Gemcitabine Intravesical System Yields Low Rate of Radical Cystectomy in BCG-Unresponsive, High-Risk NMIBC

Patients receiving the gemcitabine intravesical system (Inlexzo, formerly TAR-200) for the treatment of BCG-unresponsive, high-risk non–muscle invasive bladder cancer (NMIBC) achieved high complete response (CR) rates and favorable responses regarding disease progression and radical cystectomy rates, according to data from the phase 2bs SunRISe-1 trial (NCT04640623).1

Data from SunRISe-1 were previously published in the Journal of Clinical Oncology. That report showed a CR rate of 82% (95% CI, 72 to 90) in patients with BCG-unresponsive NMIBC with CIS receiving gemcitabine intravesical system monotherapy. Further, 51% of patients remained in CR for at least 1 year.2

For the current study, which was presented at the 2025 Society of Urologic Oncology Annual Meeting, the investigators, led by Christopher M. Pieczonka, MD, chief executive officer and director of Clinical Research for Associated Medical Professionals in New York, presented data on recurrence, progression, and time to cystectomy in patients receiving gemcitabine intravesical system monotherapy (cohort 2).

Findings showed that at a median follow-up for cohort 2 of 20.2 months (range, 2-48 months), investigators reported an 82.4% CR rate with gemcitabine intravesical system monotherapy; 70 of 85 patients achieved a CR. Of the 70 patients with a CR, 37 (52.9%) had a DoR of 12 months or longer. In addition, at the clinical cut-off, 37 responders remain in complete response; 33 were reported as ongoing with no event, and 4 were permanently censored due to study discontinuation or receipt of subsequent therapy.

The investigators also detailed recurrence and progression, as well as time to radical cystectomy. Forty-one (48.2%) of the 85 patients experienced disease persistence, progression, or recurrence. Thirty (42.9%) of these patients were initial responders. Of the 41 patients, the majority were reported to have persistence or recurrence of high-risk NMIBC. Seven (8.2%) patients progressed to T2 or higher disease. Eighteen (21.2%) of the 85 patients received a radical cystectomy; 12 (14.1%) of these patients were responders. The median time to cystectomy was not estimable, and estimated radical cystectomy-free rates were 86.6% (95% CI, 76.6-92.6) at 12 months and 75.5% (95% CI, 63.4-84.1) at 24 months. Seven deaths unrelated to study treatment were reported.

[Gemcitabine intravesical system] monotherapy is associated with a high CR rate and durable responses, with minimal risk of disease progression to a more advanced (T2 or higher) disease stage. The low rate of RC [radical cystectomy] in cohort 2 of SunRISe-1 highlights that [gemcitabine intravesical system] treatment may result in potential delay to RC,” the authors wrote in their poster.

How was the SunRISe-1 trial designed?

SunRISe-1 included adult patients with histologically confirmed high-risk NMIBC carcinoma in situ (with or without papillary disease), ECOG performance status of 0 to 2, persistent or recurrent disease within 12 months of completing BCG, and who were unresponsive to BCG and not undergoing radical cystectomy. A population of patients with papillary-only high-risk NMIBC (no CIS) were also included; these patients received gemcitabine intravesical system monotherapy (cohort 4). The rest of the population was randomly assigned to gemcitabine intravesical system plus cetrelimab (cohort 1), gemcitabine intravesical system monotherapy (cohort 2), and cetrelimab monotherapy (cohort 3). The gemcitabine intravesical system was administered every 3 weeks for the first 24 weeks, and then every 12 weeks through week 96. For cohorts 1 to 3, the primary end point was overall CR rate, and key secondary end points included duration of response (DoR), overall survival, safety, and tolerability. For cohort 4, the primary end point was disease-free survival.

The investigators reported that 85 patients with CIS had received gemcitabine intravesical system monotherapy as of March 31, 2025. Median age was 71 years (range, 40-88 years), and 68 (80.0%) were male.

References

1. Pieczonka CM, Daneshmand S, Van der Heijden MS, et al. Gemcitabine intravesical system (TAR-200) monotherapy in Bacillus Calmette-Guérin–unresponsive high-risk non–muscle-invasive bladder cancer: characterization of recurrence, progression, and time to cystectomyPresented at: Society of Urologic Oncology Annual Meeting; December 2-5, 2025; Phoenix, Arizona. Abstract 140.
2. Daneshmand S, Heijden MSV, Jacob JM, et al. TAR-200 for Bacillus Calmette-Guérin-unresponsive high-risk non-muscle-invasive bladder cancer: Results from the phase IIb SunRISe-1 study. J Clin Oncol. 2025:101200JCO2501651. doi:10.1200/JCO-25-01651