Phase 1b AKY-2519 B7-H3–targeted actinium-225 alpha radiopharmaceutical in mCRPC

Aktis Oncology’s BActinium-1 is a Phase 1b, multicenter, open-label study testing a B7-H3 (CD276)–targeted miniprotein radioconjugate: imaging with [64Cu]Cu-AKY-2519 PET to measure tumor uptake/dosimetry, and therapy with [225Ac]Ac-AKY-2519 to deliver alpha-particle radiation directly to B7-H3–expressing lesions. The trial uses dose escalation with parallel cohorts (Pluvicto-naïve vs Pluvicto-experienced) plus a backfill portion to refine safety, characterize PK/dosimetry, and select a recommended Phase 2 dose for each cohort. It enrolls metastatic castration-resistant prostate cancer with progression after prior systemic therapy; Cohort B specifically requires prior exposure to 177Lu-PSMA-617 (Novartis’ Pluvicto). B7-H3 appears prevalent in mCRPC (~90% estimate), creating a rationale for a non-PSMA target that could matter for post-Pluvicto patients or heterogeneous/low-PSMA disease. Today’s care for mCRPC is continued androgen deprivation plus sequential AR-pathway inhibitors, taxane chemotherapy, PARP inhibitors for HRR-selected disease, radiopharmaceuticals like Pluvicto in PSMA-positive disease, and later-line options (including bone-targeted radionuclide therapy in select settings); this program explores whether targeted alpha therapy against B7-H3 can extend radiopharmaceutical benefit beyond PSMA.