A Study of HLD-0117 in Patients With Metastatic Breast Cancer

Inclusion criteria

• Female (assigned at birth), ≥18 years old, and able to provide informed consent
• Histologically confirmed metastatic or locally advanced breast cancer
• Postmenopausal status defined by surgical or natural menopause, or ovarian suppression with a GnRH agonist
• Prior treatment including at least one endocrine therapy in the metastatic setting, at least one CDK4/6 inhibitor (in the adjuvant and/or metastatic setting), and no more than two prior cytotoxic regimens in the metastatic setting
• Radiologic disease progression on the most recent therapy
• Measurable disease per RECIST v1.1
• Willingness to provide baseline and on-treatment tumor biopsies, unless not feasible or medically appropriate
• ER-positive and HER2-negative status documented within 2 years
• ECOG performance status 0-1 and life expectancy of at least 3 months
• Adequate organ function Recovery from prior therapy-related toxicities to Grade ≤1 (except alopecia; neuropathy and endocrinopathies ≤Grade 2)
• Ability to swallow oral medication and comply with study procedures
• Stable dose (≥30 days) of bisphosphonates or denosumab, if applicable

Exclusion criteria

• Inflammatory breast cancer or known brain metastases
• Recent major bleeding or uncontrolled bleeding disorder
• Ongoing corticosteroid use \>10 mg/day (prednisone equivalent)
• Recent anticancer or investigational therapy within 14 days (28 days for fulvestrant)
• Untreated or unstable spinal cord compression
• Significant cardiovascular disease within 6 months or ongoing uncontrolled cardiac conditions
• Active or uncontrolled infection (controlled HIV or treated hepatitis C allowed)
• Uncontrolled renal, pancreatic, or liver disease (excluding stable conditions such as Gilbert's syndrome or liver metastases)
• Another malignancy requiring treatment within 2 years (except low-risk, curatively treated cancers)
• Major surgery within 28 days
• Any condition that may interfere with safety or study compliance
• Pregnancy or breastfeeding