Bladder Cancer Gene Therapy Detalimogene Effects 62% CRR at 6 Months Posttreatment

enGene's detalimogene voraplasmid (also known as detalimogene, and previously referred to as EG-70), an investigational nonviral immuno-oncology gene therapy being evaluated for the treatment of high-risk bacillus Calmette-Guérin (BCG)-unresponsive nonmuscle-invasive bladder cancer (NMIBC) with carcinoma in situ, has brought about a 62% complete response rate (CRR) at 6 months posttreatment, according to updated data from the phase 1/2 LEGEND clinical trial (NCT04752722).¹

This finding came from an analysis of 37 patients at 6 months posttreatment and 62 patients at 3 months posttreatment. enGene noted that all patients included in the analysis were assessed under an amended protocol for the trial that was adopted in quarter 4 of 2024 with the intent of aligning LEGEND more closely with standard of care and the American Urological Association’s Guidelines.

In addition to the 62% CRR seen in the 37 patients at 6 months, a 56% CRR had been seen across the 62 patients at 3 months. EnGene noted that 63% of the 62 patients had a CR at some point in time. Furthermore, the company pointed out that 3 of the 37 patients analyzed at 6 months had converted to CR after reinduction and that all patients (n = 5) who underwent an assessment at 9 months posttreatment showed a CR.

The trial’s pivotal cohort has enrolled 125 patients in total. With regard to safety, enGene stated that 42% of these patients had at least 1 treatment-related adverse event (TRAE), 1.6% of the patients had dose interruptions as a result of TRAEs, and 0.8% of patients discontinued dosing because of TRAEs.

“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, a senior physician, urologic oncologist, and bladder cancer regional lead at Colorado Urology, said in a statement.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.”

An analysis of 27 patients who were treated in LEGEND under trial’s original, preammendment protocol showed that at 6 months, a CRR of 41% was achieved (95% CI: 25-59). As such, enGene pointed out that the 62% CRR (95% CI: 46-76) seen at 6 months in theaforementioned 37 patients treated under the amended protocol constitutes an improvement. The company noted that in previous preliminary analyses, patients treated under the original protocol who were examined at 12 months posttreatment showed a CRR “markedly lower” than FDA-approved BCG-unresponsive NMIBC treatments.¹

“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, the chief medical officer of enGene, added to the statement.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.”

Alongside the data update, enGene reported that LEGEND’s primary end point will change from landmark 12-month CR rate to CR rate at any time and that duration of response (DOR) for patients in CR has become a key secondary end point. The company noted that this move came after discussions with the FDA and that the new primary end point is consistent with other FDA-registered programs in recent times. Furthermore, enGene stated that it plans to discuss a statistical analysis plan for which patients are to be included in the final efficacy evaluable population with the FDA. enGene anticipates that a data update on the trial’s pivotal cohort will be announced in the second half of next year and expects to submit a biologics license application (BLA) in the same window of time.

“We are highly encouraged with the preliminary data from our LEGEND study, which support our planned BLA filing,” Ron Cooper, BSc, the president and CEO of enGene, added to the statement.¹ “Based on the emerging clinical profile and detalimogene’s differentiated ease of use, we continue to believe there is a substantial commercial opportunity for detalimogene if approved.”

Notably, the FDA previously granted regenerative medicine advanced therapy (RMAT) designation to detalimogenein June 2025.² According to enGene, data from LEGEND informed the FDA’s decision to grant RMAT designation to detalimogene.

“Detalimogene has the potential to deliver what NMIBC patients and their physicians have long needed—a nonviral option with optimized delivery to the bladder, safety in handling, and ease of administration,” Cooper told CGTLive® in response to a request for comment at the time of the RMAT designation. “We’re pleased to receive this designation for detalimogene and are encouraged that we’re one step closer to potentially providing NMIBC patients a new option that may help transform the treatment landscape.”

REFERENCES
1. Detalimogene demonstrates improved complete response rate of 62% at 6 months. News release. enGene Holdings Inc. November 11, 2025. November 19, 2025. https://engene.com/detalimogene-demonstrates-improved-complete-response-rate-of-62-at-6-months/
2. FDA grants RMAT designation for enGene’sdetalimogene, enabling potential for expedited review in high-risk, non-muscle invasive bladder cancer. News release. enGene Holdings Inc. June 25, 2025. Accessed June 25, 2025. https://engene.com/fda-grants-rmat-designation-for-engenes-detalimogene-enabling-potential-for-expedited-review-in-high-risk-non-muscle-invasive-bladder-cancer/