Clinical results of a phase 1 study of intravesical EG-70 in patients with BCG-unresponsive NMIBC.

512 Background: enGene is developing non-viral gene therapy platforms to deliver nucleic acids (plasmids) to epithelial mucosal tissues such as urothelium of urinary bladder. EG-70 is a nanoparticle formulation of plasmids that activates both innate and adaptive immune responses to activate the immune system within the bladder. The plasmid encodes both IL-12 and activators of the innate immune receptor RIG-I. EG-70 is administered intravesically to elicit local stimulation of anti-tumor immune responses providing durable efficacy in high grade non-muscle invasive bladder cancer (NMIBC) while avoidingsystemic toxicities. Methods: In the Phase 1 study(LEGEND; NCT04752722), escalating doses of EG-70 were administered intravesically to patients with BCG-unresponsive Carcinoma in situ (CIS) NMIBC on weeks 1 and 2 or weeks 1, 2, 5, 6 of 12-week treatment cycle. At the week 12 assessment, patients with stable disease (SD) or complete response (CR), as assessed by urine cytology, cystoscopy, and bladder biopsy, were allowed electively to remain on EG-70 for up to 3 additional 12-week cycles. Results: To date, 19 patients have been treated. There have been no DLTs. AEs (48 GR1, 17 GR 2 and 1 GR3) have been largely consistent with urinary tract instrumentation, and were not dose related. Eighteen patients have completed one cycle of EG-70, and 67% have achieved CR. Fifteen patients with CR or SD at the end of cycle 1 elected to receive additional treatment cycles (continuation rate of 15/18 ( 83%)). Durable CRs were seen at all dose levels. Patients who receive additional cycles are followed for durability of response (Table). Complete Response. Conclusions: These results demonstrate the safety, tolerability and durable therapeutic potential of intravesical EG-70 in patients with BCG-unresponsive CIS. A Phase 2 study will proceed in 2023. Clinical trial information: NCT04752722 . [Table: see text]