TAR-200 Produces Unprecedented CR Rates in BCG-Unresponsive, High-Risk NMIBC

TAR-200 in BCG-Unresponsive

NMIBC | Image credit: ©

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TAR-200 monotherapy demonstrated the highest single-agent complete response (CR) rate reported to date in patients with BCG-unresponsive, high-risk non–muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary disease, according to data from the phase 2b SunRISe-1 study (NCT04640623) presented during the 2025 American Urological Association Annual Meeting.1

Data from cohort 2 (n = 85) of SunRISe-1 showed that patients with BCG-unresponsive, high-risk NMIBC with CIS with or without papillary disease who received TAR-200 achieved an overall CR rate of 82.4% (95% CI, 72.6%-89.8%). The 12-month CR rate was 45.9%. The Kaplan-Meier–estimated 12- and 24-month CR rates were 52.4% (95% CI, 40.7%-62.8%) and 44.7% (95% CI, 33.1%-55.7%), respectively. The median time to onset of CR was 2.8 months (range, 2.1-8.3) and 95.7% (n = 67/70) of patients achieved a CR within the first 3 months. The CR rate was consistent across patient subgroups.

“The standard of care for [patients with] BCG-unresponsive, high-risk NMIBC is radical cystectomy,” Joseph Jacob, MD, MCR, an associate professor of urology at Upstate University Hospital in Syracuse, New York, said during the presentation. “Radical cystectomy is a life changing operation with considerable morbidity and up to an 8% 90-day mortality rate. Unfortunately, many patients are unable or unwilling to undergo radical cystectomy. There are limited FDA-approved treatment options in patients with BCG-unresponsive, high-risk NMIBC.”

TAR-200 is a novel drug releasing system that employs an intravesical drug releasing application which provides sustained delivery of gemcitabine in the bladder. In December 2023, TAR-200 received breakthrough therapy designation from the FDA for the treatment of adult patients with BCG-unresponsive, high-risk NMIBC who are ineligible for or have declined radical cystectomy.2 Then in January 2025, a new drug application (NDA) was submitted to the FDA seeking the approval of the agent for the treatment of patients with BCG-unresponsive, high-risk NMIBC with CIS, regardless of the presence of papillary tumors.3

Diving Into the Design of SunRISe-1

Cohorts 1,2, and 3 of SunRISe-1 enrolled adult patients with histologically confirmed high-risk NMIBC with CIS with or without papillary disease with an ECOG performance status of 2 or less.1 Patients were also required to have persistent or recurrent disease within 12 months of completion of BCG therapy and be unresponsive to BCG therapy with no plans to undergo a radical cystectomy. Cohort 4 consisted of patients with papillary-only high-risk NMIBC without CIS.

In cohort 1, patients received TAR-200 in combination with cetrelimab and those in cohorts 2 and 3 received TAR-200 or cetrelimab monotherapy, respectively. Patients in cohort 4 also received TAR-200 monotherapy. TAR-200 was administered once every 3 weeks for the first 24 weeks then every 12 weeks through week 96 of treatment.

In cohorts 1, 2, and 3, the primary end point was overall CR rate. Key secondary end points consisted of duration of response (DOR), overall survival, safety, tolerability, and health-related quality of life (HRQOL). In cohort 4, the primary end point was disease-free survival.

At baseline, the median age in cohort 2 was 71.0 years (range, 40-88). Most patients were male (80.0%), White (87.1%), former nicotine users (58.8%), had an ECOG performance status of 0 (91.8%), and had CIS-only disease (67.1%). The median number of prior doses of BCG was 12 (range, 7-42) and the median time from last receipt of BCG to CIS diagnosis was 3.2 months (range, 0-22).

Additional Data and Safety Findings

Additional findings from SunRISe-1 displayed that the median DOR was 25.8 months (95% CI, 8.3-not evaluable). High-risk NMIBC recurrence was observed in 32.9% of responders and 5.7% experienced at least T2 disease progression. The 12-month cystectomy-free rate was 86.6% (95% CI, 76.6%-92.6%). The estimated 12- and 24-month DOR probabilities were 56.2% (95% CI, 43.4%-67.1%) and 51.8% (95% Ci, 38.7%-63.4%), resepectively. The 12-month DOR rate was 52.9% and 47.1% of responses were ongoing at the data cutoff.

In terms of safety, most treatment-emergent adverse effects (TEAEs) in cohort 2 were grade 1 or 2 and resolved after a median of 3.1 weeks. Five patients experienced at least 1 serious treatment-related adverse effect (TRAE) and 3.5% of patients discontinued TAR-200 monotherapy due to TRAEs. There were no treatment-related deaths.

Any-grade and grade 3 or higher TRAEs occurred at rates of 83.5% and 12.9%, respectively. The most common any-grade TRAEs included pollakiuria (43.5%), dysuria (40.0%), and micturition urgency (24.7%). Grade 3 or higher TRAEs consisted of urinary tract pain (4.7%), bladder pain (2.4%), and urinary tract infection (1.2%).

“HRQOL remained high [during] TAR-200 treatment and TAR-200 monotherapy was well tolerated with rare serious TRAEs and treatment discontinuation,” Jacob said in conclusion. “TAR-200 is under review by the FDA following the submission of a NDA.”

Disclosures: Jacob reported receiving consulting fees and serving as an advisory board member for Janssen, Aura Biosciences, and Pfizer.

References

1. Jacob JM, Guerrero-Ramos F, Necchi A, 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 outcomes from SunRISe-1. Presented at: American Urological Association Annual Congress; April 26-29, 2025; Las Vegas, NV. P2s.
2. 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 April 26, 2025. 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
3. New drug application initiated with US FDA for TAR-200, the first and only intravesical drug releasing system for patients with BCG-unresponsive high-risk non-muscle-invasive bladder cancer. News release. Johnson & Johnson. January 15, 2025. Accessed April 26, 2025. https://www.investor.jnj.com/news/news-details/2025/New-Drug-Application-initiated-with-U.S.-FDA-for-TAR-200-the-first-and-only-intravesical-drug-releasing-system-for-patients-with-BCG-unresponsive-high-risk-non-muscle-invasive-bladder-cancer/default.aspx