Aglatimagene Besadenovec Plus Radiotherapy in Localized Prostate Cancer

Key Takeaways

• Longer disease-free survival was observed with aglatimagene besadenovec added to radiotherapy than with placebo.
• The phase 3, randomized, double-blind, placebo-controlled trial delivered CAN-2409 intraprostatically alongside radiotherapy.
• Grade 3 or worse events, serious adverse events, and treatment-related serious adverse events were broadly similar between groups.

In men with intermediate- or high-risk localized prostate cancer, adding intraprostatic aglatimagene besadenovec plus valacyclovir to standard radiotherapy improved disease-free survival versus placebo plus valacyclovir. In a phase 3 randomized trial, the hazard ratio was 0.70 (95% CI 0.52-0.94; p=0.016). The same external beam radiotherapy backbone was used in both groups, with optional androgen deprivation therapy. Serious toxicity rates were broadly similar between groups.

The multicenter study was conducted at 51 centers in the United States and Puerto Rico. Eligible men were aged 18 years or older, had intermediate- or high-risk localized disease, an ECOG performance status of 0-2, and planned external beam radiotherapy. Patients were assigned 2:1 to three intraprostatic aglatimagene courses at 5 × 10^11 viral particles plus valacyclovir or to placebo plus valacyclovir, with stratification by risk category and ADT use. Radiotherapy consisted of EBRT 78 Gy in 2 Gy fractions or hypofractionated EBRT 60 Gy in 3 Gy fractions or 70 Gy in 2.5 Gy fractions, with optional androgen deprivation therapy. The primary endpoint was disease-free survival from randomization to prostate cancer recurrence or death in the intent-to-treat population.

Enrollment occurred between Feb 21, 2012, and Sept 9, 2021. The trial randomly assigned 745 men, including 591 White participants and 121 Black participants. Of these, 496 received aglatimagene plus valacyclovir and 249 received placebo plus valacyclovir. Median follow-up was 50.3 months, with an interquartile range of 35.2-63.3 months. The disease-free survival results showed that median disease-free survival was not reached in the investigational group, while the placebo group reached 86.1 months.

Among treated patients, grade 3 or worse treatment-emergent adverse events occurred in 40 of 479 men (8%) with aglatimagene and 17 of 232 men (7%) with placebo. Serious adverse events occurred in 28 of 479 men (6%) with aglatimagene and 17 of 232 men (7%) with placebo. Treatment-related serious adverse events occurred in 8 of 479 men (2%) and 5 of 232 men (2%), respectively. Acute kidney injury was the most common grade 3 or worse treatment-emergent adverse event in both groups, no treatment-related deaths were reported, and longer-term follow-up is ongoing.