Phase 2 TriAdeno (PSA/MUC1/brachyury Ad5 vaccine) + N-803 IL-15 superagonist in localized prostate cancer

This Phase 2 National Cancer Institute trial tests whether TriAdeno—an adenovirus type 5 (Ad5)–based therapeutic cancer vaccine expressing three tumor antigens (PSA, MUC1, and brachyury) to drive antigen-specific T-cell responses—combined with N-803 (nogapendekin alfa inbakicept-pmln), an IL-15 “superagonist” cytokine fusion protein designed to expand/activate NK cells and CD8+ T cells, can favorably remodel the immune microenvironment in clinically localized prostate cancer managed with active surveillance. The design is open-label and gives paired subcutaneous injections once every 21 days for up to four cycles, with on-treatment prostate biopsies to compare immune-cell infiltration (e.g., CD8+ and CD4+ T-cell density) before vs after therapy. Eligible participants are adults with T1a–T2a low- or intermediate-risk disease who are appropriate for continued monitoring rather than immediate curative therapy. The scientific angle is “immunotherapy in the surveillance window,” where intact primary tumor tissue allows mechanistic biopsy readouts rather than relying only on blood biomarkers. Today, most men in this setting continue active surveillance with serial PSA/MRI and repeat biopsies, moving to prostatectomy or definitive radiation (sometimes with short-course ADT for higher-risk features) only if there is grade/volume progression.