First-in-Human Phase I Trial of Novel Vaccine in Metastatic Prostate Cancer
Posted: Monday, August 3, 2020
According to Douglas G. McNeel, MD, PhD, of the University of Wisconsin Carbone Cancer Center, Madison, and colleagues, the androgen receptor may not only be a pharmacologic target, but an immunologic target as well for the treatment of prostate cancer, based on the results of a multicenter first-in-human phase I trial. A novel vaccine called pTVG-AR—a plasmid DNA encoding the androgen receptor ligand–binding domain (AR LBD)—appeared to be both safe and immunologically active in patients with metastatic castration-sensitive prostate cancer. These early study findings were presented in Clinical Cancer Research.
“No significant adverse events were observed, T-cell immunity to the AR LBD was augmented with immunization, and immunity was associated with prolonged time to castration resistance,” commented the authors in relating the translational relevance of their study findings.
A total of 40 patients from three centers were enrolled in the clinical trial. Within 18 months of follow-up, 27 patients had completed treatment. Eligible patients had to have started standard androgen-deprivation therapy within 6 months of study entry and had to demonstrate evidence of PSA decline with treatment as well as castrate levels of testosterone.
Of the 40 study patients, 27 were free of disease progression at 18 months. Of the 30 patients whose samples underwent immune analysis, approximately half of them were found to have developed Th1-type immunity to the AR LBD. In addition, compared with patients without immunity, those who developed T-cell immunity had a significantly prolonged 18-month PSA progression-free survival (hazard ratio = 0.01; P = .003). Furthermore, persistent IFNγ immune responses were reported regardless of whether or not patients received granulocyte-macrophage colony-stimulating factor.
Disclosure: For full disclosures of the study authors, visit clincancerres.aacrjournsl.org.