Background
Phase 3, multicenter, randomized, double-blind, placebo-controlled trial; N=745; intermediate- or high-risk localized prostate cancer planned for external-beam radiotherapy; 51 US/Puerto Rico centers; gene-mediated immunotherapy (aglatimagene besadenovec, CAN-2409) + valacyclovir added to radiotherapy.
Results
Interventions and follow up: Arm A: Intraprostatic aglatimagene besadenovec ×3 courses + oral valacyclovir, plus standard EBRT (78 Gy/2 Gy or hypofractionated) ± ADT (n=496)
Arm B: Placebo + valacyclovir + EBRT ± ADT (n=249)
Primary endpoint: Disease-free survival (DFS), ITT
Randomization: 2:1
mFollow up: 50.3 mo
Results: DFS: median NR vs 86.1 mo; HR 0.70 (95% CI 0.52–0.94); P=.016
Intermediate-risk subgroup (~85% of population): large reduction in time to metastasis reported on extended follow-up (sponsor data)
Arm B: Placebo + valacyclovir + EBRT ± ADT (n=249)
Primary endpoint: Disease-free survival (DFS), ITT
Randomization: 2:1
mFollow up: 50.3 mo
Results: DFS: median NR vs 86.1 mo; HR 0.70 (95% CI 0.52–0.94); P=.016
Intermediate-risk subgroup (~85% of population): large reduction in time to metastasis reported on extended follow-up (sponsor data)
Adverse events
Grade ≥3 treatment-emergent (any): 8% vs 7%
Most common grade ≥3: acute kidney injury (2% vs 2%)
Serious AEs: 6% vs 7%
Treatment-related deaths: 0
Most common grade ≥3: acute kidney injury (2% vs 2%)
Serious AEs: 6% vs 7%
Treatment-related deaths: 0
Conclusions
Adding the off-the-shelf gene-therapy aglatimagene besadenovec plus valacyclovir to standard radiotherapy significantly prolonged disease-free survival in localized prostate cancer without meaningful added toxicity — a positive pivotal phase 3 for a novel viral-vector immunotherapy combined with radiotherapy.
Key Limitations
Very long enrollment (2012–2021) spanning evolving radiotherapy technique and ADT use; composite DFS endpoint; modest hazard ratio (0.70); OS not reached/immature; predominantly White population (79%); ADT use optional/variable.
Clinical Context
Aglatimagene besadenovec (CAN-2409, Candel Therapeutics) is investigational; a Biologics License Application is anticipated in Q4 2026. If approved it would be a first-in-class gene-mediated immunotherapy adjunct to definitive radiotherapy for localized prostate cancer, addressing the ~30% of patients who recur after curative-intent radiotherapy; there is no guideline positioning pending regulatory review.