CAN-2409 (HSV‑tk adenoviral gene therapy) + valacyclovir improves DFS when added to curative EBRT in localized prostate cancer

Aglatimagene besadenovec (CAN-2409) is an intraprostatic, replication-defective adenoviral vector expressing HSV‑thymidine kinase; with valacyclovir it drives tumor cell kill and immunogenic cell death, and was tested here as an “in situ vaccination” add-on to radiotherapy. In this Phase 3, multicentre, randomized, double-blind trial in intermediate/high-risk localized prostate cancer (n=745; 2:1 randomization; optional ADT), CAN-2409+valacyclovir added to EBRT improved disease-free survival vs placebo+valacyclovir (median DFS not reached vs 86.1 months; HR 0.70, 95% CI 0.52–0.94; p=0.016) at median follow-up 50.3 months—an effect size that’s directionally meaningful vs contemporary EBRT±ADT benchmarks where ~10–20% of intermediate-risk patients recur biochemically within 5 years. Grade ≥3 TEAEs were similar (8% vs 7%); the most common grade ≥3 AE was acute kidney injury (2% in each arm), with treatment-related serious AEs 2% in both groups and no treatment-related deaths (NCT01436968).