Preliminary Data Demonstrate High CR Rate With Detalimogene in BCG-Unresponsive NMIBC With CIS

Detalimogene voraplasmid (detalimogene; previously EG-70) produced a high complete response (CR) rate in patients with high-risk non–muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) who were unresponsive to Bacillus Calmette-Guérin (BCG), according to preliminary data from the ongoing phase 1/2 LEGEND trial (NCT04752722).1

All 21 patients in the pivotal cohort were assessed at 3 months, 17 of whom were also assessed at 6 months. The CR rate at any time with the novel non-viral gene therapy was 71%. The CR rate at 3 and 6 months were 67% and 47%, respectively. 

“We are pleased with this preliminary dataset, which clearly demonstrates that detalimogene is highly active and generally well tolerated. The data are consistent with what was observed in phase 1 and give us increased confidence in the emerging profile,” Raj Pruthi, MD, chief medical officer of enGene, stated in a press release. “We are also planning protocol refinements in LEGEND, which we believe will provide patients with additional clinical benefit.”

LEGEND Overview

LEGEND is a first-in-human, open-label, multicenter, dose-escalation trial evaluating detalimogene in approximately 100 patients at least 18 years of age with BCG-unresponsive NMIBC with CIS with or without resected papillary tumors who are ineligible for or who have chosen not to undergo cystectomy. Patients are required to display persistent high-grade disease or recurrence after 1 year of 1 or more induction courses of intravesical BCG; or T1 high-grade residual disease at the first evaluation after BCG induction.2

“Detalimogene was designed to be the most practical therapy for urologists to manage NMIBC,” Ron Cooper, chief executive officer of enGene, added in the release.1 “The early results from our pivotal LEGEND study clearly demonstrate that detalimogene has the potential to offer a highly differentiated profile by striking an optimal balance between efficacy, tolerability, and ease of use.”

In the phase 2 portion, patients with NMIBC with CIS of the bladder with or without resected papillary tumors who are ineligible for or have elected not to undergo cystectomy will be enrolled. Patients must have either received at least 1 dose, but not the full course, of intravesical BCG (BCG-incomplete); or received no treatment with BCG (BCG-naive) but had prior exposure to at least 1 dose of intravesical chemotherapy following transurethral resection of bladder tumor with documented CIS.2

In the pivotal cohort, patients are treated with up to 4 cycles of 800 µg/mL of detalimogene intravesically during weeks 1,2, 5 and 6 of a 12-week cycle.1 Assessments are conducted at 6, 9, and 12 months. In phase 2, patients will receive the recommended phase 2 dose (RP2D) of the agent for up to 4 treatment cycles.2

The primary end point in phase 1 is safety; in part 2, the primary end points are CR and safety. Key secondary end points include CR rate at 12 weeks in phase 1, CR rate at 12, 24, 36 and 48 weeks, progression-free survival, duration of response, and quality of life serve as secondary end points in phase 2.

Regarding safety, the agent displayed a favorable toxicity profile and was tolerable. No treatment-related discontinuations occurred. Across all phase 2 cohorts (n = 42), 48% of patients experienced 1 or more treatment-related adverse effects (TRAEs). The majority of TRAEs were grade 1/2, excepting 2 grade 3 events of peripheral edema and urosepsis, and no grade 4/5 TRAEs were reported. Commonly reported TRAEs in at least 10% of patients were dysuria, bladder spasm, pollakiuria and fatigue. 

In addition to LEGEND’s pivotal cohort, enrollment onto 3 addition cohorts is planned for the fourth quarter of 2024. Cohorts will include BCG-exposed patients high-risk NMIBC with CIS (cohort 2a) BCG-naïve patients with NMIBC and CIS (cohort 2b); and patients with high-risk BCG-unresponsive NMIBC who have papillary-only disease (cohort 3). The company expects to file a biologics license application for detalimogene in BCG-unresponsive patients with NMIBC with CIS midway through 2026.1

“The promising initial efficacy and safety data observed in LEGEND’s pivotal cohort, combined with detalimogene’s ease of handling, administration, minimal storage requirements, and lack of post-procedural patient restrictions underscore its potential to become a broadly utilized treatment option for [patients with] NMIBC, especially in the community practice setting,” Suzanne Merrill, MD, FACS, a urologist with the United Urology Group in Lone Tree, Colorado, explained in the press release.

References

1. Detalimogene Demonstrates 71% Complete Response Rate at Any Time in Preliminary Analysis of LEGEND Pivotal Cohort. News Release. enGene. September 26, 2024. Accessed September 26, 2024. https://engene.com/detalimogene-demonstrates-71-complete-response-rate-at-any-time-in-preliminary-analysis-of-legend-pivotal-cohort/
2. LEGEND study: EG-70 in NMIBC patients who are BCG-unresponsive and high-risk NMIBC patients who have been incompletely treated with BCG or are BCG-naïve (LEGEND STUDY). ClinicalTrials.gov. Updated August 1, 2024. Accessed September 26, 2024. https://clinicaltrials.gov/ct2/show/NCT04752722