Intravesical TAR-200 device yields 82% complete regression rate in bladder cancer

The results of the phase IIb SunRISe-1 study published in the Journal of Clinical Oncology showed that the TAR-200 mini device (intravesical “pretzel capsule”) with slow release of gemcitabine provided 82.4% complete responses in patients with BCG-resistant high-risk non-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS). The responses were durable: the median duration of response was ≈25.8 months; most patients managed to avoid radical cystectomy within 1–2 years.

Background

What is already approved in the US for BCG-unresponsive HR-NMIBC (CIS ± papillary tumors).

1. Pembrolizumab (systemic, 2020) - for patients not suitable for cystectomy.
2. Nadofaragene firadenovec (ADSTILADRIN) - gene therapy (adenovector IFN-α2b), intravesically once every 3 months.
3. Nogapendekin alfa inbakicept (ANKTIVA, IL-15 agonist) + BCG - intravesically.

These options expanded the organ-preserving arsenal and set benchmarks for end points (frequency and duration of complete response).

• Why is there interest in long-term local chemotherapy? In the context of periodic BCG deficiencies and heterogeneity of responses, attention has increased to intravesical chemotherapy and drug delivery “long and smooth”. Hence, the development of controlled release systems (including with gemcitabine) as a way to maintain high local exposure with minimal systemic toxicity.
• What is TAR-200? It is a pretzel-shaped intravesical drug platform containing gemcitabine mini-tablets; it is administered via a catheter in an outpatient setting, then releases the drug uniformly in the bladder for up to 3 weeks (osmotic mechanism). Early studies have shown technical feasibility and acceptable safety.
• Where is SunRISe-1. This is a phase IIb study in patients with BCG-unresponsive HR-NMIBC with CIS. The new JCO publication reports a very high complete response rate (≈82%) and a median response duration of ~25.8 months with good tolerability - one of the best "bladder-preserving" results in this niche to date.
• How does this compare to current guidelines? Both the AUA and EAU emphasize that in BCG-unresponsive HR-NMIBC, cystectomy remains the standard with the lowest risk of progression; however, for those willing/unwilling to undergo surgery, organ-preserving options are available in approved regimens or clinical trials. The emergence of robust data on TAR-200 potentially expands the pool of such options.
• Regulatory and research context. Since 2018, the FDA has formalized endpoints for this category (CR and its stability in given windows), allowing approvals to be obtained on the basis of single-round studies. Against this background, TAR-200 has already been submitted to the FDA for review; in parallel, phase III studies are underway (e.g. SunRISe-3 in BCG-naïve HR-NMIBC: TAR-200 ± anti-PD-1 cetrelimab).
• Why is the “durability” of the response and bladder retention important? For patients, the key outcomes are organ preservation and disease control without progression/cystectomy. Therefore, TAR-200 publications separately emphasize the proportions without cystectomy at 12 and 24 months (≈87% and 76%) - this translates a high CR into a practical gain in quality of life.
• Remaining questions: Direct comparisons with other approved options (ADSTILADRIN; ANKTIVA+BCG; systemic pembrolizumab), real-world data, as well as economic evaluation (frequency of manipulations, cost of device/service procedures) and clarity on how TAR-200 will fit into BCG shortages/logistics in health systems are needed.

What did they come up with?

The TAR-200 is a small, pretzel-shaped drug platform that a urologist inserts into the bladder through a catheter in an outpatient setting. Inside are mini-tablets of gemcitabine; the device releases the drug evenly over up to 3 weeks, providing high local concentrations and minimal systemic “background.” In SunRISe-1, it was administered every 3 weeks for the first 24 weeks, then every 12 weeks until week 96.

Who was treated and what were the results?

The key analysis concerns cohort 2: patients with CIS (± papillary tumors) who had previously failed to respond to BCG and were not undergoing immediate cystectomy.

• Complete response (CR) – 82.4% (95% CI ~73–90%).
• Durability: Median duration of response was 25.8 months; Kaplan-Meier estimates showed significant response rates at 12 and 24 months.
• Bladder preservation: 86.6% without cystectomy at 12 months and 75.5% at 24 months.
• Safety: Mainly local urologic symptoms; serious adverse events occurred in ~6% of cases in cohort 2.

Why is this important?

The standard “back-up” option for BCG-resistant NMIBC remains radical cystectomy, a major operation with a significant impact on quality of life. In recent years, bladder-sparing options have emerged (gene therapy nadofaragene firadenovec/Adstiladrin, the immunotherapy ANKTIVA (N-803) + BCG), but their complete responses are usually below 80%. Against this background, TAR-200 stands out due to its high CR rate as monotherapy and the potential to reduce the number of cystectomies.

How it works "in life"

The idea is simple: instead of weekly instillations, there is a long-term “micro-pump” directly in the bladder cavity. This is:

• Simplifies logistics (less frequent visits, stable exposure),
• Increases local dose without systemic toxicity,
• May better "reach" cells in the bladder wall due to prolonged contact. Preclinical and early clinical studies have shown that the device is safely tolerated and provides a controlled 21-day release.

What's next?

Based on these results, the FDA granted priority review to TAR-200 in BCG-resistant HR-NMIBC, with parallel Phase III studies (SunRISe-3/-5), including comparisons with chemotherapy and combinations with anti-PD-1 (cetrelimab). If confirmed, this would provide urologists with a modular “drug insert” as another standard of care for bladder preservation.

Limitations and questions

This is a phase IIb with a focus on the CIS population; some of the numbers (e.g., duration of response) are based on still maturing curves and will require verification in phase III and registries. It is also important to understand how TAR-200 works in BCG deficiency (as ANKTIVA requires combination with BCG) and where the device fits optimally among the already approved Adstiladrin and ANKTIVA+BCG in terms of availability, cost, and patient preference.

Source: Daneshmand S. TAR-200 for BCG-Unresponsive High-Risk Non–Muscle-Invasive Bladder Cancer: Results From the Phase IIb SunRISe-1 Study. Journal of Clinical Oncology (accepted 24 July 2025; online publication). doi: 10.1200/JCO-25-01651.