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

Data from the pivotal phase 3 trial (NCT01436968) of aglatimagene besadenovec (CAN-2409) have been published in The Lancet Oncology, demonstrating that the agent, combined with valacyclovir (prodrug), significantly extends disease-free survival (DFS) vs placebo plus valacyclovir when added to radiotherapy in patients with localized prostate cancer.¹

According to the authors, this benefit was observed without an increase in clinically significant toxicity.

“Localized prostate cancer remains an area of significant unmet need, with many patients experiencing disease recurrence after definitive radiotherapy. Innovation in this setting has been limited over the past 2 decades, making these peer-reviewed data particularly important for patients with intermediate- to high-risk localized prostate cancer,” said study author Mark Garzotto, MD, professor of urology and radiation medicine at Oregon Health & Science University and chief of urology at the Portland VA Medical Center, in a news release on the study.² “The publication of these findings in The Lancet Oncology provides important peer-reviewed validation of the clinical significance of the results observed with aglatimagene in combination with radiotherapy.”

About the study

The phase 3, double-blind trial enrolled 745 men with intermediate- or high-risk localized prostate cancer across 51 medical centers in the US and Puerto Rico. Participants were randomly assigned 2:1 to receive aglatimagene plus valacyclovir (n = 496) or placebo plus valacyclovir (n = 249) in combination with standard-of-care external beam radiation therapy (EBRT) (78 Gy in 2 Gy fractions) or hypofractionated EBRT (60 Gy in 3 Gy fractions or 70 Gy in 2.5 Gy fractions) with optional androgen deprivation therapy (ADT). Short-term ADT was planned in 49% of patients in each arm. The primary end point was DFS.

At a median follow-up of 50.3 months, the addition of aglatimagene demonstrated a 30% improvement in DFS (HR, 0.70; 95% CI, 0.52 to 0.94; P = .016). The median DFS was not reached (95% CI, 121.78 to NR) in the aglatimagene arm vs 86.1 months (95% CI, 29.7 to 143) in the placebo arm. The aglatimagene arm also demonstrated a 38% improvement in prostate cancer-specific DFS vs placebo, with the median DFS not reached (IQR, NR to NR) in the aglatimagene arm vs 143.0 months (IQR, 34.2 to 143.0) in the placebo arm (HR, 0.62; 95% CI, 0.44 to 0.87; P = .0046).

Longer-term data from the study were recently presented at the 2026 American Urological Association Annual Meeting in Washington, DC, showing a 39% improvement in prostate cancer-specific DFS with an additional 20 months of follow-up (median follow-up, 58 months). Data presented at AUA also showed consistent trends in favor of aglatimagene across secondary and exploratory end points, including time to biochemical failure, time to metastasis, and time to salvage anti-cancer treatment.

Related: Aglatimagene plus radiotherapy improves prostate cancer-specific DFS

Overall survival (OS) was comparable between both arms (stratified HR, 1.18; 95% CI, 0.64 to 2.15; stratified log-rank P = .5), although the median OS was not reached in either group at the time of data report.

Across both arms, 61% of patients (451 of 745) completed the 2-year post-treatment biopsy. Patients who received aglatimagene demonstrated improved pathological complete response rates, with negative biopsies reported in 80% of patients in the aglatimagene arm vs 63% in the placebo arm (χ² P = .0018). 

“The statistically significant increase in pathological complete response rates—observed in prostate biopsies obtained approximately 2 years after aglatimagene treatment and reported today in The Lancet Oncology—is particularly meaningful because biopsy findings after radiotherapy have previously been shown to predict later biochemical failure and metastasis with longer follow-up,” explained Garrett Nichols, MD, Chief Medical Officer of Candel Therapeutics, in the news release.² “Together, these data strengthen our confidence that earlier tumor control, reflected in biopsy-based DFS events, may translate into durable and clinically meaningful benefit for patients.”

Safety data

Among all patients, 88% had a treatment-emergent adverse event (TEAE). Most TEAEs (80%) were grade 1 to 2, and no grade 5 TEAEs were reported. TEAEs of grade 3 or worse were reported in 8% of patients in the treatment arm and 7% in the placebo arm. The most common TEAE was acute kidney injury (2% in each arm).

Serious AEs occurred in 6% of patients in the treatment arm and 7% of patients in the placebo arm. Treatment-related serious AEs occurred in 2% of patients in each arm. No treatment-related deaths were reported.

Long-term follow-up in the study is ongoing. These data are intended to support a planned Biologics License Application submission for aglatimagene in fourth quarter of 2026.

“The publication of this pivotal phase 3 trial in The Lancet Oncology provides important peer-reviewed validation of the significance of these findings for patients with localized prostate cancer,” concluded Paul Peter Tak, MD, PhD, FMedSci, President and CEO of Candel, in the news release.² “Patients who elect to undergo radical treatment for localized prostate cancer do so with the goal of increasing their chance of living free from cancer while reducing the risk of recurrence and the need for future anti-cancer therapies that may carry additional toxicity and affect quality of life. These data showed a clinically meaningful reduction in disease recurrence in patients treated with aglatimagene in combination with radiotherapy. The primary end point findings were supported by sensitivity analyses and reinforced by secondary and exploratory end points and together provide a comprehensive and internally consistent body of evidence that supports the therapeutic potential of aglatimagene in localized prostate cancer.”

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