About the Phase 3 SunRISe-5 Study of TAR-200

SunRISe-5 (NCT06211764) was presented as a featured clinical trial in progress during the 2024 American Urological Association Annual Meeting. The phase 3 study is investigating TAR-200, an intravesical gemcitabine treatment, in patients with non-muscle invasive bladder cancer who have previously received Bacillus Calmette-Guérin (BCG). The first site recently opened, and the study plans to randomize 250 patients.

Here, Sima Porten, MD, MPH, associate professor at the University of California San Francisco, discusses the rationale for the phase 3 SunRISe-5 study of TAR-200 in non-muscle invasive bladder cancer and unmet needs in this patient population.

Transcription:

0:05 | For Su, which is looking at the efficacy of tar 200, in a BCG unresponsive population aligns with FDA guidance based on this definition. So, currently, which patients will be eligible for this trial? This is focusing on patients with papillary-only disease, so patients with high-grade TA or high-grade T1 disease that is present after BCG.

0:34| For this specific population, there are 2 groups. So, the FDA very strict BCG-unresponsive group states that patients have to have at least 5 or 6 doses of induction BCG therapy, and either 2 or 3 doses of maintenance BCG therapy, or 2 or more doses of a second induction. And based on the type of recurrence, they have a high-grade T1 or high-grade TA, that kind of sets the stage for how much BCG do they have to have prior to their recurrence right to be eligible for this trial.

1:06 | The other group of patients that are eligible for this study, it's a less restrictive definition. And we kind of term that as BCG-experienced. And so those patients are also eligible for SunRISe-5. Again, they have to have papillary-only disease, so high-grade T1 or high-grade TA, no carcinoma in situ. And for this group, they have to have induction BCG, at least 5 or 6 doses. And they may or may not have maintenance therapy. And I think that the the inclusion of this experienced population is really important and practical because of the BCG shortage we've had.

1:42 | Really, when patients experience a recurrence after BCG that meets our more strict definitions, our standard of care is up is to proceed with a radical cystectomy. And so that's a bladder removal surgery. And with that comes a whole host of [adverse] effects. And many studies have shown patients would love to avoid that large surgery. And so this has kind of created an explosion of trials and drug development in this space. So right now, if a patient declines radical cystectomy or is unfit for that, there are few FDA approved agents.

2:18 | So there's one called pembrolizumab [Keytruda], which is a systemic immunotherapy. The next approved agent in this space is called nadofaragene firadenovec [Adstiladrin], which is a viral vector sort of based therapy that's instilled in the bladder. And the most recent approval as of, I think last week, is superagonist IL-15 [nogapendekin alfa inbakicept; N-803] with a very long name that is difficult to pronounce. And that is given with BCG in patients with BCG-unresponsive disease. And so those are the kinds of main options for a variety of reasons. There still is an unmet need, despite having these 3 important options, and primarily that has to do with efficacy, as well as tolerability over time. And then for this last approval, availability of BCG.