Aglatimagene Plus Radiotherapy Improves Disease-Free Survival in Localized Prostate Cancer

Clinical Summary:

• Design/Population: This phase 3 trial evaluated aglatimagene plus valacyclovir vs placebo in 745 men with intermediate- to high-risk localized prostate cancer receiving external-beam radiotherapy, with optional short-course androgen deprivation therapy.
• Key Outcomes: Aglatimagene significantly improved disease-free and prostate cancer–specific disease-free survival, increased low prostate-specific antigen nadir and pathological complete response rates, and had manageable toxicity similar to placebo.
• Clinical Relevance: These findings support aglatimagene plus valacyclovir as a potential radiotherapy intensification strategy to improve disease control without substantial added toxicity.

Results from the phase 3 PrTK03 trial demonstrated that adding aglatimagene besadenovec plus valacyclovir to standard external-beam radiotherapy significantly improved disease-free survival (DFS) in patients with intermediate- to high-risk localized prostate cancer, supporting radiotherapy intensification as a potential strategy to improve disease control.

“Around 30% of men with localized prostate cancer treated with curative-intent radiotherapy have disease recurrence, often resulting in anxiety, disease progression, and the need for salvage therapies with substantial side-effects,” stated Theodore DeWeese, MD, Johns Hopkins University, Baltimore, Maryland, and coauthors. “Earlier clinical trials of aglatimagene besadenovec, an adenoviral-based immunotherapy delivered with a prodrug, showed promising antitumor activity across multiple solid tumors, including prostate cancer.”

In this double-blind, placebo-controlled trial, 745 patients were randomized 2:1 to receive 3 intraprostatic injections of either aglatimagene besadenovec (n = 496) or placebo (n = 249) plus valacyclovir in combination with standard-of-care external-beam radiotherapy with optional short-course androgen deprivation therapy. The primary end point was DFS in the intent-to-treat population. Key secondary end points included prostate cancer-specific DFS, prostate-specific antigen (PSA) nadir of ≤0.2 ng/mL, prostate cancer-specific survival, overall survival (OS), and quality-of-life up to 2 years post-treatment. 

At a median follow-up of 50.3 months, DFS significantly favored the aglatimagene group. Median DFS was not reached in the aglatimagene arm and 86.1 months in the placebo arm (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.52 to 0.94; P = .016).  DFS events were reported in 23% and 31% of patients, respectively. 

The improvement extended to prostate cancer–specific outcomes. Median prostate cancer-specific DFS was not reached in the aglatimagene arm and 143 months in the placebo arm (HR, 0.62; 95% CI, 0.44 to 0.87; P = .0046), representing a 38% reduction in prostate cancer recurrence or prostate cancer–related death. A PSA nadir of ≤0.2 ng/mL was achieved by 67% of patients in the aglatimagene arm and 59% of patients in the placebo arm (P = .016). 

In a post hoc blinded review of evaluable 2-year post-radiotherapy biopsies, pathological complete response was observed in 80% and 63% of patients, respectively (P = .0018). OS remained similar between treatment groups, with only 2 prostate cancer–related deaths reported during follow-up. 

Treatment was generally well tolerated, with no evidence of increased clinically significant toxicity. Grade ≥3 treatment-emergent adverse events occurred in 8% of patients in the aglatimagene arm and 7% of patients in the placebo arm. Treatment-related serious adverse events occurred in 2% of patients in both treatment groups, and no treatment-related deaths were reported. The most common treatment-related adverse events included chills, influenza-like illness, pyrexia, pollakiuria, and nausea. Patient-reported quality-of-life outcomes were similar between groups over 2 years.

“These findings support a potential framework shift in the management of intermediate-risk to high-risk localized prostate cancer, with the potential to reduce cancer-related anxiety, avoid salvage therapies associated with adverse effects, and improve long-term oncological outcomes,” concluded Dr DeWeese et al. 

Source:

DeWeese TL, Manzanera A, Sylvester J, et al. Aglatimagene besadenovec (CAN-2409) with radiotherapy for patients with localised prostate cancer: A phase 3, multicentre, randomised, double-blind, placebo-controlled trial. Lancet Oncol. Published online: June 2026. doi: 10.1016/S1470-2045(26)00071-9