Eligible participants must have ECOG 0-1, measurable HER2+ breast cancer refractory to prior therapies, and adequate organ function. Key exclusions include recent anticancer treatments (within 4 weeks), anthracycline exposure, active infections, CNS metastases, cardiac dysfunction (LVEF <50%), QTcF >470 ms, pregnancy, or uncontrolled comorbidities. The dose-expansion cohort limits prior chemotherapy regimens to two in the metastatic setting.

The study evaluates safety outcomes including adverse events (AEs) and serious AEs (SAEs) graded per NCI CTCAE v4.0 from Day 1 to study end (up to 39 months), with severity ranging from Grade 1 (mild) to Grade 5 (fatal). Dose-limiting toxicities (DLTs) are assessed during the first 21 days, including cardiac, hematologic, and hepatic events. Treatment duration and cumulative dose are tracked, along with left ventricular ejection fraction (LVEF) changes via ECHO/MUGA scans at specified intervals.

Pharmacokinetic analysis measures DHES0815A total antibody, conjugated PDB-MA, and unconjugated PDB-MA concentrations at multiple timepoints from Cycle 1 to study end (up to 39 months). Efficacy endpoints include objective response (CR/PR per RECIST v1.1), duration of response (DoR), and anti-drug antibody (ADA) incidence, with ADA-positive participants classified as treatment-induced or treatment-enhanced.