Aglatimagene Combo Shows Sustained Immune Remodeling in Prostate Cancer

Adding aglatimagene besadenovec (aglatimagene; previously CAN-2409) plus valacyclovir to external beam radiotherapy (EBRT) significantly increased lymphocyte infiltration and lymphocyte-tumor engagement in patients with intermediate- to high-risk localized prostate cancer. The changes were seen in biopsies collected more than 2 years after treatment, according to digital pathology findings from the phase 3 PrTK03 trial (NCT01436968) presented at the 2026 American Society for Radiation Oncology (ASTRO) Annual Meeting.¹

The analysis covered all biopsies evaluable by digital pathology, including 622 collected before treatment and 427 after. Overall lymphocytic fraction increased after treatment in both arms (P < .001), reflecting immune activation from radiation. Among post-treatment biopsies, the increase was significantly greater with aglatimagene than with placebo plus EBRT (n = 282 vs n = 145; P = .048).

A second analysis included 108 patients with residual tumor who had paired pre- and post-treatment biopsies (aglatimagene, n = 62; placebo, n = 46). In this group, aglatimagene significantly increased intratumoral lymphocyte fraction (P = .006), lymphocyte-tumor enrichment score (P = .003), and lymphocyte-tumor mixing score (P <.001) compared with placebo. The enrichment score measured how closely lymphocytes localized near tumor cells relative to a random distribution. The mixing score reflected how extensively lymphocytes intermingled with tumor cells.

These findings build on previously reported biopsy outcomes. Among patients with evaluable biopsies in the 2-year window after EBRT, 80% (n = 167/209) in the aglatimagene arm had negative biopsies vs 63% (n = 62/98) in the placebo arm (P = .0018).

“While radiation therapy alone drives immune infiltration into prostate tumors, these data support that aglatimagene produced a qualitatively distinct immune response,” Francesca Barone, MD, PhD, chief scientific officer of Candel Therapeutics, said in a news release on the study findings.² “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.”

The randomized, double-blind, placebo-controlled PrTK03 trial enrolled 745 patients with newly diagnosed intermediate- to high-risk localized prostate cancer. Patients were randomly assigned 2:1 to aglatimagene or placebo, each followed by valacyclovir, alongside EBRT with or without short-course androgen deprivation therapy (ADT).

Aglatimagene was injected into the 4 quadrants of the prostate under ultrasound guidance at 0.5 mL per quadrant, for a cumulative dose of 2 mL. Valacyclovir was started 1 to 3 days after each injection and continued for 14 days. For this analysis, AI models trained on pathologist-annotated, hematoxylin and eosin–stained biopsies quantified tumor cells and lymphocytes within tumor regions.

The primary end point of the parent trial was disease-free survival (DFS). Key secondary end points included freedom from biochemical failure, prostate cancer–specific outcomes, and overall survival.

In the primary analysis, aglatimagene reduced the risk of DFS events by 30% (HR, 0.70; 95% CI, 0.52-0.94; P = .0155) and the risk of prostate cancer–specific disease recurrence by 38%. More patients in the aglatimagene arm achieved a prostate-specific antigen (PSA) nadir below 0.2 ng/mL (67.1% vs 58.6%; P = .0164). After approximately 20 additional months of follow-up, new metastatic disease occurred in 1.6% of patients treated with aglatimagene vs 2.8% of those given placebo (HR, 0.58; 95% CI, 0.21-1.59).

The investigators concluded that the immune signature was still detectable more than 2 years after treatment, indicating durable rather than transient immune remodeling. They suggested that sustained immune surveillance may help explain the DFS improvement seen in PrTK03. The P values for the digital pathology analyses were nominal and not adjusted for multiple comparisons, and the paired-biopsy analysis was limited to patients with residual tumor after treatment.

The developers plan to submit a biologics license application for aglatimagene in localized prostate cancer to the FDA. The agent has received fast track and regenerative medicine advanced therapy designations for patients with intermediate- to high-risk disease.³

References

1. Barone F, Dwyer J, Manzanera A, et al. Quantitative digital pathology defines immune activation following aglatimagene besadenovec immunotherapy in localized prostate cancer. Presented at: 2026 ASTRO Annual Meeting; September 26-30, 2026; Boston, MA. Abstract LBA 30.
2. 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 September 30, 2026. https://tinyurl.com/4m9bnu53
3. Candel Therapeutics receives FDA regenerative medicine advanced therapy designation for CAN-2409 for the treatment of prostate cancer. News release. Candel Therapeutics. May 28, 2025. Accessed September 30, 2026. https://tinyurl.com/mvd3y2w3