Detalimogene Exhibits Improved Response Rate in BCG-Unresponsive NMIBC

Detalimogene voraplasmid (detalimogene) exhibited improved efficacy among patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary disease, according to a news release from the developer, enGene Holdings.¹

According to preliminary data from the phase 2 LEGEND trial (NCT04752722), which evaluated 62 patients with at least 1 post-baseline disease assessment, the complete response (CR) rate at any point on study was 63% (95% CI, 51%-74%). Additionally, the 3- and 6-month CR rates were 56% (95% CI, 44%-68%) and 62% (95% CI, 46%-76%), respectively, with 4 patients having successfully converted to CR following reinduction. Among the 5 patients who had concluded the 9-month assessment, all experienced a CR.

Additionally, among 125 patients evaluable for safety in cohort 1, treatment-related adverse effects (TRAEs) occurred in 42%. A total of 3 patients experienced grade 3 TRAEs, and no grade 4 or 5 events were reported. Among those 3, no discontinuations due to serious AEs were observed.

Furthermore, a total of 1.6% and 0.8% of patients experienced dose interruptions or discontinuations due to a TRAE. The most common TRAEs included fatigue (16.8%), dysuria (12.0%), bladder spasm (10.4%), micturition urgency (10.4%), and pollakiuria (10.4%).

A protocol amendment for the trial was implemented in the fourth quarter of 2024 to more closely align the phase 2 trial with the American Urological Association’s Guidelines, in addition to the standard of care. Prior to the amendment, the observed CR rate at any time throughout the trial was 55% (95% CI, 38%-71%), with respective 3- and 6-month CR rates of 55% (95% CI, 38%-71%) and 41% (95% CI, 25%-59%).

The developers noted that, prior to the implementation of the protocol amendment, a lower 12-month CR rate was observed with detalimogene compared with other approved agents for BCG-unresponsive NMIBC. However, the preliminary 6-month CR rate exhibited under the new protocol displayed more encouraging results, according to developers.

“We are pleased to report an improved 6-month CR rate for patients being treated with detalimogene under our amended protocol,” Hussein Sweiti, MD, MSc, chief medical officer of enGene Holdings, stated in the news release.¹ “With a competitive preliminary efficacy profile and potential for best-in-class tolerability and ease of use, we believe detalimogene could emerge as the first-line therapy for patients with high-risk, BCG-unresponsive NMIBC.”

Patients in the phase 2 trial were treated for a maximum of four 12-week cycles of drug instillations.² Complete responders following the 4 cycles received up to an additional 4 cycles of maintenance treatment, and if responses were maintained, up to another additional 4 cycles for a maximum of 12 cycles.

In the phase 1 portion of the trial, detalimogene was given via bladder instillation at 50 mL via catheter at a 2-dose regimen at days 1 and 8 or a 4-dose regimen on days 1, 8, 29, and 36. Maintenance treatment in the phase 2 portion of the trial was given as 2 doses per bladder instillation for each 12-week cycle.

The primary end point of the phase 1 portion of the trial was incidence and severity of AEs. In the phase 2 portion of the trial, it was the 48-week cystoscopic CR rate. Secondary end points included dose-limiting toxicities, progression-free survival, CR rate at 12, 24, 36, and 96 weeks, duration of response, and quality of life.

Those eligible for enrollment were classified as BCG-unresponsive––either BCG-naive or incompletely treated––and within 12 months of treatment start, experienced CIS disease. Patients must also have been 18 years or older, had an ECOG performance status of 0, 1, or 2, an absolute neutrophil count of at least 1500 mg/m³, adequate renal function with a creatinine clearance of more than 30 ml per minute, and satisfactory bladder function with the ability to retain a study drug for at least 60 minutes.

“Careful selection of an appropriate bladder-sparing therapy is of utmost importance in creating a long-term strategy to maintain a patient’s disease control and quality of life, while minimizing the logistical burden on patient and practice,” Suzanne Merrill, MD, senior physician, urologic oncologist, and Bladder Cancer Regional Lead at Colorado Urology, stated in the news release.¹ “I am pleased to see the positive trajectory of detalimogene’s efficacy and tolerability data. Combined with its ease of use, detalimogene would be an attractive option to both patient and a busy urology practice.”

References

1. Detalimogene demonstrates improved complete response rate of 62% at 6 months. News release. enGene Holdings. November 11, 2025. Accessed November 11, 2025. https://tinyurl.com/5f73nxda
2. LEGEND study: EG-70 in NMIBC patients BCG-unresponsive and high-risk NMIBC incompletely treated with BCG or BCG-naïve. ClinicalTrials.gov. Updated September 4, 2025. Accessed November 11, 2025. https://tinyurl.com/46hbnnca