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Intravesical Therapy with a TAR-200 Gem-stuffed Pretzel

Non-muscle invasive bladder cancer (NMIBC) has a long history of intravesical therapies. Intravesical treatments range from Bacillus Calmette-Guerin (BCG), valarubicin, gemcitabine/docetaxel, nadofaragene firadenovec, and most recently nogapendekin alfa inbakicept, most of which are used for BCG unresponsive NMIBC. Alternatively, intravenous pembrolizumab has FDA approval for BCG unresponsive NMIBC.

Given the convenience for urologists to manage NMIBC with intravesical therapy, with minimization of systemic adverse events, additional efforts are underway to develop more such therapies. Early localized therapy successes have driven the development of additional intravesical therapies, with consideration to extend beyond non-muscle invasive to muscle-invasive bladder cancer.

The ”pretzel” is an informal name for the TAR-200 device. The delivery system is a pretzel-shaped device inserted via urinary catheter into the bladder. It then floats in the bladder and releases pellets with gemcitabine (gem). This leads to longer dwell time inside the bladder, approximating seven days, while standard intravesical therapy remains in the bladder for approximately an hour. Importantly, there are no detectable plasma levels of gemcitabine after treatment with TAR-200.

Recently, the SunRISe-1 open-label, multicenter, phase 2b trial randomized patients with BCG-unresponsive high-risk NMIBC to TAR-200 with or without cetrelimab or cetrelimab monotherapy.1 The overall complete response (CR) rate at 3 months was impressive for TAR-200 monotherapy at 83.5%, while TAR-200 plus cetrelimab was 67.9%, and cetrelimab monotherapy was 46.4%. The estimated 12-month CR rate was 57.4% for TAR-200 monotherapy at the ESMO 2024 presentation. The treatment was tolerable, with low discontinuation rates: 6% with TAR-200 monotherapy, 7% with cetrelimab alone, but 26% TAR-200 and 23% cetrelimab in the combination arm. The most common adverse events in the TAR-200 arms were pollakiuria, dysuria, hematuria, and urinary tract infection.

The most recent updates at the 2025 American Urological Association (AUA) meeting last month saw two separate oral presentations on the phase 2b SunRISE-1 study. The first was 1-year durability data from the TAR-200 monotherapy cohort 2 of the trial with 85 patients.2 This cohort was with BCG-unresponsive high-risk NMIBC with carcinoma in situ +/- papillary disease. There was an 82.4% overall CR rate, while the 12-month observed overall CR rate was 45.9%, with a Kaplan-Meier estimated overall CR rate of 52.4%. The other presentation from the phase 2b SunRISE-1 trial at the AUA meeting was focused on Cohort 4, a high-risk papillary disease-only 52 patient cohort.3 Inclusive of both high-grade Ta and T1 disease, disease-free survival rates at 6 and 9 months were 85.3% and 81.1%, respectively.

An even earlier disease state trial is SunRISe-3 (NCT05714202), which is evaluating the BCG-naïve, high-risk NMIBC setting. This trial is also a randomized phase 3 trial evaluating TAR-200 alone or in combination with cetrelimab versus BCG. It is fully accrued, and results are pending.

Other studies with TAR-200 have been conducted in patients with muscle-invasive bladder cancer. In particular, the interim analysis of the SunRISe-4 phase 2 trial (NCT04919512), evaluating TAR-200 in combination with cetrelimab vs. cetrelimab alone in patients who are ineligible for or refusing platinum-based neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma of the bladder, revealed a pathologic CR rate of 42% (95% CI 28-56%) versus 23% (95% CI 10-41%), respectively.4 The results of the secondary endpoint of recurrence-free survival are still pending. Unfortunately, the SunRISe-2 randomized phase 3 trial (NCT04658862) was halted after an Independent Data Monitoring Committee recommendation after a pre-specified interim analysis did not appear to show superiority for TAR-200 with cetrelimab over chemoradiation in patients who were not intending to undergo radical cystectomy.5

There are still ongoing trials with TAR-200 that are actively accruing, particularly in the NMIBC disease state. We should focus our attention to completing accrual to these trials, as the early results with TAR-200 look promising for our patients.

Trials for Patients with TAR-200:

  • Pre-approval expanded access study for TAR-200 (NCT06877676)
  • SunRISe-5: TAR-200 vs. investigators’ choice intravesical chemotherapy in recurrence high-risk non-muscle invasive bladder cancer after BCG (NCT06211764)
Written by: Evan Yu, MD, Section Head of Cancer Medicine in the Clinical Research Division at Fred Hutchinson Cancer Center. He also serves as the Medical Director of Clinical Research Support at the Fred Hutchinson Cancer Research Consortium and is a Professor of Medicine in the Division of Oncology and Department of Medicine at the University of Washington School of Medicine in Seattle, WA

References:

  1. Van der Heijden M, et al. TAR-200 +/- cetrelimab (CET) and CET alone in patients (pts) with bacillus Calmette-Guérin-unresponsive (BCG UR) high-risk non-muscle-invasive bladder cancer (HR NMIBC): Updated results from SunRISe-1 (SR-1). Ann Oncol (2024) 35 (suppl_2): 1-72. LBA85.
  2. Jacob J, et al. TAR-200 monotherapy in patients with bacillus Calmette-Guerin-unresponsive high-risk non-muscle-invasive bladder cancer carcinoma in situ: 1-year durability and patient-reported outcome. American Urological Association 2025 Annual Meeting. Oral presentation P2s.
  3. Guerrero-Ramos F, et al. TAR-200 monotherapy in patients with bacillus Calmette-Guerin-unresponsive papillary disease- only high-risk non-muscle-invasive bladder cancer: first results from Cohort 4 of SunRISe-1. American Urological Association 2025 Annual Meeting. Oral presentation P2s.
  4. Necchi A, et al. TAR-200 plus cetrelimab (CET) or CET alone as neoadjuvant therapy in patients (pts) with muscle-invasive bladder cancer (MIBC) who are ineligible for or refuse neoadjuvant cisplatin-based chemotherapy (NAC): Interim analysis of SunRISe-4 (SR-4). Ann Oncol (2024) 35 (suppl_2): 1-72. LBA84.
  5. Johnson & Johnson. (2024) Johnson & Johnson Statement on the SunRISe-2 Study [Press Release]. https://www.jnj.com/media-center/press-releases/johnson-johnson-statement-on-the-sunrise-2-study.