Bristol Myers Squibb (NYSE:BMY) today announced 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 the primary endpoint with a statistically significant and clinically meaningful improvement in progression-free survival by blinded independent central review, and safety results consistent with the known RYZ101 safety profile. ACTION-1 is a randomized Phase 3 clinical trial evaluating RYZ101 (225Ac-DOTATATE) versus 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) who have progressed following Lutetium-177 (Lu177)-based therapy.

"The improvement in progression-free survival is a defining moment for RYZ101 and for the patients we built this program around — people with advanced GEP-NETs whose cancer has progressed after Lu177-based therapy and who have few remaining options," said Amreen Husain, MD, chief medical officer of RayzeBio. "This is the kind of impact we set out to deliver with actinium-based radiopharmaceuticals, and it is an important milestone supporting the pipeline we are building across our RPT platform. These are the first results from a Phase 3 trial of an alpha-isotope based targeted RPT (225Ac) in any indication, and we are moving with urgency to bring these data to the FDA and, ultimately, provide a novel option for patients."

The FDA granted RYZ101 Orphan Drug Designation for the treatment of GEP-NETs in August 2026 based on the significant unmet need facing patients with this disease. That designation, combined with the results of this interim analysis, supports RayzeBio's continued development efforts and plans to engage with the FDA to discuss next steps toward a regulatory submission. Detailed results are expected to be presented at a future medical meeting.

"Lu177-based therapy is widely used in GEP-NETs, but unfortunately the vast majority of patients will eventually progress. Determining the optimal treatment after Lu177 has been an important question for my patients, and until now there has been no randomized Phase 3 evidence to guide it," said Simron Singh, MD, medical oncologist in the Odette Cancer Centre, Sunnybrook Health Sciences Centre, Professor of Medicine at the University of Toronto, and principal investigator of the ACTION-1 study. "ACTION-1 provides the first Phase 3 results for an alpha-based targeted RPT, and a clinically meaningful improvement in progression-free survival is a crucial development in improving the care of patients with GEP-NETs."

Individuals currently enrolled will continue to receive care consistent with the study protocol, and participants will be followed for overall survival.