CAN 2409 Plus Radiotherapy Extends Disease-Free Survival

Key Takeaways

• Disease-free survival favored CAN 2409 plus valacyclovir over placebo plus valacyclovir during the reported follow-up.
• Men were randomly assigned 2:1 to three intraprostatic CAN 2409 courses at 5 × 10^11 viral particles plus valacyclovir or placebo plus valacyclovir with EBRT and optional ADT.
• Grade 3 or worse treatment-emergent adverse events and serious adverse events were similar between groups, and no treatment-related deaths were reported.

Men with intermediate- or high-risk localized prostate cancer had longer disease-free survival with aglatimagene besadenovec (CAN 2409) plus valacyclovir than with placebo plus valacyclovir in a phase 3 randomized trial, with a hazard ratio of 0.70 (95% CI, 0.52 to 0.94; p=0.016). Both groups received valacyclovir with radiotherapy, with placebo used in the control arm. Safety was broadly similar between groups, without a signal for excess clinically significant toxicity. The comparison involved localized disease treated with radiotherapy.

At 51 medical centers across the USA and Puerto Rico, the phase 3 randomized trial was multicenter, double-blind, and placebo-controlled. Eligible participants were men aged at least 18 years with intermediate- or high-risk localized prostate cancer, ECOG performance status 0 to 2, and plans for EBRT. Between Feb 21, 2012, and Sept 9, 2021, 745 men were randomly assigned 2:1, with 496 to aglatimagene plus valacyclovir and 249 to placebo plus valacyclovir. Treatment consisted of three intraprostatic aglatimagene courses at 5 × 10^11 viral particles or placebo plus valacyclovir, plus EBRT at 78 Gy, 60 Gy, or 70 Gy, with optional ADT. The primary endpoint was disease-free survival in the intent-to-treat population, measured from randomization to prostate cancer recurrence or death, and EBRT used 2 Gy, 3 Gy, or 2.5 Gy fractions.

Median follow-up was 50.3 months, with an interquartile range of 35.2 to 63.3 months. Disease-free survival was defined as prostate cancer recurrence or death after randomization. Median disease-free survival was not reached with aglatimagene plus valacyclovir and was 86.1 months with placebo plus valacyclovir. The disease-free survival comparison favored CAN 2409, with a hazard ratio of 0.70, a 95% confidence interval of 0.52 to 0.94, and p=0.016. Investigators interpreted the combination as associated with longer disease-free survival when added to standard radiotherapy during the reported follow-up.

Grade 3 or worse treatment-emergent adverse events occurred in 40 of 479 patients, or 8%, with aglatimagene and 17 of 232, or 7%, with placebo. Acute kidney injury was the most common grade 3 or worse event in both groups, affecting 9 of 479 patients and 4 of 232 patients. Serious adverse events occurred in 28 of 479 patients, or 6%, with aglatimagene and 17 of 232, or 7%, with placebo. Treatment-related serious adverse events occurred in 8 patients, or 2%, with aglatimagene and 5 patients, or 2%, with placebo. Named treatment-related serious events included acute kidney injury, pyrexia, influenza-like symptoms, urinary retention, increased creatinine levels, and skin rash. No treatment-related deaths were reported, and long-term follow-up is ongoing.