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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 difficult-to-treat non-muscle-invasive bladder cancer (NMIBC), according to data from the ongoing phase IIb presented at the American Urological Association annual meeting.

In this exclusive 番茄社区 video, Siamak Daneshmand, MD, professor of urology at the University of Southern California Norris Comprehensive Cancer Center in Los Angeles, discusses preliminary results from the trial.

Following is a transcript of his remarks:

Hi, I'm Sia Daneshmand. I'm professor of urology at the USC Norris Comprehensive Cancer Center in Los Angeles, California. And I'm here to discuss the results of the SunRISe-1 study. This was the TAR-200 in BCG [bacillus Calmette–Guérin]-unresponsive or refractory non-muscle-invasive bladder cancer.

So the rationale for the study was that there's a great unmet need in this patient population. Typically, the gold standard of care in the past has been radical cystectomy for this population. And we have very few approved drugs. There are some combination chemotherapy drugs that we use and some other medications coming down the pipe. But there still is a large unmet need for patients who don't respond to BCG.

And it's a growing population. The patients are getting older, and many of them can't tolerate cystectomy or really don't want a cystectomy for non-muscle-invasive bladder cancer.

So that was a rationale. There was a phase I study that was run in 2016 to 2017 looking at this pretzel. This is a device that's placed inside the bladder with a special catheter. It goes in the lumen of the catheter and is pushed through into the bladder, and it maintains a pretzel-like shape within the bladder. And it has gemcitabine tablets that are pushed through. There's an osmotic pump that is created, and the urine goes through this. And the gemcitabine tablets are dissolved over time through a pore in the pretzel.

So there's sustained release of the drug. Rather than putting it in for 1 hour like we do for normal intravesical therapy, we are now having sustained release over 1 week and now 3 weeks.

So the phase I study showed great tolerability of the device-drug combination, and we saw some early signals for efficacy. This was in the neoadjuvant setting prior to radical cystectomy; we are seeing some tumors actually disappear.

So that was a rationale to move this concept and this device forward to the next step, which would be in the various spaces. And we have four SunRISe studies available right now.

So I presented the SunRISe-1 study. Again, this is a three-cohort study of TAR-200 alone; cetrelimab alone, which is a PD-1 inhibitor; or the combination therapy TAR-200 plus cetrelimab in management of BCG-refractory non-muscle-invasive bladder cancer. Here we didn't have enough data to present the combination therapy, so we presented the therapy with cetrelimab or TAR-200 alone. So you can see the contribution of each one alone.

We had 22 evaluable patients for TAR-220, and 21 for the cetrelimab arm. And the main objective was a CR, complete response, at any time. The median follow-up was 11 months, and the complete response rate for the TAR-200 alone was 73% and for the cetrelimab was about 36%.

So we're seeing great efficacy in an area that we have not sort of seen these numbers before. We're used to the 20%, 30% numbers in terms of efficacy in this very resistant population. The median duration of response hasn't been met. It was, as I said, the median follow-up was 11 months, but the median duration of response hasn't been met.

So of all the complete responders, they're still on therapy except for one patient. And for those who have responded, there's been no documented recurrence. And several patients are out more than a year from therapy. So this is looking to be hopefully a very effective way of managing this.

In terms of the AEs [adverse events] this is very well tolerated, as I mentioned. We knew that from the phase I study. I've put in a lot of these devices, and it's very easy to place and remove. And again, it's very well tolerated because it's floating in the bladder.

In terms of AEs, the usual grade 1/2 urinary frequency urgency, those urinary symptoms that we see, and with the cetrelimab arm alone, there's really no additional signals. Again, what we're used to with the PD-1 and PD-L1 inhibitor. So the AEs were 8% and 4%, and only one device that's been removed early.

So, in essence, in summary, this seems to be a very effective therapy for BCG-refractory non-muscle-invasive disease. In terms of where we're going next with this, there are three other studies -- there's SunRISe-2, 3, and 4.

SunRISe-2 is in the muscle-invasive bladder cancer population who's unfit for cystectomy or refuses cystectomy, and they get the TAR-200 plus cetrelimab versus chemoradiation as an alternative. So they're randomized.

SunRISe-3 will be looking at the BCG-naive space, basically looking at the same combination versus BCG. And in SunRISe-4, we're using it in a neoadjuvant setting to see whether the TAR-200 plus cetrelimab has activity in the neoadjuvant study.

So lots of studies, we're going to get to see its efficacy across sort of the spectrum of disease.

And then there's another study, this concept, this is a drug-delivery system, so you can imagine we're not limited to gemcitabine. There's a lot of brilliant engineering that goes into making these devices and the drugs that are placed in it and how they elude over time.

So there is another study called TAR-210 that has just opened recently, globally. These are all global trials, by the way. And in TAR-210 we have erdafitinib tablets within the pretzel. And these are for patients, again, multiple cohorts, and these are patients who harbor FGFR3 alterations.

So really exciting stuff coming along.

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