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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03451162

Enrollment

Registered

2018-03-01

Start date

2018-04-17

Completion date

2021-07-16

Last updated

2024-08-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Breast Cancer

Brief summary

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.

Interventions

DRUGDHES0815A

DHES0815A will be administered via intravenous (IV) infusion on Day 1 of each 21-day cycle.

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

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)

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0	From Day 1 to end of study (up to approximately 39 months)	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.
Number of Participants With Dose-limiting Toxicity (DLT)	From Day 1 up to Day 21	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.
Duration of Treatment	From Day 1 up to last dose of study drug (up to approximately 39 months)	Treatment duration was calculated from the first dose of study drug to the last dose of study drug administration.
Total Cumulative Dose	From Day 1 up to last dose of study drug (up to approximately 39 months)	—
Change From Baseline in LVEF as Assessed by Echocardiogram (ECHO) or Multiple-Gated Acquisition (MUGA) Scan	Baseline, end of Cycle 1, Days 15-21 of Cycles 2, 4, and 6, and every four cycles thereafter up to the study discontinuation visit (up to approximately 39 months)	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.

Secondary

Measure	Time frame	Description
Concentration of DHES0815A Total Antibody	Pre-dose and 30 minutes (min) post-dose on Day 1 Cycles 1-4; 4 hour (h) post-dose on Day 1 Cycle1; post-dose on Days 2, 3, 11, 17 Cycle 1; post-dose on Days 8 and 15 Cycles 1-4; study discontinuation visit (up to approx. 39 months) (Cycle length=21 days)	DHES0815A total antibody is one of three key pharmacokinetic analytes of DHES0815A.
Number of Participants With Anti-Drug Antibody (ADA) to DHES0815A	Pre-dose on Day 1 of Cycles 1-4 and 42 days after last infusion (up to approximately 39 months)	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.
Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Pre-dose and 30 minutes (min) post-dose on Day 1 Cycles 1-4; 4 hour (h) post-dose on Day 1 Cycle1; post-dose on Days 2, 3, 11, 17 Cycle 1; post-dose on Days 8 and 15 Cycles 1-4; study discontinuation visit (up to approx. 39 months) (Cycle length=21 days)	Conjugated PDB-MA is one of three key pharmacokinetic analytes of DHES0815A.
Concentration of Plasma Unconjugated PDB-MA	Pre-dose and 30 minutes (min) post-dose on Day 1 Cycles 1-4; 4 hour (h) post-dose on Day 1 Cycle1; post-dose on Days 2, 3, 11, 17 Cycle 1; post-dose on Days 8 and 15 Cycles 1-4; study discontinuation visit (up to approx. 39 months) (Cycle length=21 days)	Plasma Unconjugated PDB-MA is one of three key pharmacokinetic analytes of DHES0815A.
Number of Participants With Objective Response Assessed According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	From start of treatment until confirmation of CR or PR (up to approximately 39 months)	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.
Duration of Response (DoR) Assessed According to RECIST v1.1	From the initial CR or PR to the time of PD or death, whichever occurs first (up to approximately 39 months)	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).

Countries

South Korea, United States

Participant flow

Recruitment details

Participants took part in this study at 5 investigative sites in Republic of Korea and United States from 17 April 2018 to 16 July 2021.

Pre-assignment details

No participants were enrolled in the Dose Expansion Cohort.

Participants by arm

Arm	Count
Dose Escalation Cohort: DHES0815A 0.6 mg/kg Participants received DHES0815A 0.6 milligrams per kilograms (mg/kg) as an intravenous (IV) infusion, every three weeks (Q3W) on Day 1 of each 21-day cycle.	3
Dose Escalation Cohort: DHES0815A 1.2 mg/kg Participants received DHES0815A 1.2 mg/kg as an IV infusion, Q3W on Day 1 of each 21-day cycle.	3
Dose Escalation Cohort: DHES0815A 2.4 mg/kg Participants received DHES0815A 2.4 mg/kg as an IV infusion, Q3W on Day 1 of each 21-day cycle.	3
Dose Escalation Cohort: DHES0815A 4 mg/kg Participants received DHES0815A 4 mg/kg as an IV infusion, Q3W on Day 1 of each 21-day cycle up to Cycle 3. Due to toxicities observed in participants after Cycle 3, dosing was capped at 2.4 mg/kg and the participants received DHES0815A at a dose of 2.4 mg/kg as an IV infusion, Q3W from Cycle 4, on Day 1 of each 21-day cycle.	3
Dose Escalation Cohort: DHES0815A 6 mg/kg Participants received DHES0815A 6 mg/kg as IV infusion, Q3W on Day 1 of each 21-day cycle. Due to toxicities observed in participants after 3 cycles of DHES0815A 4 mg/kg, dosing was capped at 2.4 mg/kg and the participants received DHES0815A at a dose of 2.4 mg/kg as an IV infusion, Q3W from Cycle 4, on Day 1 of each 21-day cycle.	2
Total	14

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Lost to Follow-up	1	0
Overall Study	Physician Decision	0	1
Overall Study	Withdrawal by Subject	1	1

Baseline characteristics

Characteristic	Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Dose Escalation Cohort: DHES0815A 4 mg/kg	Dose Escalation Cohort: DHES0815A 6 mg/kg	Total
Age, Continuous	64.3 years STANDARD_DEVIATION 6.1	58.3 years STANDARD_DEVIATION 4.5	49.3 years STANDARD_DEVIATION 8.3	48.3 years STANDARD_DEVIATION 5	50.0 years STANDARD_DEVIATION 15.6	54.4 years STANDARD_DEVIATION 9.3
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants	3 Participants	2 Participants	3 Participants	2 Participants	13 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants
Race (NIH/OMB) Asian	0 Participants	1 Participants	1 Participants	1 Participants	0 Participants	3 Participants
Race (NIH/OMB) Black or African American	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	2 Participants	2 Participants	1 Participants	2 Participants	2 Participants	9 Participants
Sex: Female, Male Female	3 Participants	3 Participants	3 Participants	3 Participants	2 Participants	14 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	0 / 3	0 / 3	0 / 3	0 / 3	0 / 2
other Total, other adverse events	3 / 3	3 / 3	3 / 3	3 / 3	2 / 2
serious Total, serious adverse events	1 / 3	1 / 3	1 / 3	0 / 3	1 / 2

Outcome results

Primary

Change From Baseline in LVEF as Assessed by Echocardiogram (ECHO) or Multiple-Gated Acquisition (MUGA) Scan

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.

Time frame: Baseline, end of Cycle 1, Days 15-21 of Cycles 2, 4, and 6, and every four cycles thereafter up to the study discontinuation visit (up to approximately 39 months)

Population: Safety evaluable population included all enrolled participants who received at least one dose of study medication.

Arm	Measure	Group	Value (MEAN)	Dispersion
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Change From Baseline in LVEF as Assessed by Echocardiogram (ECHO) or Multiple-Gated Acquisition (MUGA) Scan	Baseline	59.00 percentage points of LVEF	Standard Deviation 3.61
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Change From Baseline in LVEF as Assessed by Echocardiogram (ECHO) or Multiple-Gated Acquisition (MUGA) Scan	Change From Baseline to Worst Value	0.33 percentage points of LVEF	Standard Deviation 4.04
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Change From Baseline in LVEF as Assessed by Echocardiogram (ECHO) or Multiple-Gated Acquisition (MUGA) Scan	Baseline	63.33 percentage points of LVEF	Standard Deviation 4.04
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Change From Baseline in LVEF as Assessed by Echocardiogram (ECHO) or Multiple-Gated Acquisition (MUGA) Scan	Change From Baseline to Worst Value	-1.67 percentage points of LVEF	Standard Deviation 1.15
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Change From Baseline in LVEF as Assessed by Echocardiogram (ECHO) or Multiple-Gated Acquisition (MUGA) Scan	Baseline	64.00 percentage points of LVEF	Standard Deviation 9.54
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Change From Baseline in LVEF as Assessed by Echocardiogram (ECHO) or Multiple-Gated Acquisition (MUGA) Scan	Change From Baseline to Worst Value	-4.67 percentage points of LVEF	Standard Deviation 7.77
Dose Escalation Cohort: DHES0815A 4 mg/kg	Change From Baseline in LVEF as Assessed by Echocardiogram (ECHO) or Multiple-Gated Acquisition (MUGA) Scan	Change From Baseline to Worst Value	-1.33 percentage points of LVEF	Standard Deviation 1.53
Dose Escalation Cohort: DHES0815A 4 mg/kg	Change From Baseline in LVEF as Assessed by Echocardiogram (ECHO) or Multiple-Gated Acquisition (MUGA) Scan	Baseline	59.67 percentage points of LVEF	Standard Deviation 0.58
Dose Escalation Cohort: DHES0815A 6 mg/kg	Change From Baseline in LVEF as Assessed by Echocardiogram (ECHO) or Multiple-Gated Acquisition (MUGA) Scan	Baseline	62.50 percentage points of LVEF	Standard Deviation 3.54
Dose Escalation Cohort: DHES0815A 6 mg/kg	Change From Baseline in LVEF as Assessed by Echocardiogram (ECHO) or Multiple-Gated Acquisition (MUGA) Scan	Change From Baseline to Worst Value	-5.00 percentage points of LVEF	Standard Deviation 0

Primary

Duration of Treatment

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

Time frame: From Day 1 up to last dose of study drug (up to approximately 39 months)

Population: Safety evaluable population included all enrolled participants who received at least one dose of study medication.

Arm	Measure	Value (MEDIAN)
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Duration of Treatment	64.0 days
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Duration of Treatment	208.0 days
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Duration of Treatment	43.0 days
Dose Escalation Cohort: DHES0815A 4 mg/kg	Duration of Treatment	64.0 days
Dose Escalation Cohort: DHES0815A 6 mg/kg	Duration of Treatment	43.0 days

Primary

Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0

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.

Time frame: From Day 1 to end of study (up to approximately 39 months)

Population: Safety evaluable population included all enrolled participants who received at least one dose of study medication.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0	AEs	3 Participants
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0	SAEs	1 Participants
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0	Grade 1 AEs	0 Participants
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0	Grade 2 AEs	1 Participants
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0	Grade 3 AEs	1 Participants
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0	Grade 4 AEs	1 Participants
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0	Grade 3 AEs	1 Participants
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0	Grade 4 AEs	0 Participants
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0	AEs	3 Participants
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0	Grade 1 AEs	0 Participants
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0	Grade 2 AEs	2 Participants
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0	SAEs	1 Participants
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0	Grade 2 AEs	0 Participants
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0	Grade 3 AEs	2 Participants
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0	AEs	3 Participants
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0	Grade 1 AEs	1 Participants
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0	SAEs	1 Participants
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0	Grade 4 AEs	0 Participants
Dose Escalation Cohort: DHES0815A 4 mg/kg	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0	Grade 2 AEs	1 Participants
Dose Escalation Cohort: DHES0815A 4 mg/kg	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0	SAEs	0 Participants
Dose Escalation Cohort: DHES0815A 4 mg/kg	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0	Grade 1 AEs	0 Participants
Dose Escalation Cohort: DHES0815A 4 mg/kg	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0	Grade 4 AEs	0 Participants
Dose Escalation Cohort: DHES0815A 4 mg/kg	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0	Grade 3 AEs	2 Participants
Dose Escalation Cohort: DHES0815A 4 mg/kg	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0	AEs	3 Participants
Dose Escalation Cohort: DHES0815A 6 mg/kg	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0	Grade 3 AEs	1 Participants
Dose Escalation Cohort: DHES0815A 6 mg/kg	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0	Grade 1 AEs	0 Participants
Dose Escalation Cohort: DHES0815A 6 mg/kg	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0	SAEs	1 Participants
Dose Escalation Cohort: DHES0815A 6 mg/kg	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0	Grade 4 AEs	0 Participants
Dose Escalation Cohort: DHES0815A 6 mg/kg	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0	Grade 2 AEs	1 Participants
Dose Escalation Cohort: DHES0815A 6 mg/kg	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0	AEs	2 Participants

Primary

Number of Participants With Dose-limiting Toxicity (DLT)

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.

Time frame: From Day 1 up to Day 21

Population: Safety evaluable population included all enrolled participants who received at least one dose of study medication.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Number of Participants With Dose-limiting Toxicity (DLT)	0 Participants
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Number of Participants With Dose-limiting Toxicity (DLT)	0 Participants
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Number of Participants With Dose-limiting Toxicity (DLT)	0 Participants
Dose Escalation Cohort: DHES0815A 4 mg/kg	Number of Participants With Dose-limiting Toxicity (DLT)	0 Participants
Dose Escalation Cohort: DHES0815A 6 mg/kg	Number of Participants With Dose-limiting Toxicity (DLT)	0 Participants

Primary

Total Cumulative Dose

Time frame: From Day 1 up to last dose of study drug (up to approximately 39 months)

Population: Safety evaluable population included all enrolled participants who received at least one dose of study medication.

Arm	Measure	Value (MEAN)	Dispersion
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Total Cumulative Dose	882.33 milligrams (mg)	Standard Deviation 1355.91
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Total Cumulative Dose	2143.00 milligrams (mg)	Standard Deviation 2523.37
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Total Cumulative Dose	342.27 milligrams (mg)	Standard Deviation 157.78
Dose Escalation Cohort: DHES0815A 4 mg/kg	Total Cumulative Dose	1340.20 milligrams (mg)	Standard Deviation 586.56
Dose Escalation Cohort: DHES0815A 6 mg/kg	Total Cumulative Dose	548.80 milligrams (mg)	Standard Deviation 138.59

Secondary

Concentration of DHES0815A Total Antibody

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

Time frame: Pre-dose and 30 minutes (min) post-dose on Day 1 Cycles 1-4; 4 hour (h) post-dose on Day 1 Cycle1; post-dose on Days 2, 3, 11, 17 Cycle 1; post-dose on Days 8 and 15 Cycles 1-4; study discontinuation visit (up to approx. 39 months) (Cycle length=21 days)

Population: Pharmacokinetics (PK) evaluable population included all enrolled participants who received at least one dose of study medication. Number analyzed is the number of participants with evaluable data at specified timepoint.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 3 Day 1: 30 min Postdose	13600 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 21.6
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 4 Day 1: 30 min Postdose	8750 nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 2 Day 8	933 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 165.1
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 8	625 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 411.4
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 2 Day 1: 30 min Postdose	11900 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 29.6
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 2	8460 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 34.9
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 1: 30 min Postdose	13100 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 27.2
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 4 Day 15	50.0 nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 11	225 nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 2 Day 1: Predose	50.0 nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 3 Day 15	50.0 nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 4 Day 1: Predose	50.0 nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 2 Day 15	50.0 nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 15	64.8 nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of DHES0815A Total Antibody	Study Drug Discontinuation Visit	231 nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 3 Day 1: Predose	50.0 nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 3 Day 8	765 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 921
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 4 Day 8	2130 nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 17	50.0 nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day1: Predose	NA nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 3	6330 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 37.1
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 1: 4 h Postdose	12200 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 30.7
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day1: Predose	NA nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 2 Day 1: Predose	66.0 nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 3 Day 15	2530 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 66.3
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of DHES0815A Total Antibody	Study Drug Discontinuation Visit	483 nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 2 Day 1: 30 min Postdose	33000 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 28.8
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 4 Day 1: Predose	65.8 nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 2 Day 8	9500 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 11.1
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 1: 4 h Postdose	30500 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 13
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 2	27000 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 18.7
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 3	22000 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 14.5
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 3 Day 1: 30 min Postdose	39300 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 52.9
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 4 Day 15	3000 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 72.6
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 8	8120 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 42.1
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 3 Day 1: Predose	50.00 nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 11	4870 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 34.2
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 1: 30 min Postdose	48700 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 29
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 4 Day 8	11100 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 23.5
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 15	2160 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 69.1
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 2 Day 15	2230 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 37.2
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 17	1030 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 190.3
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 3 Day 8	9740 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 19.7
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 4 Day 1: 30 min Postdose	32800 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 16.8
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 15	2100 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 135.7
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 2 Day 15	1330 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 78.7
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 1: 4 h Postdose	46900 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 19.2
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 3 Day 1: Predose	50.0 nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day1: Predose	NA nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 3 Day 1: 30 min Postdose	56900 nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 3 Day 8	8720 nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 2	35500 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 46.5
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 3	26600 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 52.3
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of DHES0815A Total Antibody	Study Drug Discontinuation Visit	75.5 nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 8	10700 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 76.8
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 11	6840 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 90.1
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 1: 30 min Postdose	49200 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 27.3
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 17	981 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 148.8
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 2 Day 1: Predose	50.0 nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 2 Day 1: 30 min Postdose	30800 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 101
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 2 Day 8	10800 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 46.2
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 3 Day 1: 30 min Postdose	119000 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 14.1
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day1: Predose	NA nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 1: 30 min Postdose	88600 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 11.4
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 1: 4 h Postdose	85900 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 13.6
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 2	69100 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 13.2
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 3	59700 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 9.7
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 8	36000 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 8.8
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 11	26000 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 5.1
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 15	22800 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 0.3
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 17	18800 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 28.3
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 2 Day 1: Predose	10500 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 46.2
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 2 Day 1: 30 min Postdose	97700 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 15.8
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 2 Day 8	44300 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 8.5
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 2 Day 15	27600 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 12.9
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 3 Day 1: Predose	18900 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 38.9
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 3 Day 8	51900 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 20
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 3 Day 15	30200 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 24.7
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 4 Day 1: Predose	13800 nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 4 Day 1: 30 min Postdose	83900 nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 4 Day 8	24200 nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 4 Day 15	13500 nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of DHES0815A Total Antibody	Study Drug Discontinuation Visit	50.0 nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 2 Day 1: Predose	19900 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 27.3
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 17	29700 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 36.7
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 1: 30 min Postdose	119000 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 0
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 15	31300 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 27.7
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 11	42100 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 26.7
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day1: Predose	NA nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 8	48000 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 6.3
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 3	81100 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 15.8
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 2	96800 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 11.6
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 2 Day 15	31100 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 123
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of DHES0815A Total Antibody	Study Drug Discontinuation Visit	27800 nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 2 Day 8	80000 nanograms per milliliters (ng/mL)	—
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 2 Day 1: 30 min Postdose	85400 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 62.2
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of DHES0815A Total Antibody	Cycle 1 Day 1: 4 h Postdose	106000 nanograms per milliliters (ng/mL)	Geometric Coefficient of Variation 0

Secondary

Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)

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

Population: PK evaluable population included all enrolled participants who received at least one dose of study medication. Number analyzed is the number of participants with evaluable data at specified timepoint.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 1: 30 min Postdose	90.5 ng/mL	Geometric Coefficient of Variation 23.4
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 2 Day 1: Predose	0.750 ng/mL	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 17	0.750 ng/mL	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 15	0.947 ng/mL	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 8	3.52 ng/mL	Geometric Coefficient of Variation 394.8
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Study Drug Discontinuation Visit	0.750 ng/mL	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 11	2.04 ng/mL	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 4 Day 1: Predose	0.750 ng/mL	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 3 Day 15	0.750 ng/mL	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 3 Day 8	3.63 ng/mL	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 1: 4 h Postdose	84.4 ng/mL	Geometric Coefficient of Variation 28.9
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 4 Day 15	0.750 ng/mL	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day1: Predose	NA ng/mL	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 3 Day 1: 30 min Postdose	100 ng/mL	Geometric Coefficient of Variation 12.1
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 3 Day 1: Predose	0.750 ng/mL	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 2	55.6 ng/mL	Geometric Coefficient of Variation 32.8
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 4 Day 1: 30 min Postdose	112 ng/mL	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 2 Day 15	0.750 ng/mL	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 2 Day 8	5.01 ng/mL	Geometric Coefficient of Variation 182.3
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 2 Day 1: 30 min Postdose	92.8 ng/mL	Geometric Coefficient of Variation 14.7
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 3	38.2 ng/mL	Geometric Coefficient of Variation 32.5
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 3 Day 1: 30 min Postdose	236 ng/mL	Geometric Coefficient of Variation 17.5
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day1: Predose	NA ng/mL	—
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 1: 30 min Postdose	242 ng/mL	Geometric Coefficient of Variation 11.4
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 1: 4 h Postdose	234 ng/mL	Geometric Coefficient of Variation 9.4
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 2	186 ng/mL	Geometric Coefficient of Variation 7.6
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 3	147 ng/mL	Geometric Coefficient of Variation 8.1
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 8	53.8 ng/mL	Geometric Coefficient of Variation 39.5
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 11	29.9 ng/mL	Geometric Coefficient of Variation 33.7
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 15	11.6 ng/mL	Geometric Coefficient of Variation 74
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 17	4.45 ng/mL	Geometric Coefficient of Variation 313.1
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 2 Day 1: Predose	0.750 ng/mL	—
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 2 Day 1: 30 min Postdose	247 ng/mL	Geometric Coefficient of Variation 19.4
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 2 Day 8	59.5 ng/mL	Geometric Coefficient of Variation 14.7
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 2 Day 15	11.5 ng/mL	Geometric Coefficient of Variation 35.6
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 3 Day 1: Predose	0.750 ng/mL	—
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 3 Day 8	57.9 ng/mL	Geometric Coefficient of Variation 16.5
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 3 Day 15	12.1 ng/mL	Geometric Coefficient of Variation 53.9
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 4 Day 1: Predose	0.750 ng/mL	—
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 4 Day 1: 30 min Postdose	244 ng/mL	Geometric Coefficient of Variation 17
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 4 Day 8	55.8 ng/mL	Geometric Coefficient of Variation 10.6
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 4 Day 15	13.8 ng/mL	Geometric Coefficient of Variation 70.4
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Study Drug Discontinuation Visit	3.93 ng/mL	—
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 8	58.2 ng/mL	Geometric Coefficient of Variation 69.4
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 3	183 ng/mL	Geometric Coefficient of Variation 48.4
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 2 Day 1: Predose	0.750 ng/mL	—
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 2 Day 1: 30 min Postdose	232 ng/mL	Geometric Coefficient of Variation 92.5
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 2 Day 8	30.9 ng/mL	Geometric Coefficient of Variation 183.6
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 2	234 ng/mL	Geometric Coefficient of Variation 44.6
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Study Drug Discontinuation Visit	1.38 ng/mL	—
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 2 Day 15	3.25 ng/mL	Geometric Coefficient of Variation 224.3
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 3 Day 1: Predose	0.750 ng/mL	—
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 1: 4 h Postdose	338 ng/mL	Geometric Coefficient of Variation 31
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 3 Day 1: 30 min Postdose	381 ng/mL	—
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day1: Predose	NA ng/mL	—
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 3 Day 8	61.6 ng/mL	—
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 11	33.0 ng/mL	Geometric Coefficient of Variation 71.7
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 15	10.5 ng/mL	Geometric Coefficient of Variation 122.9
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 1: 30 min Postdose	381 ng/mL	Geometric Coefficient of Variation 28
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 17	4.40 ng/mL	Geometric Coefficient of Variation 120.8
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 4 Day 8	139 ng/mL	—
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 3 Day 1: 30 min Postdose	803 ng/mL	Geometric Coefficient of Variation 7.7
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 3	440 ng/mL	Geometric Coefficient of Variation 1.4
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 15	118 ng/mL	Geometric Coefficient of Variation 6.6
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 3 Day 8	294 ng/mL	Geometric Coefficient of Variation 20.7
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 1: 30 min Postdose	702 ng/mL	Geometric Coefficient of Variation 3.8
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day1: Predose	NA ng/mL	—
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 8	225 ng/mL	Geometric Coefficient of Variation 5.6
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 2 Day 1: Predose	44.9 ng/mL	Geometric Coefficient of Variation 59.5
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 4 Day 1: Predose	58.6 ng/mL	—
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 2 Day 1: 30 min Postdose	760 ng/mL	Geometric Coefficient of Variation 10.4
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 2	508 ng/mL	Geometric Coefficient of Variation 8
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 17	82.9 ng/mL	Geometric Coefficient of Variation 29.5
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 2 Day 8	283 ng/mL	Geometric Coefficient of Variation 11.5
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 11	157 ng/mL	Geometric Coefficient of Variation 6.4
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 2 Day 15	135 ng/mL	Geometric Coefficient of Variation 16.3
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 4 Day 1: 30 min Postdose	647 ng/mL	—
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 3 Day 1: Predose	76.3 ng/mL	Geometric Coefficient of Variation 47
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 1: 4 h Postdose	666 ng/mL	Geometric Coefficient of Variation 6.7
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 3 Day 15	143 ng/mL	Geometric Coefficient of Variation 30.8
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 15	174 ng/mL	Geometric Coefficient of Variation 28.4
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 2 Day 1: 30 min Postdose	636 ng/mL	Geometric Coefficient of Variation 53.8
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 2 Day 1: Predose	90.6 ng/mL	Geometric Coefficient of Variation 32.1
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 2 Day 15	324 ng/mL	—
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 1: 4 h Postdose	837 ng/mL	Geometric Coefficient of Variation 4.6
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 2	693 ng/mL	Geometric Coefficient of Variation 5.4
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 11	259 ng/mL	Geometric Coefficient of Variation 26.2
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 17	160 ng/mL	Geometric Coefficient of Variation 34.3
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 2 Day 8	451 ng/mL	—
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 3	577 ng/mL	Geometric Coefficient of Variation 12.9
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 8	328 ng/mL	Geometric Coefficient of Variation 5.2
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day1: Predose	NA ng/mL	—
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)	Cycle 1 Day 1: 30 min Postdose	864 ng/mL	Geometric Coefficient of Variation 4.4

Secondary

Concentration of Plasma Unconjugated PDB-MA

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

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 3 Day 15	0.0120 ng/mL	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 2 Day 8	0.0306 ng/mL	Geometric Coefficient of Variation 14.3
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 3 Day 1: 30 min Postdose	0.132 ng/mL	Geometric Coefficient of Variation 20.5
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day1: Predose	NA ng/mL	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 3 Day 8	0.0314 ng/mL	Geometric Coefficient of Variation 0.7
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 4 Day 15	0.0120 ng/mL	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 1: 30 min Postdose	0.107 ng/mL	Geometric Coefficient of Variation 14.4
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 1: 4 h Postdose	0.0770 ng/mL	Geometric Coefficient of Variation 20.2
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 15	0.0120 ng/mL	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 4 Day 8	0.0316 ng/mL	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 2	0.0634 ng/mL	Geometric Coefficient of Variation 27.8
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 2 Day 1: 30 min Postdose	0.0969 ng/mL	Geometric Coefficient of Variation 16.4
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 8	0.0300 ng/mL	Geometric Coefficient of Variation 6.1
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 4 Day 1: 30 min Postdose	0.0570 ng/mL	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 11	0.0172 ng/mL	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Study Drug Discontinuation Visit	0.0226 ng/mL	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 2 Day 15	0.0120 ng/mL	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 17	0.0120 ng/mL	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 3	0.0568 ng/mL	Geometric Coefficient of Variation 31.8
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 4 Day 1: Predose	0.0120 ng/mL	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 2 Day 1: Predose	0.0120 ng/mL	—
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 3 Day 1: Predose	0.0120 ng/mL	—
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 1: 30 min Postdose	0.362 ng/mL	Geometric Coefficient of Variation 40.9
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 4 Day 15	0.0574 ng/mL	Geometric Coefficient of Variation 17.3
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 17	0.0337 ng/mL	Geometric Coefficient of Variation 16.2
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 2	0.175 ng/mL	Geometric Coefficient of Variation 2.9
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 3	0.130 ng/mL	Geometric Coefficient of Variation 21.8
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 4 Day 1: 30 min Postdose	0.338 ng/mL	Geometric Coefficient of Variation 23.9
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 3 Day 15	0.0510 ng/mL	Geometric Coefficient of Variation 14.4
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 2 Day 1: 30 min Postdose	0.324 ng/mL	Geometric Coefficient of Variation 29.7
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 2 Day 8	0.0846 ng/mL	Geometric Coefficient of Variation 19.3
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 8	0.0800 ng/mL	Geometric Coefficient of Variation 15
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 2 Day 15	0.0435 ng/mL	Geometric Coefficient of Variation 8.1
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 3 Day 1: Predose	0.0120 ng/mL	—
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 11	0.0605 ng/mL	Geometric Coefficient of Variation 16.8
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 3 Day 1: 30 min Postdose	0.327 ng/mL	Geometric Coefficient of Variation 33.4
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 2 Day 1: Predose	0.0120 ng/mL	—
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 3 Day 8	0.0785 ng/mL	Geometric Coefficient of Variation 16.4
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day1: Predose	NA ng/mL	—
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 15	0.0405 ng/mL	Geometric Coefficient of Variation 19.7
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Study Drug Discontinuation Visit	0.0452 ng/mL	Geometric Coefficient of Variation 56.1
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 4 Day 8	0.108 ng/mL	Geometric Coefficient of Variation 19.1
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 1: 4 h Postdose	0.276 ng/mL	Geometric Coefficient of Variation 16.9
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 4 Day 1: Predose	0.0120 ng/mL	Geometric Coefficient of Variation 23.9
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 1: 30 min Postdose	0.497 ng/mL	Geometric Coefficient of Variation 47.1
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 2 Day 1: 30 min Postdose	0.321 ng/mL	Geometric Coefficient of Variation 73.3
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 3 Day 1: 30 min Postdose	0.716 ng/mL	—
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 2 Day 1: Predose	0.0178 ng/mL	—
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 2 Day 8	0.0662 ng/mL	Geometric Coefficient of Variation 68
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 1: 4 h Postdose	0.328 ng/mL	Geometric Coefficient of Variation 26.9
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 11	0.0806 ng/mL	Geometric Coefficient of Variation 15.2
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day1: Predose	NA ng/mL	—
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 2 Day 15	0.0266 ng/mL	Geometric Coefficient of Variation 96.3
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Study Drug Discontinuation Visit	0.0249 ng/mL	Geometric Coefficient of Variation 71.8
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 2	0.223 ng/mL	Geometric Coefficient of Variation 72.6
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 3 Day 1: Predose	0.0120 ng/mL	—
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 3	0.179 ng/mL	Geometric Coefficient of Variation 40.2
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 17	0.0389 ng/mL	Geometric Coefficient of Variation 54.4
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 8	0.0927 ng/mL	Geometric Coefficient of Variation 25
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 3 Day 8	0.102 ng/mL	—
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 15	0.0490 ng/mL	Geometric Coefficient of Variation 48.5
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 4 Day 1: Predose	0.0938 ng/mL	—
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 8	0.185 ng/mL	Geometric Coefficient of Variation 32.4
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 2 Day 15	0.164 ng/mL	Geometric Coefficient of Variation 30.7
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 4 Day 15	0.0906 ng/mL	—
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Study Drug Discontinuation Visit	0.0120 ng/mL	—
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day1: Predose	NA ng/mL	—
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 1: 30 min Postdose	0.772 ng/mL	Geometric Coefficient of Variation 9.1
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 1: 4 h Postdose	0.546 ng/mL	Geometric Coefficient of Variation 21.4
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 3	0.252 ng/mL	Geometric Coefficient of Variation 24.7
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 11	0.146 ng/mL	Geometric Coefficient of Variation 54.3
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 15	0.110 ng/mL	Geometric Coefficient of Variation 47.6
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 17	0.0896 ng/mL	Geometric Coefficient of Variation 40.4
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 2 Day 1: Predose	0.0836 ng/mL	Geometric Coefficient of Variation 69.5
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 2 Day 1: 30 min Postdose	0.953 ng/mL	Geometric Coefficient of Variation 17.6
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 2 Day 8	0.214 ng/mL	Geometric Coefficient of Variation 51.4
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 3 Day 1: Predose	0.144 ng/mL	Geometric Coefficient of Variation 49.1
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 3 Day 1: 30 min Postdose	1.09 ng/mL	Geometric Coefficient of Variation 10.3
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 3 Day 8	0.236 ng/mL	Geometric Coefficient of Variation 41.1
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 3 Day 15	0.181 ng/mL	Geometric Coefficient of Variation 40.1
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 2	0.449 ng/mL	Geometric Coefficient of Variation 43.9
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 4 Day 1: 30 min Postdose	0.633 ng/mL	—
Dose Escalation Cohort: DHES0815A 4 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 4 Day 8	0.149 ng/mL	—
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 15	0.103 ng/mL	Geometric Coefficient of Variation 4.9
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 11	0.170 ng/mL	Geometric Coefficient of Variation 43.2
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 8	0.163 ng/mL	Geometric Coefficient of Variation 37.7
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 3	0.332 ng/mL	Geometric Coefficient of Variation 14.5
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 2	0.577 ng/mL	Geometric Coefficient of Variation 18.5
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 1: 4 h Postdose	0.985 ng/mL	Geometric Coefficient of Variation 44.5
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 1: 30 min Postdose	1.05 ng/mL	Geometric Coefficient of Variation 5.4
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Study Drug Discontinuation Visit	0.0374 ng/mL	—
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day1: Predose	NA ng/mL	—
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 2 Day 15	0.149 ng/mL	Geometric Coefficient of Variation 45
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 2 Day 1: 30 min Postdose	0.693 ng/mL	Geometric Coefficient of Variation 76.5
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 2 Day 1: Predose	0.0991 ng/mL	Geometric Coefficient of Variation 60.4
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 2 Day 8	0.196 ng/mL	—
Dose Escalation Cohort: DHES0815A 6 mg/kg	Concentration of Plasma Unconjugated PDB-MA	Cycle 1 Day 17	0.101 ng/mL	Geometric Coefficient of Variation 37.4

Secondary

Duration of Response (DoR) Assessed According to RECIST v1.1

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).

Time frame: From the initial CR or PR to the time of PD or death, whichever occurs first (up to approximately 39 months)

Population: Safety evaluable population included all enrolled participants who received at least one dose of study medication. DoR was only evaluated in participants who achieved an objective response (CR or PR).

Arm	Measure	Value (MEDIAN)
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Duration of Response (DoR) Assessed According to RECIST v1.1	NA months

Secondary

Number of Participants With Anti-Drug Antibody (ADA) to DHES0815A

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.

Time frame: Pre-dose on Day 1 of Cycles 1-4 and 42 days after last infusion (up to approximately 39 months)

Population: Safety evaluable population included all enrolled participants who received at least one dose of study medication.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Number of Participants With Anti-Drug Antibody (ADA) to DHES0815A	Baseline: ADA Positive	1 Participants
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Number of Participants With Anti-Drug Antibody (ADA) to DHES0815A	Post-baseline: Treatment-enhanced ADA Positive	0 Participants
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Number of Participants With Anti-Drug Antibody (ADA) to DHES0815A	Post-baseline: Treatment-induced ADA Positive	0 Participants
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Number of Participants With Anti-Drug Antibody (ADA) to DHES0815A	Post-baseline: Treatment-induced ADA Positive	1 Participants
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Number of Participants With Anti-Drug Antibody (ADA) to DHES0815A	Baseline: ADA Positive	0 Participants
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Number of Participants With Anti-Drug Antibody (ADA) to DHES0815A	Post-baseline: Treatment-enhanced ADA Positive	0 Participants
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Number of Participants With Anti-Drug Antibody (ADA) to DHES0815A	Post-baseline: Treatment-induced ADA Positive	1 Participants
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Number of Participants With Anti-Drug Antibody (ADA) to DHES0815A	Baseline: ADA Positive	0 Participants
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Number of Participants With Anti-Drug Antibody (ADA) to DHES0815A	Post-baseline: Treatment-enhanced ADA Positive	0 Participants
Dose Escalation Cohort: DHES0815A 4 mg/kg	Number of Participants With Anti-Drug Antibody (ADA) to DHES0815A	Baseline: ADA Positive	0 Participants
Dose Escalation Cohort: DHES0815A 4 mg/kg	Number of Participants With Anti-Drug Antibody (ADA) to DHES0815A	Post-baseline: Treatment-enhanced ADA Positive	0 Participants
Dose Escalation Cohort: DHES0815A 4 mg/kg	Number of Participants With Anti-Drug Antibody (ADA) to DHES0815A	Post-baseline: Treatment-induced ADA Positive	0 Participants
Dose Escalation Cohort: DHES0815A 6 mg/kg	Number of Participants With Anti-Drug Antibody (ADA) to DHES0815A	Post-baseline: Treatment-induced ADA Positive	0 Participants
Dose Escalation Cohort: DHES0815A 6 mg/kg	Number of Participants With Anti-Drug Antibody (ADA) to DHES0815A	Baseline: ADA Positive	1 Participants
Dose Escalation Cohort: DHES0815A 6 mg/kg	Number of Participants With Anti-Drug Antibody (ADA) to DHES0815A	Post-baseline: Treatment-enhanced ADA Positive	0 Participants

Secondary

Number of Participants With Objective Response Assessed According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

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.

Time frame: From start of treatment until confirmation of CR or PR (up to approximately 39 months)

Population: Safety evaluable population included all enrolled participants who received at least one dose of study medication.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Number of Participants With Objective Response Assessed According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	Complete Response (CR)	0 Participants
Dose Escalation Cohort: DHES0815A 0.6 mg/kg	Number of Participants With Objective Response Assessed According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	Partial Response (PR)	0 Participants
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Number of Participants With Objective Response Assessed According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	Complete Response (CR)	1 Participants
Dose Escalation Cohort: DHES0815A 1.2 mg/kg	Number of Participants With Objective Response Assessed According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	Partial Response (PR)	0 Participants
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Number of Participants With Objective Response Assessed According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	Complete Response (CR)	0 Participants
Dose Escalation Cohort: DHES0815A 2.4 mg/kg	Number of Participants With Objective Response Assessed According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	Partial Response (PR)	0 Participants
Dose Escalation Cohort: DHES0815A 4 mg/kg	Number of Participants With Objective Response Assessed According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	Partial Response (PR)	0 Participants
Dose Escalation Cohort: DHES0815A 4 mg/kg	Number of Participants With Objective Response Assessed According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	Complete Response (CR)	0 Participants
Dose Escalation Cohort: DHES0815A 6 mg/kg	Number of Participants With Objective Response Assessed According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	Complete Response (CR)	0 Participants
Dose Escalation Cohort: DHES0815A 6 mg/kg	Number of Participants With Objective Response Assessed According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	Partial Response (PR)	0 Participants

Source: ClinicalTrials.gov · Data processed: Feb 13, 2026

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

Conditions

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Change From Baseline in LVEF as Assessed by Echocardiogram (ECHO) or Multiple-Gated Acquisition (MUGA) Scan

Duration of Treatment

Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0

Number of Participants With Dose-limiting Toxicity (DLT)

Total Cumulative Dose

Concentration of DHES0815A Total Antibody

Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)

Concentration of Plasma Unconjugated PDB-MA

Duration of Response (DoR) Assessed According to RECIST v1.1

Number of Participants With Anti-Drug Antibody (ADA) to DHES0815A

Number of Participants With Objective Response Assessed According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)