Phase III PrTK03 Trial Results: Aglatimagene Besadenovec (CAN-2409) Improves Survival in Localized Prostate Cancer

The phase III PrTK03 trial, reported in The Lancet Oncology, demonstrates that adding aglatimagene besadenovec (CAN-2409) plus valacyclovir to standard radiotherapy improves disease-free survival in patients with localized prostate cancer. Aglatimagene is an intratumoral adenoviral gene therapy that delivers the HSV-tk gene, enabling tumor cells to convert the prodrug valacyclovir into a cytotoxic metabolite that disrupts DNA replication and repair, ultimately inducing tumor cell death. The study enrolled 745 patients in a U.S.–Puerto Rican double-blind trial, with participants randomly assigned 2:1 between February 2012 and September 2021 to receive three courses of intraprostatic aglatimagene plus valacyclovir (n = 496) or placebo plus valacyclovir (n = 249). All patients received standard-of-care external beam radiation therapy, either 78 Gy in 2 Gy fractions or hypofractionated regimens, with optional androgen-deprivation therapy. The primary endpoint was disease-free survival.

The most important finding centers on disease-free survival and the hazard ratio. In the aglatimagene plus valacyclovir group, the median disease-free survival was not reached, with a 95 percent confidence interval extending from 121.78 months to not reached. In contrast, the placebo plus valacyclovir group had a median disease-free survival of 86.1 months.The hazard ratio was 0.70, with a 95 percent confidence interval of 0.52 to 0.94 and a p-value of .016. The hazard ratio of 0.70 means that at any given point in time during follow-up, patients receiving aglatimagene plus valacyclovir had a 30 percent lower risk of disease recurrence or death compared with those receiving placebo plus valacyclovir. This is a time-to-event interpretation: the 30 percent reduction applies continuously across the entire follow-up period, not just at a single time point. The confidence interval and p-value confirm that this reduction is statistically significant and genuinely impactful.

Safety data showed that adverse events of grade 3 or worse occurred in 8 percent of the aglatimagene plus valacyclovir group and 7 percent of the placebo plus valacyclovir group, with acute kidney injury occurring in 2 percent of each group as the most common serious event. Treatment-related serious adverse events occurred in 2 percent of both groups.  No treatment-related deaths were reported. The investigators concluded that aglatimagene plus valacyclovir was associated with longer disease-free survival than placebo plus valacyclovir when added to standard radiotherapy for localized prostate cancer, offering a meaningful benefit without increasing clinically significant toxicity. This represents a potentially practice-changing approach for intermediate- to high-risk localized prostate cancer.

Note:
One thing that stands out is the timeline. The PrTK03 trial began in February 2012, and we now have solidified phase III results in 2026, fourteen years later. For localized prostate cancer, this long follow-up is partly because patients live longer and it takes time to reach median overall survival, which is good for them individually! But from a research and public-health perspective, fourteen years is too long. We need faster ways to bring effective treatments to patients: better surrogate endpoints (like pathological complete response on biopsy, early PSA kinetics, or imaging-based metrics), adaptive trial designs, and regulatory pathways that can accept validated intermediate outcomes. Every year of delay means thousands of men continuing with the older standard instead of a therapy that reduces recurrence risk by 30%. Over fourteen years, that delay could have spared many recurrences, postponed or prevented metastases, and meaningfully prolonged survival for a large number of patients.

Source.