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

A Phase 1a/1b Study of HLD-0117 in Patients With Estrogen Receptor Positive (ER+) Metastatic Breast Cancer (MBC)

Assessment of the safety and efficacy of HLD-0117 as monotherapy in patients with estrogen receptor positive (ER+) metastatic breast cancer (MBC) or locally advanced breast cancer that have progressed on prior systemic therapies.

This study is an open-label, dose-escalation and cohort expansion study evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and anti-tumor activity of oral single-agent, HLD-0117 in patients with ER+ MBC that have progressed after at least 1 prior systemic line of therapy.

During dose escalation, patients will be enrolled into monotherapy cohorts using a Bayesian optimal interval (BOIN) design. Cohorts will enroll a minimum of three patients, with staggered enrollment between cohorts. Backfilling into dose levels determined to be safe may occur to further characterize tolerability and efficacy.

The purpose of the study is to determine the maximum tolerated dose (MTD) and/or recommended dose(s) for expansion (RDEs) of HLD-0117 as a monotherapy.

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