Siamak Daneshmand: Right. Exactly.
Ashish Kamat: Tell us what you shared at the SUO.
Siamak Daneshmand: Well, thank you, Ashish. Thank you for having me on again. It's a pleasure to speak about the study again, but this was exciting. This was the Cohort 4 of the SunRISe-1 study, and it was basically patients with papillary disease only treated with this gemcitabine intravesical system with what is now, like you said, rephrased as Gem-iDRS. Of course, we know this as TAR-200, and before that as GemRIS. So these are the one-year disease-free survival rates. These are my disclosures. I am a consultant for Johnson & Johnson. So we all know there's an unmet need still in patients who are BCG-unresponsive, have papillary disease only. And we've had a few exciting new drugs developed and approved for patients who have BCG-unresponsive CIS, but none are really approved for papillary disease only. So there are several trials looking at this for this disease state, and this was the one-year result of the Cohort 4, the DFS results. Same drug, same intravesical delivery device system with the gemcitabine.
So here's the schema of the trial. We had multiple cohorts with the GEM-iDRS alone and with cetrelimab and the cetrelimab monotherapy, but this is concentrating on Cohort 4. So Cohort 4, again, papillary disease only, no CIS. The GEM-iDRS was placed every three weeks for 24 weeks. And then after that, it was quarterly for 96 weeks. And the primary endpoint is DFS, different than CR rates because those are for CIS patients and patients who have papillary disease only because you're doing a TURBT and removing the disease, we're looking for disease recurrence and hence the disease-free survival key endpoint there. And then, of course, looking again at safety and tolerability there. Importantly, the study did not allow for reinduction for non-responders. And this is basically the same cohort as we've always seen, that 70-year-olds, mostly male. But importantly, I want to point out the high-grade T1 and Ta mix. 60% of the patients were Ta, but 40% were T1. And I think that's pretty significant that you have a large proportion of patients who have very high-risk disease. And most of them had declined radical cystectomy as their therapy of choice.
The six and 12-month DFS rates, you can see here that's concentrating on the 12-month, you can see it was about 74% DFS in this population, which is pretty significant. And we have some patients out to 18 months looking at about 69%. So median DFS is obviously not reached yet, and hopefully won't be. When you break it down between high-grade Ta versus T1 disease, it's essentially identical, about 75% and 74% DFS rates with Ta and T1. So that's very encouraging that even when patients with T1, although limited number of patients, we're still seeing excellent results there. And then the OS rates, of course, are very high. Patients, only one patient out of the 52 had progression to high-grade muscle-invasive disease. The overall survival rate was extremely high in the high 90s, so that's pretty important. Also, one more parameter they looked at was whether or time to cystectomy, whether patients went to cystectomy, how long did that take? And only four patients out of the 52 went on to cystectomy for either recurrence or progression of disease. So at 18 months, we had 91% cystectomy-free survival. So again, most of the patients are tolerating this well and not progressing on this therapy.
When you look at the safety profile, which again, we've looked at many times in the other trials, most of the AEs are at grade 1 and 2 and resolve fairly quickly. Only three patients had one serious AE, and importantly, only four patients discontinued the treatment because of these AEs. People have been asking how successful is the device placement? And they looked at this, 99.8% of the time they were able to place the system in the bladder without difficulty. So there's only one insertion difficulty in a patient with BPH. Also, importantly, quality of life was measured in this trial, looking at EORTC QLQ-C30, which is basically the global health status and the physical functioning status of the patient. And you can see on these graphs, this is maintained throughout treatment, which is very important. This is not something where the patients are having increased difficulty with the drug delivery system as time goes. They're maintaining their quality of life. So basically, this was an early look, a one-year look at the DFS rates with a monotherapy, about 74%, and it was equally high in the Ta and T1 population, high overall survival rates, obviously, and progression-free survival rates at 12 months and even 18 months, with very few people, patients undergoing radical cystectomy due to disease progression, pretty well tolerated. Again, you can see the health-related quality of life is maintained throughout the study.
And then there's a Phase-3 SunRISe-5 study, which actually recently close to accrual, it accrued all its patients quite well. It's the same basically design, but it's a randomized study between the GEM-iDRS versus intravesical chemo monotherapy. And we'll see one of the very first of the Phase-3 studies to look at the comparison between this and what's considered standard of care in many places around the world, chemotherapy, monotherapy for this disease state. So pretty exciting results. Of course, all the follow-up is ongoing, and we'll see how this pans out over time. Thank you.
Ashish Kamat: Thanks so much. Everywhere we look and every time you see the data presented with the GEM-iDRS system, it just seems like this is likely to establish a new standard of care. I think it's great that there are so many choices for patients nowadays. I remember, and you, of course, remember when we were talking about nothing being available, and then pembro and then nadofaragene and now this system. You've done a lot of work with this. Where do you see it being positioned in your discussion with a patient when you see a patient in clinic that has disease that has not responded to BCG? Let's say it's not the classic BCG unresponsive because that's hard in the clinic nowadays with all the BCG issues. But when you see a patient and you are talking to him or her about, they've got T1 disease, high grade, really doesn't want a cystectomy, how do you position this in your discussion?
Siamak Daneshmand: Well, good question. And this has FDA approval for BCG-unresponsive CIS, so it's in our hands now, and we're beginning to have those discussions in real time with the patients. So it's one of the several FDA-approved therapies. I could tell you I've started using it commercially and the discussion is one of preference for both disease control as well as the logistics. There are some patients who are better suited for the monotherapy, for instance, with nadofaragene because of geographical constraints. Albeit the response rates at one year are not quite as good. However, it is extremely well tolerated and has some reasonable one-year and two-year results there. But I tell the patients, "If you want to go for the treatment that has the highest response rates that we've seen so far that is currently FDA approved, this would be it." It does require the insertion and removal of the device every three weeks for the first six months at least, but after that it's quarterly and it is fairly well tolerated. So we have a discussion about this.
And of course, Anktiva also comes into the discussion. We've had trouble with that because of the availability of BCG or reliance on BCG. And hopefully with the recombinant BCG, we'll get that, but that also has very good results. So this is one of a very few next-line treatments right now that we talk about. I don't use any systemic therapy for this. So pembrolizumab, or Keytruda, that is FDA approved also has, I think, a fairly poor long-term response rate and has a lot of potential side effects that we don't like to see in this disease state. So really we get down to gemcitabine, docetaxel. They may have seen that before, or there may be some logistical issues with a delivery of that combination chemotherapy. Then we have the Inlexzo or TAR-200 or GEM-iDRS and then nadofaragene. So I have this discussion with every patient essentially now. And with the emergence of this important data for the papillary disease, we have more data to support its use in that setting as well.
Ashish Kamat: Absolutely. When we chat with our colleagues at different situations, whether a conference or a meal or at an advisory board or a retreat, oftentimes folks in academia will talk about being good stewards of healthcare dollars, and that's why lean towards, I guess, Gem-Doce first because it's cheap and much more economical. Given these new data, are you still leaning that way? Because I know you felt that way some time ago too, "Let's go with Gem-Doce." Are you feeling that way too, or you jump straight to this now?
Siamak Daneshmand: Certainly. I think we do need to keep that under consideration that gemcitabine-docetaxel combination therapy is very effective. The data that we all rely on as a single paper that is a retrospective data from these five institutions, it is good data, but nevertheless, it is retrospective with its constraints. So I think having prospective data obviously is much better. Now, each of us have our own institutional experience that, to some degree, mirrors the retrospective studies, but we still look forward to having actual prospective look at this. But I would say still that is very much part of my armamentarium to use gemcitabine-docetaxel as my next go to. There's some insurance issues that may come up and some payer systems that may not cover the newer therapies. So it's all, again, part of that discussion of... And some patients, the ease of insertion, honestly, even though it's every three weeks and you have to put it in gemcitabine-docetaxel, as you very well know, is a pretty long process for the patient. They're here for three hours, two to three hours at the very least. And so, that's a consideration for patients as well. And in some healthcare systems where docetaxel is not available to the urologist, they have to go to a cancer center to get it. I think most of us are lucky to have it in our clinics, but it is much, much cheaper. You're absolutely right, and we do have to consider these as part of our discussion.
Ashish Kamat: Just like you, I've actually heard patients ask for this device by name. It's not that often that you hear patients actually ask for something by name, and they'll call it the pretzel as well, which is kind of funny how patients have gotten onto that. And the relative ease of administration, like you said, is key. One last question, Sia, this is more of a practical question. At your center, how do you do it? And do you think that once this is more mainstream available, we will need or have to train APPs to be able to insert it, or do you think this is something that urologists would do it?
Siamak Daneshmand: Great question. And as part of the trial, actually, the PA who works with me, Kevin Wayne, was credentialed to both insert and remove the device. So absolutely, we see this as an extension of our practice into the APPs who do cystoscopies, who do stent removals. It's very, very easy to learn how to do. So again, our PA became very familiar with this and has been doing it with me. In terms of logistics, I think it's very easy. We don't need the cystoscopy suite anymore to place the device. It's a simple catheter placement, and it takes literally less than two minutes to place. And then the patient is out of here, we don't need to wait for anything else. So it's a very quick visit. For the removal, it's your standard cystoscopy. So I'm talking about the initial insertion, and then for the exchange or removal of the device and placement, obviously that's done in the cystoscopy suite, but again, a five-minute procedure as we remove the old device and put the new one in. So again, I love the fact that we're past the clinical trial portion where we had to fill out all this paperwork and wait for the coordinator to arrive and so on and so forth. Now it's just a very, very quick procedure. So I'm loving this as are the patients.
Ashish Kamat: Sia, always a pleasure. Thank you for taking the time and congratulations on this presentation.
Siamak Daneshmand: Thank you so much, Ashish. Thank you.