Phase 1b/2 open-label trial of 225Ac-DOTATATE (RYZ101) in subjects with ER+, HER2-negative unresectable or metastatic breast cancer expressing SSTRs.

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.