CAN-2409 significantly improves disease-free survival in localized prostate cancer

The addition of CAN-2409 plus valacyclovir (prodrug) to standard-of-care radiotherapy significantly improved disease-free survival (DFS) compared with placebo plus valacyclovir in patients with localized intermediate- to high-risk prostate cancer, according to data from the phase 3 PrTK03 trial (NCT01436968) presented at the American Society for Radiation Oncology 67th Annual Meeting in San Francisco, California.¹

The findings were presented by Glen Gejerman, MD, MBA, who is the co-director of urologic oncology at Hackensack Meridian Health in New Jersey.

“For [patients with intermediate-risk disease], we haven't made as many strides,” Gejerman explained during the presentation. “CAN-2409 is a replication-defective andenoviral vector carrying the herpes simplex virus thymidine kinase gene. CAN-2409 induces the formation of CD8+ cytotoxic T cells, and a local immunization yields a systemic CD8+ T-cell response. The localized cytologic mechanism combined with proinflammatory viral particles is synergistic with radiotherapy.”

In total, the study enrolled 745 patients who were randomly assigned 2:1 to receive 3 injections of either CAN-2409 plus prodrug (n = 496) or placebo plus prodrug (n = 249) in addition to external beam radiotherapy (EBRT) with or without short-course androgen deprivation therapy (ADT). Radiation therapy was initially offered in a conventional regimen, but a protocol amendment in 2019 allowed for patients to receive a moderate hypofractionated regimen.

Baseline characteristics were well balanced between both arms.

The primary end point for the trial was DFS, with events defined as positive biopsy at 2 years, regional metastatic disease, or death due to any cause. Key secondary end points included prostate-specific antigen (PSA) freedom from biochemical failure, prostate cancer–specific outcomes, and overall survival (OS).

At a median follow-up of 50.3 months (95% CI, 45.37 to 51.29), data showed that CAN-2409 led to a 30% improvement in DFS compared with standard of care (SOC) (HR, 0.70; 95% CI, 0.52 to 0.94; P = .0155). CAN-2409 also led to a 38% improvement in prostate cancer–specific DFS compared with SOC (HR, 0.62; 95% CI, 0.44 to 0.87; P = .0046).

According to the authors, CAN-2409 improved DFS across all subgroups, including those based on risk group and whether short-term ADT was used. DFS was also improved regardless of the radiation therapy used. The HR was 0.52 in patients who received moderately hypofractionated EBRT and 0.76 in patients who received conventional EBRT.

“These additional analyses suggest that the efficacy of CAN-2409 is independent of the modality of radiation used," added Gejerman, in a news release on the findings.² "Most importantly, the activity of CAN-2409 was maintained with moderate hypofractionated radiation, which is more convenient for patients."

On the trial's key secondary end points, CAN-2409 led to a significant increase in the proportion of patients who achieved a PSA nadir of less than 0.2 ng/mL compared with placebo. Specifically, 67.1% of patients in the CAN-2409 arm achieved a PSA nadir less than 0.2 ng/mL vs 58.6% of patients in the placebo arm (P = .0164).

CAN-2409 also significantly improved the pathological complete response (pCR) rate on 2-year biopsies. Overall, 80.4% of patients in the CAN-2409 arm vs 63.6% of patients in the placebo arm achieved a pCR on 2-year biopsy (P = .0015).

At the time of the data report, OS was similar between both treatment arms. There were 2 deaths due to prostate cancer at the median follow-up of 50 months, which included one patient in each treatment arm. Additionally, 50 patients in the study died due to other causes.

Regarding safety, CAN-2409 appeared to be safe and well tolerated. Adverse events (AEs) were generally mild to moderate and included chills (33.4% vs 8.6%), fever (25.1% vs 3.9%), and flu-like symptoms (30.5% vs 13.8%). More than 90% of these AEs resolved within 24 to 72 hours.

Serious treatment-related AEs occurred in 1.7% of patients in the CAN-2409 arm vs 2.2% of patients in the placebo arm. In total, 5.4% of patients in the CAN-2409 arm and 6.0% of patients in the placebo arm discontinued treatment due to AEs.

Data also showed that both radiotherapy regimens (conventional and moderate hypofractionated RT) were well tolerated, with no significant differences in each safety profile.

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

Candel Therapeutics is planning to submit a biologics license application for CAN-2409 in the fourth quarter of 2026.²

REFERENCES

1. Gejerman G, Manzanera A, Wheeler T, 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. Presented at: American Society of Radiation Oncology 67^th Annual Meeting; September 27-October 1, 2025; San Francisco, California. Abstract 114.

2. Candel Therapeutics presents phase 3 clinical trial of CAN-2409 in localized prostate cancer at ASTRO 2025. News release. Candel Therapeutics. September 29, 2025. Accessed September 29, 2025. https://www.globenewswire.com/news-release/2025/09/29/3157688/0/en/Candel-Therapeutics-Presents-Phase-3-Clinical-Trial-of-CAN-2409-in-Localized-Prostate-Cancer-at-ASTRO-2025.html