Detalimogene gene therapy shows promising results in bladder cancer trial

An update from the phase 2 LEGEND trial shows that the investigational nonviral gene therapy detalimogene voraplasmid has achieved a 62% complete response rate at six months in patients with high-risk, bacillus Calmette-Guérin (BCG)-unresponsive nonmuscle invasive bladder cancer with carcinoma in situ.

The findings were publicized in November 2025 in a news release issued by the therapy’s developer, enGene, a Canadian biotech company, and presented by the study’s lead author, Hussein Sweiti, M.D., M.Sc., who is enGene’s chief medical officer.

Detalimogene is designed to deliver two therapeutic genes directly into the bladder using a plasmid-based system. Once instilled, the therapy aims to stimulate a localized immune response capable of eliminating cancer cells while preserving the bladder. Because the treatment does not rely on viral vectors, researchers said it may offer a manufacturing and safety advantage compared with other gene-based therapies under development.

The LEGEND trial was amended in late 2024 to better reflect standard clinical practice. Under the updated protocol, 62 patients were evaluable at three months and demonstrated a 56% complete response rate. Among those, 37 patients remained evaluable at six months, and 62% maintained a complete response. When evaluating all patients across both assessments, the trial reported a 63% complete response at any time.

Sweiti noted the improvements observed under the amended protocol indicate that the therapy is performing in a clinically meaningful range for this difficult-to-treat population.

The safety findings also were promising. Of the 125 patients in the pivotal cohort, 42% experienced at least one treatment-related adverse event, although most were low grade. Dose interruptions were reported in 1.6% of patients, and treatment discontinuation occurred in 0.8%.

Sweiti noted the therapy has demonstrated a tolerability profile that compares favorably with other treatments used in this setting, including intravesical therapies that often cause significant irritation and systemic therapies that can carry broad side effects.

Urologic oncologist Suzanne Merrill, M.D., who served as a trial investigator, said the ease of use of deltalimogene may be a major advantage. She noted that the therapy can be administered using standard intravesical techniques already familiar to urologists and does not require specialized equipment or long in-clinic procedures. What’s more, the response rates, combined with manageable side effects, suggest the therapy could become an attractive option for practices seeking bladder-sparing approaches for patients who are not candidates for radical cystectomy.

After all, patients with high-risk, BCG-unresponsive carcinoma in situ face limited alternatives. Many of the options often include repeated tumor resections, off-label use of intravesical agents, or bladder removal. Radical cystectomy, although effective, dramatically alters quality of life and carries substantial surgical risks. As such, a therapy capable of producing durable complete responses while preserving the bladder could significantly change the treatment landscape.

enGene Holdings Inc., the company developing detalimogene, plans to finalize its statistical analysis plan in consultation with the U.S. Food and Drug Administration and expects to submit a biologics license application in the second half of 2026. Regulatory review will focus on whether the early response rates are durable and whether patients maintain remission without progression to muscle-invasive disease. Sweiti said longer-term follow-up is underway to assess durability of effect, duration of response, and recurrence-free survival.

Investigators caution that the therapy remains experimental and that additional data will be needed to confirm whether the six-month response translates into sustained disease control. They also noted that patient heterogeneity, prior BCG exposure, and tumor burden may influence long-term outcomes.

Even so, the updated results have generated optimism among clinicians who treat bladder cancer. If further study validates the findings, the therapy may become an important bladder-preserving option for high-risk non-muscle invasive bladder cancer.