Andrea Necchi, MD, San Raffaele Hospital and Scientific Institute, Milan, Italy, presented results from Cohort 2 of the phase 2b SunRISe-1 study which evaluated TAR-200 monotherapy among patients with high-risk non–muscle-invasive bladder cancer who did not respond to bacillus Calmette-Guérin (BCG) therapy. TAR-200 is a intravesical drug delivery system which provides a sustained release of gemcitabine into the bladder over time.

In cohort 2, patients exhibited “an unprecedented [complete response] rate, durable responses, a favorable tolerability profile” when treated with TAR-200 monotherapy. Dr Necchi added this study “may represent a further therapeutic option for these patients in the real world.”

Dr Necchi first presented these results at the 2023 European Society for Medical Oncology Annual Congress in Madrid, Spain.

Transcript:

Hello, I'm Professor Andrea Necchi. I'm Professor of Oncology at Vita-Salute San Raffaele University in Milan, Italy. I have pleasure to be herethis year, at ESMO 2023 presenting the first results of SunRISe-1, which is a phase 2b study testing TAR-200, as monotherapy or in combination with immunotherapy, in patients with high-risk and non-muscle-invasive disease who develop BCG-unresponsive disease.

It is clearly an unmet medical need because these patients have radical cystectomy as the only standard therapeutic option in real world. But an increasing number of patients actually are refusing to receive radical cystectomy, asking for something different. The available agents have struggled, of course, against the issues of providing sustained and continuous responses in these patients. There is clearly a need there to invest on newer therapies.

SunRISe-1 is a part of a platform study testing TAR-200. TAR-200 is a novel drug delivery system into the bladder that is made through a silicone tube, an osmotic release, a continuous, sustained release of gemcitabine into the bladder. It's put very easily into the bladder and replaced every 3 weeks for these patients. The SunRISe-1 design provides a randomization of 2-to-1-to-1, in 3 cohorts, to receive TAR-200 in combination with an anti-PD-1 agent, cetrelimab [in Cohort 1], TAR-200 in monotherapy in Cohort 2, or cetrelimab monotherapy [in Cohort 3]. There is an additional, newly-added cohort, this is Cohort 4. These patients, ongoing today, includes patients with papillary tumor alone without carcinoma in situ (CIS). Importantly, patients included have a BCG-unresponsive carcinoma in situ with or without a papillary component, and refuse or are unfit for radical cystectomy. TAR-200 is dosed every 3 weeks up to week 24 and then every 12 weeks until week 96. The primary end point is complete response in Cohort 1, 2, and 3.

Here at this meeting we presented the data relative to the expansion cohort of TAR-200 monotherapy, so Cohort 2. A total of 54 patients have been included thus far. The vast majority of the patients presented with CIS alone, with highly aggressive disease, with the median time from BCG-end to CIS recurrence of 3 months. And the study provided the complete response rate at the centralized assessment of almost 77%. It's important to underscore the fact that the complete response definition provides urine cytology, centralized urine cytology, centralized biopsy at 2 different assessments, week 24 and 48. A very, very stringent definition of complete response. And, importantly as well, the investigator-assessed, so locally-assessed, complete response was pretty much in line with the centralized data, 80% of responses.

Most of the complete responses were ongoing and durable and stable over time. Six of the patients had a duration of response of at least 12 months. And the projected estimates of complete response at 6 months and 12 months were over 90% and 84% [respectively] -- much higher theoretically in comparison to the same rates provided with systemic immunotherapy. The safety profile was quite good. The vast majority of the few side effects were grade 1 or 2, and the vast majority of the side effects were related to local symptoms.

In conclusion, the study provided the very, very promising combination of safety and efficacy with the drug and may represent further therapeutic options for these patients in real world.

Source:

Necchi A, Jacob JM, Daneshmand S, et al. Results from SunRISe-1 in patients (pts) with bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer (HR NMIBC) receiving TAR-200 monotherapy. Presented at ESMO Annual Congress; October 20-24, 2023; Madrid, Spain. LBA105