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Clinical Trial Results:
A Phase 3, Multicenter, Randomized, Open-Label, Active-Controlled Study Of Trastuzumab Deruxtecan (DS-8201A), An Anti-HER2-Antibody Drug Conjugate, Versus Treatment Of Investigator's Choice For HER2-Positive, Unresectable And/Or Metastatic Breast Cancer Subjects Previously Treated With T-DM1 (DESTINY-Breast02)

Summary
EudraCT number	2018-000221-31
Trial protocol	GB BE CZ FR GR DE IT ES
Global end of trial date	22 Dec 2025

Results information
Results version number	v2(current)
This version publication date	23 Oct 2026
First version publication date	30 Sep 2023
Other versions	v1
Version creation reason

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

DS8201-A-U301

ISRCTN number

-

US NCT number

NCT03523585

WHO universal trial number (UTN)

-

Other trial identifiers

JAPIC CTI: 184017

Sponsor organisation name

Daiichi Sankyo, Inc.

Sponsor organisation address

211 Mount Airy Rd., Basking Ridge, United States, 07920

Public contact

Contact for Clinical Trial Information, Daiichi Sankyo, Inc., +1 908 9926400, CTRinfo_us@daiichisankyo.com

Scientific contact

Contact for Clinical Trial Information, Daiichi Sankyo, Inc., +1 908 9926400, CTRinfo_us@daiichisankyo.com

Is trial part of an agreed paediatric investigation plan (PIP)

No

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

No

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

No

Analysis stage

Final

Date of interim/final analysis

04 Mar 2026

Is this the analysis of the primary completion data?

No

Global end of trial reached?

Yes

Global end of trial date

22 Dec 2025

Was the trial ended prematurely?

No

Main objective of the trial

The primary objective of the trial was to compare the progression-free survival (PFS) benefit of trastuzumab deruxtecan to investigator’s choice for HER2-positive, unresectable and/or metastatic breast cancer subjects previously treated with T-DM1.

Protection of trial subjects

The study protocol, patient information and consent form, the IB, any patient written instructions to be given to the patient, available safety information, patient recruitment procedures (eg, advertisements), information about payments and compensation available to the patients, and documentation evidencing the investigator’s qualifications should be submitted to the EC or IRB for ethical review and approval according to local regulations, prior to the study start.

Background therapy

-

Evidence for comparator

-

Actual start date of recruitment

06 Sep 2018

Long term follow-up planned

No

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 21

Country: Number of subjects enrolled

Belgium: 5

Country: Number of subjects enrolled

Brazil: 59

Country: Number of subjects enrolled

Czechia: 3

Country: Number of subjects enrolled

Germany: 19

Country: Number of subjects enrolled

Spain: 44

Country: Number of subjects enrolled

France: 57

Country: Number of subjects enrolled

United Kingdom: 35

Country: Number of subjects enrolled

Greece: 14

Country: Number of subjects enrolled

Israel: 18

Country: Number of subjects enrolled

Italy: 53

Country: Number of subjects enrolled

Japan: 70

Country: Number of subjects enrolled

Korea, Republic of: 94

Country: Number of subjects enrolled

Türkiye: 52

Country: Number of subjects enrolled

United States: 64

Worldwide total number of subjects

608

EEA total number of subjects

195

Number of subjects enrolled per age group

In utero

0

Preterm newborn - gestational age < 37 wk

0

Newborns (0-27 days)

0

Infants and toddlers (28 days-23 months)

0

Children (2-11 years)

0

Adolescents (12-17 years)

0

Adults (18-64 years)

485

From 65 to 84 years

119

85 years and over

4

Subject disposition

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Recruitment details

A total of 608 participants were enrolled at study sites in 15 countries. The final safety results are being reported based on a data cut-off date of 23 December 2025.

Screening details

Participants in TPC group were randomized to 1 of the following 2 regimens: trastuzumab/capecitabine or lapatinib/capecitabine. As prespecified in the protocol, patients were assessed and reported separately per comparator arm for the disposition, baseline characteristics, and safety tables. For efficacy, all TPC patients are reported combined.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Blinding implementation details

N/A

Are arms mutually exclusive

Yes

Trastuzumab Deruxtecan (T-DXd)

Arm description

Participants with HER2 positive, unresectable and/or metastatic breast cancer participants previously treated with standard of care HER2 therapies, including ado-trastuzumab emtansine (T-DM1), who received T-DXd as a sterile intravenous (IV) solution at a dose of 5.4 mg/kg every 3 weeks (Q3W).

Arm type

Experimental

Investigational medicinal product name

Trastuzumab deruxtecan

Investigational medicinal product code

Other name

DS-8201a, T-DXd

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

5.4 mg/kg every 3 weeks (Q3W)

Trastuzumab+Capecitabine

Arm description

Participants with HER2 positive, unresectable and/or metastatic breast cancer participants previously treated with standard of care HER2 therapies, including ado-trastuzumab emtansine (T-DM1), who received investigator's choice treatment, Trastuzumab/Capecitabine.

Arm type

Experimental

Investigational medicinal product name

Capecitabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In combination with trastuzumab: 1250 mg/m^2 administered orally (PO) twice daily approximately 12 hours apart (equivalent to 2500 mg/m^2 total daily dose) on Days 1 to 14 of a 21-day (± 2 days) schedule In combination with lapatinib: 1000 mg/m^2 PO twice daily approximately 12 hours apart (equivalent to 2000 mg/m^2 total daily dose) on Days 1 to 14 of a 21-day (± 2 days) schedule

Investigational medicinal product name

Trastuzumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigator's choice Standard of Care when combined with capecitabine

Lapatinib+Capecitabine

Arm description

Participants with HER2 positive, unresectable and/or metastatic breast cancer participants previously treated with standard of care HER2 therapies, including ado-trastuzumab emtansine (T-DM1), who received investigator's choice treatment, Lapatinib/Capecitabine.

Arm type

Experimental

Investigational medicinal product name

Lapatinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In combination with capecitabine: 1250 mg PO daily on Days 1 to 21 of a 21-day (± 2 days) schedule

Investigational medicinal product name

Capecitabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

In combination with trastuzumab: 1250 mg/m^2 administered orally (PO) twice daily approximately 12 hours apart (equivalent to 2500 mg/m^2 total daily dose) on Days 1 to 14 of a 21-day (± 2 days) schedule In combination with lapatinib: 1000 mg/m^2 PO twice daily approximately 12 hours apart (equivalent to 2000 mg/m^2 total daily dose) on Days 1 to 14 of a 21-day (± 2 days) schedule

Number of subjects in period 1	Trastuzumab Deruxtecan (T-DXd)	Trastuzumab+Capecitabine	Lapatinib+Capecitabine
Started	406	91	111
Randomized	406	91	111
Randomized but Not Treated	2	4	3
Completed	0	0	0
Not completed	406	91	111
Adverse event, serious fatal	5	5	1
Consent withdrawn by subject	38	11	6
Physician decision	3	1	-
Adverse event, non-fatal	89	-	9
Progressive Disease	204	64	80
Other, not specified	35	-	-
Study terminated by sponsor	1	-	-
Randomized But Not Treated	2	4	3
Lost to follow-up	2	-	-
Clinical Progression	26	6	11
Protocol deviation	1	-	1

Baseline characteristics

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Reporting group title

Trastuzumab Deruxtecan (T-DXd)

Reporting group description

Participants with HER2 positive, unresectable and/or metastatic breast cancer participants previously treated with standard of care HER2 therapies, including ado-trastuzumab emtansine (T-DM1), who received T-DXd as a sterile intravenous (IV) solution at a dose of 5.4 mg/kg every 3 weeks (Q3W).

Reporting group title

Trastuzumab+Capecitabine

Reporting group description

Participants with HER2 positive, unresectable and/or metastatic breast cancer participants previously treated with standard of care HER2 therapies, including ado-trastuzumab emtansine (T-DM1), who received investigator's choice treatment, Trastuzumab/Capecitabine.

Reporting group title

Lapatinib+Capecitabine

Reporting group description

Participants with HER2 positive, unresectable and/or metastatic breast cancer participants previously treated with standard of care HER2 therapies, including ado-trastuzumab emtansine (T-DM1), who received investigator's choice treatment, Lapatinib/Capecitabine.

Reporting group values	Trastuzumab Deruxtecan (T-DXd)	Trastuzumab+Capecitabine	Lapatinib+Capecitabine	Total
Number of subjects	406	91	111
Age Categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	54.6 ( 11.99 )	55.7 ( 11.4 )	54.6 ( 11.06 )	-
Gender categorical
Units: Subjects
Female	403	89	111	603
Male	3	2	0	5
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	2	0	0	2
Asian	122	20	36	178
Native Hawaiian or Other Pacific Islander	0	0	1	1
Black or African American	10	2	5	17
White	257	66	61	384
More than one race	0	0	0	0
Unknown or Not Reported	15	3	8	26
Age categorical
Units: Subjects
18-64 years	321	73	91	485
65-84 years	82	17	20	119
85 years and over	3	1	0	4

End points

Top of page

Reporting group title

Trastuzumab Deruxtecan (T-DXd)

Reporting group description

Participants with HER2 positive, unresectable and/or metastatic breast cancer participants previously treated with standard of care HER2 therapies, including ado-trastuzumab emtansine (T-DM1), who received T-DXd as a sterile intravenous (IV) solution at a dose of 5.4 mg/kg every 3 weeks (Q3W).

Reporting group title

Trastuzumab+Capecitabine

Reporting group description

Participants with HER2 positive, unresectable and/or metastatic breast cancer participants previously treated with standard of care HER2 therapies, including ado-trastuzumab emtansine (T-DM1), who received investigator's choice treatment, Trastuzumab/Capecitabine.

Reporting group title

Lapatinib+Capecitabine

Reporting group description

Participants with HER2 positive, unresectable and/or metastatic breast cancer participants previously treated with standard of care HER2 therapies, including ado-trastuzumab emtansine (T-DM1), who received investigator's choice treatment, Lapatinib/Capecitabine.

Subject analysis set title

Treatment of Investigator's/Physician's Choice (TPC)

Subject analysis set type

Full analysis

Subject analysis set description

Participants with HER2 positive, unresectable and/or metastatic breast cancer participants previously treated with standard of care HER2 therapies, including ado-trastuzumab emtansine (T-DM1), who received investigator's choice treatment, Trastuzumab/Capecitabine or Lapatinib/Capecitabine.

Primary: Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR) in Participants with HER2-positive, Unresectable and/or Metastatic Breast Cancer Participants Previously Treated with Trastuzumab Emtansine

Top of page

End point title

Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR) in Participants with HER2-positive, Unresectable and/or Metastatic Breast Cancer Participants Previously Treated with Trastuzumab Emtansine ^[1]

End point description

Progression-free survival (PFS) by BICR was defined as the time from the date of randomization to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause.

End point type

Primary

End point timeframe

Baseline up to 46 months postdose

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are reported for the T-DXd vs TPC arm.

End point values	Trastuzumab Deruxtecan (T-DXd)	Treatment of Investigator's/Physician's Choice (TPC)
Number of subjects analysed	406	202
Units: months
median (confidence interval 95%)	17.8 (14.3 to 20.8)	6.9 (5.5 to 8.4)

T-DXd vs TPC

Statistical analysis description

T-DXd vs TPC

Comparison groups

Trastuzumab Deruxtecan (T-DXd) v Treatment of Investigator's/Physician's Choice (TPC)

Number of subjects included in analysis

608

Analysis specification

Pre-specified

Analysis type

superiority ^[2]

P-value

< 0.000001 ^[3]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.3589

Confidence interval

level

95%

sides

2-sided

lower limit

0.284

upper limit

0.4535

Notes
[2] - Stratified Log-rank p-value
[3] - Stratified Log-rank p-value

Secondary: Overall Survival (OS) in Participants with HER2-positive, Unresectable and/or Metastatic Breast Cancer Participants Previously Treated with Trastuzumab Emtansine

Top of page

End point title

Overall Survival (OS) in Participants with HER2-positive, Unresectable and/or Metastatic Breast Cancer Participants Previously Treated with Trastuzumab Emtansine ^[4]

End point description

Overall survival (OS) was defined as the time from the date of randomization to the date of death due to any cause. If there is no death reported for a subject before the data cutoff for OS analysis, OS will be censored at the last contact date at which the subject is known to be alive.

End point type

Secondary

End point timeframe

Baseline up to 46 months postdose

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are reported for the T-DXd vs TPC arm.

End point values	Trastuzumab Deruxtecan (T-DXd)	Treatment of Investigator's/Physician's Choice (TPC)
Number of subjects analysed	406	202
Units: months
median (confidence interval 95%)	39.2 (32.7 to 99999)	26.5 (21.0 to 99999)

T-DXd vs TPC

Statistical analysis description

T-DXd vs TPC

Comparison groups

Trastuzumab Deruxtecan (T-DXd) v Treatment of Investigator's/Physician's Choice (TPC)

Number of subjects included in analysis

608

Analysis specification

Pre-specified

Analysis type

superiority ^[5]

P-value

= 0.0021 ^[6]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.6575

Confidence interval

level

95%

sides

2-sided

lower limit

0.5023

upper limit

0.8605

Notes
[5] - Stratified Log-rank p-value
[6] - Stratified Log-rank p-value

Secondary: Percentage of Participants with Objective Response Rate (ORR) in Participants with HER2-positive, Unresectable and/or Metastatic Breast Cancer Participants Previously Treated with Trastuzumab Emtansine

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End point title

Percentage of Participants with Objective Response Rate (ORR) in Participants with HER2-positive, Unresectable and/or Metastatic Breast Cancer Participants Previously Treated with Trastuzumab Emtansine ^[7]

End point description

The Objective Response Rate (ORR) was defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by BICR and investigator assessment based on RECIST version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Confirmed ORR based on BICR and Investigator Assessment is reported.

End point type

Secondary

End point timeframe

Baseline up to 46 months postdose

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are reported for the T-DXd vs TPC arm.

End point values	Trastuzumab Deruxtecan (T-DXd)	Treatment of Investigator's/Physician's Choice (TPC)
Number of subjects analysed	406	202
Units: Percentage of Participants
number (confidence interval 95%)
BICR	69.7 (65.0 to 74.1)	29.2 (23.0 to 36.0)
Investigator Assessment	74.1 (69.6 to 78.3)	26.7 (20.8 to 33.4)

T-DXd vs TPC

Statistical analysis description

Statistical Analysis for Investigator Assessment

Comparison groups

Trastuzumab Deruxtecan (T-DXd) v Treatment of Investigator's/Physician's Choice (TPC)

Number of subjects included in analysis

608

Analysis specification

Pre-specified

Analysis type

superiority ^[8]

P-value

< 0.0001 ^[9]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[8] - Cochran-Mantel-Haenszel test adjusted for stratification factors: hormone receptor status, prior treatment with pertuzumab, and history of visceral disease, as defined by the IXRS.
[9] - Cochran-Mantel-Haenszel test adjusted for stratification factors: hormone receptor status, prior treatment with pertuzumab, and history of visceral disease, as defined by the IXRS.

T-DXd vs TPC

Statistical analysis description

Statistical analysis for BICR Assessment

Comparison groups

Trastuzumab Deruxtecan (T-DXd) v Treatment of Investigator's/Physician's Choice (TPC)

Number of subjects included in analysis

608

Analysis specification

Pre-specified

Analysis type

superiority ^[10]

P-value

< 0.0001 ^[11]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[10] - Cochran-Mantel-Haenszel test adjusted for stratification factors: hormone receptor status, prior treatment with pertuzumab, and history of visceral disease, as defined by the IXRS.
[11] - Cochran-Mantel-Haenszel test adjusted for stratification factors: hormone receptor status, prior treatment with pertuzumab, and history of visceral disease, as defined by the IXRS.

Secondary: Duration of Response (DoR) Based on BICR in Participants with HER2-positive, Unresectable and/or Metastatic Breast Cancer Participants Previously Treated with Trastuzumab Emtansine

Top of page

End point title

Duration of Response (DoR) Based on BICR in Participants with HER2-positive, Unresectable and/or Metastatic Breast Cancer Participants Previously Treated with Trastuzumab Emtansine ^[12]

End point description

Duration of Response (DoR) was defined as the time from the date of the first documentation of objective response (complete response [CR] or partial response [PR]) to the date of the first objective documentation of progressive disease (PD) or death due to any cause. DoR in participants with confirmed CR/PR based on BICR and investigator assessment is reported.

End point type

Secondary

End point timeframe

Baseline up to 46 months postdose

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are reported for the T-DXd vs TPC arm.

End point values	Trastuzumab Deruxtecan (T-DXd)	Treatment of Investigator's/Physician's Choice (TPC)
Number of subjects analysed	283	59
Units: months
median (confidence interval 95%)	19.6 (15.9 to 99999)	8.3 (5.8 to 9.5)

No statistical analyses for this end point

Secondary: Progression-Free Survival (PFS) Based on Investigator Assessment in Participants with HER2-positive, Unresectable and/or Metastatic Breast Cancer Participants Previously Treated with Trastuzumab Emtansine

Top of page

End point title

Progression-Free Survival (PFS) Based on Investigator Assessment in Participants with HER2-positive, Unresectable and/or Metastatic Breast Cancer Participants Previously Treated with Trastuzumab Emtansine ^[13]

End point description

Progression-free survival (PFS) by investigator assessment was defined as the time from the date of randomization to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause.

End point type

Secondary

End point timeframe

Up to 46 months

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are reported for the T-DXd vs TPC arm.

End point values	Trastuzumab Deruxtecan (T-DXd)	Treatment of Investigator's/Physician's Choice (TPC)
Number of subjects analysed	406	202
Units: months
median (confidence interval 95%)	16.7 (14.3 to 19.6)	5.5 (4.4 to 7.0)

T-DXd vs TPC

Statistical analysis description

T-DXd vs TPC

Comparison groups

Trastuzumab Deruxtecan (T-DXd) v Treatment of Investigator's/Physician's Choice (TPC)

Number of subjects included in analysis

608

Analysis specification

Pre-specified

Analysis type

superiority ^[14]

P-value

< 0.000001 ^[15]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.2828

Confidence interval

level

95%

sides

2-sided

lower limit

0.227

upper limit

0.3524

Notes
[14] - Stratified Log-rank p-value.
[15] - Stratified Log-rank p-value.

Adverse events

Top of page

Timeframe for reporting adverse events

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 46 months.

Adverse event reporting additional description

A TEAE is an AE that occurs, having been absent before the first dose of drug, or has worsened in severity or seriousness after the initiating the drug until 47 days after last dose. AEs were assessed in the Safety Analysis Set at data cut-off date of 23 December 2025. Mortality was analyzed in the Full Analysis Set.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

28.1

Reporting group title

Trastuzumab Deruxtecan (T-DXd)

Reporting group description

Participants with HER2 positive, unresectable and/or metastatic breast cancer participants previously treated with standard of care HER2 therapies, including ado-trastuzumab emtansine (T-DM1), who received T-DXd as a sterile intravenous (IV) solution at a dose of 5.4 mg/kg every 3 weeks (Q3W).

Reporting group title

Lapatinib+Capecitabine

Reporting group description

Participants with HER2 positive, unresectable and/or metastatic breast cancer participants previously treated with standard of care HER2 therapies, including ado-trastuzumab emtansine (T-DM1), who received investigator's choice treatment, Lapatinib/Capecitabine.

Reporting group title

Trastuzumab+Capecitabine

Reporting group description

Participants with HER2 positive, unresectable and/or metastatic breast cancer participants previously treated with standard of care HER2 therapies, including ado-trastuzumab emtansine (T-DM1), who received investigator's choice treatment, Trastuzumab/Capecitabine.

Serious adverse events	Trastuzumab Deruxtecan (T-DXd)	Lapatinib+Capecitabine	Trastuzumab+Capecitabine
Total subjects affected by serious adverse events
subjects affected / exposed	117 / 404 (28.96%)	27 / 108 (25.00%)	19 / 87 (21.84%)
number of deaths (all causes)	143	46	40
number of deaths resulting from adverse events	15	6	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute Myeloid Leukaemia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0	0 / 0
Metastases To Meninges
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	1 / 108 (0.93%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Metastases To Ovary
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Transitional Cell Cancer of the Renal Pelvis and Ureter
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cancer Pain
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	0 / 404 (0.00%)	0 / 108 (0.00%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular disorders
Deep Vein Thrombosis
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	1 / 108 (0.93%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Brachiocephalic Vein Thrombosis
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lymphoedema
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Orthostatic Hypotension
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haemorrhage
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Embolism
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	0 / 404 (0.00%)	0 / 108 (0.00%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypertensive Urgency
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	0 / 404 (0.00%)	1 / 108 (0.93%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypotension
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	0 / 404 (0.00%)	1 / 108 (0.93%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Peripheral Ischaemia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	0 / 404 (0.00%)	1 / 108 (0.93%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vena Cava Thrombosis
alternative dictionary used: MedDRA 28.1
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Fatigue
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	3 / 404 (0.74%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	3 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pyrexia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	3 / 404 (0.74%)	0 / 108 (0.00%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	1 / 4	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Asthenia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	2 / 404 (0.50%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Disease Progression
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	3 / 404 (0.74%)	3 / 108 (2.78%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 3	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 3	0 / 3	0 / 1
General Physical Health Deterioration
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Non-Cardiac Chest Pain
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	1 / 108 (0.93%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gait disturbance
alternative dictionary used: MedDRA 28.1
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Oedema Peripheral
alternative dictionary used: MedDRA 28.1
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pain
alternative dictionary used: MedDRA 28.1
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Breast Pain
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Interstitial Lung Disease
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	5 / 404 (1.24%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	5 / 5	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonitis
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	9 / 404 (2.23%)	1 / 108 (0.93%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	9 / 9	0 / 1	0 / 0
deaths causally related to treatment / all	2 / 2	0 / 0	0 / 0
Haemoptysis
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pleural Effusion
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	2 / 404 (0.50%)	3 / 108 (2.78%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 2	0 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Dyspnoea
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Laryngeal Haemorrhage
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lung Disorder
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumothorax
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	2 / 404 (0.50%)	1 / 108 (0.93%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pulmonary Embolism
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	2 / 404 (0.50%)	1 / 108 (0.93%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pulmonary Oedema
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pulmonary Fibrosis
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	2 / 404 (0.50%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0	0 / 0
Pulmonary Haemorrhage
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypoxia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	0 / 404 (0.00%)	1 / 108 (0.93%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Malignant Pleural Effusion
alternative dictionary used: MedDRA 28.1
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Pulmonary Tumour Thrombotic Microangiopathy
alternative dictionary used: MedDRA 28.1
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Depression
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Mental Status Changes
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Suicide Attempt
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Investigations
Hepatic Enzyme Increased
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	0 / 404 (0.00%)	1 / 108 (0.93%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pancreatic Enzymes Increased
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	0 / 404 (0.00%)	1 / 108 (0.93%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Radiation Necrosis
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	2 / 404 (0.50%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hip Fracture
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Head Injury
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lumbar Vertebral Fracture
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Overdose
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Subdural Haematoma
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Wrist Fracture
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Accidental Overdose
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	0 / 404 (0.00%)	1 / 108 (0.93%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Craniocerebral Injury
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	0 / 404 (0.00%)	1 / 108 (0.93%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lower Limb Fracture
alternative dictionary used: MedDRA 28.1
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Humerus Fracture
alternative dictionary used: MedDRA 28.1
subjects affected / exposed	0 / 404 (0.00%)	0 / 108 (0.00%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
Stress Cardiomyopathy
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac Tamponade
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Acute Myocardial Infarction
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	0 / 404 (0.00%)	1 / 108 (0.93%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac Arrest
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	0 / 404 (0.00%)	1 / 108 (0.93%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Cardiac Failure
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	0 / 404 (0.00%)	1 / 108 (0.93%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Myocardial Ischaemia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	0 / 404 (0.00%)	1 / 108 (0.93%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pericardial Effusion
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	0 / 404 (0.00%)	1 / 108 (0.93%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Nervous system disorders
Brain Oedema
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	2 / 404 (0.50%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Depressed Level Of Consciousness
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Dizziness
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Epilepsy
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Generalised Tonic-Clonic Seizure
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Headache
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hemiplegia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Monoplegia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Syncope
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vasogenic Cerebral Oedema
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Seizure
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	2 / 404 (0.50%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cerebral Ischaemia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	0 / 404 (0.00%)	0 / 108 (0.00%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haemorrhage Intracranial
alternative dictionary used: MedDRA 28.1
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Dysarthria
alternative dictionary used: MedDRA 28.1
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	4 / 404 (0.99%)	1 / 108 (0.93%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	4 / 4	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Febrile Neutropenia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haemolysis
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pancytopenia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Thrombocytopenia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	2 / 404 (0.50%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Eye disorders
Scleritis
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Nausea
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	5 / 404 (1.24%)	0 / 108 (0.00%)	2 / 87 (2.30%)
occurrences causally related to treatment / all	5 / 5	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vomiting
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	6 / 404 (1.49%)	0 / 108 (0.00%)	2 / 87 (2.30%)
occurrences causally related to treatment / all	4 / 6	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Abdominal Pain
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	2 / 404 (0.50%)	0 / 108 (0.00%)	3 / 87 (3.45%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ascites
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diarrhoea
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	3 / 404 (0.74%)	1 / 108 (0.93%)	3 / 87 (3.45%)
occurrences causally related to treatment / all	2 / 3	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Colitis
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Duodenal Ulcer
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Faecaloma
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastritis
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal Haemorrhage
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haemorrhoidal Haemorrhage
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	4 / 4	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Oesophageal Varices Haemorrhage
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	2 / 404 (0.50%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Large Intestinal Obstruction
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Stomatitis
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Constipation
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	0 / 404 (0.00%)	0 / 108 (0.00%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastric Antral Vascular Ectasia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	0 / 404 (0.00%)	1 / 108 (0.93%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haematemesis
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	0 / 404 (0.00%)	1 / 108 (0.93%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Duodenal Ulcer Haemorrhage
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholangitis
alternative dictionary used: MedDRA 28.1
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cholecystitis
alternative dictionary used: MedDRA 28.1
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hyperbilirubinaemia
alternative dictionary used: MedDRA 28.1
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Skin Hyperpigmentation
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute Kidney Injury
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	1 / 108 (0.93%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cystitis Haemorrhagic
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Endocrine disorders
Autoimmune Thyroiditis
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthralgia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	2 / 404 (0.50%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Muscular Weakness
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Neck Pain
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Osteonecrosis Of Jaw
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pain In Extremity
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Back Pain
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	0 / 404 (0.00%)	1 / 108 (0.93%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Covid-19
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	12 / 404 (2.97%)	1 / 108 (0.93%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 12	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Pneumonia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	8 / 404 (1.98%)	1 / 108 (0.93%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	2 / 8	0 / 1	0 / 0
deaths causally related to treatment / all	1 / 2	0 / 0	0 / 0
Device Related Infection
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	2 / 404 (0.50%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Covid-19 Pneumonia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	2 / 404 (0.50%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Influenza
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	2 / 404 (0.50%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumocystis Jirovecii Pneumonia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	2 / 404 (0.50%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary Tract Infection
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	2 / 404 (0.50%)	1 / 108 (0.93%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Appendicitis
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cellulitis
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	2 / 404 (0.50%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastroenteritis
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	1 / 108 (0.93%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Post Procedural Infection
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatitis B
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Mastitis
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pyelonephritis
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Wound Infection
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sepsis
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Skin Infection
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Abdominal Sepsis
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lower Respiratory Tract Infection
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	0 / 404 (0.00%)	0 / 108 (0.00%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gingivitis
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	0 / 404 (0.00%)	0 / 108 (0.00%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Neutropenic Sepsis
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	0 / 404 (0.00%)	0 / 108 (0.00%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Peritonitis Bacterial
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	0 / 404 (0.00%)	1 / 108 (0.93%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory Tract Infection
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	0 / 404 (0.00%)	1 / 108 (0.93%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pseudomembranous Colitis
alternative dictionary used: MedDRA 28.1
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	4 / 404 (0.99%)	1 / 108 (0.93%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	4 / 4	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Decreased Appetite
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypercalcaemia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypokalaemia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hyponatraemia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Trastuzumab Deruxtecan (T-DXd)	Lapatinib+Capecitabine	Trastuzumab+Capecitabine
Total subjects affected by non serious adverse events
subjects affected / exposed	398 / 404 (98.51%)	102 / 108 (94.44%)	79 / 87 (90.80%)
Investigations
Weight Decreased
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	77 / 404 (19.06%)	6 / 108 (5.56%)	2 / 87 (2.30%)
occurrences all number	81	6	2
Neutrophil Count Decreased
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	83 / 404 (20.54%)	7 / 108 (6.48%)	7 / 87 (8.05%)
occurrences all number	283	17	8
Alanine Aminotransferase Increased
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	63 / 404 (15.59%)	15 / 108 (13.89%)	6 / 87 (6.90%)
occurrences all number	103	16	6
White Blood Cell Count Decreased
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	61 / 404 (15.10%)	4 / 108 (3.70%)	5 / 87 (5.75%)
occurrences all number	178	10	10
Platelet Count Decreased
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	54 / 404 (13.37%)	7 / 108 (6.48%)	5 / 87 (5.75%)
occurrences all number	116	7	7
Aspartate Aminotransferase Increased
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	70 / 404 (17.33%)	19 / 108 (17.59%)	5 / 87 (5.75%)
occurrences all number	120	21	8
Blood Bilirubin Increased
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	22 / 404 (5.45%)	17 / 108 (15.74%)	5 / 87 (5.75%)
occurrences all number	30	29	6
Blood Alkaline Phosphatase Increased
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	27 / 404 (6.68%)	4 / 108 (3.70%)	4 / 87 (4.60%)
occurrences all number	33	4	4
Lymphocyte Count Decreased
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	32 / 404 (7.92%)	2 / 108 (1.85%)	2 / 87 (2.30%)
occurrences all number	73	2	3
Gamma-Glutamyltransferase Increased
alternative dictionary used: MedDRA 28.1
subjects affected / exposed	21 / 404 (5.20%)	1 / 108 (0.93%)	1 / 87 (1.15%)
occurrences all number	24	1	1
Weight Increased
alternative dictionary used: MedDRA 28.1
subjects affected / exposed	22 / 404 (5.45%)	1 / 108 (0.93%)	4 / 87 (4.60%)
occurrences all number	23	1	5
Nervous system disorders
Headache
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	85 / 404 (21.04%)	5 / 108 (4.63%)	7 / 87 (8.05%)
occurrences all number	146	5	8
Dysgeusia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	34 / 404 (8.42%)	1 / 108 (0.93%)	3 / 87 (3.45%)
occurrences all number	41	1	3
Dizziness
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	36 / 404 (8.91%)	9 / 108 (8.33%)	5 / 87 (5.75%)
occurrences all number	45	11	5
Neuropathy Peripheral
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	12 / 404 (2.97%)	4 / 108 (3.70%)	6 / 87 (6.90%)
occurrences all number	16	4	6
Blood and lymphatic system disorders
Neutropenia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	71 / 404 (17.57%)	6 / 108 (5.56%)	4 / 87 (4.60%)
occurrences all number	193	10	4
Anaemia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	120 / 404 (29.70%)	14 / 108 (12.96%)	13 / 87 (14.94%)
occurrences all number	260	15	15
Thrombocytopenia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	45 / 404 (11.14%)	7 / 108 (6.48%)	4 / 87 (4.60%)
occurrences all number	83	15	7
Leukopenia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	26 / 404 (6.44%)	2 / 108 (1.85%)	2 / 87 (2.30%)
occurrences all number	56	2	2
Lymphopenia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	26 / 404 (6.44%)	1 / 108 (0.93%)	1 / 87 (1.15%)
occurrences all number	58	1	1
General disorders and administration site conditions
Fatigue
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	149 / 404 (36.88%)	32 / 108 (29.63%)	20 / 87 (22.99%)
occurrences all number	255	42	23
Asthenia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	101 / 404 (25.00%)	13 / 108 (12.04%)	6 / 87 (6.90%)
occurrences all number	209	13	9
Pyrexia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	58 / 404 (14.36%)	8 / 108 (7.41%)	5 / 87 (5.75%)
occurrences all number	84	9	5
Oedema Peripheral
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	32 / 404 (7.92%)	5 / 108 (4.63%)	4 / 87 (4.60%)
occurrences all number	44	5	4
Mucosal Inflammation
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	17 / 404 (4.21%)	9 / 108 (8.33%)	6 / 87 (6.90%)
occurrences all number	24	10	7
Eye disorders
Dry Eye
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	24 / 404 (5.94%)	6 / 108 (5.56%)	4 / 87 (4.60%)
occurrences all number	26	6	4
Gastrointestinal disorders
Nausea
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	293 / 404 (72.52%)	44 / 108 (40.74%)	29 / 87 (33.33%)
occurrences all number	929	54	34
Vomiting
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	154 / 404 (38.12%)	14 / 108 (12.96%)	9 / 87 (10.34%)
occurrences all number	345	22	12
Abdominal Pain
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	50 / 404 (12.38%)	11 / 108 (10.19%)	7 / 87 (8.05%)
occurrences all number	68	14	9
Dyspepsia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	50 / 404 (12.38%)	12 / 108 (11.11%)	6 / 87 (6.90%)
occurrences all number	64	12	6
Diarrhoea
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	118 / 404 (29.21%)	69 / 108 (63.89%)	33 / 87 (37.93%)
occurrences all number	258	158	44
Constipation
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	147 / 404 (36.39%)	9 / 108 (8.33%)	12 / 87 (13.79%)
occurrences all number	213	12	13
Abdominal Pain Upper
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	43 / 404 (10.64%)	11 / 108 (10.19%)	7 / 87 (8.05%)
occurrences all number	144	14	7
Stomatitis
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	49 / 404 (12.13%)	25 / 108 (23.15%)	11 / 87 (12.64%)
occurrences all number	72	28	14
Respiratory, thoracic and mediastinal disorders
Cough
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	60 / 404 (14.85%)	13 / 108 (12.04%)	7 / 87 (8.05%)
occurrences all number	77	14	8
Dyspnoea
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	34 / 404 (8.42%)	10 / 108 (9.26%)	3 / 87 (3.45%)
occurrences all number	41	13	3
Epistaxis
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	34 / 404 (8.42%)	7 / 108 (6.48%)	5 / 87 (5.75%)
occurrences all number	40	8	5
Pneumonitis
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	26 / 404 (6.44%)	0 / 108 (0.00%)	0 / 87 (0.00%)
occurrences all number	26	0	0
Skin and subcutaneous tissue disorders
Alopecia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	150 / 404 (37.13%)	4 / 108 (3.70%)	4 / 87 (4.60%)
occurrences all number	169	4	4
Rash
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	34 / 404 (8.42%)	19 / 108 (17.59%)	3 / 87 (3.45%)
occurrences all number	47	21	4
Dry Skin
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	11 / 404 (2.72%)	6 / 108 (5.56%)	3 / 87 (3.45%)
occurrences all number	11	6	3
Pruritus
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	22 / 404 (5.45%)	6 / 108 (5.56%)	2 / 87 (2.30%)
occurrences all number	27	6	2
Rash Maculo-Papular
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	6 / 404 (1.49%)	6 / 108 (5.56%)	2 / 87 (2.30%)
occurrences all number	7	6	3
Palmar-Plantar Erythrodysaesthesia Syndrome
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	7 / 404 (1.73%)	52 / 108 (48.15%)	48 / 87 (55.17%)
occurrences all number	9	66	66
Dermatitis Acneiform
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	2 / 404 (0.50%)	10 / 108 (9.26%)	0 / 87 (0.00%)
occurrences all number	2	15	0
Skin Toxicity
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	1 / 404 (0.25%)	6 / 108 (5.56%)	1 / 87 (1.15%)
occurrences all number	1	8	1
Psychiatric disorders
Insomnia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	28 / 404 (6.93%)	5 / 108 (4.63%)	6 / 87 (6.90%)
occurrences all number	31	5	6
Musculoskeletal and connective tissue disorders
Arthralgia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	49 / 404 (12.13%)	7 / 108 (6.48%)	7 / 87 (8.05%)
occurrences all number	68	7	7
Back Pain
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	42 / 404 (10.40%)	5 / 108 (4.63%)	1 / 87 (1.15%)
occurrences all number	49	5	1
Pain In Extremity
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	27 / 404 (6.68%)	4 / 108 (3.70%)	4 / 87 (4.60%)
occurrences all number	33	4	5
Myalgia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	25 / 404 (6.19%)	4 / 108 (3.70%)	4 / 87 (4.60%)
occurrences all number	44	4	4
Muscle Spasms
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	14 / 404 (3.47%)	7 / 108 (6.48%)	4 / 87 (4.60%)
occurrences all number	24	7	4
Infections and infestations
Urinary Tract Infection
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	36 / 404 (8.91%)	3 / 108 (2.78%)	3 / 87 (3.45%)
occurrences all number	63	3	3
Covid-19
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	55 / 404 (13.61%)	3 / 108 (2.78%)	1 / 87 (1.15%)
occurrences all number	67	3	1
Nasopharyngitis
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	25 / 404 (6.19%)	2 / 108 (1.85%)	3 / 87 (3.45%)
occurrences all number	35	2	3
Paronychia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	10 / 404 (2.48%)	12 / 108 (11.11%)	3 / 87 (3.45%)
occurrences all number	14	21	4
Upper Respiratory Tract Infection
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	26 / 404 (6.44%)	3 / 108 (2.78%)	3 / 87 (3.45%)
occurrences all number	38	3	3
Metabolism and nutrition disorders
Decreased Appetite
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	126 / 404 (31.19%)	20 / 108 (18.52%)	15 / 87 (17.24%)
occurrences all number	176	25	16
Hypokalaemia
alternative dictionary used: MedDRA 25.0
subjects affected / exposed	33 / 404 (8.17%)	6 / 108 (5.56%)	7 / 87 (8.05%)
occurrences all number	45	6	8

More information

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Were there any global substantial amendments to the protocol? Yes

20 Jun 2018

This amendment updated the starting dose of DS-8201a, revised eligibility criteria, clarified the process if treatment is delayed, updated criteria for dose modifications, revised definitions, and further clarified details for key study assessments.

08 Mar 2019

This amendment updated the eligibility criteria, clarified study objectives/endpoints, and further clarified details for key study assessments.

26 Apr 2019

This amendment clarified details regarding ILD biomarkers, monitoring plan, dose modification, and follow-up plans.

23 Apr 2020

This amendment was primarily driven by the addition of an interim analysis.

05 Aug 2020

This amendment was primarily driven by the addition of biomarker analyses to evaluate the impact of the global pandemic caused by COVID-19 at the patient-level and study-level. The exploratory endpoints were also revised to include evaluation of progression-free survival on the next line of therapy (PFS2), and withdrawal of consent language was clarified.

17 Mar 2022

The main purpose of this amendment is to introduce alternative timing for the primary analysis.

24 Apr 2023

Key changes include updates to frequency of tumor assessments, removal of anti-drug antibody (ADA) and biomarker sample collection for on-treatment patients, and updates to the adverse event management guidelines.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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