HSV- Thymidine-Kinase Gene Therapy CAN-2409 + Valacyclovir Cuts Recurrence 30% with EBRT in Localized Prostate Cancer

CAN-2409 is a replication-defective adenovirus delivering HSV-thymidine-kinase. When combined with oral valacyclovir, CAN-2409 triggers immunogenic cell death. In the double-blind Phase 3 trial NCT01436968, 745 intermediate/high-risk localized prostate cancer patients receiving standard external-beam radiation ± ≤6 mo ADT were randomized to three intraprostatic CAN-2409 injections + valacyclovir vs placebo + valacyclovir. After a median follow-up of 50.3 months, disease-free survival favored CAN-2409 (median not reached vs 86.1 mo; HR 0.70, p = 0.016) and prostate-cancer–specific DFS HR was 0.62. More patients who received CAN-2409 hit PSA nadir (67% vs 59%) and showed pathologic CR on 2-year biopsy (80% vs 64%). Flu-like grade 1–2 events (chills 33%, fever 25%) were common. Treatment-related serious AEs were rare (1.7% in the experimental cohort vs 2.2% in the placebo cohort).