NEW YORK – RayzeBio on Wednesday said it has begun the Phase III portion of the ACTION-1 trial of its radiopharmaceutical therapy RYZ101 in certain patients with somatostatin receptor (SSTR)-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
RYZ101 is an investigational targeted radiopharmaceutical designed to deliver actinium-225 to SSTR type 2-expressing tumors. In the Phase III trial underway, RayzeBio researchers will compare the safety, efficacy, and pharmacokinetics of RYZ101 against investigators' choice of standard-of-care therapy in patients with inoperable, advanced, well-differentiated SSTR-positive GEP-NETs who have progressed on a lutetium-177-labeled somatostatin analog.
The Phase III portion of the study follows a Phase Ib study, in which researchers evaluated RYZ101's safety and pharmacokinetics and established a Phase III dose. They also determined the relationship between exposure endpoints and clinical outcomes, observed biomarkers correlated with adverse events, and tracked efficacy endpoints such as overall survival and progression-free survival.
San Diego-based RayzeBio expects to enroll 210 patients in the Phase III randomized trial. Patients in the standard-of-care therapy arm could receive Novartis' mTOR inhibitor Afinitor (everolimus), Pfizer's multi-target receptor tyrosine kinase inhibitor Sutent (sunitinib), or long-acting somatostatin analogs.
About 18,000 patients are diagnosed with GEP-NETs in the US annually and about 80 percent express SSTR type 2. Novartis' Lu177-based somatostatin drug Lutathera (lutetium Lu 177 dotatate) has been approved in Europe since 2017 and in the US since 2018 for patients with SSTR-positive GEP-NETs, but most patients on those therapies eventually see their tumors progress.
RayzeBio is also studying RYZ101 in a Phase Ib trial involving patients with SSTR-positive extensive-stage small cell lung cancer.