Gemcitabine intravesical system delivers high 12-month DFS in papillary-only NMIBC

The gemcitabine intravesical system (Inlexzo, formerly TAR-200) demonstrated high disease-free survival (DFS) rates in patients with papillary-only high-risk non–muscle invasive bladder cancer (NMIBC), according to data from cohort 4 of the phase 2b SunRISe-1 trial (NCT04640623).¹

Siamak Daneshmand, MD, a professor of urology (clinical scholar) and director of Clinical Research at Keck School of Medicine of the University of Southern California, Los Angeles, presented the results during a session at the 2025 Society of Urologic Oncology Annual Meeting in Phoenix, Arizona.

In his presentation, Daneshmand noted the current lack of FDA-approved treatments for BCG-unresponsive papillary disease-only high-risk NMIBC, and that 12-month disease-free and recurrence-free survival rates for investigational treatments in this space range from 44% to 55%.^2-4

In addition, “Those with papillary-only disease face particularly difficult decisions, as surgical removal of the bladder has long been the standard of care for patients who are unresponsive or resistant to BCG,” said Johnson & Johnson Vice President and Disease Area Leader, Bladder Cancer Christopher Cutie, MD, in a news release about the results.⁵

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, overall survival, safety, and tolerability. For cohort 4, the primary end point was DFS, and secondary end points included safety, tolerability, and health-related quality of life.

Cohort 4 comprised 52 patients with a median age of 71.0 years (range, 42-88 years). The majority (71.2%) were male and White (86.5%). Most of the cohort (94.2%) had an ECOG performance status of 0. Ta disease was more prevalent in patients (59.6%) than T1 disease (40.4%). The median total doses of prior BCG was 12 (range, 8-45 doses), and median time from last BCG dose to high-grade papillary disease diagnosis was 2.8 months (range, 0.3-9.9 months). Regarding radical cystectomy, 82.4% declined the procedure and 17.6% were ineligible for it.

At a median follow-up of 15.9 months (range, 4-20 months), the median DFS was not reached (95% CI, not evaluable [NE]-NE). DFS rate was 85.3% at 6 months (95% CI, 71.6-92.7), 74.3% at 12 months (95% CI, 59.2-84.6), and 69.2% at 18 months (95% CI, 53.4-80.6). When stratified by tumor stage, DFS for patients with high-grade Ta disease was 85.7% at 6 months (95% CI, 66.3-94.4) and 74.8% at 12 months (95% CI, 54.3-87.1). DFS for patients with T1 disease was 84.7% at 6 months (95% CI, 59.7-94.8) and 74.1% at 12 months (95% CI, 48.5-88.3).

Twelve-month progression-free and overall survival were both high at 95.6% (95% CI, 83.5-98.9) and 98.0% (95% CI, 86.6-99.7), respectively. Out of the 52-patient cohort, only 1 patient progressed to muscle-invasive bladder cancer. Four (7.7%) patients received a radical cystectomy; the cystectomy-free rate was 93.8% at 12 months (95% CI, 81.9-97.9) and 91.0% at 18 months (95% CI, 77.5-96.6).

Daneshmand also outlined safety outcomes for the cohort. The majority of treatment-emergent adverse events (AEs) were grade 1 or 2, most of which resolved after a median of 3.3 weeks. Three (5.8%) patients had 1 or more serious treatment-related AEs, and 4 (7.7%) discontinued treatment as a result of treatment-related AEs. There were no treatment-related deaths. Success rate for insertion of the gemcitabine intravesical system was 99.8% (419/420).

Regarding health-related quality of life, the investigators assessed patients using the EORTC QLQ-C30: Global Health Status and EORTC QLQ-C30: Physical Functioning measures. Daneshmand reported that quality of life was maintained in the cohort.

“In conclusion, [gemcitabine intravesical system] monotherapy demonstrates a very high 12-month disease-free survival rate in BCG-unresponsive, papillary disease only [NMIBC],” Daneshmand said.

Daneshmand also noted that a randomized phase 3 trial, SunRISe-5 (NCT06211764), is comparing the gemcitabine intravesical system vs intravesical chemotherapy in BCG-unresponsive/experienced papillary-only high-risk NMIBC.

REFERENCES

1. Daneshmand S, Cahn D, Zainfeld D, et al. Gemcitabine intravesical system (TAR-200) monotherapy in patients with bacillus Calmette Guérin–unresponsive papillary disease–only high-risk non–muscle-invasive bladder cancer: 1-year disease-free survival results from SunRISe-1. Presented at: Society of Urologic Oncology Annual Meeting; December 2-5, 2025; Phoenix, Arizona. Late-breaking abstract

2. Necchi A, Roumiguié M, Kamat AM, et al. Pembrolizumab monotherapy for high-risk non-muscle-invasive bladder cancer without carcinoma in situ and unresponsive to BCG (KEYNOTE-057): a single-arm, multicentre, phase 2 trial. Lancet Oncol. 2024;25(6):720-730. doi:10.1016/S1470-2045(24)00178-5

3. Boorjian SA, Alemozaffar M, Konety BR, et al. Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial. Lancet Oncol. 2021;22(1):107-117. doi:10.1016/S1470-2045(20)30540-4

4. IL-15 superagonist NAI in BCG-unresponsive non-muscle-invasive bladder cancer. NEJM Evid. 2023;2(1):EVIDoa2200167. doi:10.1056/EVIDoa2200167

5. Johnson & Johnson’s INLEXZO™ (gemcitabine intravesical system) delivers 74 percent disease-free survival at one year in BCG-unresponsive, high-risk, papillary-only NMIBC. News release. Johnson & Johnson. December 5, 2025. Accessed December 6, 2025. https://www.jnj.com/media-center/press-releases/johnson-johnsons-inlexzo-gemcitabine-intravesical-system-delivers-74-percent-disease-free-survival-at-one-year-in-bcg-unresponsive-high-risk-papillary-only-nmibc