Bristol Myers Squibb has reported positive interim Phase 3 results for RYZ101, an investigational targeted radiopharmaceutical therapy, marking a potential breakthrough for patients with advanced gastroenteropancreatic neuroendocrine tumors.
The ACTION-1 trial met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS), as assessed by blinded independent central review. Safety results were consistent with the known safety profile of RYZ101, the company said.
Developed by RayzeBio, a Bristol Myers Squibb company, RYZ101 is being evaluated against standard treatment options in patients with somatostatin receptor-positive (SSTR+) GEP-NETs following progression on Lu177-based therapy.
The results address a critical gap in treatment for patients whose cancer advances despite existing radiopharmaceutical therapy, leaving them with few effective options.
"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," said A Husain, 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."
The randomized Phase 3 ACTION-1 study compared RYZ101 with investigator-selected standard of care: high-dose or high-frequency long-acting somatostatin analogues, everolimus or sunitinib.
The trial's positive interim findings are significant because most patients with GEP-NETs who receive Lu177-based radiopharmaceutical therapy eventually experience disease progression. Evidence to guide treatment after progression has remained limited.
“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, medical oncologist 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.”
Bristol Myers Squibb said patients currently enrolled in the study will continue receiving care under the trial protocol and will be followed for overall survival. expressed in an estimated 80%–90% of GEP-NET tumors, while metastatic disease is present at diagnosis in the vast majority of cases.
Although Lu177-based radiopharmaceutical therapy has demonstrated significant clinical benefit and is approved for adults with SSTR-positive GEP-NETs, most patients eventually experience disease progression, leaving a pressing need for additional treatment options.
