NMI Bladder Cancer Gene Therapy Shows Promising Safety and Efficacy in Phase 1 Trial

enGene's EG-70 (detalimogene voraplasmid), an investigational non-viral immuno-oncology gene therapy intended to treat bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC), has demonstrated promising safety and efficacy in data from the phase 1 portion of the phase 1/2 LEGEND clinical trial (NCT04752722).¹ The interim results were presented at the 2023 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, held in San Francisco, California, February 16-18, 2023.

EG-70 consists of a plasmid which encodes for IL-2, for the purpose of stimulating the adaptive immune system, and 2 RIG-I agonists, which are intended to stimulate the innate immune system.^1,2 It is intravesically administered in 2 or 4 doses in a 12-week cycle. Among the 17 patients who received at least 1 full cycle of EG-70, 12 patients (71%) achieved a complete response (CR) by 3 months based on cytology, cystoscopy, and biopsy analyses and 3 patients showed stable disease. Furthermore, IL-12 was detected in the urine of every patient at dose-responsive levels. Patients who did not show progressive disease at the 3-month mark were able to elect to remain in the study and continue receiving doses of EG-70. Fourteen (82%) of the 17 patients elected to continue treatment past 3 months.

In terms of safety, EG-70 was generally well-tolerated with adverse events (AEs) largely being consistent with urinary tract instrumentation. One patient experienced a grade 3 renal failure and discontinued treatment. However, it was later determined that the renal failure had been present before administration of EG-70.

"While the data are still early, EG-70's safety profile and efficacy are well on their way towards establishing a new benchmark for monotherapy treatment of high-risk NMIBC with BCG-unresponsive Carcinoma in situ ," Gary Steinberg, MD, professor at the Perlmutter Cancer Center and Department of Urology and director of the Goldstein Urology Bladder Cancer Program of NYU Langone Health, who presented the data, said in a statement.² "If these trends continue into phase 2, I am optimistic that EG-70 will become an important, useful, and innovative tool in the fight against NMIBC, especially given its non-viral nature and relative ease of handling and use."

Twenty patients in total received at least 1 dose of EG-70.¹ However, 1 of these patients was deemed ineligible by the independent data safety and monitoring board after being dosed, 1 voluntarily withdrew consent before receiving a full cycle, and 1 had not reached 3 months of follow-up as of the data cutoff. The average age of the 20 patients, all of whom were included in the safety analysis, was 72 years (standard deviation, 8.9); the average BMI was 28.4 (standard deviation, 5.24); and the average prior number of BCG doses was 11 (standard deviation, 3.5). The group included 16 male patients (80%) and 19 white patients (95%). enGene expects the phase 2 portion of the study to begin in the first half of 2023.

"From the start, we designed EG-70 to be a safe, practical, and effective option for both patients and physicians that will integrate seamlessly into community urology clinics," Jason Hanson, chief executive officer, enGene added to the statement.² "It is deeply rewarding to see EG-70 continuing its best-in-class trajectory, and we look forward to the upcoming initiation of the pivotal phase 2 portion of the LEGEND study."

REFERENCES

1. Steinberg GD, Kalota SJ, Lotan Y, Warner L, Dauphinee, Mazanet R. Clinical results of a phase 1 study of intravesical EG-70 in patients with BCG-unresponsive NMIBC. Presented at: American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, held in San Francisco, California, February 16-18, 2023. Abstract 512

2. enGene announces poster presentation containing interim Phase 1 clinical trial data at the 2023 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium. News release. enGene Inc. February 14, 2023. Accessed February 21, 2023. https://www.newswire.ca/news-releases/engene-announces-positive-preliminary-phase-1-2-data-with-eg-70-in-bcg-unresponsive-non-muscle-invasive-bladder-cancer-848397743.html