PRINCETON, New Jersey — October 12, 2026
Bristol Myers Squibb announced positive topline results from the planned interim analysis of the Phase 3 ACTION-1 trial evaluating RYZ101 (225Ac-DOTATATE) in patients with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The study met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with investigator-selected standard-of-care treatments. RYZ101 is an investigational targeted radiopharmaceutical therapy developed by RayzeBio, a Bristol Myers Squibb company, for patients whose GEP-NETs have progressed following lutetium-177 (Lu-177)-based radiopharmaceutical therapy. The company reported that the safety results were consistent with the known safety profile of RYZ101. These findings represent an important milestone for the investigational treatment, which uses the alpha-emitting radioisotope actinium-225 to target cancer cells. Detailed trial results are expected to be presented at a future medical meeting, while Bristol Myers Squibb and RayzeBio plan to engage with the U.S. Food and Drug Administration to discuss potential regulatory next steps.
ACTION-1 Trial Meets Primary Progression-Free Survival Endpoint
The randomized Phase 3 ACTION-1 clinical trial evaluates RYZ101 against investigator’s choice of standard-of-care treatment in patients with advanced, somatostatin receptor-positive GEP-NETs whose disease has progressed after Lu-177-based therapy. The comparator options include high-dose or high-frequency long-acting somatostatin analogues, everolimus or sunitinib. The primary endpoint is progression-free survival assessed through blinded independent central review. According to Bristol Myers Squibb, the planned interim analysis demonstrated a statistically significant and clinically meaningful improvement in PFS with RYZ101, meeting the study’s primary endpoint. The company also reported that the safety findings were consistent with the treatment’s established safety profile. However, the announcement did not disclose the numerical PFS difference, hazard ratio, confidence intervals or detailed adverse-event data. Those results will be needed to understand the magnitude of the treatment effect and evaluate the full benefit-risk profile. Patients currently enrolled in ACTION-1 will continue receiving care in accordance with the study protocol and will be followed for overall survival. The trial’s findings could help inform treatment strategies for patients whose disease progresses after existing radiopharmaceutical therapy, a population with limited effective treatment options.
Actinium-225 Radiopharmaceutical Targets Cancer Cells
RYZ101 is an investigational targeted radiopharmaceutical therapy comprising DOTATATE linked to actinium-225 (225Ac), a potent alpha-particle-emitting radioisotope. The therapy is designed to target somatostatin receptors expressed on tumor cells and deliver localized radiation. Actinium-225 emits high-energy alpha particles with a short range, which can cause double-stranded DNA damage and potentially lead to cancer-cell death. This mechanism distinguishes alpha-emitting radiopharmaceuticals from treatments that rely on other radiation emissions or systemic anticancer mechanisms. According to the company, a Phase 1b study involving 17 patients whose GEP-NETs had progressed following Lu-177-based treatment found that RYZ101 was well tolerated, with no treatment-related serious adverse events or adverse-event-related treatment discontinuations reported in that study. RYZ101 is also being evaluated in earlier-stage clinical studies for hormone receptor-positive metastatic breast cancer. The positive ACTION-1 topline announcement represents a significant clinical development milestone for an alpha-isotope-based targeted radiopharmaceutical therapy in a Phase 3 trial. Nevertheless, the treatment remains investigational, and its efficacy, detailed safety characteristics and regulatory status will require further assessment.
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Regulatory Discussions Planned Following Positive Results
The U.S. FDA granted Orphan Drug Designation to RYZ101 for GEP-NETs in August 2026, according to the company. The designation reflects the development program’s focus on a rare disease with substantial unmet medical need. Bristol Myers Squibb and RayzeBio plan to discuss the ACTION-1 interim findings with the FDA and determine appropriate next steps toward a potential regulatory submission. RayzeBio Chief Medical Officer Dr. Amreen Husain described the PFS result as an important milestone for patients whose cancer progresses after Lu-177-based therapy. ACTION-1 principal investigator Dr. Simron Singh also highlighted the need for randomized Phase 3 evidence to guide treatment decisions after progression on Lu-177 therapy. GEP-NETs are rare tumors, with approximately 18,000 patients diagnosed annually in the United States, according to the company. Somatostatin receptor type 2 is expressed in an estimated 80% to 90% of these tumors, making receptor-targeted treatments a relevant therapeutic strategy. Although Lu-177-based radiopharmaceutical therapy has provided an established option for eligible patients, disease progression remains a major challenge. The ACTION-1 results provide encouraging topline evidence for RYZ101, while detailed data and regulatory discussions will help clarify its potential role in future GEP-NET treatment.
Source::Bristol Myers Squibb, press release
