Back to 2025 Abstracts
Mechanism of action and translation to the clinic of detalimogene voraplasmid- a novel, investigational, non-viral genetic medicine for non-muscle-invasive bladder cancer (NMIBC)
Mark Preston, MD1, Raj Satkunasivam, MD
2, Yair Lotan, MD
3, Suzanne Merrill, MD
4, Ashish M. Kamat, MD
5, Vignesh T. Packiam, MD
6, Shreyas Joshi, MD
7, Sam S. Chang, MD
8, Wassim Kassouf, MD
9, Jen-Jane Liu, MD
10, Mark Tyson, MD
11, Rian Dickstein, MD
12, Neal Shore, MD
13, Amy N. Luckenbaugh, MD
8, Alberto Martini, MD
14, Shauna Dauphinee, MD
15, Daniel Veilleux, MD
15, Carlos Fleet, MD
15, Raj Pruthi, MD
16, Kate Chan, MD
16, Anthony Cheung, MD
15, Vikram Narayan, MD
7.
1Brigham and Women’s Hospital, Boston, MA, USA,
2Houston Methodist-Weill Cornell Medical College, Houston, TX, USA,
3University of Texas Southwestern Medical Center, Dallas, TX, USA,
4Colorado Urology, Brighton, CO, USA,
5University of Texas MD Anderson Cancer Center, Houston, TX, USA,
6Rutgers RWJ Barnabas Health, West Orange, NJ, USA,
7Emory University School of Medicine, Atlanta, GA, USA,
8Vanderbilt University, Nashville, TN, USA,
9McGill University, Montreal, QC, Canada,
10Oregon Health Science University, Portland, OR, USA,
11Mayo Clinic, Phoenix, AZ, USA,
12Chesapeake Urology, Hanover, MD, USA,
13Carolina Urology Research Center, Myrtle Beach, SC, USA,
14University of Cincinnati Cancer Center, Cincinnati, OH, USA,
15enGene Inc., St-Laurent, QC, Canada,
16enGene Inc., Waltham, MA, USA.
Background: Detalimogene voraplasmid (EG-70) is a novel, investigational, non-integrating, non-viral genetic medicine designed to elicit local stimulation of an anti-tumor, intravesical immune response while mitigating risk of systemic toxicities. LEGEND is an ongoing Phase 1/2 study (NCT04752722) investigating safety and efficacy of detalimogene in high-risk NMIBC.
Methods: Preclinical evaluation was conducted
in vitro and
in vivo in an orthotopic syngeneic model of bladder cancer. Immunocompetent C57BL/6 mice received two weekly intravesical instillations of a murine EG-70 surrogate (mEG-70). Efficacy was assessed by flow cytometry, immunoassays, immunohistochemistry, bioluminescence
in vivo imaging, and overall survival. The Phase 1 clinical LEGEND study evaluated detalimogene in high-risk BCG-unresponsive NMIBC with carcinoma
in situ (CIS).
Results: Immune profiling revealed remodeling of the tumor microenvironment from an immunosuppressive to a pro-inflammatory milieu. Accordingly, administration of mEG-70 was associated with a marked and dose-dependent reduction in tumor burden. Over 90% of mEG-70-treated mice had durable anti-tumor responses as demonstrated by long-term disease-free survival with no disease relapse during the 100-day monitoring period. The anti-tumor immune response in surviving tumor-free mice resulted in durable protection against subsequent tumor re-challenge, and systemic immune memory. In Phase 1 of LEGEND, detalimogene was generally well tolerated, with a complete response rate of 73% at any time in patients with BCG-unresponsive NMIBC with CIS.
Conclusions: In a preclinical model, a mouse surrogate of detalimogene elicited a durable, anti-tumor immune response and a marked, dose-dependent reduction in tumor burden. The proposed mechanism of action of detalimogene has been translated clinically into the Phase 1 portion of the LEGEND study.
Back to 2025 Abstracts
