Bristol Myers' Alpha-Emitting RYZ101 Meets Phase 3 Goal in Neuroendocrine Tumors

Bristol Myers Squibb said on October 12 that RYZ101, an investigational radiopharmaceutical developed by its RayzeBio subsidiary, met the primary endpoint of a Phase 3 trial in patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) whose disease had progressed after lutetium-177-based therapy, according to a company announcement.

The results come from a planned interim analysis of ACTION-1 and are topline data reported by the company. Bristol Myers did not disclose the size of the progression-free survival benefit, a hazard ratio or median survival figures, and said detailed results will be presented at a future medical meeting.

What the trial is testing

RYZ101 (225Ac-DOTATATE) pairs DOTATATE with actinium-225, an alpha-emitting radioisotope. According to the company, the isotope emits a short-range alpha particle that can cause double-stranded DNA damage in cancer cells.

ACTION-1 enrolled patients with somatostatin receptor-positive (SSTR-positive) GEP-NETs that had progressed after a lutetium-177 somatostatin analogue such as Lu-177 DOTATATE. Patients were randomized to RYZ101 or to the investigator's choice of standard therapy: high-dose or high-frequency long-acting somatostatin analogues, everolimus or sunitinib. The ClinicalTrials.gov record (NCT05477576), sponsored by RayzeBio, lists actual enrollment of 343 participants, an open-label design and a status of active, not recruiting.

The company said the trial showed a statistically significant and clinically meaningful improvement in progression-free survival as assessed by blinded independent central review, and that safety results were consistent with RYZ101's known profile. Enrolled patients will continue on the study protocol and be followed for overall survival, a measure for which no results were reported.

Company and investigator comments

Amreen Husain, chief medical officer of RayzeBio, said the data are "the first results from a Phase 3 trial of an alpha-isotope based targeted RPT (225Ac) in any indication," using the abbreviation for radiopharmaceutical therapy.

The trial's principal investigator is Simron Singh, a medical oncologist at Sunnybrook Health Sciences Centre and professor of medicine at the University of Toronto, according to the release.

Earlier, in the Phase 1b portion of the study, 17 patients previously treated with lutetium-177 received RYZ101. The company said the drug was well tolerated in that group, with no treatment-related serious adverse events and no dose discontinuations due to adverse events.

Regulatory path

The FDA granted RYZ101 orphan drug designation for GEP-NETs in August 2026, the company said. RayzeBio plans to discuss next steps toward a regulatory submission with the agency. RYZ101 is also being tested in earlier-stage studies in hormone receptor-positive metastatic breast cancer, RTTNews reported.

RTTNews reported that Bristol Myers shares were trading at $57.25, down 3.21%, on the day of the announcement. Trade coverage that day, including OncLive, cited the Bristol Myers release as its source for the trial results.

RayzeBio, founded in 2020 and based in San Diego, is a Bristol Myers Squibb company whose operations span discovery, development, isotope production and manufacturing, according to the release.