FDA Approves TAR-200 in BCG-Unresponsive NMIBC With CIS

The FDA has approved the gemcitabine intravesical system (formerly TAR-200; Inlexzo) for the treatment of adult patients with BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC) with carcinoma in situ, with or without papillary tumors.1

The approval is supported by data from cohort 2 of the phase 2b SunRISe-1 trial (NCT04640623), which showed that patients who received the gemcitabine intravesical system as monotherapy (n = 83) experienced a confirmed complete response (CR) rate of 82% (95% CI, 72%-90%).2 Fifty-one percent of patients remained in CR for at least 1 year.

“When we acquired this novel therapy in 2019, our ambition was to give patients with bladder cancer a renewed sense of hope and belief,” Jennifer Taubert, executive vice president and worldwide chairman of innovative medicine at Johnson & Johnson, stated in a news release.1 "In an area that has seen little progress for more than 40 years, Inlexzo delivers a first-of-its-kind breakthrough innovation with a bright future ahead.”

In July 2025, the FDA granted priority review to a new drug application seeking the approval of the gemcitabine intravesical system for the treatment of patients with BCG-unresponsive, high-risk NMIBC with carcinoma in situ (CIS), with or without papillary tumors.3

SunRISe-1 was a multicenter, open-label, parallel-cohort study that evaluated the gemcitabine intravesical system as monotherapy and in combination with cetrelimab (JNJ-63723283) in patients with BCG-unresponsive high-risk NMIBC.2,4 To be eligible for the study, patients needed to have an ECOG performance status of 0 to 2, adequate organ function, and must have refused or have been ineligible for radical cystectomy.4

Originally, eligible patients were randomly assigned 2:2:1 to receive the gemcitabine intravesical system plus cetrelimab (cohort 1), gemcitabine intravesical system as monotherapy (cohort 2), or cetrelimab monotherapy (cohort 3). However, in June 2023, the development of gemcitabine intravesical system as monotherapy was prioritized in the CIS population, and enrollment in cohorts 1 and 3 was closed based on the more favorable risk-benefit profile reported with the monotherapy in this setting.

In cohort 2, patients received the gemcitabine intravesical system containing 225 mg of gemcitabine, once every 3 weeks through month 6, then once every 12 weeks for up to 18 months.3 Patients continued treatment with the gemcitabine intravesical system for up to 2 years or until unacceptable toxicity, or confirmed high-risk disease persistence, recurrence, or progression.

The primary end point in cohort 2 was centrally assessed CR rate at any time. Secondary end points included duration of response, overall survival, changes from baseline in patient-reported outcomes, and safety and tolerability.

In the safety population (n = 85), the most common any-grade adverse effects (AEs) occurring in more than 15% of patients included urinary frequency (48%), urinary tract infection (44%), dysuria (42%), micturition urgency (34%), decreased hemoglobin levels (31%), increased lipase levels (28%), urinary tract pain (26%), decreased lymphocytes (24%), hematuria (24%), increased creatinine levels (24%), increased potassium levels (22%), increased aspartate aminotransferase levels (17%), decreased sodium levels (16%), bladder irritation (16%), and increased alanine aminotransferase levels (16%).2

Serious AEs occurred in 24% of patients treated with the gemcitabine intravesical system, and fatal AEs were reported in 1.2%. Treatment discontinuation (7%) and interruptions (41%) were also reported.

“I see many patients [who] ultimately become BCG-unresponsive and often face life-altering bladder removal. These patients now may be ideal candidates for newly approved Inlexzo,” Sia Daneshmand, MD, the principal investigator of SunRISe-1, and a professor of urology and director of urologic oncology at the USC Norris Comprehensive Cancer Center and Hospital, University of Southern California Keck School of Medicine, in Los Angeles, added in the news release.1

References

1. U.S. FDA approval of INLEXZO (gemcitabine intravesical system) set to transform how certain bladder cancers are treated. News Release. Johnson & Johnson. September 9, 2025. Accessed September 9, 2025. https://www.multivu.com/johnson-and-johnson/9342851-en-johnson-and-johnson-fda-approval-inlexzo-gemcitabine-intravesical-system
2. Inlexzo. Prescribing information. Johnson & Johnson; 2025. Accessed September 9, 2025. https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/INLEXZO-pi.pdf
3. Johnson & Johnson receives U.S. FDA priority review for TAR-200 NDA in high-risk non-muscle invasive bladder cancer. News release. Johnson & Johnson. July 17, 2025. Accessed September 9, 2025. https://www.jnj.com/media-center/press-releases/johnson-johnson-receives-u-s-fda-priority-review-for-tar-200-nda-in-high-risk-non-muscle-invasive-bladder-cancer
4. Daneshmand S, Van der Heijden MS, 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. Published online July 30, 2025. doi:10.1200/JCO-25-01651