Phase 1b sipuleucel‑T + N‑803 trial tests PAP vaccine plus IL‑15 superagonist immunostimulation

Washington University School of Medicine is running a single-center, open-label Phase 1b, modified 3+3 de-escalation study to define safety, tolerability, and the recommended Phase 2 dose for combining sipuleucel‑T (Dendreon’s autologous cellular immunotherapy that targets prostatic acid phosphatase using antigen-presenting cells prepared with a PAP–GM‑CSF fusion protein) with N‑803 / nogapendekin alfa inbakicept‑pmln (ImmunityBio’s IL‑15 superagonist complex designed to expand/activate NK cells and CD8+ T cells). Men with metastatic androgen pathway modulation–resistant prostate cancer on ongoing castration (prior orchiectomy or LHRH with testosterone ≤50 ng/dL) receive standard sipuleucel‑T on Days 1, 15, and 29, with subcutaneous N‑803 administered ~24 hours later (dose de-escalation from 15 to 10 to 6 mcg/kg), followed by expansion cohorts at the selected dose with extra “priming” or “late” N‑803 dosing. The scientific angle is immune “boosting” of a proven prostate vaccine platform by adding an IL‑15–axis cytokine agonist to potentially deepen/extend immune effector activity. For mCRPC after progression on androgen receptor pathway inhibitors, current care is sequential systemic therapy (taxane chemotherapy, ARPI switching in select cases, PARP inhibitors for HRR-altered disease, radioligand therapy such as lutetium‑177–PSMA‑617 for eligible patients, and bone-targeted agents), while sipuleucel‑T is typically used earlier in asymptomatic/minimally symptomatic disease and has limited direct tumor-shrinkage—this trial asks whether cytokine augmentation can make the immune response more clinically meaningful.