Trial of H3B-6545, in Women With Locally Advanced or Metastatic Estrogen Receptor-positive, HER2 Negative Breast Cancer

Inclusion Criteria:

Pre- or post-menopausal women.
ER-positive, HER2-negative breast cancer that is advanced or metastatic.
Progressed on prior therapy. Multiple prior lines of therapy allowed in Phase 1 and 2. Participants under amendment 6 (or subsequent amendments) must have received prior cyclin-dependent kinase (CDK4/6) inhibitor therapy. Up to one prior chemotherapy in the metastatic setting is allowed.
A recent archival tumor tissue obtained within 6 months prior to enrollment or a fresh tumor biopsy must be provided. A second biopsy after initiating trial therapy is not required.
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
Adequate bone marrow and organ function.
Participants under amendment 6 (or subsequent amendments) must have measurable disease at baseline as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
Participants under amendment 6 (or subsequent amendments) must have ESR1 Y537S mutation in absence of ESR1 D538G mutation as per the results of a central laboratory from a Nucleic Acids Whole Blood sample.

Exclusion Criteria:

Participants must have at least one measurable lesion.
Participant with inflammatory breast cancer.
Participant has received more than one prior chemotherapy regimen for metastatic disease (Phase 2 only).
Females of childbearing potential who are unable or unwilling to follow adequate contraceptive measures.