Phase 3 interim data for RYZ101, the lead asset from Bristol Myers Squibb’s $4.1 billion RayzeBio deal, meet the primary endpoint.
Bristol Myers Squibb said the phase 3 ACTION-1 trial of RYZ101, an actinium-225–based radiopharmaceutical, met its primary endpoint of progression-free survival (PFS) at a planned interim analysis, as assessed by blinded independent central review.¹ The company described safety as consistent with the therapy’s known profile but did not release efficacy figures.¹
The readout is important to the company’s oncology strategy. Bristol Myers Squibb acquired RayzeBio, the developer of RYZ101, in 2024 for about $4.1 billion, or $62.50 per share, a transaction that added radiopharmaceuticals to its pipeline.²
“The improvement in [PFS] 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.”
ACTION-1 (NCT05477576) randomizes patients with somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) whose disease progressed after lutetium-177–based therapy.¹ Participants receive RYZ101 or investigator’s choice of standard care: high-dose or high-frequency long-acting somatostatin analogues, everolimus or sunitinib.¹
Enrolled patients will continue under the protocol and be followed for overall survival.¹ Because the company has not disclosed the size of the PFS difference, a hazard ratio or event rates, the strength of the result cannot yet be judged.
A control arm built from three different treatments is also heterogeneous.
The company estimates about 18,000 U.S. diagnoses of GEP-NETs a year, with prevalence below 200,000, and says metastatic disease is present at diagnosis in the vast majority of cases.¹ Somatostatin receptor type 2 is expressed in 80% to 90% of these tumors.¹
Lutetium-177–based therapy is approved for adults with receptor-positive disease, and in the phase 3 NETTER-1 trial of 229 patients with midgut tumors, the response rate was 18% with lutetium-177 dotatate versus 3% with high-dose octreotide.³ Most patients still progress.¹
“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.”
RYZ101 pairs the somatostatin analogue DOTATATE with actinium-225, an alpha-emitting isotope that the company says releases a high-energy, short-range particle capable of causing double-stranded DNA damage in tumor cells.¹ Lutetium-177 is a beta emitter.³
In a phase 1b trial of 17 patients previously treated with lutetium-177, the company reports RYZ101 was well tolerated, with no treatment-related serious adverse events (AEs) or discontinuations because of AEs.¹ That is a small, early dataset.
The company says RayzeBio’s capabilities span isotope production and manufacturing across its sites.¹
FDA granted RYZ101 Orphan Drug Designation for GEP-NETs in August 2026.¹ The company plans to engage the agency on next steps toward a regulatory submission, without a stated timeline, and expects detailed results at a future medical meeting.¹
Open questions include the magnitude of benefit, overall survival, and the safety profile of an alpha emitter in a randomized setting. The company cautions that later results may differ and that approval is not assured.¹
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