a potential opportunity to make the device better as it relates to tolerability.

They’re kind of working on some fun things that are going to hopefully make that…because we don’t know on some of the side effects how much that is related to the actual device going in. And is there some room for improvement? It’s already pretty good. So I think there might be an opportunity as it gets out into the real world and there’s lots and lots of people using it to give some feedback to J&J and say, hey, do this this way or do it that way and use best practices to make it better.

Dr. Brown:
Yeah, we had talked about maybe even developing pathways or tips and tricks sheet or troubleshooting to try to mitigate a side effect profile.

Dr. Richardson:
Yeah, I think there’s a sweet spot between the physician and the APP. I love the fact that you can do surveillance every three weeks, but we all, I think would all agree you probably don’t need to do surveillance every three weeks. So I think it is a perfect procedure for APPs to do. And I think that’s coming in a lot of different disease states in our practices. Here before long, half the urology workforce in the country’s going to be an APP and not a urologist. And so they are going to start doing some of these technical procedures, not diagnostic procedures, but technical procedures, prostate biopsies, et cetera. So I do think that this lends into that pathway for the future, but I agree with you, you still need urology hands on it at some point for their surveillance and monitoring, but it doesn’t have to be every three weeks.

Dr. Cone:
I think from a bandwidth standpoint, depending on how you structure it, I think we calculated that it was an extra eight to 10 cystoscopies in that first 12-month period. And if you do any volume of bladder cancer, let’s say you have 50 new high-risk bladder cancer patients per year, this isn’t necessarily SunRISe-1, but for SunRISe-3, BCG naive, if that reads out positively, you’re adding potentially 500 scopes to your practice if you only see 50 new high-risk bladder cancer patients per year. I don’t have the bandwidth for that. So APPs are going to have to step in. It’s going to require some rethinking for sure. But I think that we’re going to need to have the APPs involved in at least the exchanges. And I agree, I want to be the one looking for the diagnostics of stuff.