Adding CAN-2409 to radiation significantly extends DFS in localized prostate cancer

Adding aglatimagene besadenovec (CAN-2409) to standard of care (SOC) external beam radiation (EBRT) with or without androgen deprivation therapy (ADT) led to a statistically significant improvement in disease-free survival (DFS) vs EBRT alone in patients with intermediate- to high-risk localized prostate cancer, according to data from the phase 3 PrTK03 trial (NCT01436968) presented at the 2025 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois.¹

At a median follow-up of 50.3 months, data showed that the addition of CAN-2409 to radiation therapy reduced the risk of prostate cancer recurrence or death by 30% compared with radiation alone (HR, 0.70; 95% CI, 0.52 to 0.94; P = .0155).

Theodore L. DeWeese, MD

Theodore L. DeWeese, MD, who presented the data on behalf of the investigators, stated “Given those data, along with its very favorable toxicity profile, CAN-2409, I think, offers a potential paradigm shift in how we think about treatments for men with intermediate- to high-risk prostate cancer.”

According to Candel Therapeutics, CAN-2409 is “an investigational, off-the-shelf, replication-defective adenovirus designed to deliver the herpes simplex virus thymidine kinase (HSV-tk) gene to a patient’s specific tumor and induce an individualized, systemic immune response against the tumor.”² The immunotherapy is designed to work in combination with valacyclovir (prodrug) to induce immunogenic cell death of tumor cells.

In the phase 3 study, 745 patients were randomly assigned 2:1 to receive 3 injection courses of CAN-2409 plus valacyclovir (n = 496) or placebo plus valacyclovir (n = 249) plus EBRT with or without short-course ADT. Baseline characteristics were well-balanced between both arms.

The primary end point for the study was DFS. Key secondary end points included prostate-specific antigen (PSA) freedom from biochemical failure, prostate cancer-specific outcomes, and overall survival (OS).

Data from the trial also confirmed that the DFS benefit with CAN-2409 was seen independent of the use of short-course ADT, with an HR of 0.56 (95% CI, 0.38 to 0.83) among those who did not receive ADT and an HR of 0.92 (95% CI, 0.5 to 1.67) among those who did receive ADT. In patients who did receive ADT, the HR was 0.47 (95% CI, 0.27 to 0.82) for those with favorable risk disease and 0.72 (95% CI, 0.42 to 1.24) for those with unfavorable risk disease. In patients who did receive ADT, the HR was 2.26 (95% CI, 0.27 to 18.93) for those with favorable risk disease and 0.81 (95% CI, 0.42 to 1.53) for those with unfavorable disease.

DeWeese specifically touched on the large HR seen among those with favorable risk disease who received short-course ADT, noting that the 2.26 HR is likely not reliable due to the small sample size (n = 31) and the large confidence interval.

The CAN-2409 regimen was also found to significantly improve prostate cancer-specific DFS (HR, 0.62; 95% CI, 0.44 to 0.87; P = .0046) vs the placebo regimen.

On the trial’s other key secondary end points, the CAN-2409 regimen resulted in a significant increase in the proportion of patients who achieved a PSA nadir of less than 0.2 ng/mL. Overall, 67.1% of patients in the treatment arm achieved a PSA nadir less than 0.2 ng/mL compared with 58.6% of patients in the placebo arm (P = .0164).

Further, at a median follow-up of 50 months, OS was similar across the 2 arms. There were 2 deaths due to prostate cancer in the study, with 1 from each arm. Fifty patients died due to other causes over the study period.

CAN-2409 also improved the rate of pathological complete response (pCR) in biopsies conducted at 2 years. Overall, pCR was achieved in 80.4% of patients in the CAN-2409 arm vs 63.6% of patients in the placebo arm (P = .0015).

Put another way, at 2 years, 19.6% of patients in the CAN-2409 arm vs 36.4% of patients in the placebo arm had a positive biopsy at 2 years.

Treatment with CAN-2409 was generally well-tolerated, with the most common treatment-related adverse events (TRAEs) being chills, fever, and flu-like symptoms. These were generally mild to moderate and self-limited.

Additionally, serious AEs and serious TRAEs were lower in the treatment arm. Overall, 5.8% of patients in the CAN-2409 arm experienced a serious AE vs 7.3% of patients in the placebo arm. Additionally, 1.7% of patients in the CAN-2409 arm experienced a serious TRAE compared with 2.2% of patients in the placebo arm.

Based on these data, the authors concluded, “CAN-2409 immunotherapy could represent the first new therapy for men with localized prostate cancer in over 20 years.”

REFERENCES

1. DeWeese T, Wheeler T, Sylvester J, et al. Phase 3, randomized, placebo-controlled clinical trial of CAN-2409+prodrug in combination with standard of care external beam radiation (EBRT) for newly diagnosed localized prostate cancer. J Clin Oncol. 2025;43(suppl 17):5000. doi:10.1200/JCO.2025.43.16_suppl.5000

2. Candel Therapeutics presents positive phase 3 CAN-2409 results in localized prostate cancer at ASCO 2025. News release. Candel Therapeutics. May 22, 2025. Accessed June 3, 2025. https://ir.candeltx.com/news-releases/news-release-details/candel-therapeutics-presents-positive-phase-3-can-2409-results