Aglatimagene besadenovec shows sustained immune remodeling in localized prostate cancer

New biomarker findings from the phase 3 PrTK03 trial (NCT01436968) and ongoing phase 2 PrTK05 study (NCT07332000) provide additional evidence of local and systemic immune activation following treatment with investigational aglatimagene besadenovec in men with localized prostate cancer.

The findings, presented at the 2026 American Society for Radiation Oncology (ASTRO) Annual Meeting¹ and reported by Candel Therapeutics,^2,3 build on peer-reviewed phase 3 data showing longer disease-free survival when aglatimagene was added to external beam radiation therapy (EBRT) and valacyclovir.⁴

PrTK03 clinical findings

In the PrTK03 trial, which enrolled 745 patients with intermediate- or high-risk localized prostate cancer, aglatimagene plus valacyclovir and EBRT was associated with longer disease-free survival than placebo plus valacyclovir and EBRT after a median follow-up of 50.3 months (HR, 0.70; 95% CI, 0.52 to 0.94; P = .016). Updated follow-up through March 15, 2026 (median, 58.0 months), reported by the sponsor showed a 41% reduction in the risk of prostate cancer-specific disease-free survival events among the 635 patients with intermediate-risk disease (HR, 0.59; 95% CI, 0.41 to 0.84; P = .0034).²

Related: Published data show DFS benefit with aglatimagene besadenovec in localized prostate cancer

Exploratory descriptive analyses also demonstrated that the addition of aglatimagene extended the time to biochemical failure (HR, 0.48; 95% CI, 0.22 to 1.03), time to metastasis (HR, 0.10; 95% CI, 0.01 to 0.85), and time to salvage anticancer therapy (HR, 0.51; 95% CI, 0.24 to 1.10).

Immune remodeling after radiation

At ASTRO 2026, investigators presented an exploratory digital pathology analysis of hematoxylin and eosin-stained prostate biopsy specimens from the PrTK03 study.¹ The analysis used machine-learning models trained on expert-annotated samples to quantify lymphocytic infiltration and assess the spatial relationship between lymphocytes and tumor regions.

Across digitally evaluable biopsies, lymphocytic fraction increased after treatment in both the aglatimagene and control groups (P < .001). The increase was greater in the aglatimagene group compared with EBRT alone (P = .048). Among 108 patients with paired biopsies and residual tumor after treatment, aglatimagene was associated with increased intratumoral lymphocyte fraction (P = .006), lymphocyte-tumor enrichment (P = .003), and lymphocyte-tumor mixing (P < .001).

“While radiation therapy alone drives immune infiltration into prostate tumors, these data support that aglatimagene produced a qualitatively distinct immune response,” said presenting author Francesca Barone, MD, PhD, Chief Scientific Officer of Candel Therapeutics, in a news release from the company.³ “The significantly greater lymphocyte infiltration and sustained lymphocyte-tumor engagement which we observed, more than 2 years after treatment, supports durable immune remodeling rather than transient inflammation. This mechanistic insight may help explain the clinical improvements in disease-free survival and pathologic outcomes we reported in the phase 3 trial.”

Separately, Candel reported centrally reviewed biopsy results from 277 evaluable patients with intermediate-risk disease.² At 22 to 26 months after treatment, 76.6% of patients receiving aglatimagene had negative biopsies compared with 60.7% of those in the control group. Positive biopsies were reported in 20.7% and 38.2% of patients, respectively.

These results are consistent with the earlier data, which reported higher rates of negative posttreatment biopsies with aglatimagene (P = .0018).³

PrTK05 results provide biological rationale for aglatimagene

The PrTK05 study is evaluating biomarkers, biodistribution, and shedding in men with intermediate-risk localized prostate cancer receiving EBRT. The phase 2a, open-label study is designed to enroll 45 participants, with 30 receiving aglatimagene plus valacyclovir and EBRT and 15 receiving EBRT alone.⁵

In the September 2026 report, serial blood samples from 13 patients treated with aglatimagene plus EBRT and 6 receiving standard-of-care EBRT alone showed expansion of circulating CD8-positive effector and effector-memory T-cell populations in the aglatimagene group.² The investigators also observed expansion of Ki67-positive proliferating CD8-positive T cells and granzyme B-positive cytotoxic CD8-positive T cells.

According to Candel Therapeutics, these observations suggest a coordinated immune response detectable outside the treated prostate. The company stated that formal comparisons with the control group are ongoing.

Candel also reported that it plans to submit a Biologics License Application for aglatimagene in localized prostate cancer during the fourth quarter of 2026, with biodistribution and shedding data from PrTK05 planned for inclusion. These data have also been submitted for presentation at an upcoming medical meeting.

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REFERENCES

1. Barone F, Dwyer J, Manzanera A, et al. Digital Pathology in Relation to Immune Activation Following Aglatimagene Besadenovec Immunotherapy in Localized Prostate Cancer. Presented at: 2026 American Society for Radiation Oncology Annual Meeting. September 26 – 30, 2026. Boston, Massachusetts. Abstract LBA 30

2. Candel Therapeutics announces integrated clinical and biomarker data that showed durable local and systemic immune activation after aglatimagene besadenovec in intermediate-risk localized prostate cancer. News release. Candel Therapeutics. September 30, 2026. Accessed October 2, 2026. https://www.globenewswire.com/news-release/2026/09/30/3371862/0/en/candel-therapeutics-announces-integrated-clinical-and-biomarker-data-that-showed-durable-local-and-systemic-immune-activation-after-aglatimagene-besadenovec-in-intermediate-risk-lo.html

3. Candel Therapeutics announces new data showing sustained immune remodeling more than two years after aglatimagene besadenovec treatment in localized prostate cancer at ASTRO 2026. News release. Candel Therapeutics. September 30, 2026. Accessed October 2, 2026. https://www.globenewswire.com/news-release/2026/09/30/3371847/0/en/candel-therapeutics-announces-new-data-showing-sustained-immune-remodeling-more-than-two-years-after-aglatimagene-besadenovec-treatment-in-localized-prostate-cancer-at-astro-2026.html

4. DeWeese TL, Manzanera A, Slyvester J, et al. Aglatimagene besadenovec (CAN-2409) with radiotherapy for patients with localised prostate cancer: a phase 3, multicentre, randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2026 Jun;27(6):673-685. doi:10.1016/S1470-2045(26)00071-9

5. A Biomarker Study in Men With Localized Prostate Cancer Treated With Aglatimagene Besadenovec. ClinicalTrials.gov. Last updated September 15, 2026. Accessed October 2, 2026. https://clinicaltrials.gov/study/NCT07332000