Detalimogene shows continued activity in BCG-unresponsive NMIBC

Detalimogene voraplasmid demonstrated a 56% complete response (CR) rate at any time among patients with high-risk, BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC), according to updated data from the phase 2 LEGEND trial, enGene announced.¹

The findings reflect longer follow-up from the pivotal Cohort 1 and will serve as the basis for a planned Biologics License Application (BLA) to the FDA. Detalimogene is an investigational nonviral gene therapy administered directly into the bladder. The agent was granted regenerative medicine advanced therapy designation in June 2025.

“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,” said lead investigator Ashish M. Kamat, MD, professor of urologic oncology at The University of Texas MD Anderson Cancer Center, in the news release.¹ “The updated LEGEND data are encouraging, demonstrating clinically meaningful antitumor activity with a favorable tolerability profile. 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.”

Updated efficacy findings from LEGEND

LEGEND (NCT04752722) is an ongoing, open-label, phase 1/2 study evaluating the safety and efficacy of intravesical detalimogene in patients with NMIBC. The pivotal phase 2 Cohort 1 enrolled 125 patients with high-risk, BCG-unresponsive NMIBC with carcinoma in situ (CIS), with or without concomitant papillary disease.

The updated analysis included 120 efficacy-evaluable patients, with a data cutoff of October 29, 2026. The primary efficacy end point was CR at any time, with secondary end points including duration of response (DoR), landmark CR rates, and safety.

Among 120 patients, the CR rate at any time was 56% (95% CI, 47 to 65), which improved from 54% in the company's April 2026 analysis. The preliminary Kaplan-Meier estimate of the proportion of patients maintaining a response for at least 12 months increased to 43% (95% CI, 30 to 55), compared with 25% in the earlier analysis.

The landmark 12-month CR rate was 24% (95% CI, 16 to 33) among 110 evaluable patients, which improved from 13% in the earlier analysis. One additional patient was awaiting the 12-month disease assessment at the time of data report. Median duration of complete response was 10.1 months (95% CI, 7.5 months to not estimable), compared with 8.6 months in the April analysis. Median follow-up among responders also increased from 9.2 to 12.0 months since the last data report.

The company noted that 9 patients were still awaiting assessment for a response lasting at least 12 months, including 8 patients receiving maintenance treatment. Among patients who had entered maintenance and completed a durability assessment, all had maintained their responses.

Additional disease-control outcomes included freedom from progression to muscle-invasive or metastatic bladder cancer (defined as T2 or greater disease) in 97% of all efficacy-evaluable patients. All patients who achieved a CR remained free from progression to T2 or greater disease in the bladder at the time of analysis.

Regarding bladder preservation, 86% of all efficacy-evaluable patients remained free from cystectomy, as did 96% of patients who achieved a CR.

Safety and tolerability

Safety was evaluated in all 125 patients enrolled in Cohort 1. At least 1 treatment-related adverse event (TRAE) occurred in 59% of patients, with most events being grade 1 or 2. The most frequently reported 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, and 2% experienced a serious TRAE. No grade 4 or 5 TRAEs were reported. TRAEs resulting in treatment discontinuation and treatment interruption occurred in 1% and 4% of patients, respectively.

The findings suggest that treatment-related toxicity was predominantly low grade in this cohort. However, the relatively small study population and ongoing follow-up limit the ability to characterize less common or delayed adverse events.

Next steps

According to enGene, the company recently completed a pre-BLA meeting with the FDA and reached alignment with the agency on key components of the planned submission, including the efficacy-evaluable population. The company expects to initiate its BLA submission by the end of 2026 and complete the submission during the first half of 2027.

In parallel, enGene is evaluating detalimogene in an additional LEGEND cohort incorporating a surfactant bladder rinse before drug administration. The company expects to provide an update on this cohort in mid-2027.

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REFERENCE

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. November 11, 2026. Accessed November 12, 2026. https://investors.engene.com/English/investor/press-releases/news-details/2026/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/default.aspx