Detalimogene Shows 54% Response Rate in Bladder Cancer Trial

Updated interim results from the pivotal cohort of the ongoing phase 2 LEGEND trial (NCT04752722) evaluating detalimogene voraplasmid demonstrated a 54% complete response (CR) rate at any time and a 43% CR rate at 6 months in patients with high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive non–muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without concomitant papillary disease. The manufacturer, enGene, plans to present the full dataset during the American Urological Association meeting on May 15, 2026.¹

“These updated data continue to reinforce the favorable safety and tolerability profile of detalimogene and its clinical activity in a heavily pretreated, high-risk NMIBC patient population with limited therapeutic options. Importantly, the low rate of progression to muscle-invasive disease leaves patients eligible for other bladder-sparing therapies,” Ron Cooper, president and CEO, enGene, said in a release.¹

In the primary efficacy analysis, detalimogene achieved a CR rate at any time of 54% (95% CI, 45%-63%) in 124 evaluable patients. The 6-month CR rate was 43% (95% CI, 34%-52%), based on 52 of 121 evaluable patients. Ninety-one percent of responses occurred at the first disease assessment. Among patients who had not responded initially, 14% (6 of 43) successfully converted from non-CR to CR following re-induction; 2 patients who were re-induced had not yet reached their 6-month assessment at the time of this analysis.

Among the 52 patients who achieved a CR at 6 months, 84% (37 of 44) who had a 9-month assessment remained in CR, with an additional 8 pending evaluation. At 12 months, 59% (13 of 22) patients with an available assessment achieved a CR, with 11 additional patients pending evaluation. A maximum of 21 patients, including the 2 currently undergoing re-induction, retain the potential to achieve a CR at 12 months. The Kaplan-Meier (KM) estimate of the 12-month duration of response (DOR) was 25% (95% CI, 11%-41%), with a KM estimate for median DOR of 37.3 weeks (range, 31.6-43.9).

The rate of progression to muscle-invasive or more advanced disease was low at 3.2%, an important finding for a population in which disease advancement typically eliminates bladder-sparing options.

Among the 32 patients who had their first disease assessment after the October 24, 2025, data cutoff, CR rates were lower than those observed in previously reported patients. The CR rate at any time was 39% and the 6-month CR rate was 32% in this subgroup. A preliminary analysis has not identified material differences in demographics or disease characteristics, and a more comprehensive investigation of potential contributing factors is ongoing.

Safety and Toxicity

Of 125 patients assessed for safety in cohort 1, 69 (55%) experienced at least 1 treatment-related adverse event (TRAE), the majority of which were grade 1 or grade 2. The most common TRAEs were fatigue (22%), dysuria (14%), micturition urgency (12%), pollakiuria (12%), and bladder spasm (11%). Grade 3 or higher TRAEs were reported in 6 patients (4.8%), including 1 grade 4 event that has since resolved. No grade 5 TRAEs were reported. TRAEs leading to dose interruption and those leading to treatment discontinuation each occurred in 2.4% of patients.

Trial Design and Methods

LEGEND is an ongoing, open-label, multicohort phase 2 trial evaluating the safety and efficacy of detalimogene in patients with high-risk NMIBC. The pivotal cohort, cohort 1, enrolled 125 patients with high-risk, BCG-unresponsive NMIBC with CIS, with or without papillary disease, and is intended to serve as the basis for a planned biologics license application (BLA) filing. The trial also includes 3 additional cohorts: BCG-naive patients with CIS (cohort 2a), patients with CIS who received BCG but not adequate treatment (cohort 2b), and BCG-unresponsive patients with papillary-only disease (cohort 3).

Preliminary findings were presented at the 2025 ASCO Genitourinary Cancers Symposium.² Investigators reported that 71% of patients dosed with detalimogene voraplasmid achieved a CR, with 67% achieving a CR at 3 months and 47% achieving a CR at 6 months.

Detalimogene is a novel, investigational, nonviral gene therapy designed to be instilled directly into the bladder to elicit a localized antitumor immune response. Patients who discontinued without any disease evaluation or who discontinued after achieving a CR were considered not evaluable for subsequent landmark CR analysis.

The company plans further engagement with the FDA as it approaches a potential BLA filing and expects to provide an update in the second half of 2026.¹

REFERENCES

1. enGene announces updated interim results from LEGEND pivotal cohort. News release. enGENE. May 7, 2026. Accessed May 7, 2026. https://tinyurl.com/4mhuy9sk

2. Taylor JA, Joshi S, Satkunasivam R, et al. Preliminary results from LEGEND: A phase 2 study of detalimogene voraplasmid (EG-70), a novel, non-viral intravesical gene therapy for patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS). J Clin Oncol. 2025;43(suppl 5):802. doi:10.1200/JCO.2025.43.5_suppl.802