CAN-2409 NCT01436968
ForIntermediate or high-risk localised prostate cancer, EBRT candidates, ECOG 0-2
HR 0.70
95% CI 0.52-0.94, p=0.016; median NR vs 86.1 mo
TL;DRDFS HR 0.70 (0.52-0.94), 2y biopsy persistence/recurrence 19.6% vs 36.4%, adding intraprostatic aglatimagene to EBRT in intermediate/high-risk localised prostate cancer.
The effect is local: 2y post-treatment biopsy persistence/recurrence 19.6% vs 36.4% (p=0.0015), while OS and PCSM were not different (1 PCSM event per arm). That places it beside ADT, SIB and brachy boost as a local-intensification option; the discussant's RTOG 9408 benchmark, 4mo ADT added to 66.6 Gy, showed 2y positive biopsy 40% vs 20%.
In intermediate or high-risk localised prostate cancer planned for 78 Gy in 2 Gy, 60 Gy in 3 Gy or 70 Gy in 2.5 Gy fractions, this supports intraprostatic aglatimagene as a DFS-improving addition; it does not extend to pts whose EBRT includes a brachytherapy or SIB boost.
Local control is the RT read: 2y biopsy persistence/recurrence 19.6% vs 36.4% (p=0.0015) on 78 Gy or hypofractionated EBRT, with OS and PCSM not different. It sits beside ADT, SIB and brachy boost as local intensification, none of which was tested with it here.
| Trial | Arms | Local endpoint | Control vs intensified |
|---|---|---|---|
| RTOG 9408 | RT 66.6Gy vs + 4m ADT | 2yr post-Rx biopsy positive | 40% vs 20% |
| ASCENDE-RT | 46Gy + DE-EBRT 23Gy vs 46Gy + LDR-BT | 10y local failure | 7.1% vs 1.5% |
| FLAME | RT 77Gy vs + SIB 95Gy | Crude local failure | 7.7% vs 2.7% |
| CAN-2409 | RT 78Gy + placebo vs + CAN-2409 | 2yr post-Rx biopsy positive | 36.4% vs 19.6% |
8 details
Phase 3, randomised 2:1, double-blind, placebo-controlled at 51 US and Puerto Rico centres (26 community, 25 institutional or military). Accrual Feb 2012 to Sept 2021; median follow-up 50.3 mo (IQR 35.2-63.3).
Intermediate or high-risk localised prostate cancer planned for EBRT, age ≥18, ECOG 0-2. N=745 (496 vs 249); 591 (79%) White, 121 (16%) Black.
Three courses of intraprostatic aglatimagene (5 × 10^11 viral particles) plus valacyclovir vs placebo plus valacyclovir. Stratified by risk category and ADT use; ADT optional.
78 Gy in 2 Gy fractions, or hypofractionated 60 Gy in 3 Gy or 70 Gy in 2.5 Gy fractions. No boost regimen described in source.
Primary: DFS, time from randomisation to prostate cancer recurrence or death, ITT. Safety in all pts receiving ≥1 injection.
Per the discussant, the DFS gain was driven mainly by 2y post-treatment biopsy pCR; OS and PCSM not significantly different.
| Endpoint | Aglatimagene + valacyclovir | Placebo + valacyclovir | Effect |
|---|---|---|---|
| Median DFS | NR (95% CI 121.78-NR) | 86.1 mo | HR 0.70 (0.52-0.94), p=0.016 |
| 2y post-Rx biopsy pCR | 80.4% | 63.6% | not stated |
| 2y biopsy persistence/recurrence | 19.6% | 36.4% | p=0.0015 |
G3+ TEAEs 8% vs 7%; most common G3+ event AKI (2% each). SAEs 6% vs 7%, treatment-related SAEs 2% each. No treatment-related deaths.
The discussant set it against established local-intensification strategies: ADT in RTOG 9408, LDR brachy boost in ASCENDE-RT and focal SIB in FLAME. None was tested head-to-head or in combination with aglatimagene.
Long accrual (Feb 2012 to Sept 2021). Safety population (479 and 232) smaller than randomised arms (496 and 249). MFS and biochemical recurrence not presented; funded by Candel Therapeutics and NIH.
A positive blinded phase 3 of an oncolytic-viral agent with RT and no toxicity penalty, but the benefit currently rests on biopsy-defined local persistence. Whether that converts to MFS or PCSM, and whether it holds against boost-level dose intensification, is unsettled.
CONSORT flow
Blinded phase 3 met DFS at 50.3mo, but gain driven by 2y biopsy persistence; OS/PCSM not different, and no boost-level dose intensification in control.
- Does the biopsy-driven DFS gain translate into MFS or PCSM benefit?
- Added value over brachytherapy boost or focal SIB dose intensification
- Interaction with ADT use and duration
📚 Sources · 🐦 1 tweet · 📄 1 paper
🗣️Prostate Oral Abstract #ASCO25
— Michael Serzan, MD (@MikeSerzanMD) June 3, 2025
👉Dr @angela_jia_ discusses "Better Treatments, Better Selection: Improving Patient Outcomes in Localized Prostate Cancer"
🔑 KEY TAKE AWAYS
- #CAN2409 improves DFS and 2yr PathCR however PCSM and OS remain immature.
❓How to integrate with… pic.twitter.com/WamsneYBI1
Abstract
The longer read
This is a blinded, placebo-controlled phase 3 showing that an intraprostatic agent given alongside curative EBRT improves disease-free survival in intermediate or high-risk localised prostate cancer, and it does so without an obvious toxicity cost: grade 3 or worse TEAEs were 8% vs 7%, and treatment-related SAEs were 2% in each arm. The design choices that matter most for credibility hold up. Placebo injections plus valacyclovir in both arms preserve blinding for a procedure-based intervention, randomisation was stratified by risk group and ADT use, and the primary analysis is intent-to-treat.
The harder question is what DFS HR 0.70 actually represents. The discussant's read is that the effect was driven mainly by 2-year post-treatment biopsies, with persistence or recurrence 19.6% vs 36.4%, while OS and PCSM were not significantly different and PCSM carried a single event per arm. A composite that counts biopsy findings registers a local effect earlier and more often than one built on PSA failure, metastasis, or death. Because the trial is blinded, differential detection between arms is unlikely, so this is not a flaw in the comparison. It does mean the trial has established a local-control effect and not yet a clinical one. MFS and biochemical recurrence, the endpoints a radiation oncologist would weigh most heavily, were not presented in the discussant summary.
Framed against existing ways of reducing local recurrence, the discussant placed the biopsy effect beside RTOG 9408, where adding 4 months of ADT to 66.6 Gy reduced 2-year positive biopsies from 40% to 20%, and beside ASCENDE-RT and FLAME, where brachytherapy boost and focal SIB lowered local failure. Those comparisons span different endpoints, timepoints and eras, so they are directional rather than quantitative. The structural point matters more. The control arm here received 78 Gy or moderate hypofractionation without a boost, and ADT was optional. The trial tells us aglatimagene improves on a standard dose-escalated backbone. It does not tell us whether the agent adds anything once residual intraprostatic disease has been addressed by a boost, or how much of its effect overlaps with what ADT already achieves on the same biopsy endpoint.
Generalisability is reasonable: 51 centres including 26 community sites, and 16% of enrolled men were Black. Accrual ran from 2012 to 2021, and a median follow-up of 50.3 months is short for a disease in which cancer deaths arrive late. One PCSM event per arm means the survival question is unanswered, not answered in the negative. For the trial to be wrong in the sense that matters, biopsy-defined persistence at 2 years would have to fail to translate into fewer metastases, which is possible given that histologic clearance after RT can lag, and not something the current data can settle. Until MFS is reported, the defensible position is that aglatimagene is a well-tolerated local-intensification option with a demonstrated effect on local disease and an undemonstrated one on the outcomes that define long-term benefit, and its place relative to boost strategies remains an open comparison rather than a settled hierarchy.