Trial of 225Ac-DOTATATE (RYZ101) in Subjects With ER+, HER2-negative Unresectable or Metastatic Breast Cancer Expressing SSTRs. (TRACY-1)

Subjects must meet all the following criteria for enrollment in the study:

• Histologically confirmed, ER+, HER2-negative, locally advanced and unresectable or metastatic breast cancer not amenable to treatment with curative intent.

• Adequate renal, hematologic, and hepatic function

• Additional inclusion criteria for Monotherapy arm:

  • Measurable disease with at least 80% SSTR-positive lesions by SSTR-PET imaging
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤2
  • Documented radiologic progression after at least 2 and no more than 4 prior chemotherapy or ADC regimens in the metastatic setting

• Additional inclusion criteria for ET Combination arms:

  • Prior treatment with CDK4/6 inhibitors in combination with endocrine therapy in the advanced or metastatic setting.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤1
  • Bone only or bone dominant disease. At least 1 bone lesion must be SSTR-positive on SSTR-PET imaging. For bone dominant disease, at least 50% of soft tissue measurable lesions must be SSTR-positive on SSTR-PET imaging. At least one bone lesion must be positive on both SSTR-PET and on FDG-PET imaging
  • Brain metastases are allowed if definitively treated and clinically stable as confirmed by interval imaging