ASCO GU 2025: Preliminary Results from LEGEND: A Phase 2 Study of Detalimogene Voraplasmid (EG-70), a Novel, Non-Viral Intravesical Gene Therapy for Patients with BCG-Unresponsive NMIBC with CIS

(UroToday.com) The 2025 GU ASCO annual meeting featured a urothelial carcinoma session and a presentation by Dr. John Taylor discussing preliminary results from LEGEND, a phase 2 study of detalimogene voraplasmid (EG-70) for patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with CIS. Bladder sparing therapies for high risk NMIBC address an important unmet need:

Detalimogene voraplasmid is a novel, investigational, non-integrating, non-viral genetic medicine-based immunotherapy carrying a plasmid that simultaneously expresses IL-12 and regulators of RIG-I. This simulates innate and adaptive immunity:

There is durable and promising efficacy in patients with high-risk NMIBC, including BCG-unresponsive disease, while mitigating the risk of systemic toxicities from immune stimulation. The lyophilized powder is easily reconstituted in clinic with sterile water, and no special handling and no ultra cold chain storage is required (intravesical administration via a catheter). Results from the phase 1 portion of LEGEND demonstrated a promising safety and tolerability profile and an overall complete response rate of 73% in patients with NMIBC with CIS. The pivotal phase 2 portion is ongoing, with the preliminary outcomes from Cohort 1 (BCG unresponsive with CIS) reported at the GU ASCO 2025 annual meeting.

Patient eligibility criteria included (i) age ≥18 years, (ii) ECOG PS 0−2, (iii) BCG-unresponsive NMIBC with CIS ± Ta/T1 disease, ineligible for, or elected not to undergo, cystectomy, and (iv) satisfactory bladder function with ability to retain study drug for ≥60 minutes. Based on the phase 1 portion of the study, a dose concentration of 0.8 mg/mL was administered at a four-dose 50 mL instillation schedule at study weeks 1, 2, 5 and 6 of a 12-week cycle. After completing the initial 12-week cycle, patients without progressive disease remained on detalimogene voraplasmid for up to three additional 12-week cycles:

The primary endpoint was week 48 complete response rate, and the secondary endpoints included safety and tolerability. Efficacy data on BCG-unresponsive patients with CIS (n = 21; Cohort 1) and safety data on all patients dosed (n = 42) are reported.

Twenty-one patients (15 males/6 females; median age 74 [range 59–92] years) have been enrolled in Cohort 1. The median number of prior BCG doses is 11 (range 8-33):
Treatment-related adverse events (any grade) were reported in 20 (47.6%) patients and were all Grade 1/2 in severity. The most common treatment-related adverse events were dysuria in 9 (21.4%) patients, bladder spasm in 8 (19.0%), pollakiuria in 5 (11.9%), and fatigue in 5 (11.9%) patients:
In the efficacy-evaluable population for Cohort 1, the overall complete response rate was 71% (15/21), with a complete response rate of 67% (14/21) at 3 months, and 47% (8/17) at 6 months. The Kaplan-Meier estimate of the 6-month complete response is 51%:
Dr. Taylor concluded his presentation discussing preliminary results from LEGEND, a phase 2 study of detalimogene voraplasmid (EG-70), a novel, non-viral intravesical gene therapy for patients with BCG-unresponsive NMIBC with CIS with the following take-home points:

• Preliminary data from the pivotal phase 2 portion of the LEGEND study suggest a promising safety and tolerability profile, with treatment-related adverse events that were largely consistent with instrumentation and intravesical administration
• Overall, 71% of patients dosed with detalimogene voraplasmid achieved a complete response, with 67% achieving a complete response at 3 months and 47% achieving a complete response at 6 months
• The LEGEND trial is now enrolling patients in multiple cohorts, with a target accrual of ~300 patients

Presented by: John A. Taylor, MD, MS, University of Kansas Medical Center Department of Internal Medicine, Kansas City, MO

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2025 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 13 – Sat, Feb 15, 2025.