About 30% of men with localised prostate cancer undergoing radiotherapy with curative intent have disease recurrence associated with progression-related symptoms and substantial toxicity of salvage therapies.
Previous studies with aglatimagene besadenovec (CAN-2409, hereafter referred to as aglatimagene) showed synergy with radiation and immune-mediated cytotoxicity in patients with prostate cancer. We aimed to assess whether addition of aglatimagene plus prodrug (valacyclovir) to standard-of-care external beam radiation therapy (EBRT) could improve disease-free survival in this population.
We conducted a phase 3, randomised, double-blind, placebo-controlled trial at 51 medical centres (26 community and 25 institutional or military) across the USA and Puerto Rico in patients with intermediate or high-risk prostate cancer. Patients aged at least 18 years who were planning to undergo EBRT and with an Eastern Cooperative Oncology Group score of 0-2 were eligible. Patients were randomly assigned (2:1) via central block-randomisation to receive either three courses of intraprostatic aglatimagene (5 × 1011 viral particles) plus valacyclovir or placebo plus valacyclovir, with randomisation stratified by risk category and androgen deprivation therapy (ADT) use. Patients received standard-of-care 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 ADT. The primary endpoint was disease-free survival, defined as time-from-randomisation to prostate cancer recurrence or death in the intent-to-treat population (all randomly assigned patients). Safety was assessed in all individuals who received at least one injection. The trial is registered at ClinicalTrials.gov, NCT01436968, and long-term follow-up is ongoing.
Between Feb 21, 2012, and Sept 9, 2021, 745 men (591 [79%] White, 121 [16%] Black) were randomly assigned to receive aglatimagene plus valacyclovir (n=496) or placebo plus valacyclovir (n=249). After a median follow-up of 50·3 months (IQR 35·2-63·3), median disease-free survival was not reached (95% CI 121·78 to not reached) in the aglatimagene plus valacyclovir group versus 86·1 (IQR 29·7-143·0) months in the placebo plus valacyclovir group (hazard ratio 0·70, 95% CI 0·52-0·94; p=0·016). Treatment-emergent adverse events (TEAEs) of grade 3 or worse occurred in 40 (8%) of 479 patients in the aglatimagene group and 17 (7%)of 232 patients in the placebo group. The most common TEAE of grade 3 or worse was acute kidney injury in both the aglatimagene group (nine [2%] of 479 patients) and the placebo group (four [2%] of 232 patients). Serious adverse events occurred in 28 (6%) of 479 patients in the aglatimagene group and 17 (7%) of 232 in the placebo group. Treatment-related serious adverse events occurred in eight (2%) patients in the aglatimagene group (four acute kidney injury, two pyrexia, and one each influenza-like symptoms and urinary retention) and five (2%) in the placebo group (four acute kidney injury, and one each increased creatinine levels and skin rash; one patient reported two serious adverse events). No treatment-related deaths were reported.
Aglatimagene plus valacyclovir was associated with longer disease-free survival than placebo plus valacyclovir when added to standard of radiotherapy for the treatment of localised prostate cancer, offering a meaningful benefit without increasing clinically significant toxicity.
Candel Therapeutics and US National Institutes of Health.
The Lancet. Oncology. 2026 Jun [Epub]
Theodore L DeWeese, Andrea Manzanera, John Sylvester, Thomas Wheeler, Thomas Schroeder, Glen Gejerman, Gregory Chesnut, Thomas M Facelle, Mark G Garzotto, Christopher Pieczonka, Nilay M Gandhi, Steven Sukin, Michael A Liss, Ronald Tutrone, Bryan Mehlhaff, Stephen J Savage, Megan Goody, Jenessa Vogt, Shangbang Rao, Maria Lucia Silva Polanco, Francesca Barone, W Garrett Nichols, Paul P Tak, PrTK03 study team
Departments of Radiation Oncology, Urology, and Oncology, Johns Hopkins School of Medicine, Baltimore MD, USA., Candel Therapeutics, Needham, MA, USA., Atlantic Urology Clinics, Myrtle Beach, SC, USA., Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA., University of New Mexico, Albuquerque, NM, USA., New Jersey Urology, Summit Health, Saddlebrook, NJ, USA., Walter Reed National Military Medical Center, Bethesda, MD, USA., Colorado Clinical Research, Golden, CO, USA., VA Portland Health Care System/OHSU, Portland, OR, USA., Associated Medical Professionals of NY, US Urology Partners, Syracuse, NY, USA., Potomac Urology Center, Alexandria, VA, USA., Texas Urology Specialists, Tomball, TX, USA., University of California San Diego, San Diego, CA, USA., Chesapeake Urology Research Associates, Towson, MD, USA., Oregon Urology Institute, Springfield, OR, USA., Ralph H Johnson VA Medical Center, Charleston, SC, USA., Candel Therapeutics, Needham, MA, USA; Faculdade de Medicina, Universidade de Lisboa, Portugal. Electronic address: .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/42225101
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