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

AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. SAE is any AE that is fatal, is life threatening, requires or prolongs inpatient hospitalization, results in persistent/significant disability/incapacity and is congenital anomaly/birth defect. Severity of AEs were graded per NCI CTCAE v4.0. Grade 1: Mild; asymptomatic/mild symptoms; clinical/diagnostic observations only; or intervention not indicated; Grade 2: Moderate; minimal, local/non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living; Grade 3: Severe/medically significant, but not immediately life-threatening: hospitalization/prolongation of hospitalization indicated; disabling/limiting self-care activities of daily living; Grade 4: Life-threatening consequences/urgent intervention indicated; Grade 5: Death related to AE.

DLT=any one events occurring during DLT assessment window: ≥15% decrease from baseline in left ventricular ejection fraction (LVEF)/≥10% decrease to <50% LVEF; Grade ≥ 3 non-hematologic toxicity; Grade ≥4 neutropenia (absolute neutrophil count <500 cells/microliters [μL]) lasting <7 days; Grade ≥3 febrile neutropenia; Grade ≥4 anemia; Grade ≥4 thrombocytopenia; Grade 3 thrombocytopenia associated with clinically significant bleeding; Any increase in hepatic transaminase (ALT or AST) >3*baseline in combination with either an increase in direct bilirubin >2*upper limit of normal/clinical jaundice, in absence of cholestasis/other contributory factors. NCI CTCAE v4.0. was used to grade these events.Grade1: Mild; asymptomatic/mild symptoms; clinical/diagnostic observations only; Grade2: Moderate; minimal, local/non-invasive intervention indicated;Grade3: Severe/medically significant, but not immediately life-threatening;Grade4: Life-threatening consequences/urgent intervention indicated.

Treatment duration was calculated from the first dose of study drug to the last dose of study drug administration.

LVEF is the fraction of blood (in percent) pumped out of the heart's left ventricular chamber with each heartbeat and is a measure of cardiac output for the heart. Baseline LVEF value and the change from baseline to the worst value in LVEF measurement were reported. LVEF was measured by ECHO or MUGA scan.

DHES0815A total antibody is one of three key pharmacokinetic analytes of DHES0815A.

Conjugated PDB-MA is one of three key pharmacokinetic analytes of DHES0815A.

Plasma Unconjugated PDB-MA is one of three key pharmacokinetic analytes of DHES0815A.

Objective response was defined as a complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1. CR, defined as disappearance of all target lesions. PR, defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR.

DOR was defined as the time from the first occurrence of a documented objective response to disease progression (PD) or death from any cause, whichever occurred first, as determined by the investigator according to RECIST v1.1. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 millimeters (mm).

Number of participants with treatment induced and treatment-enhanced ADA are reported here. Participants were considered to have treatment-induced ADA responses if they were ADA negative at baseline and developed an ADA response following DHES0815A administration. Participants were considered to have treatment-enhanced ADA if they were ADA positive at baseline and the titer of one or more postbaseline samples is at least 4-fold greater than baseline titer (i.e., ≥ 0.60 titer units) following study drug administration.