Phase 1 FH-STEAP1 IL-18 CAR T tests STEAP1-targeted CAR-T armored with IL-18

Fred Hutchinson Cancer Center is running a first-in-human Phase 1 dose-escalation/expansion study of FH-STEAP1 IL-18 CAR T cells, an autologous anti-STEAP1 CAR-T therapy engineered to secrete IL-18 (a pro-inflammatory cytokine that can enhance innate and T-cell–mediated anti-tumor immunity) to better function in an immunosuppressive prostate tumor microenvironment. Participants undergo leukapheresis, then lymphodepleting chemotherapy with cyclophosphamide (DNA-alkylating cytotoxic) and fludarabine (purine analog that inhibits DNA synthesis) on days -5 to -3, followed by a single CAR-T infusion on day 0, with ongoing imaging and biospecimen collections to track safety, pharmacology, and early efficacy signals. The population is metastatic castration-resistant prostate adenocarcinoma / stage IVB prostate cancer, generally later-line, with continuation of androgen deprivation therapy allowed. The commercial/scientific angle is bringing “armored” cytokine-secreting CAR-T into mCRPC, where trafficking, antigen heterogeneity, and on-target/off-tumor risk have historically limited CAR-T performance in solid tumors. Today’s care for post–novel hormonal agent mCRPC is typically sequential androgen receptor pathway inhibitors when still sensitive, taxane chemotherapy (docetaxel/cabazitaxel), radioligand therapy when eligible, PARP inhibitors for HRR-altered disease, and clinical trials—this study tests whether STEAP1-directed cellular therapy can add a new immune modality beyond those systemic standards.