RYZ101, a DOTATATE Peptide Radiopharmaceutical, Meets Phase 3 Endpoint in ACTION-1 GEP-NET Trial
Bristol Myers Squibb announced on October 12, 2026 that the Phase 3 ACTION-1 trial of RYZ101 (225Ac-DOTATATE), developed by its RayzeBio subsidiary, met its primary endpoint at a planned interim analysis. Per the sponsor announcement, the trial showed a statistically significant and clinically meaningful improvement in progression-free survival by blinded independent central review, with safety results consistent with the known profile of the candidate. Full numerical results were not disclosed in the topline release and are expected at a future medical meeting.
ACTION-1 (NCT05477576) is a randomized Phase 3 trial in people with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors, or GEP-NETs, whose disease had progressed after lutetium-177-based therapy. The comparator was investigator-choice standard of care, described by the sponsor as long-acting somatostatin analogues, everolimus, or sunitinib. Participants remain in follow-up for overall survival, so the interim readout addresses progression-free survival only.
The peptide link is DOTATATE itself. DOTATATE is a somatostatin analogue peptide that binds somatostatin receptor type 2, a receptor the sponsor notes is expressed in 80 to 90 percent of GEP-NET tumors, and therapies built on radiolabeled versions of this peptide are known as peptide receptor radionuclide therapy. RYZ101 binds that same DOTATATE targeting peptide to actinium-225, a potent alpha-emitting isotope. The sponsor described ACTION-1 as the first Phase 3 results for an alpha-isotope targeted radiopharmaceutical in any indication, a claim that belongs to the sponsor and has not been independently adjudicated by the FDA.
The regulatory record so far is a designation, not an approval. The FDA granted RYZ101 Orphan Drug Designation for GEP-NETs in August 2026, reflecting the rare-disease setting: the sponsor estimates about 18,000 new GEP-NET diagnoses a year in the United States and a prevalence under 200,000. Bristol Myers Squibb said the designation, combined with the interim result, supports its plan to engage the FDA on next steps toward a regulatory submission. No submission, review timeline, or approval date was announced.
For readers tracking peptide regulation, the distinction that matters is the same one this site applies to every pipeline story. Approved lutetium Lu 177 dotatate products were approved by the FDA for a specific product and a specific labeled use in somatostatin receptor-positive GEP-NETs. RYZ101 has reached a positive Phase 3 interim readout and holds an orphan designation, but it remains an investigational research candidate. Its status changes only if and when the FDA acts on a future submission.