Safety, Tolerability, and Pharmacokinetic (PK) Study of DHES0815A in Participants With Human Epidermal Growth Factor Receptor (HER)2-Positive Breast Cancer

A Phase I, Open-Label Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Escalating Doses of DHES0815A in Patients With HER2-Positive Breast Cancer

This first-in-human, Phase 1, open-label, multicenter, dose-escalation study will evaluate the safety, tolerability, and PK of DHES0815A as a single agent in participants with advanced and/or metastatic HER2-positive breast cancer for whom established treatment has proven ineffective or intolerable or is unavailable. The study may include a dose-expansion cohort (based on an ongoing assessment of the totality of data obtained in this study) to further assess safety, tolerability, PK, and preliminary anti-tumor activity.

Key Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Measurable disease by RECIST v1.1 with at least one measurable target lesion
• Locally advanced or metastatic HER2-positive breast cancer that has relapsed or is refractory to established therapies
• Adequate hematologic and end-organ function
• For dose-expansion cohort only: no more than two prior systemic chemotherapy-containing regimens in the advanced/metastatic setting (excluding trastuzumab emtansine, which is considered a targeted cytotoxic agent)

Key Exclusion Criteria:

• Treatment with chemotherapy, hormonal therapy (except hormone replacement therapy, oral contraceptives), immunotherapy, biologic therapy, radiation therapy (except palliative radiation to bony metastases), or herbal therapy as cancer therapy within 4 weeks prior to initiation of DHES0815A
• History of exposure to the protocol specified doses of anthracyclines
• Pregnancy, lactation, or breastfeeding
• Major surgical procedure within 4 weeks prior to Day 1
• Evidence of a significant uncontrolled concomitant disease of the nervous system, pulmonary, autoimmune, renal, hepatic, endocrine, or gastrointestinal disorders; or a serious non-healing wound or fracture
• Known active bacterial, viral, fungal, mycobacterial, or other infection
• Clinically significant history of liver disease, including active viral or other hepatitis, current alcohol abuse, or cirrhosis
• Untreated or active central nervous system (CNS) metastases
• Cardiopulmonary dysfunction, including inadequate left ventricular ejection function at baseline, less than 50% by either echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)
• QT interval corrected through use of Fridericia's formula (QTcF) > 470 milliseconds (ms)