Trial Outcomes & Findings for Trastuzumab Deruxtecan in Participants With HER2-overexpressing Advanced or Metastatic Colorectal Cancer (NCT NCT04744831)

NCT ID: NCT04744831

Last Updated: 2026-01-14

Results Overview

Confirmed objective response rate (ORR), defined as the number (percentage) of participants with complete response (CR) or partial response (PR), were assessed by blinded independent central review (BICR) based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR was defined as the disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 122 participants
• Primary outcome timeframe: 6 months post-dose administration to data cut off, up to 20 months
• Results posted on: 2026-01-14

Participant Flow

A total of 122 participants who met all inclusion criteria and no exclusion criteria were randomized/registered to T-DXd treatment in the United States, Asia-Pacific, and Europe.

Following adequate study explanation by the investigator or their designee, subjects voluntarily offered signed, informed consent prior to participation in any study procedures.

Participant milestones

Measure	T-DXd 5.4 mg/kg Q3W Participants were randomized to receive intravenous T-DXd administered at a dose of 5.4 mg/kg every 3 weeks (Q3W).	T-DXd 6.4 mg/kg Q3W Participants were randomized to receive intravenous T-DXd administered at a dose of 6.4 mg/kg every 3 weeks (Q3W).
Overall Study STARTED	82	40
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	82	40

Reasons for withdrawal

Measure	T-DXd 5.4 mg/kg Q3W Participants were randomized to receive intravenous T-DXd administered at a dose of 5.4 mg/kg every 3 weeks (Q3W).	T-DXd 6.4 mg/kg Q3W Participants were randomized to receive intravenous T-DXd administered at a dose of 6.4 mg/kg every 3 weeks (Q3W).
Overall Study Adverse Event	6	4
Overall Study Clinical Progression	5	5
Overall Study Death	2	1
Overall Study Other	5	1
Overall Study Progressive Disease	63	29
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.

Baseline characteristics by cohort

Measure	T-DXd 5.4 mg/kg Q3W n=82 Participants Participants were randomized to receive intravenous T-DXd administered at a dose of 5.4 mg/kg every 3 weeks (Q3W).	T-DXd 6.4 mg/kg Q3W n=40 Participants Participants were randomized to receive intravenous T-DXd administered at a dose of 6.4 mg/kg every 3 weeks (Q3W).	Total n=122 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=14 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.	0 Participants n=10 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.	0 Participants n=24 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.
Age, Categorical Between 18 and 65 years	54 Participants n=14 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.	23 Participants n=10 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.	77 Participants n=24 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.
Age, Categorical >=65 years	28 Participants n=14 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.	17 Participants n=10 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.	45 Participants n=24 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.
Age, Continuous	58.5 years STANDARD_DEVIATION 13.05 • n=14 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.	61.1 years STANDARD_DEVIATION 12.13 • n=10 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.	59.3 years STANDARD_DEVIATION 12.77 • n=24 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.
Sex: Female, Male Female	37 Participants n=14 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.	21 Participants n=10 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.	58 Participants n=24 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.
Sex: Female, Male Male	45 Participants n=14 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.	19 Participants n=10 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.	64 Participants n=24 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.
Race/Ethnicity, Customized White	35 Participants n=14 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.	15 Participants n=10 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.	50 Participants n=24 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.
Race/Ethnicity, Customized Black or African American	0 Participants n=14 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.	0 Participants n=10 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.	0 Participants n=24 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.
Race/Ethnicity, Customized Asian	42 Participants n=14 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.	24 Participants n=10 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.	66 Participants n=24 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=14 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.	0 Participants n=10 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.	0 Participants n=24 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=14 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.	0 Participants n=10 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.	0 Participants n=24 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.
Race/Ethnicity, Customized Other	5 Participants n=14 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.	1 Participants n=10 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.	6 Participants n=24 Participants • The baseline demographic characteristics were assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.

PRIMARY outcome

Timeframe: 6 months post-dose administration to data cut off, up to 20 months

Population: ORR was assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.

Confirmed objective response rate (ORR), defined as the number (percentage) of participants with complete response (CR) or partial response (PR), were assessed by blinded independent central review (BICR) based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR was defined as the disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.

Outcome measures

Measure	T-DXd 5.4 mg/kg Q3W n=82 Participants Participants were randomized to receive intravenous T-DXd administered at a dose of 5.4 mg/kg every 3 weeks (Q3W).	T-DXd 6.4 mg/kg Q3W n=40 Participants Participants were randomized to receive intravenous T-DXd administered at a dose of 6.4 mg/kg every 3 weeks (Q3W).
Percentage of Participants With Objective Response Rate (ORR) Based on Blinded Independent Central Review Following IV Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2-overexpressing Metastatic Colorectal Cancer	37.8 percentage of participants Interval 27.3 to 49.2	27.5 percentage of participants Interval 14.6 to 43.9

SECONDARY outcome

Timeframe: From first dose administration to data cut off, up to approximately 19 months

Population: ORR was assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.

Confirmed objective response rate (ORR), defined as the number (percentage) of participants with complete response (CR) or partial response (PR), were assessed by Investigator assessment based on RECIST version 1.1. CR was defined as the disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. ORR was assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022.

Outcome measures

Measure	T-DXd 5.4 mg/kg Q3W n=82 Participants Participants were randomized to receive intravenous T-DXd administered at a dose of 5.4 mg/kg every 3 weeks (Q3W).	T-DXd 6.4 mg/kg Q3W n=40 Participants Participants were randomized to receive intravenous T-DXd administered at a dose of 6.4 mg/kg every 3 weeks (Q3W).
Confirmed Objective Response Rate by Investigator Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer	31.7 percentage of participants Interval 21.9 to 42.9	30.0 percentage of participants Interval 16.6 to 46.5

SECONDARY outcome

Timeframe: From the first documented evidence of a response (complete or partial) until disease progression or death, up to approximately 19 months.

Population: DoR was assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.

DoR, defined as time from the initial response (CR or PR) by BICR and Investigator assessment until documented tumor progression or death from any cause. DoR was assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022.

Outcome measures

Measure	T-DXd 5.4 mg/kg Q3W n=82 Participants Participants were randomized to receive intravenous T-DXd administered at a dose of 5.4 mg/kg every 3 weeks (Q3W).	T-DXd 6.4 mg/kg Q3W n=40 Participants Participants were randomized to receive intravenous T-DXd administered at a dose of 6.4 mg/kg every 3 weeks (Q3W).
Duration of Response Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer BICR	5.5 months Interval 4.2 to 8.1	5.5 months Interval 3.7 to Not estimable due to insufficient data.
Duration of Response Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer Investigator	5.6 months Interval 4.2 to 8.0	6.9 months Interval 4.9 to 9.9

SECONDARY outcome

Timeframe: From first dose administration to data cut off, up to approximately 19 months.

Population: DCR was assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.

Disease Control Rate (DCR), defined as the proportion of subjects who achieved CR, PR, or SD for a minimum of 6 weeks during study treatment; DCR based on BICR and DCR based on Investigator assessments assessed according to RECIST version 1.1. DCR was assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022.

Outcome measures

Measure	T-DXd 5.4 mg/kg Q3W n=82 Participants Participants were randomized to receive intravenous T-DXd administered at a dose of 5.4 mg/kg every 3 weeks (Q3W).	T-DXd 6.4 mg/kg Q3W n=40 Participants Participants were randomized to receive intravenous T-DXd administered at a dose of 6.4 mg/kg every 3 weeks (Q3W).
Disease Control Rate Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) -Overexpressing Metastatic Colorectal Cancer BICR	86.6 percentage of participants Interval 77.3 to 93.1	85.0 percentage of participants Interval 70.2 to 94.3
Disease Control Rate Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) -Overexpressing Metastatic Colorectal Cancer Investigator	89.0 percentage of participants Interval 80.2 to 94.9	85.0 percentage of participants Interval 70.2 to 94.3

SECONDARY outcome

Timeframe: From first dose administration to data cut off, up to approximately 19 months.

Population: CBR was assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.

Clinical Benefit Rate (CBR), defined as proportion of subjects who achieved CR, PR, or SD for at least 6 months; CBR based on BICR and CBR based on Investigator assessments will both be determined based on RECIST version 1.1. CBR was assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022.

Outcome measures

Measure	T-DXd 5.4 mg/kg Q3W n=82 Participants Participants were randomized to receive intravenous T-DXd administered at a dose of 5.4 mg/kg every 3 weeks (Q3W).	T-DXd 6.4 mg/kg Q3W n=40 Participants Participants were randomized to receive intravenous T-DXd administered at a dose of 6.4 mg/kg every 3 weeks (Q3W).
Clinical Benefit Rate Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) -Overexpressing Metastatic Colorectal Cancer BICR	45.1 percentage of participants Interval 34.1 to 56.5	32.5 percentage of participants Interval 18.6 to 49.1
Clinical Benefit Rate Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) -Overexpressing Metastatic Colorectal Cancer Investigator	51.2 percentage of participants Interval 39.9 to 62.4	42.5 percentage of participants Interval 27.0 to 59.1

SECONDARY outcome

Timeframe: From randomization to data cut off, up to approximately 19 months.

Population: PFS was assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.

Progression Free Survival (PFS) defined as the time from date of randomization/registration until first objective radiographic tumor progression or death from any cause, based on BICR and Investigator assessment according to RECIST version 1.1. PFS was assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022.

Outcome measures

Measure	T-DXd 5.4 mg/kg Q3W n=82 Participants Participants were randomized to receive intravenous T-DXd administered at a dose of 5.4 mg/kg every 3 weeks (Q3W).	T-DXd 6.4 mg/kg Q3W n=40 Participants Participants were randomized to receive intravenous T-DXd administered at a dose of 6.4 mg/kg every 3 weeks (Q3W).
Progression Free Survival Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer BICR	5.8 month Interval 4.6 to 7.0	5.5 month Interval 4.2 to 7.0
Progression Free Survival Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer Investigator	5.8 month Interval 4.7 to 7.0	5.7 month Interval 4.2 to 8.3

SECONDARY outcome

Timeframe: From randomization to data cut off, up to approximately 19 months.

Population: OS was assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.

Overall Survival (OS) defined as the time from date of randomization/ registration until death from any cause, according to RECIST version 1.1. OS was assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022.

Outcome measures

Measure	T-DXd 5.4 mg/kg Q3W n=82 Participants Participants were randomized to receive intravenous T-DXd administered at a dose of 5.4 mg/kg every 3 weeks (Q3W).	T-DXd 6.4 mg/kg Q3W n=40 Participants Participants were randomized to receive intravenous T-DXd administered at a dose of 6.4 mg/kg every 3 weeks (Q3W).
Overall Survival Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer	13.4 months Interval 13.4 to 16.8	NA months Not estimable due to insufficient data.

SECONDARY outcome

Timeframe: From first dose administration to data cut off, up to approximately 19 months.

Population: The Safety Analysis Set (SAS) included all randomized/registered subjects who received at least 1 dose of study treatment. Subjects were summarized according to treatment received.

A Treatment-emergent Adverse Events (TEAE) is defined as an AE that occurs, having been absent before the first dose of study drug or has worsened in severity or seriousness after initiating the study drug until 47 days after the last dose of the study drug. Serious AEs with an onset or worsening 48 days or more after the last dose of study drug, if considered related to study treatment. are also TEAEs. TEAEs were assessed in the Safety Analysis Set at data cut-off date of 01 Nov 2022.

Outcome measures

Measure	T-DXd 5.4 mg/kg Q3W n=83 Participants Participants were randomized to receive intravenous T-DXd administered at a dose of 5.4 mg/kg every 3 weeks (Q3W).	T-DXd 6.4 mg/kg Q3W n=39 Participants Participants were randomized to receive intravenous T-DXd administered at a dose of 6.4 mg/kg every 3 weeks (Q3W).
Percentage of Participants Reporting Treatment-emergent Adverse Events Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer	98.8 percentage of participants	100 percentage of participants

SECONDARY outcome

Timeframe: C1D1 (Before infusion (BI), end of infusion (EOI) and 5 hours after infusion), C1D8 (7 days after infusion), C1D15 (14 days after infusion), C2D1 (BI and EOI), C3D1 (BI and EOI), C4D1, (BI and EOI), C6D1 (BI and EOI)

Population: The PK Analysis Set included all subjects randomized/registered in Stage 1 and/or Stage 2 who received at least 1 dose of T-DXd and had measurable serum concentrations of T-DXd. Subjects were analyzed according to the treatment received

Descriptive statistics will be provided for serum concentration data of T-DXd, DXd, and total anti-HER2 antibody. Serum concentrations were assessed in the Pharmacokinetics Analysis Set at data cut-off date of 01 Nov 2022.

Outcome measures

Measure	T-DXd 5.4 mg/kg Q3W n=83 Participants Participants were randomized to receive intravenous T-DXd administered at a dose of 5.4 mg/kg every 3 weeks (Q3W).	T-DXd 6.4 mg/kg Q3W n=39 Participants Participants were randomized to receive intravenous T-DXd administered at a dose of 6.4 mg/kg every 3 weeks (Q3W).
Serum Concentration of T-DXd C2D1 - Before Infusion	2827.01 ug/L Geometric Coefficient of Variation 118.8	4420.63 ug/L Geometric Coefficient of Variation 73.0
Serum Concentration of T-DXd C2D1 - End of Infusion	109777.43 ug/L Geometric Coefficient of Variation 67.2	135637.46 ug/L Geometric Coefficient of Variation 22.2
Serum Concentration of T-DXd C3D1 - Before Infusion	4823.41 ug/L Geometric Coefficient of Variation 83.6	7543.17 ug/L Geometric Coefficient of Variation 74.3
Serum Concentration of T-DXd C3D1 - End of Infusion	122218.96 ug/L Geometric Coefficient of Variation 25.8	139264.52 ug/L Geometric Coefficient of Variation 24.7
Serum Concentration of T-DXd C4D1 - Before Infusion	5846.34 ug/L Geometric Coefficient of Variation 89.5	11013.81 ug/L Geometric Coefficient of Variation 51.8
Serum Concentration of T-DXd C4D1 - End of Infusion	124240.37 ug/L Geometric Coefficient of Variation 23.4	134129.68 ug/L Geometric Coefficient of Variation 30.3
Serum Concentration of T-DXd C6D1 - Before Infusion	7507.28 ug/L Geometric Coefficient of Variation 74.5	10793.89 ug/L Geometric Coefficient of Variation 59.0
Serum Concentration of T-DXd C6D1 - End of Infusion	117769.64 ug/L Geometric Coefficient of Variation 25.3	35753.88 ug/L Geometric Coefficient of Variation 1079.6
Serum Concentration of T-DXd C1D8 - 7 Days After Infusion	22261.67 ug/L Geometric Coefficient of Variation 38.9	28142.80 ug/L Geometric Coefficient of Variation 51.5
Serum Concentration of T-DXd C1D15 - 14 Days After Infusion	8092.08 ug/L Geometric Coefficient of Variation 61.7	11396.97 ug/L Geometric Coefficient of Variation 60.3
Serum Concentration of T-DXd C1D1 - Before Infusion	NA ug/L Geometric Coefficient of Variation NA Concentrations below the lower limit of quantitation (BLQ) are set to zero for the calculation of descriptive statistics. If any concentration at a time point is BLQ, the geometric mean at that time point is not calculated and is presented as "NC", NC = NA	NA ug/L Geometric Coefficient of Variation NA Concentrations below the lower limit of quantitation (BLQ) are set to zero for the calculation of descriptive statistics. If any concentration at a time point is BLQ, the geometric mean at that time point is not calculated and is presented as "NC", NC = NA
Serum Concentration of T-DXd C1D1 - End of Infusion	118452.77 ug/L Geometric Coefficient of Variation 27.5	134613.79 ug/L Geometric Coefficient of Variation 18.1
Serum Concentration of T-DXd C1D1 - 5Hrs After Infusion	123433.28 ug/L Geometric Coefficient of Variation 23.0	142399.71 ug/L Geometric Coefficient of Variation 19.8

SECONDARY outcome

Timeframe: C1D1 (Before infusion (BI), end of infusion (EOI) and 5 hours after infusion), C1D8 (7 days after infusion), C1D15 (14 days after infusion), C2D1 (BI and EOI), C3D1 (BI and EOI), C4D1, (BI and EOI), C6D1 (BI and EOI)

Population: The PK Analysis Set included all subjects randomized/registered in Stage 1 and/or Stage 2 who received at least 1 dose of T-DXd and had measurable serum concentrations of T-DXd. Subjects were analyzed according to the treatment received

Descriptive statistics will be provided for serum concentration data of T-DXd, DXd, and total anti-HER2 antibody. Serum concentrations were assessed in the Pharmacokinetics Analysis Set at data cut-off date of 01 Nov 2022.

Outcome measures

Measure	T-DXd 5.4 mg/kg Q3W n=83 Participants Participants were randomized to receive intravenous T-DXd administered at a dose of 5.4 mg/kg every 3 weeks (Q3W).	T-DXd 6.4 mg/kg Q3W n=39 Participants Participants were randomized to receive intravenous T-DXd administered at a dose of 6.4 mg/kg every 3 weeks (Q3W).
Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody C1D1 - Before Infusion	5211.18 ug/L Geometric Coefficient of Variation 388.5	11934.79 ug/L Geometric Coefficient of Variation 2058.9
Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody C1D1 - End of Infusion	110871.93 ug/L Geometric Coefficient of Variation 28.8	121423.37 ug/L Geometric Coefficient of Variation 20.3
Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody C1D1 - 5Hrs After Infusion	107339.74 ug/L Geometric Coefficient of Variation 23.4	124274.05 ug/L Geometric Coefficient of Variation 23.0
Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody C1D8 - 7 Days After Infusion	27646.77 ug/L Geometric Coefficient of Variation 40.3	32741.77 ug/L Geometric Coefficient of Variation 49.9
Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody C1D15 - 14 Days After Infusion	10920.88 ug/L Geometric Coefficient of Variation 71.7	14293.10 ug/L Geometric Coefficient of Variation 63.0
Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody C2D1 - Before Infusion	3723.58 ug/L Geometric Coefficient of Variation 123.1	4841.90 ug/L Geometric Coefficient of Variation 107.5
Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody C2D1 - End of Infusion	106755.21 ug/L Geometric Coefficient of Variation 66.0	127427.43 ug/L Geometric Coefficient of Variation 23.2
Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody C3D1 - Before Infusion	6286.00 ug/L Geometric Coefficient of Variation 93.2	9100.39 ug/L Geometric Coefficient of Variation 90.0
Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody C3D1 - End of Infusion	114763.30 ug/L Geometric Coefficient of Variation 22.8	134111.33 ug/L Geometric Coefficient of Variation 19.5
Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody C4D1 - Before Infusion	7388.01 ug/L Geometric Coefficient of Variation 101.8	14007.95 ug/L Geometric Coefficient of Variation 67.2
Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody C4D1 - End of Infusion	113711.08 ug/L Geometric Coefficient of Variation 21.5	133956.61 ug/L Geometric Coefficient of Variation 30.5
Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody C6D1 - Before Infusion	9033.08 ug/L Geometric Coefficient of Variation 94.9	13535.33 ug/L Geometric Coefficient of Variation 73.5
Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody C6D1 - End of Infusion	104328.76 ug/L Geometric Coefficient of Variation 35.4	37091.52 ug/L Geometric Coefficient of Variation 816.2

SECONDARY outcome

Timeframe: C1D1 (Before infusion (BI), end of infusion (EOI) and 5 hours after infusion), C1D8 (7 days after infusion), C1D15 (14 days after infusion), C2D1 (BI and EOI), C3D1 (BI and EOI), C4D1, (BI and EOI), C6D1 (BI and EOI)

Population: The PK Analysis Set included all subjects randomized/registered in Stage 1 and/or Stage 2 who received at least 1 dose of T-DXd and had measurable serum concentrations of T-DXd. Subjects were analyzed according to the treatment received

Descriptive statistics will be provided for serum concentration data of T-DXd, DXd, and total anti-HER2 antibody. Serum concentrations were assessed in the Pharmacokinetics Analysis Set at data cut-off date of 01 Nov 2022.

Outcome measures

Measure	T-DXd 5.4 mg/kg Q3W n=83 Participants Participants were randomized to receive intravenous T-DXd administered at a dose of 5.4 mg/kg every 3 weeks (Q3W).	T-DXd 6.4 mg/kg Q3W n=39 Participants Participants were randomized to receive intravenous T-DXd administered at a dose of 6.4 mg/kg every 3 weeks (Q3W).
Serum Concentration of Active Metabolite MAAA-1181a C6D1 - Before Infusion	332.07 pg/mL Geometric Coefficient of Variation 81.3	578.72 pg/mL Geometric Coefficient of Variation 55.8
Serum Concentration of Active Metabolite MAAA-1181a C1D1 - Before Infusion	NA pg/mL Geometric Coefficient of Variation NA NA - Concentrations below the lower limit of quantitation (BLQ) are set to zero for the calculation of descriptive statistics. If any concentration at a time point is BLQ, the geometric mean at that time point is not calculated and is presented as "NC", NC = NA	NA pg/mL Geometric Coefficient of Variation NA NA - Concentrations below the lower limit of quantitation (BLQ) are set to zero for the calculation of descriptive statistics. If any concentration at a time point is BLQ, the geometric mean at that time point is not calculated and is presented as "NC", NC = NA
Serum Concentration of Active Metabolite MAAA-1181a C1D1 - End of Infusion	4101.40 pg/mL Geometric Coefficient of Variation 56.6	4313.38 pg/mL Geometric Coefficient of Variation 45.3
Serum Concentration of Active Metabolite MAAA-1181a C1D1 - 5Hrs After Infusion	12063.71 pg/mL Geometric Coefficient of Variation 52.8	15773.44 pg/mL Geometric Coefficient of Variation 39.0
Serum Concentration of Active Metabolite MAAA-1181a C1D8 - 7 Days After Infusion	1372.33 pg/mL Geometric Coefficient of Variation 75.8	1761.02 pg/mL Geometric Coefficient of Variation 67.1
Serum Concentration of Active Metabolite MAAA-1181a C1D15 - 14 Days After Infusion	475.30 pg/mL Geometric Coefficient of Variation 62.4	602.43 pg/mL Geometric Coefficient of Variation 54.1
Serum Concentration of Active Metabolite MAAA-1181a C2D1 - Before Infusion	209.06 pg/mL Geometric Coefficient of Variation 74.6	291.07 pg/mL Geometric Coefficient of Variation 55.4
Serum Concentration of Active Metabolite MAAA-1181a C2D1 - End of Infusion	1474.48 pg/mL Geometric Coefficient of Variation 71.2	1649.91 pg/mL Geometric Coefficient of Variation 65.8
Serum Concentration of Active Metabolite MAAA-1181a C3D1 - Before Infusion	279.56 pg/mL Geometric Coefficient of Variation 64.0	427.33 pg/mL Geometric Coefficient of Variation 89.5
Serum Concentration of Active Metabolite MAAA-1181a C3D1 - End of Infusion	1559.93 pg/mL Geometric Coefficient of Variation 52.6	1647.92 pg/mL Geometric Coefficient of Variation 53.1
Serum Concentration of Active Metabolite MAAA-1181a C4D1 - Before Infusion	284.38 pg/mL Geometric Coefficient of Variation 81.4	494.17 pg/mL Geometric Coefficient of Variation 61.2
Serum Concentration of Active Metabolite MAAA-1181a C4D1 - End of Infusion	1448.53 pg/mL Geometric Coefficient of Variation 48.5	1404.67 pg/mL Geometric Coefficient of Variation 54.1
Serum Concentration of Active Metabolite MAAA-1181a C6D1 - End of Infusion	1182.53 pg/mL Geometric Coefficient of Variation 36.8	1512.25 pg/mL Geometric Coefficient of Variation 32.3

SECONDARY outcome

Timeframe: From baseline to data cut off, up to approximately 19 months

Population: The Immunogenicity Analysis Set included all subjects randomized/registered in Stage 1 and/or Stage 2 who received at least 1 dose of the study drug and who had at least 1 baseline or postbaseline immunogenicity assessment. Subjects were analyzed according to the treatment received.

Immunogenicity will be assessed through characterization of incidence and titer of Anti-drug Antibodies (ADAs), the number and percentage of subjects positive for NAb of T-DXd by dose level will also be determined. ADAs and NAbs were assessed in the Immunogenicity Analysis Set at data cut-off date of 01 Nov 2022.

Outcome measures

Measure	T-DXd 5.4 mg/kg Q3W n=82 Participants Participants were randomized to receive intravenous T-DXd administered at a dose of 5.4 mg/kg every 3 weeks (Q3W).	T-DXd 6.4 mg/kg Q3W n=39 Participants Participants were randomized to receive intravenous T-DXd administered at a dose of 6.4 mg/kg every 3 weeks (Q3W).
Percentage of Participants Positive for Treatment-emergent Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (NAb) in Participants Who Were Administered T-DXd ADA	1.3 percentage of participants	0 percentage of participants
Percentage of Participants Positive for Treatment-emergent Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (NAb) in Participants Who Were Administered T-DXd NAb	0 percentage of participants	0 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to data cut off, up to approximately 19 months.

Population: Exploratory outcome, results not included in this submission

Exploratory outcome, results not included in this submission. The QLQ-C30 is composed of both multi-item scales and single-item measures. These include 5 functional scales, 3 symptom scales, a global health status/QoL scale, and 6 single items. Each of the multi-item scales includes a different set of items and no item occurs in more than 1 scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Patient questionnaires were assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to data cut off, up to approximately 19 months

Population: Exploratory outcome, results not included in this submission

Exploratory outcome, results not included in this submission. EORTC QLQ-CR29 is designed to be administered in addition to EORTC QLQ-C30. The EORTC QLQ-CR29 is a specific questionnaire for Colorectal Cancer. Scale from 0 to 100, A higher scale represents better function and a higher quality of life.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to data cut off, up to approximately 19 months

Population: Exploratory outcome, results not included in this submission

Exploratory outcome, results not included in this submission. The EQ-5D-5L is self-administered and consists of 2 parts, the EQ-5D-5L descriptive system and the EQ-visual analogue scale. On each dimension, a score of 1 indicates no patient problems in that dimension, 2 indicates slight problems in that dimension, 3 indicates moderate problems in that dimension, 4 indicates severe problems in that dimension and 5 indicates extreme problems in that dimension.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to data cut off, up to approximately 19 months

Population: Exploratory outcome, results not included in this submission

Exploratory outcome, results not included in this submission. The PGI-TT item is included to assess how a patient perceives the overall tolerability of the study treatment over the past 7 days. This is a single-item questionnaire, and patients will rate the bother associated with any treatment-related symptoms using response options ranging from "Not at all" to "Very much".

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to data cut off, up to approximately 19 months

Population: Exploratory outcome, results not included in this submission

Exploratory outcome, results not included in this submission. The PGIS item is included to assess how a patient perceives the overall severity of cancer symptoms over the past 7 days. This is a single-item questionnaire, and patients will choose the response that best describes the severity of their overall cancer symptoms with options ranging from "No Symptoms" to "Very Severe".

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to data cut off, up to approximately 19 months

Population: Exploratory outcome, results not included in this submission

Exploratory outcome, results not included in this submission. The PGIC item is included to assess how a patient perceives their overall change in health status since the start of study treatment. This is a single-item questionnaire, and patients will choose from response options ranging from "Much Better" to "Much Worse".

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to data cut off, up to approximately 19 months

Population: Exploratory outcome, results not included in this submission

Exploratory outcome, results not included in this submission. The impact of treatment and disease on healthcare resource use (including inpatient admissions, intensive care unit admissions, and length of stay in hospital) will be captured/collected in this study on an event-driven basis.

Outcome measures

Outcome data not reported

Adverse Events

T-DXd 5.4 mg/kg Q3W

Serious events: 21 serious events

Other events: 81 other events

Deaths: 26 deaths

T-DXd 6.4 mg/kg Q3W

Serious events: 12 serious events

Other events: 38 other events

Deaths: 13 deaths

Serious adverse events

Measure	T-DXd 5.4 mg/kg Q3W n=83 participants at risk Participants were randomized to receive intravenous T-DXd administered at a dose of 5.4 mg/kg every 3 weeks (Q3W).	T-DXd 6.4 mg/kg Q3W n=39 participants at risk Participants were randomized to receive intravenous T-DXd administered at a dose of 6.4 mg/kg every 3 weeks (Q3W).
Blood and lymphatic system disorders Anaemia	2.4% 2/83 • Number of events 2 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	2.6% 1/39 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Blood and lymphatic system disorders Febrile neutropenia	2.4% 2/83 • Number of events 2 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	2.6% 1/39 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Blood and lymphatic system disorders Pancytopenia	1.2% 1/83 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	0.00% 0/39 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/83 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	2.6% 1/39 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Gastrointestinal disorders Nausea	3.6% 3/83 • Number of events 3 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	0.00% 0/39 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Gastrointestinal disorders Small intestinal obstruction	2.4% 2/83 • Number of events 3 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	2.6% 1/39 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Gastrointestinal disorders Vomiting	2.4% 2/83 • Number of events 2 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	0.00% 0/39 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Gastrointestinal disorders Gastrointestinal perforation	1.2% 1/83 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	0.00% 0/39 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Gastrointestinal disorders Ileus paralytic	1.2% 1/83 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	0.00% 0/39 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Gastrointestinal disorders Abdominal pain	0.00% 0/83 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	2.6% 1/39 • Number of events 2 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Gastrointestinal disorders Diarrhoea	0.00% 0/83 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	2.6% 1/39 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Gastrointestinal disorders Gastritis	0.00% 0/83 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	2.6% 1/39 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/83 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	2.6% 1/39 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
General disorders Fatigue	2.4% 2/83 • Number of events 4 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	2.6% 1/39 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
General disorders Pyrexia	1.2% 1/83 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	0.00% 0/39 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
General disorders Asthenia	0.00% 0/83 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	2.6% 1/39 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
General disorders Disease progression	0.00% 0/83 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	2.6% 1/39 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Hepatobiliary disorders Hepatic failure	1.2% 1/83 • Number of events 4 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	0.00% 0/39 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Infections and infestations COVID-19	2.4% 2/83 • Number of events 2 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	0.00% 0/39 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Infections and infestations Pneumonia bacterial	2.4% 2/83 • Number of events 2 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	0.00% 0/39 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Infections and infestations Anal abscess	1.2% 1/83 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	0.00% 0/39 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Infections and infestations Candida infection	1.2% 1/83 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	0.00% 0/39 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Infections and infestations Clostridium difficile infection	1.2% 1/83 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	0.00% 0/39 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Infections and infestations Klebsiella sepsis	1.2% 1/83 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	0.00% 0/39 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Infections and infestations Sepsis	1.2% 1/83 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	0.00% 0/39 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Infections and infestations Urinary tract infection	1.2% 1/83 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	0.00% 0/39 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Investigations Platelet count decreased	1.2% 1/83 • Number of events 3 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	2.6% 1/39 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Investigations Neutrophil count decreased	0.00% 0/83 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	5.1% 2/39 • Number of events 2 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Metabolism and nutrition disorders Decreased appetite	1.2% 1/83 • Number of events 2 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	0.00% 0/39 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Metabolism and nutrition disorders Hypoalbuminaemia	1.2% 1/83 • Number of events 3 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	0.00% 0/39 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Musculoskeletal and connective tissue disorders Sacral pain	1.2% 1/83 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	0.00% 0/39 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Nervous system disorders Hepatic encephalopathy	0.00% 0/83 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	2.6% 1/39 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Nervous system disorders Seizure	0.00% 0/83 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	2.6% 1/39 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Renal and urinary disorders Acute kidney injury	1.2% 1/83 • Number of events 2 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	2.6% 1/39 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.2% 1/83 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	0.00% 0/39 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Respiratory, thoracic and mediastinal disorders Epistaxis	1.2% 1/83 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	0.00% 0/39 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.2% 1/83 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	2.6% 1/39 • Number of events 2 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Vascular disorders Inferior vena cava syndrome	0.00% 0/83 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	2.6% 1/39 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.

Other adverse events

Measure	T-DXd 5.4 mg/kg Q3W n=83 participants at risk Participants were randomized to receive intravenous T-DXd administered at a dose of 5.4 mg/kg every 3 weeks (Q3W).	T-DXd 6.4 mg/kg Q3W n=39 participants at risk Participants were randomized to receive intravenous T-DXd administered at a dose of 6.4 mg/kg every 3 weeks (Q3W).
Blood and lymphatic system disorders Anaemia	26.5% 22/83 • Number of events 52 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	41.0% 16/39 • Number of events 43 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Blood and lymphatic system disorders Neutropenia	9.6% 8/83 • Number of events 22 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	5.1% 2/39 • Number of events 6 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Blood and lymphatic system disorders Thrombocytopenia	6.0% 5/83 • Number of events 6 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	2.6% 1/39 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Eye disorders Retinal haemorrhage	0.00% 0/83 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	5.1% 2/39 • Number of events 2 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Gastrointestinal disorders Nausea	59.0% 49/83 • Number of events 102 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	56.4% 22/39 • Number of events 36 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Gastrointestinal disorders Constipation	24.1% 20/83 • Number of events 20 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	15.4% 6/39 • Number of events 8 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Gastrointestinal disorders Diarrhoea	22.9% 19/83 • Number of events 38 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	28.2% 11/39 • Number of events 14 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Gastrointestinal disorders Vomiting	20.5% 17/83 • Number of events 29 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	7.7% 3/39 • Number of events 4 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Gastrointestinal disorders Stomatitis	14.5% 12/83 • Number of events 17 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	15.4% 6/39 • Number of events 13 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Gastrointestinal disorders Abdominal pain	8.4% 7/83 • Number of events 9 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	5.1% 2/39 • Number of events 4 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Gastrointestinal disorders Dyspepsia	3.6% 3/83 • Number of events 3 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	5.1% 2/39 • Number of events 2 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
General disorders Asthenia	20.5% 17/83 • Number of events 31 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	15.4% 6/39 • Number of events 20 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
General disorders Fatigue	19.3% 16/83 • Number of events 37 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	15.4% 6/39 • Number of events 9 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
General disorders Pyrexia	15.7% 13/83 • Number of events 19 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	10.3% 4/39 • Number of events 8 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
General disorders Oedema peripheral	6.0% 5/83 • Number of events 5 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	17.9% 7/39 • Number of events 8 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
General disorders Malaise	4.8% 4/83 • Number of events 5 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	12.8% 5/39 • Number of events 5 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
General disorders Mucosal inflammation	4.8% 4/83 • Number of events 4 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	5.1% 2/39 • Number of events 2 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Hepatobiliary disorders Hepatic function abnormal	1.2% 1/83 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	5.1% 2/39 • Number of events 4 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Infections and infestations COVID-19	16.9% 14/83 • Number of events 16 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	12.8% 5/39 • Number of events 5 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Infections and infestations Urinary tract infection	4.8% 4/83 • Number of events 5 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	5.1% 2/39 • Number of events 2 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Infections and infestations Upper respiratory tract infection	2.4% 2/83 • Number of events 2 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	7.7% 3/39 • Number of events 4 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Infections and infestations Pneumonia	0.00% 0/83 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	5.1% 2/39 • Number of events 2 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Investigations Neutrophil count decreased	21.7% 18/83 • Number of events 39 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	41.0% 16/39 • Number of events 47 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Investigations Platelet count decreased	21.7% 18/83 • Number of events 41 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	30.8% 12/39 • Number of events 25 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Investigations White blood cell count decreased	13.3% 11/83 • Number of events 28 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	17.9% 7/39 • Number of events 22 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Investigations Aspartate aminotransferase increased	12.0% 10/83 • Number of events 12 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	17.9% 7/39 • Number of events 13 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Investigations Alanine aminotransferase increased	9.6% 8/83 • Number of events 13 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	15.4% 6/39 • Number of events 12 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Investigations Blood creatinine increased	4.8% 4/83 • Number of events 4 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	5.1% 2/39 • Number of events 3 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Investigations Lymphocyte count decreased	4.8% 4/83 • Number of events 8 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	5.1% 2/39 • Number of events 2 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Investigations Blood alkaline phosphatase increased	3.6% 3/83 • Number of events 4 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	5.1% 2/39 • Number of events 4 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Investigations Blood bilirubin increased	3.6% 3/83 • Number of events 5 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	15.4% 6/39 • Number of events 13 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Investigations Weight decreased	3.6% 3/83 • Number of events 3 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	5.1% 2/39 • Number of events 2 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Metabolism and nutrition disorders Decreased appetite	30.1% 25/83 • Number of events 41 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	15.4% 6/39 • Number of events 9 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Metabolism and nutrition disorders Hypokalaemia	7.2% 6/83 • Number of events 8 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	10.3% 4/39 • Number of events 5 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Musculoskeletal and connective tissue disorders Back pain	7.2% 6/83 • Number of events 6 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	5.1% 2/39 • Number of events 2 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Nervous system disorders Headache	9.6% 8/83 • Number of events 10 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	5.1% 2/39 • Number of events 2 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Nervous system disorders Dizziness	3.6% 3/83 • Number of events 3 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	5.1% 2/39 • Number of events 2 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
General disorders Dysgeusia	1.2% 1/83 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	5.1% 2/39 • Number of events 2 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Respiratory, thoracic and mediastinal disorders Cough	9.6% 8/83 • Number of events 10 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	7.7% 3/39 • Number of events 4 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.2% 6/83 • Number of events 7 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	7.7% 3/39 • Number of events 3 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Respiratory, thoracic and mediastinal disorders Epistaxis	7.2% 6/83 • Number of events 10 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	7.7% 3/39 • Number of events 5 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Respiratory, thoracic and mediastinal disorders Pneumonitis	6.0% 5/83 • Number of events 5 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	12.8% 5/39 • Number of events 6 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	2.4% 2/83 • Number of events 2 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	5.1% 2/39 • Number of events 2 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Skin and subcutaneous tissue disorders Alopecia	22.9% 19/83 • Number of events 22 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	28.2% 11/39 • Number of events 12 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.
Vascular disorders Hypotension	1.2% 1/83 • Number of events 1 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.	7.7% 3/39 • Number of events 3 • Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up to approximately 44 months. For Final Results, data was collected up until 04 Dec 2024. Safety parameters were collected, analyzed, and reported based on the dosage of treatment drug administered as specified in the study protocol, therefore as 2 arms, T-DXd 5.4 mg/kg Q3W and T-DXd 6.4 mg/kg Q3W.

Additional Information

Contact for Clinical Trial Information

Daiichi Sanyko, Inc

Phone: 908-992-6400

Email: CTRinfo@dsi.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place