Monotherapy with a gemcitabine intravesical system (TAR-200; Gem-iDRS) demonstrated high disease-free survival rates in patients with bacillus Calmette-Guérin (BCG)-unresponsive papillary-only high-risk non–muscle-invasive bladder cancer (NMIBC), according to data presented at the 26th Annual Meeting of the Society of Urologic Oncology (SUO).¹

Findings from the SunRISe-1 trial showed that TAR-200 appears to be safe and active, signaling a step forward for papillary-only disease (Ta or T1) in BCG-unresponsive NMIBC. These results highlight a potential new treatment option for a patient population facing limited alternatives beyond radical cystectomy, the authors emphasized.

“I don’t think we’ve seen these types of high recurrence-free survival rates and disease-free survival rates at 1 and 1.5 years,” said lead study author Siamak Daneshmand, MD, of the University of Southern California, Los Angeles. “Looking at historical data, these are very exciting results.”

As Dr. Daneshmand explained, there remains a substantial unmet need for patients with BCG-unresponsive papillary-only high-risk NMIBC. Approximately 75% of all patients with bladder cancer have NMIBC, and nearly 50% of these are classified as high risk. Disease recurrence or progression with BCG treatment is observed in roughly 50% of high-risk NMIBC cases. For such patients, radical cystectomy is often the standard of care, but it has been associated with high morbidity, significant impact on quality of life, and a 3% to 8% mortality rate.

“Tolerable, effective, and durable bladder-sparing therapies are urgently needed, especially since there are currently no approved treatments specifically for BCG-unresponsive papillary-only high-risk NMIBC,” said Dr. Daneshmand, who noted that historical 12-month disease-free survival or recurrence-free survival rates for investigational treatments in this setting have ranged from 44% to 55%.

Although newer therapies have emerged, most are approved for carcinoma in situ disease, often with or without papillary components, leaving a critical gap for patients with papillary-only disease.

The SunRISe-1 (cohort 4) study evaluated TAR-200 monotherapy. This system delivers gemcitabine continuously into the bladder, with dosing every 3 weeks for the first 24 weeks, followed by quarterly doses up to week 96. The study enrolled patients with papillary-only (no carcinoma in situ) disease, of whom 60% had high-grade Ta disease and 40% had T1 disease, signifying a high-risk population. A total of 80% of patients had declined radical cystectomy, and 18% were ineligible. Patients had received extensive prior BCG treatment, with a median of 12 doses. The primary outcome was disease-free survival.

Disease-Free Survival and Other Outcomes

As Dr. Daneshmand reported, results from SunRISe-1 demonstrated robust efficacy with TAR-200 monotherapy. At a median follow-up of 15.9 months, the median disease-free survival was not reached. The 6-month disease-free survival rate was 85.3%, and the 12-month rate was 74.3%. The 18-month disease-free survival rate was 69.2%.

Efficacy was found to be consistently high across both the high-grade Ta and T1 disease subsets. For patients with high-grade Ta disease, the 12-month disease-free survival rate was 74.8%; the rate was 74.1% among those with T1 disease.

At 12 months, the overall survival rate was 98.0%, with median overall survival not estimable.

The 12-month progression-free survival rate (defined as not advancing to muscle-invasive bladder cancer [MIBC], lymph node or distant disease, or death) was 95.6%, with the median not estimable. Only one case (1.9%) of disease progression to MIBC was observed among the 52 patients, said Dr. Daneshmand. Two deaths (3.8%) were reported, due to renal failure and cardiac arrest, both of which were unrelated to treatment.

The cystectomy-free rate was 93.8% at 12 months and 91.0% at 18 months. Overall, 7.7% of patients (n = 4 of 52) underwent radical cystectomy during the study period.

TAR-200 was reported to be well tolerated, consistent with prior clinical experience. Most treatment-emergent adverse events were of grade 1 or 2, and the majority were seen to resolve quickly, with a median resolution time of 3.3 weeks. Three patients (5.8%) experienced at least one serious treatment-related adverse event, and four patients (7.7%) discontinued treatment because of treatment-emergent adverse events. No treatment-related deaths were reported.

The most frequent treatment-emergent adverse events (any grade) included dysuria (40.4%), pollakiuria (30.8%), micturition urgency (28.8%), and urinary tract infection (26.9%). Grade 3 or higher treatment-emergent adverse events occurred in seven patients (13.5%), primarily bladder pain (3.8%), urinary tract infection (1.9%), pelvic pain (1.9%), and urinary incontinence (1.9%).

Catheter placement was successful in 99.8% of cases, and quality of life was maintained, as measured by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) for both global health status and physical functioning.

Ultimately, said Dr. Daneshmand, the SunRISe-1 results offer significant hope for patients with BCG-unresponsive papillary-only NMIBC.

“The high disease-free survival rates, coupled with favorable safety and quality of life, set a new benchmark for this challenging disease,” Dr. Daneshmand concluded. “The phase III randomized SunRISe-5 study comparing [TAR-200] vs intravesical chemotherapy is fully accrued, and its results are eagerly awaited.”

Future Directions in Papillary-Only NMIBC

In a discussion following the presentation, moderator Patrick Hensley, MD, of the University of Kentucky, Lexington, posed a question to Dr. Daneshmand: “What’s next for papillary-only patients? Are these just signal-finding data, or are they going to be practice-changing data and lead to label change in the future?”

“We definitely do need randomized studies in the future,” Dr. Daneshmand responded. “This is the very beginning of looking at papillary [disease–only NMIBC]. We’ve been concentrating on carcinoma in situ with or without papillary disease for the past 5 years. This is the next era, and what I envision in the future are trials looking at…these agents vs some kind of standard of care.”

“Unfortunately, we often don’t have a standard of care in this setting,” Dr. Daneshmand added, “but thoughtful trials will hopefully answer that question.”

DISCLOSURE: Dr. Daneshmand has received grants/research funding from Photocure; has received consulting/advisory fees from Ferring, Photocure, Protara, UroGen Pharma, Pfizer, CG Oncology, Vesica Health, ImmunityBio, enGene, AstraZeneca, Allergan (immediate family member), Bristol Myers Squibb, Johnson & Johnson, Olympus, Pacific Edge, and TARIS; has received travel reimbursement from Photocure, Ferring, and Johnson & Johnson; and has stock/other ownership interests in TARIS. For full disclosures of all study authors, visit https://suonet.org/meetings/.

Reference

1. Daneshmand S, Cahn D, Zainfeld D, et al: Gemcitabine intravesical system (Gem-iDRS) monotherapy in patients with bacillus Calmette-Guérin–unresponsive papillary disease–only high-risk non–muscle-invasive bladder cancer: 1-year disease-free survival results from SunRISe-1. 26th Annual Meeting of the Society of Urologic Oncology. Presented December 5, 2025.