Development

Candel's genetic therapy set for BLA in prostate cancer after showing 39% improvement in disease-free survival

Candel Therapeutics (Nasdaq: CADL) reported extended follow-up data from its Phase III trial of prospective adenoviral gene therapy aglatimagene besadenovec in localized prostate cancer. The molecule produced a sustained 39% improvement in prostate cancer–specific disease-free survival versus placebo at a median follow-up of 58 months, with the company planning a Biologics License Application submission to the US FDA in Q4 2026.

The Phase III study is a randomized, double-blind, placebo-controlled pivotal trial enrolling 745 patients with intermediate- to high-risk localized prostate cancer, conducted under a Special Protocol Assessment agreed with the US FDA. The data presented at the American Urological Association 2026 Annual Meeting in Washington, D.C., reflect a March 15, 2026 cutoff — approximately 20 months beyond the December 2024 topline readout.

Key results

In the intention-to-treat population, aglatimagene besadenovec delivered a statistically significant improvement in the primary endpoint of prostate cancer–specific disease-free survival (HR 0.61; 95% CI: 0.44, 0.85; p=0.0031). Secondary and exploratory endpoints trended in the same direction across the full ITT population, including time to biochemical failure (HR 0.72), time to metastasis (HR 0.58), and time to next treatment (HR 0.72), though event counts remained too low for statistical significance on most of these measures.

The intermediate-risk subgroup — comprising 635 patients, or 85% of the ITT population — showed a 41% improvement in prostate cancer–specific DFS (HR 0.59; 95% CI: 0.41, 0.84; p=0.0034). Within this subgroup, descriptive analyses showed a 90% reduction in time to metastasis (HR 0.10; 95% CI: 0.01, 0.85) and a metastasis rate of 0.24% (1/422) in the aglatimagene arm versus 2.35% (5/213) in the placebo arm. These figures are exploratory and should be interpreted with caution given the small absolute number of events.

No new safety signals were reported. Candel noted that more than 1,000 patients have been dosed with aglatimagene across its clinical program, with a tolerability profile described as favorable.

The research context

Aglatimagene besadenovec — also referred to as CAN-2409 — is a replication-defective adenoviral vector engineered to deliver the herpes simplex virus thymidine kinase (HSV-tk) gene directly into tumor tissue. Following intratumoral injection, HSV-tk converts subsequently administered oral valacyclovir into cytotoxic nucleotide analogs that induce immunogenic cell death in proliferating tumor cells. The resulting antigen release, combined with pro-inflammatory signaling from the adenoviral capsid, is designed to prime a systemic CD8+ T cell response against both the injected tumor and potential distant disease — a mechanism the company characterizes as in situ immunization.

This approach is mechanistically distinct from the oncolytic viral therapies that have attracted the most regulatory attention in recent years. Amgen's Imlygic (talimogene laherparepvec), the first FDA-approved oncolytic viral therapy, relies on direct viral replication and GM-CSF–mediated immune priming and is approved for unresectable melanoma. Replimune's vusolimogene oderparepvec, an enhanced oncolytic HSV encoding GALV-GP R− and GM-CSF, demonstrated activity in combination with pembrolizumab in melanoma and supported a BLA submission. Neither agent has been developed for localized prostate cancer, and cross-trial comparisons are limited by differences in tumor biology, patient selection, and trial design.

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Aglatimagene's suicide-gene/prodrug mechanism does not depend on active viral replication, which may confer advantages in tumor types where replicating viruses face greater biological barriers, including the prostate microenvironment. The combination with standard-of-care external beam radiotherapy — rather than replacing it — positions aglatimagene as an add-on immunotherapy rather than an alternative local treatment.

Current standard-of-care for intermediate- to high-risk localized prostate cancer combines external beam radiotherapy with androgen deprivation therapy, typically using GnRH agonists such as leuprolide acetate or goserelin acetate, or the oral GnRH antagonist relugolix. Antiandrogens including enzalutamide have received more recent approvals in adjacent settings — enzalutamide gained US FDA approval in November 2023 for non-metastatic castration-sensitive prostate cancer with high-risk biochemical recurrence following definitive therapy — but no novel systemic agent has been approved specifically for upfront treatment of localized disease in combination with radiotherapy for more than two decades, according to Candel.

The CAN-2409 clinical trial results presented at AUA 2026 build on the December 2024 topline readout, which first established the primary endpoint benefit, and on earlier data showing a statistically significant improvement in pathological complete response at two-year biopsies. Published literature cited by Candel suggests that positive biopsies two or more years after radiotherapy predict subsequent biochemical failure and metastatic progression, lending biological plausibility to the observed DFS benefit as a harbinger of longer-term clinical outcomes — though the durability of these findings will require continued patient follow-up as events accumulate.

The FDA has granted aglatimagene both Fast Track Designation and Regenerative Medicine Advanced Therapy Designation for intermediate- to high-risk localized prostate cancer, designations that provide for more frequent agency interaction and, in the case of RMAT, potential eligibility for accelerated approval pathways.


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