Pivotal cohort in LEGEND trial reaches target enrollment

The pivotal cohort in the phase 2 LEGEND trial (NCT04752722), exploring detalimogene voraplasmid (formerly EG-70) in high-risk non–muscle invasive bladder cancer (NMIBC) with carcinoma in-situ (CIS) with or without concomitant papillary disease, has reached its enrollment goal, enGene announced in a news release.¹

Detalimogene is an investigational non-viral gene therapy designed to be instilled in the bladder to elicit an anti-tumor immune response. The agent has received Regenerative Medicine Advanced Therapy and Fast Track designations from the FDA.

“Achieving our target enrollment goal for detalimogene in LEGEND’s pivotal cohort represents an important milestone for enGene. It brings us a step closer to our goal of providing patients and physicians with the first non-viral gene therapy that offers a unique balance of efficacy, safety, and ease-of-use,” said Ron Cooper, CEO of enGene, in the news release.¹ “We are grateful to study participants, investigators, and our clinical organization for their contributions to advancing the development of detalimogene.”

In total, the pivotal cohort—cohort 1—enrolled 100 patients with high-risk NMIBC with CIS with or without concomitant papillary disease. According to enGene, patients who are in the screening process remain eligible for enrollment in the study, and the company expects to over-enroll in the trial’s pivotal cohort.

An update on the pivotal cohort is expected in Q4 of 2025. enGene plans to submit a biologics license application (BLA) seeking approval of detalimogene voraplasmid in second half of 2026.

About LEGEND

In addition to cohort 1, the open-label LEGEND study is also enrolling patients with BCG-naïve NMIBC with CIS (cohort 2a), patients with NMIBC with CIS who have been exposed to BCG but have not received an adequate amount of treatment (cohort 2b), and patients with high-risk BCG-unresponsive NMIBC with papillary-only disease (cohort 3).

Patients in the LEGEND study are being enrolled through clinical trial sites across the US, Canada, Europe, and the Asia-Pacific region. Those enrolled in the study need to be ineligible for or have elected not to undergo cystectomy. Further, patients must have an ECOG Performance Score of 0 to 2, adequate renal function, and satisfactory bladder function with the ability to retain the study drug for at least 60 minutes.

In the study, participants will receive up to four 12-week cycles of intravesical detalimogene. Those who achieve a complete response (CR) following the four 12-week cycles will receive 4 maintenance treatment cycles, and those who remain in CR will undergo an additional set of 4 maintenance treatment cycles.

The primary end point is the CR rate at 48 weeks. Secondary end points include CR rates at 12, 24, 36, and 96 weeks; duration of response; progression-free survival; and safety and tolerability.

Primary completion of the study is anticipated for June 2026.

REFERENCES

1. enGene achieves target enrollment milestone for LEGEND trial pivotal cohort. enGene. September 3, 2025. Accessed September 4, 2025. https://engene.com/engene-achieves-target-enrollment-milestone-for-legend-trial-pivotal-cohort/

2. LEGEND study: EG-70 in NMIBC patients BCG-unresponsive and high-risk NMIBC incompletely treated with BCG or BCG-naïve. ClinicalTrials.gov. Last updated August 13, 2025. Accessed September 3, 2025. https://clinicaltrials.gov/study/NCT04752722