SUMMARY: The FDA on September 9, 2025, approved Gemcitabine intravesical system (INLEXZO®) for adults with Bacillus Calmette-Guérin (BCG)-unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC) with Carcinoma in Situ (CIS), with or without papillary tumors. Gemcitabine intravesical system is co-packaged with a urinary catheter and stylet, used for insertion through the urinary catheter into the bladder.
Background
According to the American Cancer Society, it is estimated that 84,870 new cases of bladder cancer will be diagnosed in 2025 and 17,420 will die of the disease. Bladder cancer is the fourth most common cancer in men but is less common in women and the average age at the time of diagnosis is 73 years. With regards to racial predisposition, Caucasians are more likely to be diagnosed with bladder cancer than African Americans or Hispanic Americans.
Approximately 50% of all bladder cancers are non-invasive or in situ cancers. The current standard intervention for superficial bladder cancers-Non-Muscle Invasive Bladder Cancer (NMIBC) involves removing the bladder tumor and intravesical treatment with Bacillus Calmette-Guérin (BCG) immunotherapy, for patients with high-risk Non-Muscle Invasive Bladder Cancer, including those with Carcinoma in Situ, High Grade T1, or large-volume or recurrent Ta tumors, to reduce the risk of recurrence. Although 80% of patients have an initial complete response to BCG, more than half of patients have recurrence and progression within the first year, and develop resistance to BCG.
FDA-approved therapies for BCG-unresponsive carcinoma in situ (CIS) include systemic Pembrolizumab (KEYTRUDA®), intravesical Nadofaragene firadenovec (ADSTILADRIN®), and intravesical Nogapendekin alfa inbakicept (ANKTIVA®) plus BCG. However, these options are constrained by modest Complete Response (CR) rates, limited response durability, immune-related toxicities, procedural burden from repeated catheterizations, and the need for concurrent BCG in some regimens. Moreover, there are no approved therapies specifically indicated for BCG-unresponsive high-risk papillary disease–only NMIBC, highlighting an urgent unmet need for effective, durable, and tolerable bladder-sparing alternatives.
A Novel Intravesical Approach
TAR-200 is an innovative, miniature, pretzel-shaped intravesical drug delivery system engineered to provide continuous local release of Gemcitabine directly into the bladder. The passive, non-resorbable device is placed via catheter in a brief outpatient procedure, without anesthesia, and remains in situ for three weeks. During that time, it slowly releases 225 mg of Gemcitabine before being removed through cystoscopy. This sustained, controlled drug exposure overcomes the short dwell time limitations of conventional intravesical chemotherapy and may enhance local tumor control with reduced systemic exposure.
The SunRISe-1 Trial Design
SunRISe-1 (NCT04640623) is a global, Phase IIb, parallel-cohort study designed to evaluate TAR-200 monotherapy and TAR-200 plus Cetrelimab (an anti–PD-1 antibody) in patients with BCG-unresponsive high-risk NMIBC. Between March 2021 and April 2024, patients were enrolled at 142 sites across 14 countries.
Initially, three cohorts were planned:
- Cohort 1: TAR-200 plus Cetrelimab
- Cohort 2: TAR-200 monotherapy
- Cohort 3: Cetrelimab monotherapy
Based on emerging safety and efficacy data, the protocol was amended in June 2023 to prioritize TAR-200 monotherapy for CIS populations and to expand enrollment in this arm. A fourth cohort was subsequently added to evaluate TAR-200 monotherapy in patients with high-risk papillary disease-only NMIBC, an area with no approved therapies.
Efficacy and Safety Outcomes
The FDA approval of TAR-200 (INLEXZO®) was supported by data from Cohort 2, which included 85 patients with BCG-unresponsive CIS with or without papillary tumors. Eligible patients had histologically confirmed high-grade disease following adequate BCG exposure and an ECOG performance status of 0–2. The median patient age was 71 years, 80% were male, and two-thirds presented with CIS alone. Patients received TAR-200 once every 3 weeks for 6 months, followed by maintenance dosing every 12 weeks through month 24. Tumor assessments were performed via cystoscopy and cytology every 12 weeks, with mandatory biopsies at weeks 24 and 48.
At the data cutoff (March 31, 2025), the overall CR rate was 82.4%, representing the highest single-agent response rate reported in this disease setting. The median Duration of Response (DOR) reached 25.8 months, with estimated 12-month CR and DOR rates of 57.4% and 65.7%, respectively. Median follow-up among responders was 9.2 months.
Treatment was well tolerated, with most adverse events localized and manageable. The most frequent treatment-related events (≥10%) were pollakiuria (35%), dysuria (29%), urinary urgency (15%), and urinary tract infection (15%), consistent with localized bladder irritation rather than systemic toxicity.
Clinical Implications
The results from SunRISe-1 mark a pivotal advance in the management of BCG-unresponsive NMIBC. TAR-200 monotherapy demonstrated durable, high-level intravesical activity without the need for re-induction or systemic immune checkpoint inhibition. Its favorable risk-benefit profile, coupled with the logistical simplicity of outpatient placement, positions TAR-200 as a transformative bladder-sparing therapy for patients ineligible or unwilling to undergo cystectomy.
Unlike conventional intravesical treatments requiring patients to retain fluid instillations for 1–2 hours before voiding, TAR-200 provides continuous, controlled Gemcitabine release over weeks, fundamentally shifting the procedural and pharmacologic paradigm of NMIBC care in the urology clinic.
Conclusion
SunRISe-1 establishes TAR-200 monotherapy (INLEXZO®) as the first intravesical drug-releasing system with proven efficacy and safety in localized bladder cancer. With an 82% CR rate and durable responses extending beyond two years, TAR-200 represents a significant step forward in meeting the long-standing need for effective, tolerable, and durable bladder-sparing therapy in patients with BCG-unresponsive high-risk NMIBC.
TAR-200 for Bacillus Calmette-Guérin–Unresponsive High-Risk Non–Muscle-Invasive Bladder Cancer: Results From the Phase IIb SunRISe-1 Study. Daneshmand S, Van der Heijden MS, Jacob JM, et al. Journal of Clinical Oncology. https://doi.org/10.1200/JCO-25-01651
