FDA Considers TAR-200 in BCG-Unresponsive High-Risk NMIBC

• The FDA has received a new drug application for TAR-200 for Bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer (HR-NMIBC) with carcinoma in situ (CIS).
• Data from a phase 2b trial (NCT04640623) show an 83.5% complete response rate, with 82% durable at 9 months and low severe adverse events (AEs).
• TAR-200, an intravesical drug system, previously received FDA breakthrough therapy designation in December 2023.

A new drug application has been initiated with the FDA for TAR-200 to treat BCG-unresponsive HR-NMIBC with CIS, with or without papillary tumors.¹ The submission is being reviewed under the FDA's real-time oncology review program.

Data from the phase 2b SunRISe-1 registration study presented at the 2024 European Society of Medical Oncology (ESMO) Annual Meeting support the initiation of this new drug application. An 83.5% complete response rate was observed with TAR-200, with 82% of responses durable at 9 months.

For safety, grade 3 or higher treatment-related adverse events (TRAEs) occurred in 9%, with no treatment-related deaths observed at the time of the data cutoff in May 2024. Additionally, 5 patients (6%) had TRAEs which led to treatment discontinuation.

“Just as important as complete response rate, we want to know that this is also a durable treatment, meaning that patients, when they respond, tend to respond for a long period of time. We want to know how these patients are doing at 1 year, at 18 months, at 24 months, and so that is the next step. It is to show patients that this not only is an effective treatment, but it can be a long-term solution as well,” Joseph M. Jacob, MD, urological oncologist, Department of Urology, Upstate Medical University, Syracuse, New York, told Targeted Oncology^TM in an interview.

TAR-200 is an investigational intravesical drug releasing system which aims to provide sustained local delivery of gemcitabine into the bladder. The agent is placed into the bladder by a healthcare professional using a co-packaged urinary placement catheter in an outpatient setting in under 5 minutes. TAR-200 can be given to patients without the need for anesthesia.

In December 2023, the FDA granted TAR-200 breakthrough therapy designation for the treatment of adult patients with BCG-unresponsive HR-NMIBC with CIS who are ineligible for or have elected not to undergo radical cystectomy.

Bladder cancer with organs and cancerous cells: matthieu - stock.adobe.com

"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, oncology, Johnson & Johnson Innovative Medicine, in a press release. "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."

In the SunRISe-1 trial, a randomized, parallel-assignment, open-label, phase 2b study, investigators evaluated the combination of TAR-200 with cetrelimab vs each agent individually in patients with carcinoma in situ with or without concomitant high-grade Ta or T1 papillary disease.²

TAR-200 was given to patients transurethrally every 3 weeks for the first 24 weeks, then every 12 weeks through 99 weeks. Cetrelimab was dosed every 3 weeks through 78 weeks.

Enrollment was open to patients who were ineligible for or elected not to have radical cystectomy, those who received treatment with adequate BCG therapy, and those with an ECOG performance status of 0, 1, or 2. Patients must not be eligible to participate if they have muscle-invasive or metastatic disease, have received a live virus vaccine within 30 days of study initiation, have active hepatitis B or C infection, or have received prior therapy with an anti–PD-1 or anti–PD-L2 agent.

The primary end points are overall complete response rate and disease-free survival. The secondary end points are duration of response, overall survival, gemcitabine concentrations in urine and plasma, serum concentrations of anti-cetrelimab antibodies, number of patients with anti-cetrelimab antibodies, change from baseline in quality-of-life, and number of patients with AEs.

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. https://tinyurl.com/33ras87k

2. A study of TAR-200 in combination with cetrelimab, TAR-200 alone, or cetrelimab alone in participants with non-muscle invasive bladder cancer (NMIBC) unresponsive to intravesical Bacillus Calmette-Guérin who are ineligible or elected not to undergo radical cystectomy (SunRISe-1). ClinicalTrials.gov. Updated January 10, 2025. Accessed January 15, 2025. https://clinicaltrials.gov/study/NCT04640623