Detalimogene Responses Improve With Longer Follow-Up in BCG-Unresponsive NMIBC Ahead of BLA Submission

Treatment with the non-viral gene therapy detalimogene voraplasmid (EG-70) produced improved complete response (CR) rates and durability with longer follow-up in patients with high-risk, BCG-unresponsive non–muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without concomitant papillary disease, according to updated data from pivotal cohort 1 of the phase 1/2 LEGEND trial (NCT04752722).¹

Following a pre–biologics license application (BLA) meeting with the FDA, enGene Therapeutics reached alignment with the agency on key components of the planned BLA for detalimogene, including the efficacy-evaluable patient population. The company expects to initiate the BLA submission by the end of 2026 and complete it in the first half of 2027. Data from cohort 1 are expected to form the basis of the application.

Updated findings from cohort 1 showed that as of the October 29, 2026, data cutoff, the CR rate at any time was 56% (95% CI, 47%-65%) among efficacy-evaluable patients (n = 120), improving from 54% at the April 2026 data analysis. The landmark 12-month CR rate (n = 110) was 24% (95% CI, 16%-33%), up from 13% in the prior analysis, with 1 patient pending the 12-month landmark assessment. Median follow-up for responders increased from 9.2 months to 12.0 months.

The preliminary Kaplan-Meier estimate of a duration of response (DOR) of at least 12 months, a key secondary end point, was 43% (95% CI, 30%-55%), improving from 25%; 9 patients were pending the 12-month DOR assessment. The median duration of CR was 10.1 months (95% CI, 7.5-not estimable), up from 8.6 months. All patients who entered maintenance and had been assessed for durability had recorded durable responses, and 8 patients in maintenance were pending a durability assessment.

Additionally, 97% of efficacy-evaluable patients were free from progression to muscle-invasive or metastatic disease, defined as T2 or greater disease, as were 100% of responders in the bladder. Overall, 86% of efficacy-evaluable patients and 96% of responders remained free from cystectomy.

Of the patients evaluable for safety in cohort 1 (n = 125), 59% experienced at least 1 treatment-related adverse effect (TRAE), which were mainly grade 1 or 2 in severity. The most common TRAEs were fatigue (21%), dysuria (16%), pollakiuria (16%), bladder spasm (13%), micturition urgency (13%), and urinary tract infection (10%). Grade 3 TRAEs occurred in 4% of patients, serious TRAEs occurred in 2%, and no grade 4 or 5 TRAEs were reported. TRAEs led to dose discontinuation in 1% of patients and dose interruption in 4%.

"For patients with high-risk BCG-unresponsive NMIBC, we need therapies that provide meaningful and durable disease control while minimizing treatment-related toxicity and burden," Ashish M. Kamat, MD, professor of urologic oncology at The University of Texas MD Anderson Cancer Center and primary investigator of the LEGEND trial, stated in a news release. "Combined with its straightforward administration and handling requirements, detalimogene has the potential to become a valuable addition to our bladder-preserving treatment options, particularly in community urology practices where ease of administration and practical considerations can influence treatment selection."

What is the mechanism of action of detalimogene, and how is it being evaluated in the LEGEND trial?

Detalimogene is designed to be instilled into the bladder to elicit a localized antitumor immune response and previously received Regenerative Medicine Advanced Therapy and Fast Track designations from the FDA in this population.^1,2

The open-label, multi-cohort LEGEND trial included a phase 1 dose-escalation portion followed by the phase 2 portion, with a planned enrollment of 350 patients.³ Cohort 1 enrolled patients with BCG-unresponsive NMIBC with CIS, with or without papillary Ta/T1 tumors, who were ineligible for or had elected not to undergo cystectomy and who had CIS within 12 months of adequate BCG therapy.

Patients needed to be at least 18 years of age, have an ECOG performance status of 0 to 2, and be able to retain the study drug for 60 minutes; those with metastatic disease or prior investigational gene therapy or immunotherapy for NMIBC were excluded. Other cohorts are evaluating patients with BCG-naive or inadequately BCG-treated CIS, BCG-unresponsive papillary-only disease, and BCG-unresponsive CIS treated with polidocanol plus detalimogene.^1,2

In cohort 1, patients received detalimogene as a 50-mL intravesical instillation with a targeted retention time of 60 minutes, given as 4 instillations per 12-week cycle for up to 4 cycles.² Patients who achieve a CR enter maintenance with 2 instillations per 12-week cycle for up to 8 cycles.

The primary end points of the phase 2 portion are CR rate at any time and safety, and secondary end points include DOR, progression-free survival, CR rates at prespecified time points, and quality of life.²

References

1. enGene to initiate a BLA submission for detalimogene by year end and reports new data from LEGEND trial pivotal cohort 1 in BCG-unresponsive NMIBC. News release. enGene Therapeutics Inc. November 11, 2026. Accessed November 12, 2026. https://www.businesswire.com/news/home/20261111573459/en/enGene-to-Initiate-a-BLA-Submission-for-Detalimogene-by-Year-End-and-Reports-New-Data-from-LEGEND-Trial-Pivotal-Cohort-1-in-BCG-Unresponsive-NMIBC
2. FDA grants RMAT designation for enGene’s detalimogene, enabling potential for expedited review in high-risk, non-muscle invasive bladder cancer. News release. June 25, 2025. Accessed November 12, 2026. https://engene.com/fda-grants-rmat-designation-for-engenes-detalimogene-enabling-potential-for-expedited-review-in-high-risk-non-muscle-invasive-bladder-cancer/
3. LEGEND study: EG-70 in NMIBC patients BCG-unresponsive and high-risk NMIBC incompletely treated with BCG or BCG-naïve. ClinicalTrials.gov. Updated August 7, 2026. Accessed November 12, 2026. https://clinicaltrials.gov/study/NCT04752722