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CHICAGO -- An investigational intravesical delivery system designed to provide sustained local release of gemcitabine into the bladder produced high rates of complete response (CR) in difficult-to-treat non-muscle-invasive bladder cancer (NMIBC), data from an ongoing phase IIb study showed.

Preliminary results from the trial demonstrated that monotherapy with the novel treatment, dubbed TAR-200, led to CRs in 16 of 22 patients (72.7%, 95% CI 49.8-89.3) with bacillus Calmette-Guérin (BCG)-unresponsive, high-risk NMIBC, reported Siamak Daneshmand, MD, of the Keck School of Medicine of the University of Southern California in Los Angeles.

After a median follow-up of 10.6 months, 15 of these CRs were ongoing, with six patients maintaining their response beyond 12 months; none had documented recurrence or progression, according to his presentation at the annual meeting of the American Urological Association.

In a second cohort of the study, involving a similar group of NMIBC patients, eight of 21 achieved a CR (38.1%, 95% CI 18.1-61.6) with the investigational PD-1 inhibitor cetrelimab alone. Data were immature for a third cohort testing TAR-200 and cetrelimab in combination.

"The first efficacy and safety data from SunRISe-1 support the ongoing investigation of TAR-200 with or without cetrelimab in patients with BCG-unresponsive disease, as well as BCG-naive high-risk NMIBC," said Daneshmand.

Most patients with high-risk NMIBC who are treated with intravesical BCG do not experience sustained remissions, he noted, with up to 60% experiencing recurrence or progression within the first year, and up to 80% within 5 years. While the standard of care for patients with BCG-unresponsive NMIBC is radical cystectomy, many are ineligible for treatment or are unwilling to undergo the procedure.

"There is still a high unmet need in this patient population," he said.

is a small, flexible, pretzel-shaped silicone tube that contains gemcitabine. Implanted into the bladder, the device is designed to release the chemotherapy over a 3-week period. Previous studies have shown that continuous low-dose intravesical gemcitabine inhibits muscle-invasive bladder tumors in a concentration-dependent manner.

By delivering a significantly lower dose of the cytotoxic agent, TAR-200 is designed to limit systemic exposure and reduce bladder toxicity compared with standard intravesical administration.

Patients in the TAR-200 arm had a median age of 72 years, and 83% were men, while those in the cetrelimab arm had a median age of 70, and 79% were men. Most patients in each group (about 96%) had an ECOG performance status of 0. In the TAR-200 cohort, 70% had carcinoma in situ (CIS) and 30% had CIS plus papillary disease. In the cetrelimab cohort, those rates were 65% and 35%, respectively.

TAR-200 dosing occurred every 3 weeks for the first 24 weeks, then every 12 weeks through week 96. Cetrelimab was dosed through week 78.

Adverse events (AEs) in the cohorts were as expected, Daneshmand said, and one treatment-related serious AE (SAE) was reported in each group. Two patients (8.7%) discontinued TAR-200 and one discontinued cetrelimab due to treatment-related AEs -- no new safety signals were seen with the PD-1 inhibitor.

TAR-200 is "well tolerated" and associated with low-grade events, he said, with most involving irritation during voiding, typical of any treatment inside the bladder. Specifically, the most frequent AEs of any grade were micturition urgency (34.8%), pollakiuria (34.8%), dysuria (26.1%), non-infective cystitis (21.7%), and urinary tract infections (21.7%).

"I've put a lot of these devices in," Daneshmand said. "I speak from experience, and the SAEs and the grade 3 or higher AEs are rather infrequent with this treatment."

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