New Drug Application initiated with FDA for TAR-200 for NMIBC

Johnson & Johnson has initiated the submission of a new drug application (NDA) with the FDA to support regulatory approval of TAR-200 for patients with BCG-unresponsive high-risk non–muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors, the company announced in a news release.¹

The complete response rate at any time point was 83.5%.

The application is being submitted through the FDA’s Real-Time Oncology Review program, which enables the agency to review data in the submission before the full application is complete. The FDA previously granted TAR-200 a breakthrough therapy designation in December 2023 for the treatment of patients with BCG-unresponsive high-risk NMIBC with CIS who are ineligible for or have elected to not undergo radical cystectomy.

"Upon approval, TAR-200 promises to be a meaningful additional treatment option for certain patients with NMIBC, addressing a critical need for people who have had relatively limited therapeutic alternatives. Many patients face life-altering surgical options such as radical cystectomy, which is complete bladder removal," said Yusri Elsayed, MD, MHSc, PhD, global therapeutic head of oncology at Johnson & Johnson Innovative Medicine, in the 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."

The NDA is supported by data from cohort 2 of the phase 2b SunRISe-1 trial (NCT04640623), which was presented at the European Society for Medical Oncology (ESMO) 2024 Congress in Barcelona, Spain.² Cohort 2 in the trial assessed TAR-200 as a monotherapy in patients with BCG-unresponsive high-risk NMIBC.

Overall, the complete response rate among the 85 patients enrolled in cohort 2 was 83.5% (95% CI, 74%-91%) per central assessment and 85.9% per investigator assessment. At a median follow-up of 9 months, 82% of patients remained in complete response. The estimated complete response rate at 12 months was 57.4% per Kaplan-Meier estimate.

Updated data on the safety and tolerability of TAR-200 monotherapy were presented at the Society of Urologic Oncology 25th Annual Meeting in Dallas, Texas.³

A total of 71 (83.5%) patients reported treatment-related adverse events (TRAEs), most of which were grade 1-2 lower urinary tract symptoms.

The median duration of all TRAEs that recovered/resolved was 22 days (IQR, 8-112). Eight (9.4%) patients had grade 3-4 TRAEs, and 5 (5.9%) patients had serious TRAEs. Five (6%) patients had TRAEs that resulted in discontinuation of TAR-200 treatment. These TRAEs included noninfective cystitis, pollakiuria, and urinary retention. There were no treatment-related deaths.

Overall, the open-label SunRISe-1 trial is assessing the safety and efficacy of TAR-200 in combination with cetrelimab (cohort 1), TAR-200 monotherapy (cohort 2), and cetrelimab monotherapy (cohort 3). There was also a fourth cohort of approximately 50 patients with papillary-only high-risk NMIBC who were treated with TAR-200 monotherapy.

Cohort 2 in the trial enrolled adult patients with histologically confirmed CIS with or without papillary disease. Patients also needed to have an ECOG performance status of 0 to 2, persistent or recurrent disease within 12 months of the completion of BCG, and were unresponsive to BCG and not receiving radical cystectomy.

The median age of patients in cohort 2 was 71 years (range, 40-88 years), and the majority of patients were male (80%) and White (72.9%). Fifty-seven (67.1%) patients had CIS only, whereas 28 (32.9%) had CIS plus papillary disease. The median total doses of prior BCG was 12 (range, 7-42), and the median time from last BCG to CIS diagnosis was 3.4 months (range, 0-22 months).

The primary end point in cohort 2 was complete response rate at any time point. Key secondary end points included duration of response, overall survival, pharmacokinetics, quality of life, safety, and tolerability.

References

1. 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. News release. Johnson & Johnson. Published online and accessed January 15, 2025. https://www.jnj.com/media-center/press-releases/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

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). Presented at: 2024 European Society for Medical Oncology Congress. Barcelona, Spain. September 13-17, 2024. Abstract LBA85. Accessed January 15, 2025. https://s3.eu-central-1.amazonaws.com/m-anage.com.storage.esmo/static/esmo2024_abstracts/LBA85.html.pdf

3. Daneshmand S, Zainfeld D, Pieczonka C, et al. Safety and tolerability of TAR-200 monotherapy in patients with bacillus Calmette–Guérin (BCG)-unresponsive high-risk non–muscle-invasive bladder cancer (HR NMIBC) in SunRISe-1. Presented at: Society of Urologic Oncology 25th Annual Meeting. December 4-6, 2024. Dallas, Texas. Abstract 135. Accessed January 15, 2025. https://suo-abstracts.secure-platform.com/a/gallery/rounds/21/details/3800