Trial of 225Ac-DOTATATE (RYZ101) in Subjects With ER+, HER2-negative Unresectable or Metastatic Breast Cancer Expressing SSTRs.

Inclusion Criteria

• Inclusion Criteria Subjects must meet all the following criteria for enrollment in the study: - Eastern Cooperative Oncology Group performance status ≤2. - Histologically confirmed, ER+, HER2-negative, locally advanced and unresectable or metastatic breast cancer not amenable to treatment with curative intent. - At least one RECIST v1.1-measurable tumor lesion that is SSTR-PET positive (defined as maximum standard uptake value (SUVmax) higher than liver mean standard uptake value (SUVmean) on SSTR-PET imaging) and at least 80% of RECIST v1.1measurable tumor lesions are SSTR-PET positive - Sufficient renal function, as evidenced by eGFR ≥60 mL/min/1.73m2 calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation - Adequate hematologic and hepatic function Exclusion Criteria Subjects who meet any of the following criteria will be excluded from the study: - Prior radiopharmaceutical therapy, including radioembolization. - Any toxicities from prior treatments that have not recovered to CTCAE Grade ≤1, except for alopecia. - Significant cardiovascular disease - Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, spinal cord compression, or leptomeningeal disease. - History of hypersensitivity or allergy to 225Ac, 68Ga, 64Cu, octreotate, or any of the excipients of DOTATATE imaging agents. - Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the study safety or efficacy assessments. - Pregnancy or lactation.