A phase I/II study of EG-70 (detalimogene voraplasmid) intravesical monotherapy for patients (pts) with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS)

BackgroundHigh-risk NMIBC is treated with adjuvant intravesical Bacille Calmette-Guérin (BCG); however, ∼50% of pts experience recurrence and/or progression after BCG treatment and are considered unresponsive. EG-70 is an investigational, intravesically administered therapy designed to elicit local stimulation of anti-tumor immune responses in the bladder and drive durable efficacy in pts with BCG-unresponsive NMIBC, while mitigating the risk of systemic toxicities from immune stimulation. The phase 1 (dose-escalation) portion of the first-in-human LEGEND (NCT04752722) phase 1/2, open-label, multicenter study of EG-70 is complete, and the phase 2 dose was identified. Here we describe the ongoing phase 2 portion of the study, which opened to enrollment in May 2023.Trial designEligibility criteria: age ≥18 years; ECOG PS 0−2; BCG-unresponsive NMIBC with CIS, with/without resected coexisting papillary tumors, ineligible for, or elected not to undergo, cystectomy; satisfactory bladder function with ability to retain study drug for ≥60 minutes. Pts are treated with EG-70 0.8 mg/mL in 50 mL by intravesical administration on weeks (wk) 1, 2, 5, and 6 of a 12-wk cycle, for 4 cycles in one of two cohorts: BCG-unresponsive (Cohort 1); BCG-naïve or BCG-incompletely treated (Cohort 2). Pts in either cohort who exhibit stable disease (SD) or CR at wk 12 will continue treatment until wk 24; pts with progressive disease (PD) will discontinue treatment. Pts who experience or maintain CR at wk 24 will receive additional cycles every 12 wks until wk 48; pts with SD or PD at wk 24 will discontinue treatment. Pts with PD at any time after wk 24 will discontinue treatment. Phase 2 primary endpoints: efficacy (CR rate at wk 48), and safety. Secondary endpoints: progression-free survival, CR rate at wks 12, 24, 36 and 48, and duration of response. The study is being conducted in accordance with the ethical principles of the Declaration of Helsinki and is consistent with ICH/GCP. All pts provide written informed consent. The phase 2 portion of the study will recruit ∼100 pts from sites in North America, Europe, and the Asia-Pacific region.Clinical trial identificationNCT04752722.Editorial acknowledgementEditorial/writing assistance for this abstract was provided by Lee Miller (Miller Medical Communications Ltd). This work was funded by the study sponsor (enGene, Inc.).Legal entity responsible for the studyenGene Inc.FundingenGene Inc.DisclosureJ. Palou: Financial Interests, Personal, Advisory Board: Arquer Diagnostics, Combat, JenaBCG; Financial Interests, Personal, Steering Committee Member: BMS, Janssen, AstraZeneca; Financial Interests, Institutional, Research Funding: Cepheid, Arquer, Taris, Urominotor, Seattle Genetics, Fidia, Urogen, Pfizer. G. Steinberg: Financial Interests, Personal, Other, Consultant and Equity: CG Oncology, EnGene Inc.; Financial Interests, Personal, Speaker, Consultant, Advisor: Merck, Pfizer, Janssen, AZ, Urogen, Aura Biosciences, Asieris, PhotoCure, Nonagen, Imugene. C. Toscone, T. Linback, R. Pruthi, R. Bryce: Financial Interests, Personal, Full or part-time Employment: enGene Inc.; Financial Interests, Personal, Stocks or ownership: enGene Inc. J. Sullivan: Financial Interests, Personal, Stocks or ownership: enGene Inc.; Financial Interests, Personal, Full or part-time Employment: enGene Inc. G. Brown: Financial Interests, Personal, Advisory Role: Janssen, Bayer, Merck, Astellas, Pfizer; Financial Interests, Personal, Invited Speaker: Janssen, Bayer, Merck, Astellas, Pfizer. All other authors have declared no conflicts of interest.