Detalimogene voraplasmid (EG-70) non-viral IL-12/RIG-I gene therapy achieves 73% complete response in BCG-unresponsive NMIBC, Phase 2 LEGEND trial now enrolling broader cohorts

Detalimogene voraplasmid is an intravesical, non-integrating plasmid that co-expresses IL-12 and a RIG-I agonist to trigger local innate and adaptive immunity. In the Phase 1 dose-escalation of the open-label LEGEND study (NCT04752722), 30 BCG-unresponsive high-risk NMIBC patients (CIS ± Ta/T1) received 0.8 mg/mL EG-70 weekly in weeks 1–2 and 5–6 of a 12-week cycle for four cycles. The treatment was generally well tolerated, with no grade ≥3 TRAEs. It achieved a 73% complete response (CR) at the first evaluation, surpassing benchmark 3-month CR rates of 53% with nadofaragene firadenovec and 41% with systemic pembrolizumab in similar populations. The now-active Phase 2 portion (≈ 300 pts) is testing the same schedule across four cohorts, adding a papillary-only, BCG-unresponsive group and incorporating maintenance dosing for up to two years.