detalimogene voraplasmid (EG-70)

In parallel, we highlight emerging intravesical immunotherapies for BCG-unresponsive NMIBC with carcinoma in situ, including nadofaragene firadenovec (Adstiladrin), nogapendekin alfa inbakicept-pmln (Anktiva), cretostimogene grenadenorepvec (CG0070), and detalimogene voraplasmid (EG-70). The lack of comparative data, coupled with the absence of predictive biomarkers of response, complicates treatment selection. Our review underscores that developing effective therapies for BCG-unresponsive disease will require combination strategies targeting multiple immune escape mechanisms that shape immune dynamics within the TME.

Nadofaragene firadenovec, a recombinant adenovirus delivering interferon alpha-2b (IFNα2b), is the first FDA-approved gene therapy for BCG-unresponsive NMIBC with carcinoma in situ (CIS)...Cretostimogene grenadenorepvec (CG0070), an oncolytic vector, demonstrated a 47% 6-month CR rate in a phase II study (NCT02365818). Detalimogene voraplasmid (EG-70), a nonviral gene therapy, demonstrated a 47% 6-month CR in a phase I/II study (NCT04752722). Future advances are likely to focus on patient selection, novel vectors, and combination strategies to improve treatment outcomes. Gene therapy represents a significant addition to the bladder cancer treatment landscape by offering bladder-sparing alternatives where conventional therapies are limited.

P1/2, N=350, Recruiting, enGene, Inc. | N=222 --> 350 | Trial completion date: May 2027 --> Nov 2028 | Trial primary completion date: Jun 2025 --> Jun 2026

P1/2, N=222, Recruiting, enGene, Inc. | Trial completion date: Feb 2026 --> May 2027 | Trial primary completion date: Jul 2024 --> Jun 2025