Bristol Myers Squibb has announced positive topline results from a planned interim analysis of the Phase 3 ACTION-1 trial, evaluating RYZ101 (225Ac-DOTATATE) in patients with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumours (GEP-NETs) whose disease progressed following lutetium-177 (Lu-177)-based therapy.

The trial, conducted by RayzeBio, a Bristol Myers Squibb company, met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival, assessed by blinded independent central review. Safety results were consistent with the known safety profile of RYZ101.

ACTION-1 is a randomised Phase 3 study comparing RYZ101 with investigator-selected standard-of-care treatments, including high-dose or high-frequency long-acting somatostatin analogues, everolimus or sunitinib. The study involves patients whose cancer has progressed after Lu-177-based treatment, a setting in which additional therapeutic options remain limited.

RYZ101 is an investigational targeted radiopharmaceutical therapy comprising DOTATATE linked to actinium-225 (225Ac), an alpha-emitting radioisotope. The treatment is designed to target somatostatin receptors on cancer cells and deliver radiation intended to damage their DNA.

The FDA granted RYZ101 Orphan Drug Designation for GEP-NETs in August 2026. The company said the designation and interim trial findings support continued development of the candidate. Detailed results are expected to be presented at a future medical meeting.

GEP-NETs are rare tumours arising in the gastrointestinal tract and pancreas. An estimated 18,000 people are diagnosed with the disease annually in the United States. Somatostatin receptor type 2 is expressed in approximately 80–90% of GEP-NET tumours. Although Lu-177-based radiopharmaceutical therapy is an established treatment for eligible adults with somatostatin receptor-positive GEP-NETs, disease progression after treatment remains a challenge.

RYZ101 is also being evaluated in earlier-stage clinical studies for hormone receptor-positive metastatic breast cancer. RayzeBio develops targeted radiopharmaceutical candidates and has capabilities spanning discovery, development, isotope production and manufacturing.