Phase 1/2 AZD8359 STEAP2-targeted CD8-guided T cell–engaging antibody in metastatic prostate cancer

This first-in-human, modular, open-label Phase 1/2 study (CRIUS-1) from AstraZeneca evaluates AZD8359, a T cell–engaging antibody designed to direct CD8 T cells toward STEAP2-expressing prostate cancer cells (STEAP2 is commonly expressed in prostate tumors). Part A dose-escalates across doses/schedules to define tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and a recommended dose for expansion; Part B then expands at ≥2 dose levels in defined populations, including progressive metastatic castration-resistant/hormone-refractory prostate cancer (mCRPC/mHRPC) after at least an androgen receptor pathway inhibitor and progressive neuroendocrine prostate cancer in later-line settings. Different “modules” test different delivery/administration approaches for AZD8359. The commercial/scientific angle is AstraZeneca pushing a solid-tumor T cell engager against a prostate lineage target, aiming to improve tumor-selective immune activation while monitoring classic TCE risks (e.g., cytokine release syndrome/neurologic toxicity). Today’s care for progressive mCRPC is sequential AR-pathway therapy, taxane chemotherapy (docetaxel/cabazitaxel), radioligand therapy in PSMA-eligible patients, PARP inhibitors in HRR-altered disease, and supportive bone-directed therapy; for neuroendocrine prostate cancer, care often resembles small-cell regimens such as platinum + etoposide with limited durable options.