TAR-200 Receives Breakthrough Therapy Designation From FDA for BCG-Unresponsive High-Risk NMIBC


A breakthrough therapy designation has been granted by the FDA to TAR-200 for the treatment of Bacillus Calmette-Guérin–unresponsive, high-risk non–muscle invasive bladder cancer who are not eligible for or opted not to receive radical cystectomy.

TAR-200 Receives Breakthrough Therapy Designation From FDA for BCG-Unresponsive High-Risk NMIBC

TAR-200 Receives Breakthrough Therapy Designation From FDA for BCG-Unresponsive High-Risk NMIBC

A breakthrough therapy designation has been granted by the FDA for a potential treatment option for Bacillus Calmette-Guérin (BCG)­–unresponsive, high-risk non­–muscle invasive bladder cancer who are not eligible for or opted out of receiving radical cystectomy.1

The designation for TAR-200 is supported by findings from the phase 2b SunRISe-1 trial (NCT04640623) in which TAR-200 elicited durable responses in this population.2 Data from cohort 2 were presented at the 2023 ESMO Congress and indicated that the centrally-assessed complete response (CR) achieved with the monotherapy was 76.7% (95% CI, 57.7%-90.1%) in evaluable patients with high-risk NMIBC with carcinoma in situ (CIS; n = 23). The investigator-assessed CR rate was 80.0% (95% CI, 61.4%-92.3%).

At a median follow-up of 48 weeks (range, 12-121) in responders, the median duration of response (DOR) had not yet been reached (NR). The 6-month Kaplan-Meier estimated DOR rate was 93% (95% CI, 61%-99%), and the estimated rate at 12 months was 84% (95% CI, 49%-96%). At the data cutoff date of August 24, 2023, 21 of 23 responses were ongoing, with 11 and 6 patients experiencing a DOR that lasted for at least 6 or 12 months, respectively.

“TAR-200 represents a novel interventional approach for the treatment of localized bladder cancer where today, unfortunately, options are limited and include antiquated BCG therapy or radical cystectomy,” Kiran Patel, MD, vice president of clinical development in solid tumors at Johnson & Johnson Innovative Medicine, stated in a press release.1 “This breakthrough therapy designation recognizes TAR-200 as a promising advancement and marks an important step forward in our innovative focus to transform the treatment of bladder cancer.”

TAR-200 is a targeted drug delivery system that allows for sustained, controlled release of gemcitabine into the bladder.1,2 The product was designed to address the unmet need in patients with high-risk NMIBC who experience recurrence or disease progression following treatment with BCG.2

The open-label, randomized, phase 2b study enrolled patients with histologically confirmed high-risk NMIBC with CIS, with or without papillary disease. Patients were required to be at least 18 years of age and have an ECOG performance status of 0 to 2. They could not have responded to BCG, nor could they be receiving radical cystectomy.

Approximately 200 participants were randomized 2:1:1 to 1 of 3 cohorts, where they would receive the following: TAR-200 plus cetrelimab (JNJ-63723283; cohort 1), TAR-200 monotherapy (cohort 2), or cetrelimab monotherapy (cohort 3). The trial also has a fourth cohort of patients who have high-risk NMIBC and papillary disease only—no CIS—who are receiving TAR-200 alone. TAR-200 is administered every 3 weeks for the first 24 weeks of treatment and then every 12 weeks through week 96.

For cohorts 1 to 3, overall CR rate represents the trial’s primary end point, and key secondary end points include DOR, overall survival, safety, and tolerability. For cohort 4, the primary end point is disease-free survival.

Data from cohort 2 were shared at the 2023 ESMO Congress. In the 500 total patients, the median age was 71 years (range, 40-85). Most patients were male (77.8%) and White (68.5%) and 55.6% were former smokers. Moreover, 96.3% of patients had an ECOG performance status of 0. Regarding tumor stage, 66.7% had CIS only and 33.3% had CIS and papillary disease. Patients had received a median of 12 total doses of prior BCG, with a range of 7 to 42. The median time from the last BCG treatment received to the diagnosis of CIS was 3.0 months (range, 0.2-22.4). The most common reason for not receiving radical cystectomy was that the patients declined (94.4%); 5.6% were not eligible.

Regarding safety, most adverse effects (AEs) experienced in cohort 2 were grade 1 or 2. Approximately half (53.7%) of patients experienced at least 1 AE that was related to treatment; 1 patient experienced at least 1 serious treatment-related AE (TRAE). Four patients experienced TRAEs that were grade 3 or higher in severity.

The most common AEs included pollakiuria (any grade, 22.2%; grade ≥3, 0%), dysuria (20.4%; 0%), micturition urgency (18.5%; 0%), hematuria (11.1%; 0%), noninfective cystitis (7.4%; 0%), urinary tract pain (5.6%; 1.9%), urinary retention (3.7%; 1.9%), renal impairment (1.9%; 1.9%), and urosepsis (1.9%; 1.9%).

Two patients discontinued treatment due to AEs, and no deaths occurred.

The safety and efficacy of TAR-200 in combination with cetrelimab are being compared with current chemoradiation in patients with muscle-invasive bladder cancer (MIBC) as part of the phase 3 SunRISe-2 study (NCT04658862), and the safety and efficacy of TAR-200 paired with cetrelimab is being compared with cetrelimab alone in this population as part of the phase 2 SunRISE-4 trial (NCT04919512).1 The phase 3 SunRISe-3 study (NCT05714202) is also recruiting patients with BCG-naive, high-risk NMIBC to further evaluate TAR-200 alone or plus cetrelimab compared with intravesical BCG.


  1. Johnson & Johnson’s investigational TAR-200 granted US FDA breakthrough therapy designation for the treatment of high-risk non-muscle-invasive bladder cancer. News release. Johnson & Johnson. December 4, 2023. Accessed January 5, 2024. https://www.jnj.com/johnson-johnsons-investigational-tar-200-granted-u-s-fda-breakthrough-therapy-designation-for-the-treatment-of-high-risk-non-muscle-invasive-bladder-cancer
  2. Necchi A, Jacob JM, Daneshmand S, et al. LBA105 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. Ann Oncol. 2023;34(suppl 2):S1343-S1344. doi:10.1016/j.annonc.2023.10.111
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