Clinical Summary:

• Design/Population: Cohort 1 of the phase 2 LEGEND trial evaluated detalimogene voraplasmid in patients with Bacillus Calmette-Guérin-unresponsive non-muscle invasive bladder cancer who were either ineligible for or declined cystectomy.
• Key Outcomes: Detalimogene demonstrated durable complete responses with low rates of progression to muscle-invasive disease and a favorable safety profile.
• Clinical Relevance: These findings support detalimogene voraplasmid as a potential bladder-sparing option for patients with heavily pretreated Bacillus Calmette-Guérin-unresponsive non-muscle invasive bladder cancer.

Interim results from cohort 1 of the phase 2 LEGEND study showed that detalimogene voraplasmid, a novel, non-viral investigational intravesical gene therapy, demonstrated encouraging activity and safety among patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer.

These results were presented by Ashish Kamat, MD, MD Anderson Cancer Center, Houston, Texas, at the 2026 American Urological Association (AUA) Annual Meeting in Washington, District of Columbia.

In this study, 125 patients with BCG-unresponsive carcinoma in situ with or without papillary Ta/T1 disease who either declined or were ineligible for cystectomy received 4 intravesical doses of detalimogene voraplasmid (50 mL) at weeks 1, 2, 5, and 6 of each 12-week cycle during the first year of treatment. Patients with persistent or recurrent disease after cycle 1 were eligible for re-induction. Patients achieving complete response transitioned to maintenance treatment for up to 2 years.

Patients underwent quarterly urine cytology and cystoscopy and mandatory templated biopsies at 12-months and as clinically indicated. The primary end point was complete response at any time. Key secondary end points included duration of response, landmark complete response rates, and safety.

At analysis, the rate of complete response any point was 54%, with 43% of patients achieving 6-month complete response. The median time to complete response was 2.1 months and 91% of responses occurred at the first assessment. At the data cutoff point, 96.8% of patients remained free from progression to muscle-invasive disease. 

Treatment-related adverse events were reported in 55.2% of patients, 91.3% of which were grade 1/2. The most common treatment-related adverse events included fatigue (21.6%), dysuria (13.6%), urinary urgency (12.0%), pollakiuria (12.0%), and bladder spasm (11.2%). Grade ≥3 treatment-related adverse events were reported in 4.8% of patients and serious treatment-related adverse events were reported in 1.6% of patients. Treatment-related adverse events led to dose interruptions and discontinuations in 2.4% of patients. 

“The rapid onset of response, non-viral platform, and favorable safety profile support detalimogene voraplasmid as a promising bladder-sparing option in this setting,” concluded Dr Kamat. 

Source:

Kamat AM, Tyson M, Rendon R, et al. A non-viral intravesical gene thereapy for BCG-unresponsive NMIBC with CIS, with or without papillary disease: Pivotal phase 2 interim results of detalimogene voraplasmid. J Urol. Published online: May 1, 2026. doi:10.1097/01.JU.0001192572.07890.f8.04