Results of a multicenter clinical trial found that adding the investigational adenoviral-based viral immunotherapy aglatimagene besadenovec (alglatimagene, CAN-2409) to standard radiation therapy improved disease-free survival for patients with intermediate- or high-risk localized prostate cancer. The study was led by researchers at the Johns Hopkins University School of Medicine, Johns Hopkins Kimmel Cancer Center, Department of Radiation Oncology and Molecular Radiation Sciences, and Brady Urological Institute.
Findings from the study, funded in part by the National Institutes of Health, were published June 1 in The Lancet Oncology.
The study evaluated 745 men with localized prostate cancer treated at 51 medical centers across the United States and Puerto Rico. The men had prostate cancer confined to the prostate region but with features that increase the likelihood of recurrence or spread. Patients received either aglatimagene injected into the prostate in combination with the generic oral prodrug valacyclovir, which only becomes activated in the prostate, and radiation therapy, or a placebo plus valacyclovir and radiation therapy.
After a median follow-up of 50.3 months, patients treated with aglatimagene experienced significantly longer disease-free survival compared with patients receiving the placebo. Twenty-three percent of patients in the aglatimagene group had progression or recurrence of their cancers, or died, compared with 31% in the placebo group. Median disease-free survival was not yet reached in the aglatimagene group, meaning more than half of patients remained free of cancer recurrence at the time of analysis, compared with 86.1 months in the placebo group.
"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," says first author and prostate cancer expert Theodore DeWeese, M.D., The Frances Watt Baker, M.D., and Lenox D. Baker Jr., M.D., Dean of the Medical Faculty and CEO of Johns Hopkins Medicine.
About 30% of patients with intermediate- to high-risk localized prostate cancer experience recurrence after curative-intent treatment, often requiring additional therapies with side effects that can affect quality of life, the researchers say.
Aglatimagene is an investigational therapy that uses a modified virus to deliver a cancer-fighting gene into tumor cells. When injected into the prostate and used with a drug such as valacyclovir, the therapy disrupts DNA replication in tumor cells and stimulates an immune response against the cancer.
Prostate cancer recurrence or prostate cancer-related death occurred in 17% of patients receiving aglatimagene, compared with 25% in the placebo group. A higher proportion of patients (67%) receiving aglatimagene achieved very low prostate specific antigen (PSA) levels — a sign of better prostate cancer control — compared with patients receiving the placebo (59%).
Among patients with evaluable biopsy samples obtained approximately two years after radiation therapy, 80% of patients treated with aglatimagene had negative biopsies, compared with 63% in the placebo group.
"This pivotal phase 3 trial, showing a clinically meaningful reduction in disease recurrence in patients treated with aglatimagene in combination with radiotherapy, provides important peer-reviewed validation of the significance of these findings for patients with localized prostate cancer who elect to undergo radical treatment with curative intent," said Paul Peter Tak, M.D., Ph.D., F.Med.Sci., president and CEO of Candel Therapeutics, which funded the study with the National Institutes of Health.
Most treatment-related side effects were mild to moderate. Serious side effects occurred at similar rates among both groups: 8% of patients in the aglatimagene group and 7% in the placebo group. No treatment-related deaths were reported.
"These findings could represent a meaningful advance for men with localized prostate cancer. If approved, aglatimagene immunotherapy may be the first new therapy for men with localized prostate cancer in over 20 years," says prostate cancer expert Ana Kiess, M.D., Ph.D., associate professor of radiation oncology and molecular radiation sciences.
The trial was conducted under a Special Protocol Assessment agreed upon with the U.S. Food and Drug Administration. Long-term follow-up is ongoing and is needed to determine whether the approach will ultimately reduce the need for later therapies, such as hormone treatment, or improve long-term survival outcomes, the researchers say.
