Phase 1 RYZ401 Actinium-225 SSTR2-targeted alpha radiopharmaceutical in SSTR+ tumors.

This first-in-human Phase 1, open-label dose-escalation and dose-expansion trial tests RYZ401, RayzeBio’s somatostatin receptor (SSTR2)-targeted peptide radiopharmaceutical labeled with actinium-225, an alpha-emitting isotope that delivers short-range, high–DNA-damage radiation to SSTR-expressing tumor cells. The study’s goals are to define safety/tolerability, pharmacokinetics/dosimetry, and determine the recommended Phase 2 dose and regimen, with early anti-tumor activity assessed across neuroendocrine tumors (NETs) and selected SSTR+ solid tumors. Enrollment includes locally advanced/unresectable Grade 1–3 NET (including gastroenteropancreatic NET expansion cohorts) and an additional solid-tumor expansion for SSTR-expressing cancers, reflecting that SSTR2 is common in GEP-NET (~80–90%+) and enables imaging-based selection. Commercially, this extends RayzeBio’s SSTR radiopharmaceutical franchise into next-generation alpha therapy, aiming to improve depth/durability versus beta-emitting PRRT. Today’s care for advanced well-differentiated NET commonly includes long-acting somatostatin analogs, targeted agents (everolimus, sunitinib for pancreatic NET), liver-directed therapy when relevant, and lutetium-177 DOTATATE PRRT for SSTR+ disease.