BAT (Supraphysiologic Testosterone) + Sipuleucel‑T Drives 100% PA2024 ELISPOT Responses in mCRPC

Bipolar androgen therapy (BAT; testosterone cypionate 400mg IM q4w with ongoing ADT) was given for two cycles before sipuleucel‑T (autologous PAP–GM‑CSF–primed cellular immunotherapy) in a Phase II, Simon two‑stage study in progressive mCRPC selected for “sip‑T-appropriate” features (PSA<20ng/mL, no visceral/hepatic mets, no prior mCRPC chemo, minimal symptoms) (n=11 evaluable; NCT06100705). The primary endpoint—PA2024 IFN‑γ ELISPOT positivity—was 11/11 (100%) vs a ~50% historical ELISPOT positivity rate cited for sipuleucel‑T alone; mean ELISPOT was 232 spots (95% CI 147–317), and T‑cell proliferation to PA2024 was also 100% with mean stimulation index 23 (95% CI 17–30). Early clinical signals were limited (RECIST‑evaluable n=2 with 1 confirmed PR; PSA50 2/11), but tolerability looked clean in this small cohort (no Grade ≥3 AEs/SAEs), whereas sipuleucel‑T in IMPACT improved median OS by ~4.1 months (25.8–25.9 vs 21.4–21.7 months; HR ~0.78) with ~6.7% Grade ≥3 events within 1 day of infusion—so this combo’s differentiator would need to be downstream clinical benefit, not just immune assay uplift.