Olema: This Phase I trial is seeking to determine the recommended dose, safety and tolerability of a new hormone therapy (OP-1250) in combination with targeted therapy (palbociclib) in people with advanced or metastatic HR+ and HER2- breast cancerA Phase 1 Dose Escalation and Dose Expansion Open-label, Multicenter, Study of OP-1250 in Combination with the CDK4/6 Inhibitor Palbociclib in Adult Subjects with Advanced or Metastatic HR-positive, HER2-negative Breast Cancer

Exclusion

 1. Prior or concurrent malignancy whose natural history or treatment may interfere with the safety or efficacy assessment of the investigational regimen as determined by the medical monitor.
2. Known impaired cardiac function or clinically significant cardiac disease, such as ventricular arrhythmia requiring therapy, congestive heart failure (New York Heart Association Functional Classification Class 2B-4), and uncontrolled hypertension (defined as systolic blood pressure greater than 150 mm Hg and/or diastolic blood pressure greater than 100 mm Hg while on anti-hypertensive medications).
3. Myocardial infarction or unstable angina within 6 months prior to the first administration of study drug.
4. History of cerebral vascular disease within 6 months prior to the first administration of study drug.