FDA Approval Is Sought for TAR-200 in BCG-Unresponsive High-Risk NMIBC With CIS

An original new drug application (NDA) has been submitted to the FDA seeking the approval of the intravesical drug-releasing system TAR-200 for the treatment of patients with Bacillus Calmette-Guérin (BCG)–unresponsive high-risk non–muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without papillary tumors.¹

The NDA submission was supported by findings from the TAR-200 monotherapy cohort (n = 85) of the phase 2b SunRISE-1 trial (NCT04640623), findings from which were presented at the 2024 ESMO Congress. At a data cutoff date of May 13, 2024, treatment with TAR-200 monotherapy elicited an 83.5% (95% CI, 73.9%-90.7%) complete response (CR) rate in patients with high-risk NMIBC with CIS with or without papillary disease.² The estimated 12-month CR and duration of response (DOR) rates were 57.4% (95% CI, 40.6%-71.0%) and 65.7% (95% CI, 45.2%-80.1%), respectively. At a median follow-up of 9.2 months (range, 3.7-36.6), 81.6% of responders were still in response.

“Upon approval, TAR-200 promises to be a meaningful additional treatment option for certain patients with NMIBC, addressing a critical need for [patients] who have had relatively limited therapeutic alternatives. Many patients face life-altering surgical options, such as radical cystectomy, which is complete bladder removal,” Yusri Elsayed, MD, MHSc, PhD, global therapeutic head of Oncology at Johnson & Johnson Innovative Medicine, stated in a news release.¹ “By combining our expertise in innovative medicine and medical devices, Johnson & Johnson is uniquely positioned to transform how we treat certain types of bladder cancer through the first and only intravesical drug-releasing system for this disease. We look forward to working with the FDA in review of this application.”

SunRIse-1 enrolled patients at least 18 years of age with histologically confirmed high-risk NMIBC with CIS with or without papillary disease.² Patients needed to have an ECOG performance status of 0 to 2, have persistent or recurrent disease within 12 months of BCG completion, and be unresponsive to BCG and not receiving radical cystectomy. Patients in this population were randomly assigned to receive TAR-200 plus cetrelimab (cohort 1; n = 53), TAR-200 monotherapy (cohort 2), or cetrelimab monotherapy (cohort 3; n = 28). Enrollment to cohort 2 was completed; cohorts 1 and 3 were closed. Data from cohorts 1, 2, and 3 were presented at the 2024 ESMO Congress.

A secondary population of patients with papillary-only high-risk NMIBC with no CIS (n = 52) received TAR-200 monotherapy (cohort 4). Enrollment to this cohort has been completed.

All patients received indwelling TAR-200 every 3 weeks for the first 24 weeks, then every 12 weeks through week 96.

For cohorts 1 through 3, the primary end point was overall CR rate. Key secondary end points included DOR, overall survival, safety, and tolerability. For cohort 4, the primary end point is disease-free survival rate at 12 months.

The most common any-grade treatment-related adverse effects (TRAEs) observed in cohort 2 were pollakiuria (38.8%), dysuria (35.3%), urinary tract infection (UTI; 20.0%), hematuria (14.1%), and pruritus (1.2%). Grade 3 or higher TRAEs were reported in 9.4% of patients in cohort 2 and included urinary tract pain (3.5%) and UTI (1.2%). Serious TRAEs occurred in 5.9% of patients in this cohort, and 5.9% of patients experienced TRAEs leading to treatment discontinuation. No treatment-related deaths occurred.

Previously, in December 2023, TAR-200 received breakthrough therapy designation from the FDA for the treatment of adult patients with BCG-unresponsive high-risk NMIBC with CIS who are ineligible for or have declined radical cystectomy.³

References

1. 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 January 15, 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
2. van der Heijden MS, Simone G, Boegemann 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): S1272-S1273. doi:10.1016/j.annonc.2024.08.2329
3. 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 15, 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