Trial Outcomes & Findings for SYD985 vs. Physician's Choice in Participants With HER2-positive Locally Advanced or Metastatic Breast Cancer (NCT NCT03262935)

Last Updated: 2023-10-19

Results Overview

Progression-free survival is defined as the time from the date of randomization to the date of first documented disease progression by central assessment according to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurred earlier.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

437 participants

Primary outcome timeframe

baseline until primary analysis data cut-off date of 31March2021

Results posted on

2023-10-19

Participant Flow

A total of 751 participants were screened, out of which, 437 participants were randomized into the study.

Participant milestones

Participant milestones
Measure	(Vic-)Trastuzumab Duocarmazine SYD985, every 3 weeks (Q3W) (vic-)trastuzumab duocarmazine: Intravenous SYD985, Q3W	Physician's Choice 1. Lap/Cap 2. T/Cap 3. T/Vino 4. T/Eri Physician's choice: See drug label
Overall Study STARTED	291	146
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	291	146

Reasons for withdrawal

Reasons for withdrawal
Measure	(Vic-)Trastuzumab Duocarmazine SYD985, every 3 weeks (Q3W) (vic-)trastuzumab duocarmazine: Intravenous SYD985, Q3W	Physician's Choice 1. Lap/Cap 2. T/Cap 3. T/Vino 4. T/Eri Physician's choice: See drug label
Overall Study Withdrawal by Subject	6	7
Overall Study End Of Follow Up By Sponsor	90	41
Overall Study Death	181	94
Overall Study Lost to Follow-up	9	4
Overall Study Other reason	5	0

Baseline Characteristics

The number analyzed differs from the overall because height was missing for 3 patients in the SYD985 group and for 1 patient in the Physician's choice group.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	(Vic-)Trastuzumab Duocarmazine n=291 Participants SYD985, every 3 weeks (Q3W) (vic-)trastuzumab duocarmazine: Intravenous SYD985, Q3W	Physician's Choice n=146 Participants 1. Lap/Cap 2. T/Cap 3. T/Vino 4. T/Eri Physician's choice: See drug label	Total n=437 Participants Total of all reporting groups
Age, Continuous	55.9 years STANDARD_DEVIATION 11.2 • n=291 Participants	57.3 years STANDARD_DEVIATION 10.97 • n=146 Participants	56.4 years STANDARD_DEVIATION 11.13 • n=437 Participants
Sex: Female, Male Female	291 Participants n=291 Participants	146 Participants n=146 Participants	437 Participants n=437 Participants
Sex: Female, Male Male	0 Participants n=291 Participants	0 Participants n=146 Participants	0 Participants n=437 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	11 Participants n=291 Participants	8 Participants n=146 Participants	19 Participants n=437 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	225 Participants n=291 Participants	103 Participants n=146 Participants	328 Participants n=437 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	55 Participants n=291 Participants	35 Participants n=146 Participants	90 Participants n=437 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=291 Participants	0 Participants n=146 Participants	1 Participants n=437 Participants
Race (NIH/OMB) Asian	29 Participants n=291 Participants	17 Participants n=146 Participants	46 Participants n=437 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=291 Participants	0 Participants n=146 Participants	0 Participants n=437 Participants
Race (NIH/OMB) Black or African American	4 Participants n=291 Participants	2 Participants n=146 Participants	6 Participants n=437 Participants
Race (NIH/OMB) White	202 Participants n=291 Participants	95 Participants n=146 Participants	297 Participants n=437 Participants
Race (NIH/OMB) More than one race	0 Participants n=291 Participants	0 Participants n=146 Participants	0 Participants n=437 Participants
Race (NIH/OMB) Unknown or Not Reported	55 Participants n=291 Participants	32 Participants n=146 Participants	87 Participants n=437 Participants
Region of Enrollment Canada	15 participants n=291 Participants	9 participants n=146 Participants	24 participants n=437 Participants
Region of Enrollment Netherlands	3 participants n=291 Participants	0 participants n=146 Participants	3 participants n=437 Participants
Region of Enrollment Sweden	4 participants n=291 Participants	4 participants n=146 Participants	8 participants n=437 Participants
Region of Enrollment Singapore	20 participants n=291 Participants	15 participants n=146 Participants	35 participants n=437 Participants
Region of Enrollment Belgium	25 participants n=291 Participants	15 participants n=146 Participants	40 participants n=437 Participants
Region of Enrollment United States	34 participants n=291 Participants	19 participants n=146 Participants	53 participants n=437 Participants
Region of Enrollment Denmark	7 participants n=291 Participants	3 participants n=146 Participants	10 participants n=437 Participants
Region of Enrollment Italy	50 participants n=291 Participants	20 participants n=146 Participants	70 participants n=437 Participants
Region of Enrollment United Kingdom	43 participants n=291 Participants	16 participants n=146 Participants	59 participants n=437 Participants
Region of Enrollment France	46 participants n=291 Participants	22 participants n=146 Participants	68 participants n=437 Participants
Region of Enrollment Spain	44 participants n=291 Participants	23 participants n=146 Participants	67 participants n=437 Participants
BMI	25.14 kg/m2 STANDARD_DEVIATION 5.0 • n=288 Participants • The number analyzed differs from the overall because height was missing for 3 patients in the SYD985 group and for 1 patient in the Physician's choice group.	25.54 kg/m2 STANDARD_DEVIATION 6.1 • n=145 Participants • The number analyzed differs from the overall because height was missing for 3 patients in the SYD985 group and for 1 patient in the Physician's choice group.	25.28 kg/m2 STANDARD_DEVIATION 5.4 • n=433 Participants • The number analyzed differs from the overall because height was missing for 3 patients in the SYD985 group and for 1 patient in the Physician's choice group.
Childbearing potential Yes	64 Participants n=291 Participants	32 Participants n=146 Participants	96 Participants n=437 Participants
Childbearing potential No - postmenopausal	204 Participants n=291 Participants	105 Participants n=146 Participants	309 Participants n=437 Participants
Childbearing potential No - surgically sterilized	23 Participants n=291 Participants	9 Participants n=146 Participants	32 Participants n=437 Participants

PRIMARY outcome

Timeframe: baseline until primary analysis data cut-off date of 31March2021

Population: Full-analysis set (FAS) was used for this primary endpoint analysis. FAS comprises all randomized patients, which were analyzed according to the treatment group and strata they have been assigned to during the randomization procedure.

Outcome measures

Outcome measures
Measure	(Vic-)Trastuzumab Duocarmazine n=291 Participants SYD985, every 3 weeks (Q3W) (vic-)trastuzumab duocarmazine: Intravenous SYD985, Q3W	Physician's Choice n=146 Participants 1. Lap/Cap 2. T/Cap 3. T/Vino 4. T/Eri Physician's choice: See drug label
Progression Free Survival	7.0 months Interval 5.4 to 7.2	4.9 months Interval 4.0 to 5.5

SECONDARY outcome

Timeframe: baseline until final Overall Survival analysis data cut-off date of 30June2022

Population: Full-analysis set (FAS) was used for the overall survival analysis. FAS comprises all randomized patients, which were analyzed according to the treatment group and strata they have been assigned to during the randomization procedure.

Overall survival is defined as the time from date of randomization to death due to any cause.

Outcome measures

Outcome measures
Measure	(Vic-)Trastuzumab Duocarmazine n=291 Participants SYD985, every 3 weeks (Q3W) (vic-)trastuzumab duocarmazine: Intravenous SYD985, Q3W	Physician's Choice n=146 Participants 1. Lap/Cap 2. T/Cap 3. T/Vino 4. T/Eri Physician's choice: See drug label
Overall Survival	21.0 months Interval 18.1 to 25.0	19.5 months Interval 14.2 to 23.1

SECONDARY outcome

Timeframe: baseline until primary analysis data cut-off date of 31March2021

Objective Response Rate is defined as the proportion of patients with a centrally assessed best overall response of complete response or partial response according to RECIST v1.1.

Outcome measures

Outcome measures
Measure	(Vic-)Trastuzumab Duocarmazine n=252 Participants SYD985, every 3 weeks (Q3W) (vic-)trastuzumab duocarmazine: Intravenous SYD985, Q3W	Physician's Choice n=122 Participants 1. Lap/Cap 2. T/Cap 3. T/Vino 4. T/Eri Physician's choice: See drug label
Objective Response Rate	27.8 percentage of patients Interval 22.3 to 33.7	29.5 percentage of patients Interval 21.6 to 38.4

SECONDARY outcome

Timeframe: baseline until primary analysis data cut-off date of 31March2021

Progression-free survival is defined as the time from the date of randomization to the date of first documented disease progression by investigator assessment according to RECIST v1.1 or death due to any cause, whichever occurred earlier.

Outcome measures

Outcome measures
Measure	(Vic-)Trastuzumab Duocarmazine n=291 Participants SYD985, every 3 weeks (Q3W) (vic-)trastuzumab duocarmazine: Intravenous SYD985, Q3W	Physician's Choice n=146 Participants 1. Lap/Cap 2. T/Cap 3. T/Vino 4. T/Eri Physician's choice: See drug label
Investigator Assessed Progression Free Survival	6.9 months Interval 6.0 to 7.2	4.6 months Interval 4.0 to 5.6

SECONDARY outcome

Timeframe: baseline until primary analysis data cut-off date of 31March2021

Change in the global health status/Quality of Life (QoL) scale score of the European Organization for Research and Treatment for Cancer (EORTC) Quality of Life Questionnaire C30 from baseline (cycle 1). The raw score (1 to 7) has been transformed to a score ranging from 0 to 100. A higher score means a better outcome: hence a positive change from baseline means an improvement in global health status/Quality of Life and a negative change from baseline means a worsening of global health status/Quality of Life.

Outcome measures

Outcome measures
Measure	(Vic-)Trastuzumab Duocarmazine n=291 Participants SYD985, every 3 weeks (Q3W) (vic-)trastuzumab duocarmazine: Intravenous SYD985, Q3W	Physician's Choice n=146 Participants 1. Lap/Cap 2. T/Cap 3. T/Vino 4. T/Eri Physician's choice: See drug label
Patient Reported Outcomes for Health Related Quality of Life Cycle 2	0.17 scores on a scale Interval -2.7 to 3.04	-3.88 scores on a scale Interval -7.79 to 0.03
Patient Reported Outcomes for Health Related Quality of Life Cycle 3	-1.88 scores on a scale Interval -4.83 to 1.07	-2.99 scores on a scale Interval -7.0 to 1.02
Patient Reported Outcomes for Health Related Quality of Life Cycle 4	-2.48 scores on a scale Interval -5.46 to 0.5	-9.01 scores on a scale Interval -13.23 to -4.8
Patient Reported Outcomes for Health Related Quality of Life Cycle 5	-2.51 scores on a scale Interval -5.69 to 0.67	-5.77 scores on a scale Interval -10.34 to -1.21
Patient Reported Outcomes for Health Related Quality of Life Cycle 7	-5.65 scores on a scale Interval -9.19 to -2.1	-6.75 scores on a scale Interval -11.92 to -1.58
Patient Reported Outcomes for Health Related Quality of Life Cycle 9	-8.14 scores on a scale Interval -12.27 to -4.02	-11.25 scores on a scale Interval -17.41 to -5.09
Patient Reported Outcomes for Health Related Quality of Life Cycle 11	-10.70 scores on a scale Interval -15.66 to -5.75	-10.38 scores on a scale Interval -18.08 to -2.69
Patient Reported Outcomes for Health Related Quality of Life Cycle 13	-13.40 scores on a scale Interval -20.31 to -6.48	-12.89 scores on a scale Interval -21.33 to -4.45
Patient Reported Outcomes for Health Related Quality of Life Cycle 15	-11.90 scores on a scale Interval -20.41 to -3.39	-14.12 scores on a scale Interval -23.91 to -4.33
Patient Reported Outcomes for Health Related Quality of Life Cycle 17	-4.31 scores on a scale Interval -14.48 to 5.86	-0.71 scores on a scale Interval -13.26 to 11.83
Patient Reported Outcomes for Health Related Quality of Life Cycle 19	-5.45 scores on a scale Interval -21.05 to 10.16	1.66 scores on a scale Interval -13.84 to 17.16
Patient Reported Outcomes for Health Related Quality of Life Cycle 21	11.68 scores on a scale Interval -9.76 to 33.12	-11.23 scores on a scale Interval -26.16 to 3.71
Patient Reported Outcomes for Health Related Quality of Life Cycle 23	5.30 scores on a scale Interval -26.04 to 36.65	-7.00 scores on a scale Interval -29.18 to 15.17
Patient Reported Outcomes for Health Related Quality of Life Cycle 25	18.76 scores on a scale Interval -14.63 to 52.16	-11.48 scores on a scale Interval -42.96 to 19.99
Patient Reported Outcomes for Health Related Quality of Life Cycle 27	0.49 scores on a scale Interval -33.4 to 34.37	-5.41 scores on a scale Interval -38.83 to 28.02
Patient Reported Outcomes for Health Related Quality of Life Cycle 29	—	-6.54 scores on a scale Interval -40.45 to 27.37
Patient Reported Outcomes for Health Related Quality of Life Cycle 33	—	-7.11 scores on a scale Interval -41.14 to 26.92
Patient Reported Outcomes for Health Related Quality of Life Cycle 35	—	-15.73 scores on a scale Interval -49.79 to 18.33

Adverse Events

(Vic-)Trastuzumab Duocarmazine

Serious events: 53 serious events

Other events: 278 other events

Deaths: 181 deaths

Physician's Choice

Serious events: 12 serious events

Other events: 132 other events

Deaths: 94 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Development

Byondis B.V.

Phone: 0031246795101

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The PI agrees to provide to the Sponsor 60 days prior to intended submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the study. The Sponsor has the right to review and comment with respect to publications, abstracts, slides, and manuscripts including the data analysis and presentation. In case of disagreement, efforts will be undertaken to resolve any such issues, but the ultimate decision remains with the Sponsor.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	(Vic-)Trastuzumab Duocarmazine n=288 participants at risk SYD985, every 3 weeks (Q3W) (vic-)trastuzumab duocarmazine: Intravenous SYD985, Q3W	Physician's Choice n=137 participants at risk 1. Lap/Cap 2. T/Cap 3. T/Vino 4. T/Eri Physician's choice: See drug label
Cardiac disorders Pericardial effusion	0.35% 1/288 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic myeloid leukaemia	0.35% 1/288 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Haemorrhagic tumour necrosis	0.35% 1/288 • Number of events 2 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Infected neoplasm	0.35% 1/288 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.35% 1/288 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Vascular disorders Orthostatic hypotension	0.35% 1/288 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
General disorders Catheter site pain	0.35% 1/288 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
General disorders Drug intolerance	0.35% 1/288 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
General disorders Pyrexia	0.35% 1/288 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.73% 1/137 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
General disorders General physical health deterioration	0.00% 0/288 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.73% 1/137 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Reproductive system and breast disorders Uterine haemorrhage	0.35% 1/288 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Respiratory, thoracic and mediastinal disorders Pneumonitis	2.4% 7/288 • Number of events 8 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.69% 2/288 • Number of events 2 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.35% 1/288 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.35% 1/288 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.35% 1/288 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.35% 1/288 • Number of events 2 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Respiratory, thoracic and mediastinal disorders Pneumomediastinum	0.35% 1/288 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.35% 1/288 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.73% 1/137 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.35% 1/288 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/288 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	2.2% 3/137 • Number of events 3 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract infection	0.35% 1/288 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.73% 1/137 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Psychiatric disorders Anxiety	0.35% 1/288 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Product Issues Device occlusion	0.35% 1/288 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Investigations Platelet count decreased	0.69% 2/288 • Number of events 3 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Investigations Ejection fraction decreased	0.35% 1/288 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Investigations Staphylococcus test positive	0.35% 1/288 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Injury, poisoning and procedural complications Infusion related reaction	0.69% 2/288 • Number of events 3 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Injury, poisoning and procedural complications Lower limb fracture	0.35% 1/288 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Cardiac disorders Atrial fibrillation	0.35% 1/288 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Cardiac disorders Cardiac failure	0.35% 1/288 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Cardiac disorders Cardiac tamponade	0.35% 1/288 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Cardiac disorders Myocardial infarction	0.35% 1/288 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Nervous system disorders Depressed level of consciousness	0.35% 1/288 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Blood and lymphatic system disorders Anaemia	0.69% 2/288 • Number of events 5 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Blood and lymphatic system disorders Thrombocytopenia	0.35% 1/288 • Number of events 2 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/288 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.73% 1/137 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Eye disorders Keratitis	0.69% 2/288 • Number of events 3 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Eye disorders Conjunctivitis	0.35% 1/288 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Eye disorders Eyelid ptosis	0.35% 1/288 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.

Other adverse events
Measure	(Vic-)Trastuzumab Duocarmazine n=288 participants at risk SYD985, every 3 weeks (Q3W) (vic-)trastuzumab duocarmazine: Intravenous SYD985, Q3W	Physician's Choice n=137 participants at risk 1. Lap/Cap 2. T/Cap 3. T/Vino 4. T/Eri Physician's choice: See drug label
Investigations Weight decreased	10.1% 29/288 • Number of events 45 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	1.5% 2/137 • Number of events 2 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Investigations Aspartate aminotransferase increased	5.6% 16/288 • Number of events 26 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	7.3% 10/137 • Number of events 14 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Investigations Platelet count decreased	5.6% 16/288 • Number of events 28 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Investigations Neutrophil count decreased	4.9% 14/288 • Number of events 25 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	10.2% 14/137 • Number of events 26 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Investigations Alanine aminotransferase increased	4.2% 12/288 • Number of events 19 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	7.3% 10/137 • Number of events 17 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Nervous system disorders Headache	11.5% 33/288 • Number of events 37 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	11.7% 16/137 • Number of events 23 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Nervous system disorders Dysgeusia	7.6% 22/288 • Number of events 26 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	2.9% 4/137 • Number of events 5 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Nervous system disorders Dizziness	7.3% 21/288 • Number of events 22 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	5.1% 7/137 • Number of events 7 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Nervous system disorders Neuropathy peripheral	5.6% 16/288 • Number of events 29 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	5.8% 8/137 • Number of events 16 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Nervous system disorders Peripheral sensory neuropathy	1.7% 5/288 • Number of events 7 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	5.1% 7/137 • Number of events 11 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
General disorders Fatigue	33.3% 96/288 • Number of events 162 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	29.9% 41/137 • Number of events 66 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
General disorders Asthenia	20.1% 58/288 • Number of events 91 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	16.8% 23/137 • Number of events 34 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
General disorders Pyrexia	8.0% 23/288 • Number of events 26 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	9.5% 13/137 • Number of events 15 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
General disorders Oedema peripheral	7.6% 22/288 • Number of events 30 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	2.2% 3/137 • Number of events 4 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
General disorders Mucosal inflammation	5.9% 17/288 • Number of events 20 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	5.8% 8/137 • Number of events 10 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Blood and lymphatic system disorders Anaemia	14.2% 41/288 • Number of events 85 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	12.4% 17/137 • Number of events 35 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Blood and lymphatic system disorders Neutropenia	10.8% 31/288 • Number of events 75 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	24.1% 33/137 • Number of events 76 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Blood and lymphatic system disorders Thrombocytopenia	5.9% 17/288 • Number of events 23 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	5.1% 7/137 • Number of events 13 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Eye disorders Conjunctivitis	38.2% 110/288 • Number of events 218 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	2.2% 3/137 • Number of events 3 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Eye disorders Keratitis	38.2% 110/288 • Number of events 202 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	8.0% 11/137 • Number of events 11 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Eye disorders Dry eye	30.2% 87/288 • Number of events 117 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	10.2% 14/137 • Number of events 15 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Eye disorders Lacrimation increased	18.4% 53/288 • Number of events 74 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	1.5% 2/137 • Number of events 2 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Eye disorders Blepharitis	12.5% 36/288 • Number of events 53 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	1.5% 2/137 • Number of events 2 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Eye disorders Punctate keratitis	11.1% 32/288 • Number of events 45 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	2.2% 3/137 • Number of events 4 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Eye disorders Vision blurred	8.0% 23/288 • Number of events 30 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.73% 1/137 • Number of events 1 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Eye disorders Periorbital oedema	5.9% 17/288 • Number of events 29 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Gastrointestinal disorders Nausea	25.3% 73/288 • Number of events 103 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	31.4% 43/137 • Number of events 64 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Gastrointestinal disorders Diarrhoea	20.8% 60/288 • Number of events 82 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	35.8% 49/137 • Number of events 92 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Gastrointestinal disorders Constipation	18.1% 52/288 • Number of events 74 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	17.5% 24/137 • Number of events 28 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Gastrointestinal disorders Vomiting	12.5% 36/288 • Number of events 52 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	16.8% 23/137 • Number of events 37 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Gastrointestinal disorders Dry mouth	9.0% 26/288 • Number of events 28 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	4.4% 6/137 • Number of events 6 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Gastrointestinal disorders Stomatitis	8.3% 24/288 • Number of events 34 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	12.4% 17/137 • Number of events 17 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Gastrointestinal disorders Abdominal pain	6.6% 19/288 • Number of events 30 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	8.0% 11/137 • Number of events 17 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Gastrointestinal disorders Abdominal pain upper	6.2% 18/288 • Number of events 20 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	6.6% 9/137 • Number of events 12 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Gastrointestinal disorders Dyspepsia	4.5% 13/288 • Number of events 15 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	6.6% 9/137 • Number of events 11 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Respiratory, thoracic and mediastinal disorders Cough	16.7% 48/288 • Number of events 60 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	10.2% 14/137 • Number of events 17 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Respiratory, thoracic and mediastinal disorders Dyspnoea	14.6% 42/288 • Number of events 52 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	12.4% 17/137 • Number of events 27 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Respiratory, thoracic and mediastinal disorders Pneumonitis	6.6% 19/288 • Number of events 23 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	0.00% 0/137 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Respiratory, thoracic and mediastinal disorders Epistaxis	4.9% 14/288 • Number of events 17 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	5.8% 8/137 • Number of events 9 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.
Skin and subcutaneous tissue disorders Alopecia	21.5% 62/288 • Number of events 74 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.	11.7% 16/137 • Number of events 21 • Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.