Bristol Myers Squibb announced positive topline results from the planned interim analysis of the Phase 3 ACTION-1 trial evaluating RayzeBio’s RYZ101 in patients with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors who had progressed following Lutetium-177-based therapy.
The study met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival by blinded independent central review.
Safety findings were consistent with the known safety profile of RYZ101.
ACTION-1 is a randomized Phase 3 study comparing RYZ101, also known as 225Ac-DOTATATE, with investigator’s choice of standard of care.
The standard-of-care options in the trial include high-dose or high-frequency long-acting somatostatin analogues, everolimus, or sunitinib.
The company said the findings represent the first Phase 3 results for an alpha-isotope-based targeted radiopharmaceutical therapy using Actinium-225 in any indication.
RYZ101 is an investigational targeted radiopharmaceutical therapy that combines DOTATATE with Actinium-225, a potent alpha-emitting radioisotope.
The therapy targets cancer cells expressing somatostatin receptor type 2.
Actinium-225 emits high-energy, short-range alpha particles that can cause double-stranded DNA damage in cancer cells, potentially increasing the likelihood of cancer cell death.
The FDA granted RYZ101 Orphan Drug Designation for treating GEP-NETs in August 2026.
Bristol Myers Squibb and RayzeBio said the interim results, together with the designation, support continued development and plans to engage with the FDA regarding next steps toward a regulatory submission.
Detailed ACTION-1 results are expected at a future medical meeting.
Patients currently enrolled in the study will continue receiving care according to the trial protocol and will be followed for overall survival.
GEP-NETs are rare tumors with an estimated incidence of approximately 18,000 new diagnoses annually in the U.S. and a prevalence of fewer than 200,000 patients.
Somatostatin receptor type 2 is expressed in approximately 80% to 90% of GEP-NET tumors.
Lu177-based radiopharmaceutical therapy is already approved for adult patients with SSTR-positive GEP-NETs, but Bristol Myers Squibb said most patients eventually progress following treatment and have few effective options available afterward.
Earlier clinical experience with RYZ101 included a Phase 1b trial involving 17 previously Lu177-treated patients with disease progression.
In that study, RYZ101 was well tolerated, with no treatment-related serious adverse events or dose discontinuations due to adverse events.
RYZ101 is also being evaluated in earlier-stage trials in hormone receptor-positive metastatic breast cancer.
RayzeBio, which Bristol Myers Squibb owns, is developing a broader radiopharmaceutical pipeline that includes programs targeting GPC3, ACP3, next-generation SSTR2-directed therapies, and other undisclosed targets.
KEY QUOTES:
“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. 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.”
Amreen Husain, M.D., Chief Medical Officer of RayzeBio
“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. 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.”
Simron Singh, M.D., Medical Oncologist at the Odette Cancer Centre, Sunnybrook Health Sciences Centre, Professor of Medicine at the University of Toronto, and Principal Investigator of the ACTION-1 Study
