Detalimogene Generates Improved, Compelling Efficacy Signals in NMIBC

Detalimogene voraplasmid (detalimogene; formerly EG-70) demonstrated promising responses in patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non–muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), according to updated preliminary data from the phase 2 LEGEND trial (NCT04752722).¹

Under the trial’s amended protocol, the new data showed a 63% complete response (CR) rate at any time among 62 patients who had at least 1 post-baseline disease assessment. At 3 months (n = 62) and 6 months (n = 37), the respective CR rates were 56% and 62%, showing pronounced improvement from data prior to protocol amendment.

The new protocol went into effect at the end of 2024 and was implemented to more closely align with the American Urological Association’s guidelines, other FDA-registered programs, and standard of care. Key changes included a shifting of the primary end point from 12-month CR rate to CR rate at any time, with its key secondary end point becoming duration of response for patients in CR.

Regarding safety, the agent also demonstrated a favorable safety and tolerability profile. Of the total 125 patients enrolled in the trial, 42% experienced a treatment-related adverse event (TRAE); 1.6% experienced dose interruptions and 0.8% experienced dose discontinuations due to TRAEs. The most frequent TRAEs included bladder spasm (10.4%), dysuria (12.0%), fatigue (16.8%), micturition urgency (10.4%), and pollakiuria (10.4%). Most TRAEs were grade 1 or 2 except for 3 patients with grade 3 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,” said Suzanne Merrill, MD, urologic oncologist at Colorado Urology, in a news release.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.”

Earlier this year, detalimogene, a novel nonviral gene therapy, was granted FDA regenerative medicine advanced therapy designation and fast track designation for the same indication. These compelling efficacy and safety profiles further support potential first-line use of the agent for this indication, and the sponsors have announced plans to file a biologics license application in the latter half of 2026. The sponsor and FDA will be in communication regarding a statistical analysis plan which will help finalize the efficacy evaluation framework, ensuring readiness for submission.

Prior Findings

Data from the trial’s phase 1 dose-escalation stage and phase 2 under the original protocol were presented at the 2024 American Urological Association Annual Meeting. Phase 1 saw CR rates of 68% and 45% at 3 and 6 months, respectively (n = 24). Here, patients received 2 or 4 doses of the agent over a 12-week cycle in a 3+3 dose escalation design at 3 dose levels: 0.25 mg/mL, 0.8 mg/mL, and 2.5 mg/mL.

In phase 2, the dosing schedule increased to 4 0.8-mg/mL doses at weeks 1, 2, 5, and 6 in a 12-week cycle. The 3-month and 6-month CR rates were 70% and 60%. Safety findings were similar to the recent findings, with mainly grade 1 and 2 AEs observed.

LEGEND Trial: Background and Design

The phase 2 LEGEND trial is an ongoing, open-label, multi-cohort study evaluating detalimogene in high-risk NMIBC.² This clinical investigation was prompted by detalimogene’s promising mechanism of action, which is proposed to trigger a potent, local immune response at the tumor site while reducing systemic toxicity. Through direct intravesical delivery to the bladder urothelium, its ease of use would enable streamlined administration in urology clinics.

Enrollment for the trial’s pivotal cohort (cohort 1) has completed, accumulating a total of 125 BCG-unresponsive adult patients with NMIBC. The trial also includes 3 additional cohorts: BCG treatment-naive patients with NMIBC with CIS (cohort 2a; n = 30), BCG-exposed high-risk patients with NMIBC with CIS who have received inadequate BCG treatment (cohort 2b; n = 45), and BCG-unresponsive high-risk patients with papillary-only disease (cohort 3; n = 36).

REFERENCES

1. Detalimogene demonstrates improved complete response rate of 62% at 6 months. News release. Business Wire. November 11, 2025. Accessed November 12, 2025. https://tinyurl.com/2nx4me3b

2. LEGEND study: EG-70 in NMIBC patients BCG-unresponsive and high-risk NMIBC incompletely treated with BCG or BCG-naïve. ClinicalTrials.gov. Updated November 12, 2025. Accessed November 12, 2025. https://www.clinicaltrials.gov/study/NCT04752722