Trial Outcomes & Findings for Safety, Tolerability, and Pharmacokinetic (PK) Study of DHES0815A in Participants With Human Epidermal Growth Factor Receptor (HER)2-Positive Breast Cancer (NCT NCT03451162)

NCT ID: NCT03451162

Last Updated: 2024-08-05

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 14 participants
• Primary outcome timeframe: From Day 1 to end of study (up to approximately 39 months)
• Results posted on: 2024-08-05

Participant Flow

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.

No participants were enrolled in the Dose Expansion Cohort.

Participant milestones

Measure	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.	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.	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.	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.	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.
Overall Study STARTED	3	3	3	3	2
Overall Study COMPLETED	1	1	3	3	2
Overall Study NOT COMPLETED	2	2	0	0	0

Reasons for withdrawal

Measure	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.	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.	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.	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.	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.
Overall Study Lost to Follow-up	1	0	0	0	0
Overall Study Physician Decision	0	1	0	0	0
Overall Study Withdrawal by Subject	1	1	0	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Dose Escalation Cohort: DHES0815A 0.6 mg/kg n=3 Participants 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.	Dose Escalation Cohort: DHES0815A 1.2 mg/kg n=3 Participants Participants received DHES0815A 1.2 mg/kg as an IV infusion, Q3W on Day 1 of each 21-day cycle.	Dose Escalation Cohort: DHES0815A 2.4 mg/kg n=3 Participants Participants received DHES0815A 2.4 mg/kg as an IV infusion, Q3W on Day 1 of each 21-day cycle.	Dose Escalation Cohort: DHES0815A 4 mg/kg n=3 Participants 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.	Dose Escalation Cohort: DHES0815A 6 mg/kg n=2 Participants 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.	Total n=14 Participants Total of all reporting groups
Age, Continuous	64.3 years STANDARD_DEVIATION 6.1 • n=93 Participants	58.3 years STANDARD_DEVIATION 4.5 • n=4 Participants	49.3 years STANDARD_DEVIATION 8.3 • n=27 Participants	48.3 years STANDARD_DEVIATION 5.0 • n=483 Participants	50.0 years STANDARD_DEVIATION 15.6 • n=36 Participants	54.4 years STANDARD_DEVIATION 9.3 • n=10 Participants
Sex: Female, Male Female	3 Participants n=93 Participants	3 Participants n=4 Participants	3 Participants n=27 Participants	3 Participants n=483 Participants	2 Participants n=36 Participants	14 Participants n=10 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=93 Participants	3 Participants n=4 Participants	2 Participants n=27 Participants	3 Participants n=483 Participants	2 Participants n=36 Participants	13 Participants n=10 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	1 Participants n=10 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	1 Participants n=10 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants	1 Participants n=483 Participants	0 Participants n=36 Participants	3 Participants n=10 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	1 Participants n=10 Participants
Race (NIH/OMB) White	2 Participants n=93 Participants	2 Participants n=4 Participants	1 Participants n=27 Participants	2 Participants n=483 Participants	2 Participants n=36 Participants	9 Participants n=10 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Dose Escalation Cohort: DHES0815A 0.6 mg/kg n=3 Participants 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.	Dose Escalation Cohort: DHES0815A 1.2 mg/kg n=3 Participants Participants received DHES0815A 1.2 mg/kg as an IV infusion, Q3W on Day 1 of each 21-day cycle.	Dose Escalation Cohort: DHES0815A 2.4 mg/kg n=3 Participants Participants received DHES0815A 2.4 mg/kg as an IV infusion, Q3W on Day 1 of each 21-day cycle.	Dose Escalation Cohort: DHES0815A 4 mg/kg n=3 Participants 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.	Dose Escalation Cohort: DHES0815A 6 mg/kg n=2 Participants 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.
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	3 Participants	3 Participants	3 Participants	2 Participants
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	0 Participants	1 Participants	0 Participants	0 Participants
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	1 Participants	2 Participants	2 Participants	1 Participants
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	1 Participants	1 Participants	0 Participants	1 Participants
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	2 Participants	0 Participants	1 Participants	1 Participants
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	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From Day 1 up to Day 21

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

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.

Outcome measures

Measure	Dose Escalation Cohort: DHES0815A 0.6 mg/kg n=3 Participants 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.	Dose Escalation Cohort: DHES0815A 1.2 mg/kg n=3 Participants Participants received DHES0815A 1.2 mg/kg as an IV infusion, Q3W on Day 1 of each 21-day cycle.	Dose Escalation Cohort: DHES0815A 2.4 mg/kg n=3 Participants Participants received DHES0815A 2.4 mg/kg as an IV infusion, Q3W on Day 1 of each 21-day cycle.	Dose Escalation Cohort: DHES0815A 4 mg/kg n=3 Participants 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.	Dose Escalation Cohort: DHES0815A 6 mg/kg n=2 Participants 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.
Number of Participants With Dose-limiting Toxicity (DLT)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Dose Escalation Cohort: DHES0815A 0.6 mg/kg n=3 Participants 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.	Dose Escalation Cohort: DHES0815A 1.2 mg/kg n=3 Participants Participants received DHES0815A 1.2 mg/kg as an IV infusion, Q3W on Day 1 of each 21-day cycle.	Dose Escalation Cohort: DHES0815A 2.4 mg/kg n=3 Participants Participants received DHES0815A 2.4 mg/kg as an IV infusion, Q3W on Day 1 of each 21-day cycle.	Dose Escalation Cohort: DHES0815A 4 mg/kg n=3 Participants 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.	Dose Escalation Cohort: DHES0815A 6 mg/kg n=2 Participants 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.
Duration of Treatment	64.0 days Interval 62.0 to 533.0	208.0 days Interval 85.0 to 960.0	43.0 days Interval 43.0 to 66.0	64.0 days Interval 64.0 to 127.0	43.0 days Interval 43.0 to 43.0

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Dose Escalation Cohort: DHES0815A 0.6 mg/kg n=3 Participants 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.	Dose Escalation Cohort: DHES0815A 1.2 mg/kg n=3 Participants Participants received DHES0815A 1.2 mg/kg as an IV infusion, Q3W on Day 1 of each 21-day cycle.	Dose Escalation Cohort: DHES0815A 2.4 mg/kg n=3 Participants Participants received DHES0815A 2.4 mg/kg as an IV infusion, Q3W on Day 1 of each 21-day cycle.	Dose Escalation Cohort: DHES0815A 4 mg/kg n=3 Participants 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.	Dose Escalation Cohort: DHES0815A 6 mg/kg n=2 Participants 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.
Total Cumulative Dose	882.33 milligrams (mg) Standard Deviation 1355.91	2143.00 milligrams (mg) Standard Deviation 2523.37	342.27 milligrams (mg) Standard Deviation 157.78	1340.20 milligrams (mg) Standard Deviation 586.56	548.80 milligrams (mg) Standard Deviation 138.59

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Dose Escalation Cohort: DHES0815A 0.6 mg/kg n=3 Participants 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.	Dose Escalation Cohort: DHES0815A 1.2 mg/kg n=3 Participants Participants received DHES0815A 1.2 mg/kg as an IV infusion, Q3W on Day 1 of each 21-day cycle.	Dose Escalation Cohort: DHES0815A 2.4 mg/kg n=3 Participants Participants received DHES0815A 2.4 mg/kg as an IV infusion, Q3W on Day 1 of each 21-day cycle.	Dose Escalation Cohort: DHES0815A 4 mg/kg n=3 Participants 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.	Dose Escalation Cohort: DHES0815A 6 mg/kg n=2 Participants 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.
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	63.33 percentage points of LVEF Standard Deviation 4.04	64.00 percentage points of LVEF Standard Deviation 9.54	59.67 percentage points of LVEF Standard Deviation 0.58	62.50 percentage points of LVEF Standard Deviation 3.54
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	-1.67 percentage points of LVEF Standard Deviation 1.15	-4.67 percentage points of LVEF Standard Deviation 7.77	-1.33 percentage points of LVEF Standard Deviation 1.53	-5.00 percentage points of LVEF Standard Deviation 0.00

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Dose Escalation Cohort: DHES0815A 0.6 mg/kg n=3 Participants 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.	Dose Escalation Cohort: DHES0815A 1.2 mg/kg n=3 Participants Participants received DHES0815A 1.2 mg/kg as an IV infusion, Q3W on Day 1 of each 21-day cycle.	Dose Escalation Cohort: DHES0815A 2.4 mg/kg n=3 Participants Participants received DHES0815A 2.4 mg/kg as an IV infusion, Q3W on Day 1 of each 21-day cycle.	Dose Escalation Cohort: DHES0815A 4 mg/kg n=3 Participants 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.	Dose Escalation Cohort: DHES0815A 6 mg/kg n=2 Participants 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.
Concentration of DHES0815A Total Antibody Cycle 1 Day1: Predose	NA nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA The data was not evaluable as the samples were below limit of quantification (BLQ).	NA nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA The data was not evaluable as the samples were BLQ.	NA nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA The data was not evaluable as the samples were BLQ.	NA nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA The data was not evaluable as the samples were BLQ.	NA nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA The data was not evaluable as the samples were BLQ.
Concentration of DHES0815A Total Antibody Cycle 1 Day 1: 30 min Postdose	13100 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 27.2	48700 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 29.0	49200 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 27.3	88600 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 11.4	119000 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 0.0
Concentration of DHES0815A Total Antibody Cycle 1 Day 1: 4 h Postdose	12200 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 30.7	30500 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 13.0	46900 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 19.2	85900 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 13.6	106000 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 0.0
Concentration of DHES0815A Total Antibody Cycle 1 Day 2	8460 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 34.9	27000 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 18.7	35500 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 46.5	69100 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 13.2	96800 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 11.6
Concentration of DHES0815A Total Antibody Cycle 1 Day 3	6330 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 37.1	22000 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 14.5	26600 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 52.3	59700 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 9.7	81100 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 15.8
Concentration of DHES0815A Total Antibody Cycle 1 Day 8	625 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 411.4	8120 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 42.1	10700 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 76.8	36000 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 8.8	48000 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 6.3
Concentration of DHES0815A Total Antibody Cycle 1 Day 11	225 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Values were less than reportable (LTR) for 1 participant. Since data was evaluable only for 1 participant geometric co-efficient of variation was not evaluable.	4870 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 34.2	6840 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 90.1	26000 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 5.1	42100 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 26.7
Concentration of DHES0815A Total Antibody Cycle 1 Day 15	64.8 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	2160 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 69.1	2100 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 135.7	22800 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 0.3	31300 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 27.7
Concentration of DHES0815A Total Antibody Cycle 1 Day 17	50.0 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	1030 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 190.3	981 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 148.8	18800 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 28.3	29700 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 36.7
Concentration of DHES0815A Total Antibody Cycle 2 Day 1: Predose	50.0 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	66.0 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	50.0 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	10500 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 46.2	19900 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 27.3
Concentration of DHES0815A Total Antibody Cycle 2 Day 1: 30 min Postdose	11900 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 29.6	33000 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 28.8	30800 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 101.0	97700 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 15.8	85400 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 62.2
Concentration of DHES0815A Total Antibody Cycle 2 Day 8	933 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 165.1	9500 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 11.1	10800 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 46.2	44300 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 8.5	80000 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.
Concentration of DHES0815A Total Antibody Cycle 2 Day 15	50.0 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	2230 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 37.2	1330 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 78.7	27600 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 12.9	31100 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 123.0
Concentration of DHES0815A Total Antibody Cycle 3 Day 1: Predose	50.0 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	50.00 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	50.0 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.	18900 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 38.9	—
Concentration of DHES0815A Total Antibody Cycle 3 Day 1: 30 min Postdose	13600 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 21.6	39300 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 52.9	56900 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.	119000 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 14.1	—
Concentration of DHES0815A Total Antibody Cycle 3 Day 8	765 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 921.0	9740 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 19.7	8720 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.	51900 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 20.0	—
Concentration of DHES0815A Total Antibody Cycle 3 Day 15	50.0 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	2530 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 66.3	—	30200 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 24.7	—
Concentration of DHES0815A Total Antibody Cycle 4 Day 1: Predose	50.0 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Values were LTR for 1 participant. Since data was evaluable only for 1 participant geometric co-efficient of variation was not evaluable.	65.8 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	—	13800 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.	—
Concentration of DHES0815A Total Antibody Cycle 4 Day 1: 30 min Postdose	8750 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.	32800 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 16.8	—	83900 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.	—
Concentration of DHES0815A Total Antibody Cycle 4 Day 8	2130 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.	11100 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 23.5	—	24200 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.	—
Concentration of DHES0815A Total Antibody Cycle 4 Day 15	50.0 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.	3000 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 72.6	—	13500 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.	—
Concentration of DHES0815A Total Antibody Study Drug Discontinuation Visit	231 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Values were LTR for 1 participant. Since data was evaluable only for 1 participant geometric co-efficient of variation was not evaluable.	483 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Values were LTR for 1 participant. Since data was evaluable only for 1 participant geometric co-efficient of variation was not evaluable.	75.5 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	50.0 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	27800 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.

SECONDARY outcome

Timeframe: 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: 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.

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

Outcome measures

Measure	Dose Escalation Cohort: DHES0815A 0.6 mg/kg n=3 Participants 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.	Dose Escalation Cohort: DHES0815A 1.2 mg/kg n=3 Participants Participants received DHES0815A 1.2 mg/kg as an IV infusion, Q3W on Day 1 of each 21-day cycle.	Dose Escalation Cohort: DHES0815A 2.4 mg/kg n=3 Participants Participants received DHES0815A 2.4 mg/kg as an IV infusion, Q3W on Day 1 of each 21-day cycle.	Dose Escalation Cohort: DHES0815A 4 mg/kg n=3 Participants 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.	Dose Escalation Cohort: DHES0815A 6 mg/kg n=2 Participants 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.
Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA) Cycle 3 Day 15	0.750 ng/mL Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	12.1 ng/mL Geometric Coefficient of Variation 53.9	—	143 ng/mL Geometric Coefficient of Variation 30.8	—
Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA) Cycle 1 Day1: Predose	NA ng/mL Geometric Coefficient of Variation NA The data was not evaluable as the samples were BLQ.	NA ng/mL Geometric Coefficient of Variation NA The data was not evaluable as the samples were BLQ.	NA ng/mL Geometric Coefficient of Variation NA The data was not evaluable as the samples were BLQ.	NA ng/mL Geometric Coefficient of Variation NA The data was not evaluable as the samples were BLQ.	NA ng/mL Geometric Coefficient of Variation NA The data was not evaluable as the samples were BLQ.
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	242 ng/mL Geometric Coefficient of Variation 11.4	381 ng/mL Geometric Coefficient of Variation 28.0	702 ng/mL Geometric Coefficient of Variation 3.8	864 ng/mL Geometric Coefficient of Variation 4.4
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	234 ng/mL Geometric Coefficient of Variation 9.4	338 ng/mL Geometric Coefficient of Variation 31.0	666 ng/mL Geometric Coefficient of Variation 6.7	837 ng/mL Geometric Coefficient of Variation 4.6
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	186 ng/mL Geometric Coefficient of Variation 7.6	234 ng/mL Geometric Coefficient of Variation 44.6	508 ng/mL Geometric Coefficient of Variation 8.0	693 ng/mL Geometric Coefficient of Variation 5.4
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	147 ng/mL Geometric Coefficient of Variation 8.1	183 ng/mL Geometric Coefficient of Variation 48.4	440 ng/mL Geometric Coefficient of Variation 1.4	577 ng/mL Geometric Coefficient of Variation 12.9
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	53.8 ng/mL Geometric Coefficient of Variation 39.5	58.2 ng/mL Geometric Coefficient of Variation 69.4	225 ng/mL Geometric Coefficient of Variation 5.6	328 ng/mL Geometric Coefficient of Variation 5.2
Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA) Cycle 1 Day 11	2.04 ng/mL Geometric Coefficient of Variation NA Values were LTR for 1 participant. Since data was evaluable only for 1 participant geometric co-efficient of variation was not evaluable.	29.9 ng/mL Geometric Coefficient of Variation 33.7	33.0 ng/mL Geometric Coefficient of Variation 71.7	157 ng/mL Geometric Coefficient of Variation 6.4	259 ng/mL Geometric Coefficient of Variation 26.2
Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA) Cycle 1 Day 15	0.947 ng/mL Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	11.6 ng/mL Geometric Coefficient of Variation 74.0	10.5 ng/mL Geometric Coefficient of Variation 122.9	118 ng/mL Geometric Coefficient of Variation 6.6	174 ng/mL Geometric Coefficient of Variation 28.4
Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA) Cycle 1 Day 17	0.750 ng/mL Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	4.45 ng/mL Geometric Coefficient of Variation 313.1	4.40 ng/mL Geometric Coefficient of Variation 120.8	82.9 ng/mL Geometric Coefficient of Variation 29.5	160 ng/mL Geometric Coefficient of Variation 34.3
Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA) Cycle 2 Day 1: Predose	0.750 ng/mL Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	0.750 ng/mL Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	0.750 ng/mL Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	44.9 ng/mL Geometric Coefficient of Variation 59.5	90.6 ng/mL Geometric Coefficient of Variation 32.1
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	247 ng/mL Geometric Coefficient of Variation 19.4	232 ng/mL Geometric Coefficient of Variation 92.5	760 ng/mL Geometric Coefficient of Variation 10.4	636 ng/mL Geometric Coefficient of Variation 53.8
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	59.5 ng/mL Geometric Coefficient of Variation 14.7	30.9 ng/mL Geometric Coefficient of Variation 183.6	283 ng/mL Geometric Coefficient of Variation 11.5	451 ng/mL Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.
Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA) Cycle 2 Day 15	0.750 ng/mL Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	11.5 ng/mL Geometric Coefficient of Variation 35.6	3.25 ng/mL Geometric Coefficient of Variation 224.3	135 ng/mL Geometric Coefficient of Variation 16.3	324 ng/mL Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.
Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA) Cycle 3 Day 1: Predose	0.750 ng/mL Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	0.750 ng/mL Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	0.750 ng/mL Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.	76.3 ng/mL Geometric Coefficient of Variation 47.0	—
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	236 ng/mL Geometric Coefficient of Variation 17.5	381 ng/mL Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.	803 ng/mL Geometric Coefficient of Variation 7.7	—
Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA) Cycle 3 Day 8	3.63 ng/mL Geometric Coefficient of Variation NA Values were LTR for 1 participant. Since data was evaluable only for 1 participant geometric co-efficient of variation was not evaluable.	57.9 ng/mL Geometric Coefficient of Variation 16.5	61.6 ng/mL Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.	294 ng/mL Geometric Coefficient of Variation 20.7	—
Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA) Cycle 4 Day 1: Predose	0.750 ng/mL Geometric Coefficient of Variation NA Values were LTR for 1 participant. Since data was evaluable only for 1 participant geometric co-efficient of variation was not evaluable.	0.750 ng/mL Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	—	58.6 ng/mL Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.	—
Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA) Cycle 4 Day 1: 30 min Postdose	112 ng/mL Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.	244 ng/mL Geometric Coefficient of Variation 17.0	—	647 ng/mL Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.	—
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	—	139 ng/mL Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.	—
Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA) Cycle 4 Day 15	0.750 ng/mL Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.	13.8 ng/mL Geometric Coefficient of Variation 70.4	—	—	—
Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA) Study Drug Discontinuation Visit	0.750 ng/mL Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.	3.93 ng/mL Geometric Coefficient of Variation NA Values were LTR for 1 participant. Since data was evaluable only for 1 participant geometric co-efficient of variation was not evaluable.	1.38 ng/mL Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	—	—

SECONDARY outcome

Timeframe: 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: 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.

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

Outcome measures

Measure	Dose Escalation Cohort: DHES0815A 0.6 mg/kg n=3 Participants 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.	Dose Escalation Cohort: DHES0815A 1.2 mg/kg n=3 Participants Participants received DHES0815A 1.2 mg/kg as an IV infusion, Q3W on Day 1 of each 21-day cycle.	Dose Escalation Cohort: DHES0815A 2.4 mg/kg n=3 Participants Participants received DHES0815A 2.4 mg/kg as an IV infusion, Q3W on Day 1 of each 21-day cycle.	Dose Escalation Cohort: DHES0815A 4 mg/kg n=3 Participants 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.	Dose Escalation Cohort: DHES0815A 6 mg/kg n=2 Participants 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.
Concentration of Plasma Unconjugated PDB-MA Cycle 4 Day 1: Predose	0.0120 ng/mL Geometric Coefficient of Variation NA Values were LTR for 1 participant. Since data was evaluable only for 1 participant geometric co-efficient of variation was not evaluable.	0.0120 ng/mL Geometric Coefficient of Variation 23.9	—	0.0938 ng/mL Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.	—
Concentration of Plasma Unconjugated PDB-MA Study Drug Discontinuation Visit	0.0226 ng/mL Geometric Coefficient of Variation NA Values were LTR for 1 participant. Since data was evaluable only for 1 participant geometric co-efficient of variation was not evaluable.	0.0452 ng/mL Geometric Coefficient of Variation 56.1	0.0249 ng/mL Geometric Coefficient of Variation 71.8	0.0120 ng/mL Geometric Coefficient of Variation NA Values were LTR for 1 participant. Since data was evaluable only for 1 participant geometric co-efficient of variation was not evaluable.	0.0374 ng/mL Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.
Concentration of Plasma Unconjugated PDB-MA Cycle 1 Day1: Predose	NA ng/mL Geometric Coefficient of Variation NA The data was not evaluable as the samples were BLQ.	NA ng/mL Geometric Coefficient of Variation NA The data was not evaluable as the samples were BLQ.	NA ng/mL Geometric Coefficient of Variation NA The data was not evaluable as the samples were BLQ.	NA ng/mL Geometric Coefficient of Variation NA The data was not evaluable as the samples were BLQ.	NA ng/mL Geometric Coefficient of Variation NA The data was not evaluable as the samples were BLQ.
Concentration of Plasma Unconjugated PDB-MA Cycle 1 Day 1: 30 min Postdose	0.107 ng/mL Geometric Coefficient of Variation 14.4	0.362 ng/mL Geometric Coefficient of Variation 40.9	0.497 ng/mL Geometric Coefficient of Variation 47.1	0.772 ng/mL Geometric Coefficient of Variation 9.1	1.05 ng/mL Geometric Coefficient of Variation 5.4
Concentration of Plasma Unconjugated PDB-MA Cycle 1 Day 1: 4 h Postdose	0.0770 ng/mL Geometric Coefficient of Variation 20.2	0.276 ng/mL Geometric Coefficient of Variation 16.9	0.328 ng/mL Geometric Coefficient of Variation 26.9	0.546 ng/mL Geometric Coefficient of Variation 21.4	0.985 ng/mL Geometric Coefficient of Variation 44.5
Concentration of Plasma Unconjugated PDB-MA Cycle 1 Day 2	0.0634 ng/mL Geometric Coefficient of Variation 27.8	0.175 ng/mL Geometric Coefficient of Variation 2.9	0.223 ng/mL Geometric Coefficient of Variation 72.6	0.449 ng/mL Geometric Coefficient of Variation 43.9	0.577 ng/mL Geometric Coefficient of Variation 18.5
Concentration of Plasma Unconjugated PDB-MA Cycle 1 Day 3	0.0568 ng/mL Geometric Coefficient of Variation 31.8	0.130 ng/mL Geometric Coefficient of Variation 21.8	0.179 ng/mL Geometric Coefficient of Variation 40.2	0.252 ng/mL Geometric Coefficient of Variation 24.7	0.332 ng/mL Geometric Coefficient of Variation 14.5
Concentration of Plasma Unconjugated PDB-MA Cycle 1 Day 8	0.0300 ng/mL Geometric Coefficient of Variation 6.1	0.0800 ng/mL Geometric Coefficient of Variation 15.0	0.0927 ng/mL Geometric Coefficient of Variation 25.0	0.185 ng/mL Geometric Coefficient of Variation 32.4	0.163 ng/mL Geometric Coefficient of Variation 37.7
Concentration of Plasma Unconjugated PDB-MA Cycle 1 Day 11	0.0172 ng/mL Geometric Coefficient of Variation NA Values were LTR for 1 participant. Since data was evaluable only for 1 participant geometric co-efficient of variation was not evaluable.	0.0605 ng/mL Geometric Coefficient of Variation 16.8	0.0806 ng/mL Geometric Coefficient of Variation 15.2	0.146 ng/mL Geometric Coefficient of Variation 54.3	0.170 ng/mL Geometric Coefficient of Variation 43.2
Concentration of Plasma Unconjugated PDB-MA Cycle 1 Day 15	0.0120 ng/mL Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	0.0405 ng/mL Geometric Coefficient of Variation 19.7	0.0490 ng/mL Geometric Coefficient of Variation 48.5	0.110 ng/mL Geometric Coefficient of Variation 47.6	0.103 ng/mL Geometric Coefficient of Variation 4.9
Concentration of Plasma Unconjugated PDB-MA Cycle 1 Day 17	0.0120 ng/mL Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	0.0337 ng/mL Geometric Coefficient of Variation 16.2	0.0389 ng/mL Geometric Coefficient of Variation 54.4	0.0896 ng/mL Geometric Coefficient of Variation 40.4	0.101 ng/mL Geometric Coefficient of Variation 37.4
Concentration of Plasma Unconjugated PDB-MA Cycle 2 Day 1: Predose	0.0120 ng/mL Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	0.0120 ng/mL Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	0.0178 ng/mL Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	0.0836 ng/mL Geometric Coefficient of Variation 69.5	0.0991 ng/mL Geometric Coefficient of Variation 60.4
Concentration of Plasma Unconjugated PDB-MA Cycle 2 Day 1: 30 min Postdose	0.0969 ng/mL Geometric Coefficient of Variation 16.4	0.324 ng/mL Geometric Coefficient of Variation 29.7	0.321 ng/mL Geometric Coefficient of Variation 73.3	0.953 ng/mL Geometric Coefficient of Variation 17.6	0.693 ng/mL Geometric Coefficient of Variation 76.5
Concentration of Plasma Unconjugated PDB-MA Cycle 2 Day 8	0.0306 ng/mL Geometric Coefficient of Variation 14.3	0.0846 ng/mL Geometric Coefficient of Variation 19.3	0.0662 ng/mL Geometric Coefficient of Variation 68.0	0.214 ng/mL Geometric Coefficient of Variation 51.4	0.196 ng/mL Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.
Concentration of Plasma Unconjugated PDB-MA Cycle 2 Day 15	0.0120 ng/mL Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	0.0435 ng/mL Geometric Coefficient of Variation 8.1	0.0266 ng/mL Geometric Coefficient of Variation 96.3	0.164 ng/mL Geometric Coefficient of Variation 30.7	0.149 ng/mL Geometric Coefficient of Variation 45.0
Concentration of Plasma Unconjugated PDB-MA Cycle 3 Day 1: Predose	0.0120 ng/mL Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	0.0120 ng/mL Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	0.0120 ng/mL Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.	0.144 ng/mL Geometric Coefficient of Variation 49.1	—
Concentration of Plasma Unconjugated PDB-MA Cycle 3 Day 1: 30 min Postdose	0.132 ng/mL Geometric Coefficient of Variation 20.5	0.327 ng/mL Geometric Coefficient of Variation 33.4	0.716 ng/mL Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.	1.09 ng/mL Geometric Coefficient of Variation 10.3	—
Concentration of Plasma Unconjugated PDB-MA Cycle 3 Day 8	0.0314 ng/mL Geometric Coefficient of Variation 0.7	0.0785 ng/mL Geometric Coefficient of Variation 16.4	0.102 ng/mL Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.	0.236 ng/mL Geometric Coefficient of Variation 41.1	—
Concentration of Plasma Unconjugated PDB-MA Cycle 3 Day 15	0.0120 ng/mL Geometric Coefficient of Variation NA Since majority of the values were LTR and data was evaluable only for 1 participant, geometric co-efficient of variation was not evaluable.	0.0510 ng/mL Geometric Coefficient of Variation 14.4	—	0.181 ng/mL Geometric Coefficient of Variation 40.1	—
Concentration of Plasma Unconjugated PDB-MA Cycle 4 Day 1: 30 min Postdose	0.0570 ng/mL Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.	0.338 ng/mL Geometric Coefficient of Variation 23.9	—	0.633 ng/mL Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.	—
Concentration of Plasma Unconjugated PDB-MA Cycle 4 Day 8	0.0316 ng/mL Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.	0.108 ng/mL Geometric Coefficient of Variation 19.1	—	0.149 ng/mL Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.	—
Concentration of Plasma Unconjugated PDB-MA Cycle 4 Day 15	0.0120 ng/mL Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.	0.0574 ng/mL Geometric Coefficient of Variation 17.3	—	0.0906 ng/mL Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Dose Escalation Cohort: DHES0815A 0.6 mg/kg n=3 Participants 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.	Dose Escalation Cohort: DHES0815A 1.2 mg/kg n=3 Participants Participants received DHES0815A 1.2 mg/kg as an IV infusion, Q3W on Day 1 of each 21-day cycle.	Dose Escalation Cohort: DHES0815A 2.4 mg/kg n=3 Participants Participants received DHES0815A 2.4 mg/kg as an IV infusion, Q3W on Day 1 of each 21-day cycle.	Dose Escalation Cohort: DHES0815A 4 mg/kg n=3 Participants 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.	Dose Escalation Cohort: DHES0815A 6 mg/kg n=2 Participants 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.
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	0 Participants	0 Participants	0 Participants	0 Participants
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	1 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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).

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).

Outcome measures

Measure	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.	Dose Escalation Cohort: DHES0815A 1.2 mg/kg n=1 Participants Participants received DHES0815A 1.2 mg/kg as an IV infusion, Q3W on Day 1 of each 21-day cycle.	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.	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.	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.
Duration of Response (DoR) Assessed According to RECIST v1.1	—	NA months Since only one participant showed response, median and 95% confidence interval (CI) were not evaluable.	—	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Dose Escalation Cohort: DHES0815A 0.6 mg/kg n=3 Participants 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.	Dose Escalation Cohort: DHES0815A 1.2 mg/kg n=3 Participants Participants received DHES0815A 1.2 mg/kg as an IV infusion, Q3W on Day 1 of each 21-day cycle.	Dose Escalation Cohort: DHES0815A 2.4 mg/kg n=3 Participants Participants received DHES0815A 2.4 mg/kg as an IV infusion, Q3W on Day 1 of each 21-day cycle.	Dose Escalation Cohort: DHES0815A 4 mg/kg n=3 Participants 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.	Dose Escalation Cohort: DHES0815A 6 mg/kg n=2 Participants 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.
Number of Participants With Anti-Drug Antibody (ADA) to DHES0815A Baseline: ADA Positive	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Anti-Drug Antibody (ADA) to DHES0815A Post-baseline: Treatment-induced ADA Positive	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Anti-Drug Antibody (ADA) to DHES0815A Post-baseline: Treatment-enhanced ADA Positive	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

Adverse Events

Dose Escalation Cohort: DHES0815A 0.6 mg/kg

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Dose Escalation Cohort: DHES0815A 1.2 mg/kg

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Dose Escalation Cohort: DHES0815A 2.4 mg/kg

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Dose Escalation Cohort: DHES0815A 4 mg/kg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Dose Escalation Cohort: DHES0815A 6 mg/kg

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	Dose Escalation Cohort: DHES0815A 0.6 mg/kg n=3 participants at risk 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.	Dose Escalation Cohort: DHES0815A 1.2 mg/kg n=3 participants at risk Participants received DHES0815A 1.2 mg/kg as an IV infusion, Q3W on Day 1 of each 21-day cycle.	Dose Escalation Cohort: DHES0815A 2.4 mg/kg n=3 participants at risk Participants received DHES0815A 2.4 mg/kg as an IV infusion, Q3W on Day 1 of each 21-day cycle.	Dose Escalation Cohort: DHES0815A 4 mg/kg n=3 participants at risk 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.	Dose Escalation Cohort: DHES0815A 6 mg/kg n=2 participants at risk 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.
Cardiac disorders Bradycardia	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Infections and infestations Appendicitis	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Infections and infestations Pneumonia	33.3% 1/3 • Number of events 2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Nervous system disorders Headache	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	50.0% 1/2 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Renal and urinary disorders Acute kidney injury	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Dyspnoea	33.3% 1/3 • Number of events 2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Hypoxia	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Vascular disorders Thrombosis	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.

Other adverse events

Measure	Dose Escalation Cohort: DHES0815A 0.6 mg/kg n=3 participants at risk 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.	Dose Escalation Cohort: DHES0815A 1.2 mg/kg n=3 participants at risk Participants received DHES0815A 1.2 mg/kg as an IV infusion, Q3W on Day 1 of each 21-day cycle.	Dose Escalation Cohort: DHES0815A 2.4 mg/kg n=3 participants at risk Participants received DHES0815A 2.4 mg/kg as an IV infusion, Q3W on Day 1 of each 21-day cycle.	Dose Escalation Cohort: DHES0815A 4 mg/kg n=3 participants at risk 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.	Dose Escalation Cohort: DHES0815A 6 mg/kg n=2 participants at risk 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.
Blood and lymphatic system disorders Anaemia	66.7% 2/3 • Number of events 2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Cardiac disorders Atrial fibrillation	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Cardiac disorders Bradycardia	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Ear and labyrinth disorders Tinnitus	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Eye disorders Blepharitis	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Eye disorders Cataract	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Eye disorders Dry eye	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Eye disorders Eye pain	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	50.0% 1/2 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Eye disorders Eyelid oedema	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Eye disorders Periorbital oedema	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Eye disorders Photophobia	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	66.7% 2/3 • Number of events 2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	50.0% 1/2 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Eye disorders Punctate keratitis	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Eye disorders Retinal tear	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	50.0% 1/2 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Eye disorders Vision blurred	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Gastrointestinal disorders Abdominal distension	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	50.0% 1/2 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Gastrointestinal disorders Constipation	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Gastrointestinal disorders Diarrhoea	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	100.0% 2/2 • Number of events 3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Gastrointestinal disorders Dysphagia	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Gastrointestinal disorders Nausea	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	66.7% 2/3 • Number of events 2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	50.0% 1/2 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Gastrointestinal disorders Toothache	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Gastrointestinal disorders Vomiting	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
General disorders Fatigue	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	66.7% 2/3 • Number of events 2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	100.0% 2/2 • Number of events 2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
General disorders Oedema	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
General disorders Oedema peripheral	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
General disorders Pain	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
General disorders Peripheral swelling	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
General disorders Pyrexia	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	50.0% 1/2 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Infections and infestations Conjunctivitis	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	50.0% 1/2 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Infections and infestations Pneumonia	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Infections and infestations Upper respiratory tract infection	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	50.0% 1/2 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Infections and infestations Urinary tract infection	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Injury, poisoning and procedural complications Fall	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Investigations Alanine aminotransferase increased	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	66.7% 2/3 • Number of events 3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Investigations Aspartate aminotransferase increased	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	66.7% 2/3 • Number of events 3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Investigations Blood alkaline phosphatase increased	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	66.7% 2/3 • Number of events 3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	50.0% 1/2 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Metabolism and nutrition disorders Decreased appetite	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Metabolism and nutrition disorders Dehydration	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Metabolism and nutrition disorders Hypoalbuminaemia	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Arthralgia	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Back pain	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Pain in extremity	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	50.0% 1/2 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Nervous system disorders Dizziness	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Nervous system disorders Headache	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	66.7% 2/3 • Number of events 2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	50.0% 1/2 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Nervous system disorders Tremor	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Renal and urinary disorders Haematuria	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Renal and urinary disorders Micturition urgency	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Renal and urinary disorders Urinary incontinence	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Renal and urinary disorders Urinary tract obstruction	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Reproductive system and breast disorders Vaginal discharge	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Dyspnoea	66.7% 2/3 • Number of events 2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	50.0% 1/2 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	50.0% 1/2 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	50.0% 1/2 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Sneezing	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	100.0% 3/3 • Number of events 4 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	50.0% 1/2 • Number of events 2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Rash	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	66.7% 2/3 • Number of events 4 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	50.0% 1/2 • Number of events 2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Rash macular	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	66.7% 2/3 • Number of events 2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Skin lesion	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Telangiectasia	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Vascular disorders Hypotension	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.
Vascular disorders Lymphoedema	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/3 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 1 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	33.3% 1/3 • Number of events 2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.	0.00% 0/2 • From Day 1 to end of study (up to approximately 39 months) Safety evaluable population included all enrolled participants who received at least one dose of study medication.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER