Aglatimagene Besadenovec (CAN-2409) with Radiotherapy for Patients with Localised Prostate Cancer: A Phase 3, Multicentre, Randomised, Double-Blind, Placebo-Controlled Trial - Beyond the Abstract
Looking Beyond Traditional Clinical Endpoints
One of the longstanding challenges in localized prostate cancer research is the prolonged natural history of the disease. Demonstrating meaningful improvements in long-term clinical outcomes often requires many years of follow-up. Consequently, there is substantial interest in objective biological markers that may provide earlier insight into treatment effectiveness while remaining clinically relevant.
In our phase 3 study, patients underwent per-protocol two-year prostate biopsies that were centrally reviewed in a blinded fashion. These biopsies provide a direct and objective assessment of residual or recurrent cancer within the prostate after treatment.
Pathological response assessment offers several advantages. Unlike serum biomarkers or imaging findings, biopsy evaluation directly measures the presence or absence of viable tumor cells within the treated organ. As such, it represents a sensitive and reliable research tool for understanding the biological effects of therapy.
Importantly, the significance of these biopsy findings is supported by published literature. Singh and colleagues demonstrated that post-treatment prostate biopsies after radiotherapy are predictive of subsequent clinical outcomes, including metastatic disease progression, highlighting their value as a clinically meaningful surrogate marker of long-term benefit (Singh S et al. Prostate Cancer and Prostatic Diseases. 2021;24:612-622).
Against this backdrop, the statistically significantly increased pathological complete response rate observed with aglatimagene besadenovec versus placebo is particularly noteworthy. The pathological findings provide direct evidence at a microscopic level that the therapy enhances the eradication of cancer cells within the prostate beyond what is achieved with radiotherapy alone.
From Pathology to Patient Outcomes
Of course, pathological response only matters if it translates into outcomes that are meaningful for patients.
At the 2026 Annual Meeting of the American Urological Association, Dr. Mark Garzotto presented updated long-term follow-up data from this phase 3 study during a plenary oral session. These analyses demonstrated that the improvements observed in pathological response were associated with favorable effects on clinically important endpoints.
Patients treated with aglatimagene besadenovec experienced improved time to biochemical failure, indicating more durable disease control. Importantly, they also experienced longer time to salvage anti-cancer therapy, delaying the need for additional treatments that are frequently associated with toxicity, side effects, inconvenience, and substantial impact on quality of life.
Perhaps most compelling was the observation that these benefits extended to metastatic progression. In the intermediate-risk population (n=635), treatment with aglatimagene besadenovec was associated with a 90% reduction in the time to metastasis (HR=0.10; 95% CI 0.01–0.85). While the absolute number of metastatic events remains low in this curative-intent setting after a median follow up of 58 months, the finding is directionally consistent with the broader pattern of benefit observed across pathological and clinical endpoints.
Taken together, these data suggest a coherent biological narrative: enhanced local eradication of cancer cells, demonstrated through objective pathological assessment, translates into improved disease control and reduced progression to clinically significant events.
Why This Matters to Patients
For men diagnosed with intermediate-risk or high-risk localized prostate cancer, cure remains the primary goal. However, there is a risk of recurrence after standard-of-care radical treatment of ~30%; the journey to cure is equally important.
Patients increasingly seek treatment strategies that maximize their chances of long-term cancer control while minimizing exposure to additional therapies and their associated burdens. Delaying biochemical recurrence, postponing salvage interventions, and reducing the likelihood of metastatic progression are outcomes that matter deeply to patients and their families.
The multimodal mechanism of aglatimagene besadenovec is particularly attractive in this regard. By combining direct tumor cell killing with activation of anti-tumor immunity, the therapy is designed not merely to augment local treatment, but to generate systemic immune responses that may contribute to durable cancer control.
A Potential Framework Shift
The conclusion of the Lancet Oncology publication (DeWeese TL et al. Lancet Oncol 2026;27:673-685) captures the significance of these findings:
"To our knowledge, this study is the first, multicentre, randomised phase 3 clinical trial that achieved its primary and secondary endpoints in localised prostate cancer in more than 20 years, offering a potential framework shift in the treatment of patients with intermediate-risk to high-risk localised prostate cancer who seek cure. If approved, aglatimagene immunotherapy could represent, to the best of our knowledge, the first new therapy for men with localised prostate cancer in over 20 years."
This statement reflects not only the positive outcome of a single clinical trial but also the possibility that immunotherapy may have a meaningful role in the treatment of localized, curable malignancies.
For decades, innovation in localized prostate cancer has focused primarily on refining surgery, radiotherapy, and hormonal approaches. Our findings suggest that activating the patient's own immune system may become an important additional component of curative-intent treatment.
While continued follow-up remains essential, the convergence of pathological, biological, and clinical evidence observed in this study provides encouraging support for this emerging paradigm.
Ultimately, our goal is simple: to help more men diagnosed with localized prostate cancer achieve what they seek most—to live free from recurrence, free from metastasis, and free from cancer.
Written by: Paul Peter Tak, MD, PhD, FMedSci, President & CEO, Candel Therapeutics. X: @PaulPeterTak
Read the Abstract
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