Clinical Summary: 

• Design/Population: This randomized, phase 3 trial evaluated aglatimagene plus standard radiotherapy with or without short-course androgen deprivation therapy in patients with localized intermediate- or high-risk prostate cancer.
• Key Outcomes: Aglatimagene improved prostate cancer-specific disease-free survival and demonstrated favorable trends across secondary clinical outcomes, including biochemical failure, metastasis, and need for additional therapy.
• Clinical Relevance: These findings support aglatimagene as a potential addition to curative-intent radiotherapy strategies for localized prostate cancer.

Results from a phase 3 trial demonstrated that aglatimagene, a replication-defective adenovirus encoding HSV-tk, improved prostate cancer-specific survival when added to standard external beam radiotherapy (EBRT) with or without androgen deprivation therapy (ADT) among patients with localized prostate cancer.

These results were presented by Mark Garzotto, MD, Oregon Health and Science University, Portland, Oregon, at the 2026 American Urological Association (AUA) Annual Meeting in Washington, District of Columbia.

In this study, 745 patients were randomized 2:1 to receive either 5×10¹¹vp/2 mL of aglatimagene CAN-2409 (n = 496) or placebo (n = 249) in 3 intraprostatic injections, each followed by valacyclovir for 14 days, in combination with standard EBRT with or without ADT for up to 6 months. The primary end point was prostate cancer-specific disease-free survival (DFS). Secondary and exploratory end points included time to biochemical failure, time to metastasis, and time to new therapy.

At analysis, aglatimagene improved prostate cancer-specific DFS by 39% (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.44 to 0.85; P = .0031). Prostate cancer-specific deaths were reported in 1 patient in each treatment arm. The rate of metastasis was 1.6% in the aglatimagene arm and 2.8% in the placebo arm. Data on time to metastasis and time to new therapy were immature at analysis. 

In the subgroup of patients with intermediate-risk disease (aglatimagene n = 422; placebo n = 213), aglatimagene improved prostate cancer-specific DFS by 41% (HR, 0.59; 95% CI, 0.41 to 0.84; P = .0034). The rate of metastasis was 0.24% in the aglatimagene arm and 2.35% in the placebo arm. Aglatimagene improved time to biochemical failure (HR, 0.48), time to metastasis (HR, 0.1), and time to new therapy (HR, 0.51). 

“Further exploratory analyses after extended follow-up show accumulating benefit for [prostate cancer]-specific clinical outcomes,” concluded Dr Garzotto. “If approved, aglatimagene could represent a new therapy for [patients] treated with EBRT with curative intent for localized [prostate cancer].” 

Source: 

Garzotto M, Sylvester J, Wheeler T, et al. Extended follow-up shows accumulating benefit for patients treated with aglatimagene besadenovec (CAN-2409)+ prodrug in combination with standard of care external beam radiation (EBRT) in men with localized prostate cancer: Update from a randomized placebo-controlled phase 3 clinical trial. J Urol. Published online: May 1, 2026. doi:10.1097/01.JU.0001192572.07890.f8.01