RYZ101 slows disease progression in Phase 3 ACTION-1 interim analysis for gastroenteropancreatic neuroendocrine tumours

Bristol Myers Squibb has reported positive topline results from a planned interim analysis of the ACTION-1 trial, run by RayzeBio, Inc., a Bristol Myers Squibb company. The study met its primary endpoint, showing a statistically significant and clinically meaningful improvement in progression free survival as judged by blinded independent central review. Safety results matched the known profile of RYZ101.

ACTION-1 is a randomised Phase 3 trial that compares RYZ101 (225Ac DOTATATE) with the investigator’s choice of standard care, which could be high dose or high frequency long acting somatostatin analogues, everolimus or sunitinib. It enrolled patients with somatostatin receptor positive gastroenteropancreatic neuroendocrine tumours (GEP-NETs) whose disease had progressed after treatment based on Lutetium 177 (Lu177).

Amreen Husain, MD, chief medical officer of RayzeBio, called the progression free survival result a defining moment for RYZ101 and for people with advanced GEP-NETs who have few options left once Lu177 therapy stops working. She said the result is the kind of impact the company hoped to achieve with actinium based radiopharmaceuticals and marks an important step for the wider pipeline it is building on its radiopharmaceutical therapy platform. She added that these are the first Phase 3 results for an alpha isotope based targeted radiopharmaceutical therapy (225Ac) in any condition, and that the company is moving urgently to take the data to the US Food and Drug Administration and ultimately offer patients a new option.

The FDA granted RYZ101 Orphan Drug Designation for GEP-NETs in August 2026, citing the significant unmet need in the disease. Together with the interim results, this supports RayzeBio’s continued development and its plans to talk to the agency about next steps towards a regulatory submission. Detailed results are expected at a future medical meeting.

Simron Singh, MD, a medical oncologist at the Odette Cancer Centre at Sunnybrook Health Sciences Centre, professor of medicine at the University of Toronto and principal investigator of ACTION-1, said Lu177 therapy is widely used in GEP-NETs but most patients eventually progress. He said deciding on the best treatment after Lu177 has been an important question for his patients, and until now there has been no randomised Phase 3 evidence to guide it. He said ACTION-1 delivers the first Phase 3 results for an alpha based targeted radiopharmaceutical therapy, and that a clinically meaningful gain in progression free survival is a crucial step in improving care for people with GEP-NETs.

Patients currently enrolled will keep receiving care in line with the study protocol, and participants will continue to be followed for overall survival.

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Related Topics and Keywords

Bristol-Myers Squibb, gastroenteropancreatic neuroendocrine tumours, Phase 3 ACTION-1, RYZ101, tumour