Bristol Myers Squibb posted what it described as the first Phase III results for an alpha-emitting targeted radiopharmaceutical therapy. The Phase III ACTION-1 trial of RYZ101 (225Ac-DOTATATE) met its primary endpoint with a statistically significant improvement in progression-free survival (PFS) in patients with somatostatin receptor-positive (SSTR+) gastroenteropancreatic neuroendocrine tumors (GEP-NETs) who had progressed following lutetium-177-based therapy. The result positions RYZ101 for a regulatory submission discussion with the FDA, addressing a setting where no randomized Phase III evidence had previously guided treatment selection.
The topline interim analysis compared RYZ101 against investigator's choice of standard of care — comprising high-dose or high-frequency long-acting somatostatin analogues, everolimus, or sunitinib — in patients with SSTR+ GEP-NETs progressing after Lu177-based therapy; no numerical PFS figures, hazard ratio, confidence intervals, p-value, or patient count were reported. Safety results were described as consistent with the known RYZ101 profile, with no specific adverse event data disclosed for ACTION-1. Enrolled participants will continue on protocol and be followed for overall survival, and Bristol Myers Squibb said it plans to engage the FDA on next steps toward a regulatory submission, with detailed results expected at a future medical meeting.
RYZ101 combines the somatostatin receptor-targeting peptide DOTATATE with actinium-225, an alpha-emitting isotope that delivers high-energy, short-range radiation capable of causing double-strand DNA damage. In contrast, existing radioligand therapies such as Novartis' Lutathera and Curium's Bexlutry use the beta-emitting isotope lutetium-177. Bexlutry received US FDA approval in September 2026 as a therapeutic equivalent to Lutathera. RYZ101 is being developed for patients whose disease has progressed despite prior Lu-177 treatment, a setting with limited established treatment options.