Phase 3 ACTION-1: RayzeBio's RYZ101 met progression-free survival endpoint in post-Lu177 GEP-NETs

Bristol Myers Squibb announced on October 12, 2026 positive topline results from the planned interim analysis of the ACTION-1 trial (NCT05477576), conducted by RayzeBio, Inc., a Bristol Myers Squibb company. The study met its primary endpoint with a statistically significant and clinically meaningful improvement in progression-free survival by blinded independent central review, with safety results consistent with the known RYZ101 safety profile.

ACTION-1 is a randomized Phase 3 trial evaluating RYZ101 (225Ac-DOTATATE) against investigator's choice of standard of care - high-dose or high-frequency long-acting somatostatin analogues, everolimus, or sunitinib - in patients with somatostatin receptor-positive (SSTR+) gastroenteropancreatic neuroendocrine tumors (GEP-NETs) whose disease progressed following Lutetium-177 (Lu177)-based therapy.

According to RayzeBio, these are the first results from a Phase 3 trial of an alpha-isotope based targeted radiopharmaceutical therapy (225Ac) in any indication. 'The improvement in progression-free survival is a defining moment for RYZ101 and for the patients we built this program around,' said Amreen Husain, MD, chief medical officer of RayzeBio. The FDA granted RYZ101 Orphan Drug Designation for GEP-NETs in August 2026, and the company says the interim results support plans to engage with the FDA on next steps toward a regulatory submission. Detailed results are expected at a future medical meeting.

GEP-NETs are rare tumors, with an estimated 18,000 patients diagnosed annually in the United States and a prevalence of fewer than 200,000. SSTR2 is expressed in 80-90% of GEP-NET tumors, and while Lu177-based radiopharmaceutical therapy is approved and widely used, most patients eventually progress with few effective options afterward. 'Until now there has been no randomized Phase 3 evidence to guide it,' said principal investigator Simron Singh, MD, of the Odette Cancer Centre, Sunnybrook Health Sciences Centre and the University of Toronto.

RYZ101 is an investigational targeted radiopharmaceutical comprising DOTATATE bound to Actinium-225, an alpha-emitting radioisotope. In a Phase 1b trial of 17 previously Lu177-treated patients, RYZ101 was well tolerated with no treatment-related serious adverse events or dose discontinuations due to adverse events; it is also being evaluated in earlier-stage trials in hormone receptor-positive metastatic breast cancer. Context and limits: these are company-announced topline interim results; full data, including effect sizes and detailed safety tables, have not yet been presented or peer reviewed. Participants remain on protocol and will be followed for overall survival. RYZ101 has no regulatory approval for any indication. This brief is not medical advice and does not recommend any treatment.