At 51 medical centers across the United States and Puerto Rico, 745 men with intermediate- to high-risk localized prostate cancer participated in a landmark trial that has reshaped the conversation around treatment options for one of the most common cancers diagnosed worldwide. The results, led by researchers at Johns Hopkins University School of Medicine and published June 1 in The Lancet Oncology, demonstrate that combining an investigational immunotherapy called aglatimagene with standard radiation therapy significantly improves disease-free survival — and does so without increasing serious side effects.
About 30 percent of men with intermediate- to high-risk localized prostate cancer experience recurrence after curative-intent treatment, often requiring additional therapies that can compromise quality of life. This reality has made the search for better frontline options urgent. Aglatimagene, developed by Candel Therapeutics, works through an elegant mechanism: a modified virus delivers a cancer-fighting gene directly into tumor cells, where it disrupts DNA replication and triggers an immune response against the cancer. When combined with an oral drug called valacyclovir—which activates only within the prostate—and radiation therapy, the approach appears to offer meaningful protection.
The trial's results speak clearly. After a median follow-up of 50.3 months, just 23 percent of patients receiving aglatimagene experienced cancer progression, recurrence, or death, compared with 31 percent in the placebo group. The median disease-free survival in the aglatimagene group had not yet been reached at the time of analysis, meaning more than half of treated patients remained free from cancer recurrence, whereas the placebo group reached a median of 86.1 months. When looking specifically at cancer recurrence or death, the advantage was even starker: 17 percent in the aglatimagene arm versus 25 percent in placebo.
Additional markers of tumor control favored the immunotherapy combination. Sixty-seven percent of aglatimagene patients achieved very low prostate-specific antigen (PSA) levels—an indicator of better cancer control—compared with 59 percent of placebo recipients. Among patients who underwent biopsies approximately two years after radiation, 80 percent of those treated with aglatimagene had negative results, compared with 63 percent in the placebo group.
Theodore DeWeese, M.D., dean of the Johns Hopkins Medical Faculty and first author of the study, emphasizes that safety remained intact: "This study demonstrates that adding aglatimagene to standard radiotherapy can improve disease-free survival for patients with localized prostate cancer without increasing clinically significant side effects." Serious adverse events occurred at nearly identical rates in both groups—8 percent with aglatimagene and 7 percent with placebo. No treatment-related deaths were reported, and most side effects were mild to moderate.
The implications reach beyond statistics. If approved by regulators, aglatimagene would represent the first genuinely new therapy for localized prostate cancer in over two decades, offering men facing this diagnosis a chance to reduce recurrence risk while maintaining quality of life. For patients who elect radical treatment with curative intent, this combination approach could fundamentally change outcomes, giving thousands of men each year a more effective path forward.