LAS VEGAS — Patients with high-risk, treatment-unresponsive non-muscle invasive bladder cancer (NMIBC) had an unprecedented response rate and disease-free survival (DFS) with an investigational intravesical treatment system, data from an ongoing trial showed.

Complete responses (CR) occurred in 82.4% of 85 patients treated with TAR-200, a system that delivers gemcitabine directly into the bladder. The treatment had a rapid onset of action, as almost all responses occurred within 3 months. More than half of the CRs were ongoing at 12 months.

The CR rate was consistent across subgroups including men and women, patients with and without papillary disease, and irrespective of the type of prior Bacille Calmette-Guérin (BCG) treatment, reported Joseph M. Jacob, MD, of Upstate Medical University in Syracuse, New York, at the American Urological Association annual meeting.

“This is the highest response rate reported to date in patients with BCG-unresponsive high-risk non-muscle invasive bladder cancer,” said Jacob. “The responses were durable, with a median duration of response of 25.8 months. Few responders had disease progression, and the 12-month cystectomy-free rate was 86.6%. Overall health status and high physical functioning were maintained during treatment with TAR-200.”

A second report from the ongoing multi-cohort study showed that 81.1% of patients with papillary-only disease remained disease-free at 9 months, and almost all of the patients remained progression-free. After a median follow-up of 12.8 months, all but three of 52 patients had avoided radical cystectomy, reported Félix Guerrero-Ramos, MD, of Hospital Universitario 12 de Octubre in Madrid.

For patients with high-risk BCG-unresponsive NMIBC, radical cystectomy remains standard of care, a “life-changing operation associated with considerable morbidity and impact on quality of life,” Jacob noted. A large proportion of patients are unwilling or unable to undergo the operations; fewer than 20% in one recent study of NMIBC recurrence after BCG. FDA-approved alternatives to cystectomy consistent of pembrolizumab (Keytruda, 41% CR rate), nadofaragene firadenovec (Adstiladrin, 51%), and nogapendekin alfa inbakicept plus BCG (Anktiva, 62%).

TAR-200 consists of a pretzel-shaped silicone device for intravesical delivery of continuous-release low-dose gemcitabine directly into the bladder, associated with reduced systemic exposure and bladder toxicity and improved tolerability. Preliminary clinical data suggested a potential for durable complete responses in a high proportion of patients.

Jacob reported findings from the phase IIb SunRISe-1 study, evaluating single-agent TAR-200 in 85 patients with high-risk NMIBC carcinoma in situ (CIS) with or without papillary disease. The trial includes additional cohorts treated with TAR-200 plus cetrelimab. The primary endpoint is overall CR rate.

The 85 patients had a median age of 71, two-thirds were current or former smokers, one-third had CIS plus papillary disease, and all but three had refused radical cystectomy.

Subsequently, 70 patients attained CRs. High response rates were consistent in men (79.4%) and women (94.1%), patients with CIS only (82.5%), and those with papillary disease (82.1%), and regardless of the strain of prior BCG treatment (87.9% with TICE and 70.4% with non-TICE). A majority of the the responses (37 of 70, 52.9%) lasted 12 months or longer, and 33 of 70 responses (47.1%) were ongoing at last follow-up. Nine of 11 patients who completed 2 years of treatment maintained CRs, and duration of response ranged as high as 44 months.

Treatment-related adverse events (TRAEs) were common but mostly grade 1/2 and resolved after a median of 3.1 weeks. The most common grade ≥3 TRAEs were urinary tract pain (4.7%), bladder pain (2.4%), and urinary tract infection (1.2%). Only three patients discontinued treatment because of TRAEs. Device insertions (n=755) were successful in 99% of attempts.

Worldwide, NMIBC accounts for 75% of the 650,000-plus cases of bladder cancer diagnosed each year, and half of NMIBC has high-risk characteristics, Guerrero-Ramos noted in his introduction. BCG-unresponsive disease represents a high unmet clinical need, but especially those patients with papillary-only disease, which has no approved therapies. The 12-month rates of disease-free and relapse-free survival (DFS, RFS) with investigational therapies under evaluation have ranged from 44-55%.

The 52 patients in the papillary cohort had baseline characteristics similar to the overall patient population. Similar to the mixed-disease cohort, 82% of patients had refused radical cystectomy.

Treatment with TAR-200 achieved a 6-month DFS of 85.3%, declining only slightly to 81.1% at 9 months. Median DFS had yet to be reached. The 9-month DFS was similar in patients with Ta and T1 disease (82.1% and 79.4%, respectively). Progression to muscle-invasive disease occurred in only one patient, and the 9-month overall survival was 98.0%.

Seven patients had grade ≥3 treatment-emergent AEs (TEAE), the most common being bladder pain (3.8%). Four patients discontinued treatment because of TEAEs. Device insertion was successful in 99.5% of 389 attempts.

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