Trial Outcomes & Findings for Compare Efficacy, Safety and Immunogenicity of HLX02 and Herceptin in Previously Untreated HER2 +Overexpressing Metastatic Breast Cancer (NCT NCT03084237)

Last Updated: 2024-05-17

Results Overview

calculated as the proportion of patients with a best response of complete response (CR) or partial response (PR) from first assessment until Week 24 according to RECIST 1.1 by central imaging review (CIR). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions,Complete Response (CR): Disappearance of all target lesions.Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to\<10 mm, Partial Response (PR): At least a 30% decrease in the sum ofdiameters of target lesions, taking as reference thebaseline sum diameters.Overall Response (OR) = CR + PR.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

652 participants

Primary outcome timeframe

From time of First treatment to week 24

Results posted on

2024-05-17

Participant Flow

Participant milestones

Participant milestones
Measure	HLX02+Docetaxel HLX02: 8 mg/kg administered intravenously over 90 minutes as a loading dose on Day 1, Cycle 1 then 6 mg/kg every 3 weeks for subsequent cycles for up to a maximum of 12 months. Docetaxel: 75 mg/m2 will be administered on Day 2, Cycle 1.then be given every 3 weeks on Day 1 of each subsequent cycle e for at least 8 cycles (until Week 24) and thereafter at the Investigator's discretion for up to a maximum of 12 months.	Herceptin®+Docetaxel Herceptin®: 8 mg/kg administered intravenously over 90 minutes as a loading dose on Day 1, Cycle 1 then 6 mg/kg every 3 weeks for subsequent cycles for up to a maximum of 12 months. Docetaxel: 75 mg/m2 will be administered on Day 2, Cycle 1.then be given every 3 weeks on Day 1 of each subsequent cycle for at least 8 cycles (until Week 24) and thereafter at the Investigator's discretion for up to a maximum of 12 months.
Overall Study STARTED	325	327
Overall Study COMPLETED	155	137
Overall Study NOT COMPLETED	170	190

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Compare Efficacy, Safety and Immunogenicity of HLX02 and Herceptin in Previously Untreated HER2 +Overexpressing Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	HLX02+Docetaxel n=325 Participants HLX02: 8 mg/kg administered intravenously over 90 minutes as a loading dose on Day 1, Cycle 1 then 6 mg/kg every 3 weeks for subsequent cycles for up to a maximum of 12 months. Docetaxel: 75 mg/m2 will be administered on Day 2, Cycle 1.then be given every 3 weeks on Day 1 of each subsequent cycle e for at least 8 cycles (until Week 24) and thereafter at the Investigator's discretion for up to a maximum of 12 months.	Herceptin®+Docetaxel n=327 Participants Herceptin®: 8 mg/kg administered intravenously over 90 minutes as a loading dose on Day 1, Cycle 1 then 6 mg/kg every 3 weeks for subsequent cycles for up to a maximum of 12 months. Docetaxel: 75 mg/m2 will be administered on Day 2, Cycle 1.then be given every 3 weeks on Day 1 of each subsequent cycle for at least 8 cycles (until Week 24) and thereafter at the Investigator's discretion for up to a maximum of 12 months.	Total n=652 Participants Total of all reporting groups
Age, Continuous	54 years n=5 Participants	53 years n=7 Participants	54 years n=5 Participants
Sex: Female, Male Female	325 Participants n=5 Participants	327 Participants n=7 Participants	652 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	249 Participants n=5 Participants	252 Participants n=7 Participants	501 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	76 Participants n=5 Participants	75 Participants n=7 Participants	151 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment China	238 participants n=5 Participants	237 participants n=7 Participants	475 participants n=5 Participants
Region of Enrollment Philippines	11 participants n=5 Participants	15 participants n=7 Participants	26 participants n=5 Participants
Region of Enrollment Ukraine	76 participants n=5 Participants	75 participants n=7 Participants	151 participants n=5 Participants
ECOG performance status 0(Fully active, able to carry on all pre-disease performance without restriction)	138 Participants n=5 Participants	139 Participants n=7 Participants	277 Participants n=5 Participants
ECOG performance status 1(Restricted in physically strenuous activity but ambulatory and able to carry out light work )	186 Participants n=5 Participants	186 Participants n=7 Participants	372 Participants n=5 Participants
ECOG performance status Missing	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: From time of First treatment to week 24

Population: ITT set

Outcome measures

Outcome measures
Measure	HLX02+Docetaxel n=325 Participants HLX02: 8 mg/kg administered intravenously over 90 minutes as a loading dose on Day 1, Cycle 1 then 6 mg/kg every 3 weeks for subsequent cycles for up to a maximum of 12 months. Docetaxel: 75 mg/m2 will be administered on Day 2, Cycle 1.then be given every 3 weeks on Day 1 of each subsequent cycle e for at least 8 cycles (until Week 24) and thereafter at the Investigator's discretion for up to a maximum of 12 months.	Herceptin®+Docetaxel n=327 Participants Herceptin®: 8 mg/kg administered intravenously over 90 minutes as a loading dose on Day 1, Cycle 1 then 6 mg/kg every 3 weeks for subsequent cycles for up to a maximum of 12 months. Docetaxel: 75 mg/m2 will be administered on Day 2, Cycle 1.then be given every 3 weeks on Day 1 of each subsequent cycle for at least 8 cycles (until Week 24) and thereafter at the Investigator's discretion for up to a maximum of 12 months.
ORR 24	71.1 percentage of responders	70.9 percentage of responders

SECONDARY outcome

Timeframe: Up to 2 years

The time from first documentation of CR or PR to the first documentation of progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1)，At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm or Unequivocal progression of existing non-target lesions (Note: the appearance of one or more new lesions is also considered progression).

Outcome measures

Outcome measures
Measure	HLX02+Docetaxel n=325 Participants HLX02: 8 mg/kg administered intravenously over 90 minutes as a loading dose on Day 1, Cycle 1 then 6 mg/kg every 3 weeks for subsequent cycles for up to a maximum of 12 months. Docetaxel: 75 mg/m2 will be administered on Day 2, Cycle 1.then be given every 3 weeks on Day 1 of each subsequent cycle e for at least 8 cycles (until Week 24) and thereafter at the Investigator's discretion for up to a maximum of 12 months.	Herceptin®+Docetaxel n=327 Participants Herceptin®: 8 mg/kg administered intravenously over 90 minutes as a loading dose on Day 1, Cycle 1 then 6 mg/kg every 3 weeks for subsequent cycles for up to a maximum of 12 months. Docetaxel: 75 mg/m2 will be administered on Day 2, Cycle 1.then be given every 3 weeks on Day 1 of each subsequent cycle for at least 8 cycles (until Week 24) and thereafter at the Investigator's discretion for up to a maximum of 12 months.
DoR	10.61 months Interval 10.22 to 11.66	10.25 months Interval 8.97 to 11.53

SECONDARY outcome

Timeframe: Up to 2 years

Population: ITT set

The percentage of patients who achieve CR, PR, or stable disease (SD) of at least 12 weeks

Outcome measures

Outcome measures
Measure	HLX02+Docetaxel n=325 Participants HLX02: 8 mg/kg administered intravenously over 90 minutes as a loading dose on Day 1, Cycle 1 then 6 mg/kg every 3 weeks for subsequent cycles for up to a maximum of 12 months. Docetaxel: 75 mg/m2 will be administered on Day 2, Cycle 1.then be given every 3 weeks on Day 1 of each subsequent cycle e for at least 8 cycles (until Week 24) and thereafter at the Investigator's discretion for up to a maximum of 12 months.	Herceptin®+Docetaxel n=327 Participants Herceptin®: 8 mg/kg administered intravenously over 90 minutes as a loading dose on Day 1, Cycle 1 then 6 mg/kg every 3 weeks for subsequent cycles for up to a maximum of 12 months. Docetaxel: 75 mg/m2 will be administered on Day 2, Cycle 1.then be given every 3 weeks on Day 1 of each subsequent cycle for at least 8 cycles (until Week 24) and thereafter at the Investigator's discretion for up to a maximum of 12 months.
DCR	84.3 percentage of participants Interval 80.4 to 88.3	87.2 percentage of participants Interval 83.5 to 90.8

SECONDARY outcome

Timeframe: Up to 2 years

Population: ITT set

The proportion of patients who achieve CR, PR, or durable SD (SD ≥24 weeks)

Outcome measures

Outcome measures
Measure	HLX02+Docetaxel n=325 Participants HLX02: 8 mg/kg administered intravenously over 90 minutes as a loading dose on Day 1, Cycle 1 then 6 mg/kg every 3 weeks for subsequent cycles for up to a maximum of 12 months. Docetaxel: 75 mg/m2 will be administered on Day 2, Cycle 1.then be given every 3 weeks on Day 1 of each subsequent cycle e for at least 8 cycles (until Week 24) and thereafter at the Investigator's discretion for up to a maximum of 12 months.	Herceptin®+Docetaxel n=327 Participants Herceptin®: 8 mg/kg administered intravenously over 90 minutes as a loading dose on Day 1, Cycle 1 then 6 mg/kg every 3 weeks for subsequent cycles for up to a maximum of 12 months. Docetaxel: 75 mg/m2 will be administered on Day 2, Cycle 1.then be given every 3 weeks on Day 1 of each subsequent cycle for at least 8 cycles (until Week 24) and thereafter at the Investigator's discretion for up to a maximum of 12 months.
CBR	80.9 Clinical Benefit Rate(%) Interval 76.7 to 85.2	80.4 Clinical Benefit Rate(%) Interval 76.1 to 84.7

SECONDARY outcome

Timeframe: From time of first treatment to 12 months

Population: ITT set

Median Progression Survival time assessed at 12 months.The probability of being alive without documented progression up to 12 months after randomization.

Outcome measures

Outcome measures
Measure	HLX02+Docetaxel n=325 Participants HLX02: 8 mg/kg administered intravenously over 90 minutes as a loading dose on Day 1, Cycle 1 then 6 mg/kg every 3 weeks for subsequent cycles for up to a maximum of 12 months. Docetaxel: 75 mg/m2 will be administered on Day 2, Cycle 1.then be given every 3 weeks on Day 1 of each subsequent cycle e for at least 8 cycles (until Week 24) and thereafter at the Investigator's discretion for up to a maximum of 12 months.	Herceptin®+Docetaxel n=327 Participants Herceptin®: 8 mg/kg administered intravenously over 90 minutes as a loading dose on Day 1, Cycle 1 then 6 mg/kg every 3 weeks for subsequent cycles for up to a maximum of 12 months. Docetaxel: 75 mg/m2 will be administered on Day 2, Cycle 1.then be given every 3 weeks on Day 1 of each subsequent cycle for at least 8 cycles (until Week 24) and thereafter at the Investigator's discretion for up to a maximum of 12 months.
Median PFS up to 12 Months	11.73 months Interval 11.53 to 12.06	10.55 months Interval 9.49 to 11.73

SECONDARY outcome

Timeframe: From time of first treatment to 36 months

Population: ITT set

the probability of being alive 12, 24, and 36 months after randomization

Outcome measures

Outcome measures
Measure	HLX02+Docetaxel n=325 Participants HLX02: 8 mg/kg administered intravenously over 90 minutes as a loading dose on Day 1, Cycle 1 then 6 mg/kg every 3 weeks for subsequent cycles for up to a maximum of 12 months. Docetaxel: 75 mg/m2 will be administered on Day 2, Cycle 1.then be given every 3 weeks on Day 1 of each subsequent cycle e for at least 8 cycles (until Week 24) and thereafter at the Investigator's discretion for up to a maximum of 12 months.	Herceptin®+Docetaxel n=327 Participants Herceptin®: 8 mg/kg administered intravenously over 90 minutes as a loading dose on Day 1, Cycle 1 then 6 mg/kg every 3 weeks for subsequent cycles for up to a maximum of 12 months. Docetaxel: 75 mg/m2 will be administered on Day 2, Cycle 1.then be given every 3 weeks on Day 1 of each subsequent cycle for at least 8 cycles (until Week 24) and thereafter at the Investigator's discretion for up to a maximum of 12 months.
Overall Survival at 12, 24, and 36 Months 12 months (%)	88.9 percentage of participants with OS	88.4 percentage of participants with OS
Overall Survival at 12, 24, and 36 Months 24 months (%)	71.4 percentage of participants with OS	67.6 percentage of participants with OS
Overall Survival at 12, 24, and 36 Months 36 months (%)	57.5 percentage of participants with OS	54.0 percentage of participants with OS

Adverse Events

HLX02+Docetaxel

Serious events: 78 serious events

Other events: 320 other events

Deaths: 128 deaths

Herceptin®+Docetaxel

Serious events: 81 serious events

Other events: 321 other events

Deaths: 142 deaths

Serious adverse events

Other adverse events

Additional Information

Head of Clinical Development

Shanghai Henlius Biotech

Phone: +86 021-33395800

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Serious adverse events
Measure	HLX02+Docetaxel n=325 participants at risk HLX02: 8 mg/kg administered intravenously over 90 minutes as a loading dose on Day 1, Cycle 1 then 6 mg/kg every 3 weeks for subsequent cycles for up to a maximum of 12 months. Docetaxel: 75 mg/m2 will be administered on Day 2, Cycle 1.then be given every 3 weeks on Day 1 of each subsequent cycle e for at least 8 cycles (until Week 24) and thereafter at the Investigator's discretion for up to a maximum of 12 months.	Herceptin®+Docetaxel n=327 participants at risk Herceptin®: 8 mg/kg administered intravenously over 90 minutes as a loading dose on Day 1, Cycle 1 then 6 mg/kg every 3 weeks for subsequent cycles for up to a maximum of 12 months. Docetaxel: 75 mg/m2 will be administered on Day 2, Cycle 1.then be given every 3 weeks on Day 1 of each subsequent cycle for at least 8 cycles (until Week 24) and thereafter at the Investigator's discretion for up to a maximum of 12 months.
Investigations Neutrophil count decreased	10.2% 33/325 • Number of events 58 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	7.3% 24/327 • Number of events 42 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Investigations White blood cell count decreased	4.9% 16/325 • Number of events 31 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	3.7% 12/327 • Number of events 20 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Investigations Aspartate aminotransferase increased	0.31% 1/325 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.31% 1/327 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Investigations Activated partial thromboplastin time prolonged	0.31% 1/325 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.31% 1/327 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Investigations Alanine aminotransferase increased	0.31% 1/325 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.31% 1/327 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Investigations Platelet count decreased	0.31% 1/325 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.31% 1/327 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Infections and infestations Pneumonia	2.5% 8/325 • Number of events 9 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	3.7% 12/327 • Number of events 13 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Infections and infestations Upper respiratory tract infection	0.92% 3/325 • Number of events 3 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.31% 1/327 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Infections and infestations Device related infection	0.31% 1/325 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.31% 1/327 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Infections and infestations Gastroenteritis	0.62% 2/325 • Number of events 2 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.00% 0/327 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Infections and infestations Urinary tract infection	0.31% 1/325 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.31% 1/327 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Infections and infestations Bacteraemia	0.31% 1/325 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.00% 0/327 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Infections and infestations Bronchitis	0.00% 0/325 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.31% 1/327 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Infections and infestations Cellulitis	0.31% 1/325 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.00% 0/327 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Infections and infestations Febrile infection	0.00% 0/325 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.31% 1/327 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Infections and infestations Hepatitis E	0.00% 0/325 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.31% 1/327 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Infections and infestations Herpes zoster	0.00% 0/325 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.31% 1/327 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Infections and infestations Infusion site infection	0.00% 0/325 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.31% 1/327 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Infections and infestations Neutropenic infection	0.00% 0/325 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.31% 1/327 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Infections and infestations Puncture site infection	0.00% 0/325 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.31% 1/327 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Infections and infestations Respiratory tract infection	0.31% 1/325 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.00% 0/327 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Infections and infestations Tonsillitis bacterial	0.31% 1/325 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.00% 0/327 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Blood and lymphatic system disorders Febrile neutropenia	3.7% 12/325 • Number of events 12 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	3.7% 12/327 • Number of events 13 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Blood and lymphatic system disorders Myelosuppression	1.5% 5/325 • Number of events 5 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	1.8% 6/327 • Number of events 6 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Blood and lymphatic system disorders Anaemia	0.31% 1/325 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.31% 1/327 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Blood and lymphatic system disorders Agranulocytosis	0.00% 0/325 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.31% 1/327 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.2% 4/325 • Number of events 4 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	1.5% 5/327 • Number of events 7 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.31% 1/325 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.92% 3/327 • Number of events 3 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.31% 1/325 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.31% 1/327 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Respiratory, thoracic and mediastinal disorders Bronchial haemorrhage	0.00% 0/325 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.31% 1/327 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.31% 1/325 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.00% 0/327 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.31% 1/325 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.00% 0/327 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Cardiac disorders Cardiac failure congestive	0.00% 0/325 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.61% 2/327 • Number of events 2 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Cardiac disorders Arrhythmia	0.00% 0/325 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.31% 1/327 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Cardiac disorders Atrial fibrillation	0.31% 1/325 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.00% 0/327 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Cardiac disorders Bradycardia	0.00% 0/325 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.31% 1/327 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Cardiac disorders Cardiovascular disorder	0.00% 0/325 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.31% 1/327 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Cardiac disorders Coronary artery disease	0.00% 0/325 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.31% 1/327 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Cardiac disorders Left ventricular dysfunction	0.31% 1/325 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.00% 0/327 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Cardiac disorders Pericardial effusion	0.31% 1/325 • Number of events 1 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	0.00% 0/327 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.

Other adverse events
Measure	HLX02+Docetaxel n=325 participants at risk HLX02: 8 mg/kg administered intravenously over 90 minutes as a loading dose on Day 1, Cycle 1 then 6 mg/kg every 3 weeks for subsequent cycles for up to a maximum of 12 months. Docetaxel: 75 mg/m2 will be administered on Day 2, Cycle 1.then be given every 3 weeks on Day 1 of each subsequent cycle e for at least 8 cycles (until Week 24) and thereafter at the Investigator's discretion for up to a maximum of 12 months.	Herceptin®+Docetaxel n=327 participants at risk Herceptin®: 8 mg/kg administered intravenously over 90 minutes as a loading dose on Day 1, Cycle 1 then 6 mg/kg every 3 weeks for subsequent cycles for up to a maximum of 12 months. Docetaxel: 75 mg/m2 will be administered on Day 2, Cycle 1.then be given every 3 weeks on Day 1 of each subsequent cycle for at least 8 cycles (until Week 24) and thereafter at the Investigator's discretion for up to a maximum of 12 months.
Investigations White blood cell count decreased	82.2% 267/325 • Number of events 1498 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	84.4% 276/327 • Number of events 1489 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Investigations Neutrophil count decreased	81.8% 266/325 • Number of events 1470 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	82.0% 268/327 • Number of events 1389 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Investigations Aspartate aminotransferase increased	25.2% 82/325 • Number of events 150 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	22.6% 74/327 • Number of events 128 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Investigations Alanine aminotransferase increased	23.1% 75/325 • Number of events 154 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	21.1% 69/327 • Number of events 111 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Investigations Weight increased	14.8% 48/325 • Number of events 60 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	15.3% 50/327 • Number of events 70 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Investigations Gamma-glutamyltransferase increased	11.4% 37/325 • Number of events 62 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	10.1% 33/327 • Number of events 45 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Investigations Platelet count decreased	9.5% 31/325 • Number of events 62 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	10.1% 33/327 • Number of events 56 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Investigations Blood alkaline phosphatase increased	8.0% 26/325 • Number of events 40 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	5.8% 19/327 • Number of events 26 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Investigations Weight decreased	5.5% 18/325 • Number of events 22 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	4.9% 16/327 • Number of events 16 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Skin and subcutaneous tissue disorders Alopecia	55.7% 181/325 • Number of events 182 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	53.2% 174/327 • Number of events 174 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Skin and subcutaneous tissue disorders Rash	9.8% 32/325 • Number of events 43 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	8.0% 26/327 • Number of events 43 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	5.2% 17/325 • Number of events 17 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	6.1% 20/327 • Number of events 21 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Skin and subcutaneous tissue disorders Nail discolouration	4.0% 13/325 • Number of events 13 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	5.5% 18/327 • Number of events 18 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Blood and lymphatic system disorders Anaemia	51.1% 166/325 • Number of events 455 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	57.2% 187/327 • Number of events 498 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Blood and lymphatic system disorders Myelosuppression	6.2% 20/325 • Number of events 53 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	7.3% 24/327 • Number of events 73 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Blood and lymphatic system disorders Febrile neutropenia	4.9% 16/325 • Number of events 18 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	6.1% 20/327 • Number of events 21 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
General disorders Oedema peripheral	19.4% 63/325 • Number of events 84 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	16.5% 54/327 • Number of events 69 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
General disorders Pyrexia	17.2% 56/325 • Number of events 74 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	15.0% 49/327 • Number of events 74 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
General disorders Asthenia	9.5% 31/325 • Number of events 51 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	12.8% 42/327 • Number of events 79 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
General disorders Fatigue	8.9% 29/325 • Number of events 53 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	9.2% 30/327 • Number of events 55 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Blood and lymphatic system disorders Malaise	9.2% 30/325 • Number of events 44 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	8.3% 27/327 • Number of events 58 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
General disorders Peripheral swelling	7.1% 23/325 • Number of events 30 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	6.4% 21/327 • Number of events 28 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
General disorders Face oedema	5.5% 18/325 • Number of events 18 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	4.0% 13/327 • Number of events 14 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Gastrointestinal disorders Diarrhoea	23.4% 76/325 • Number of events 163 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	22.9% 75/327 • Number of events 121 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Gastrointestinal disorders Nausea	15.1% 49/325 • Number of events 87 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	17.7% 58/327 • Number of events 94 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Gastrointestinal disorders Vomiting	9.8% 32/325 • Number of events 40 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	10.7% 35/327 • Number of events 48 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Gastrointestinal disorders Constipation	8.3% 27/325 • Number of events 48 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	7.3% 24/327 • Number of events 31 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Gastrointestinal disorders Stomatitis	5.5% 18/325 • Number of events 30 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	6.4% 21/327 • Number of events 56 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Gastrointestinal disorders Abdominal pain upper	3.7% 12/325 • Number of events 13 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	6.1% 20/327 • Number of events 28 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Metabolism and nutrition disorders Hypoalbuminaemia	12.3% 40/325 • Number of events 67 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	13.8% 45/327 • Number of events 89 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Metabolism and nutrition disorders Decreased appetite	10.8% 35/325 • Number of events 48 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	10.7% 35/327 • Number of events 40 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Metabolism and nutrition disorders Hypocalcaemia	8.9% 29/325 • Number of events 61 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	11.9% 39/327 • Number of events 69 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Metabolism and nutrition disorders Hypokalaemia	8.0% 26/325 • Number of events 43 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	9.2% 30/327 • Number of events 41 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Metabolism and nutrition disorders Hyperglycaemia	8.9% 29/325 • Number of events 48 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	5.5% 18/327 • Number of events 43 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Metabolism and nutrition disorders Hyperuricaemia	4.9% 16/325 • Number of events 23 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	8.9% 29/327 • Number of events 49 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Metabolism and nutrition disorders Hypertriglyceridaemia	3.7% 12/325 • Number of events 18 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	6.4% 21/327 • Number of events 33 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Infections and infestations Urinary tract infection	16.3% 53/325 • Number of events 78 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	18.7% 61/327 • Number of events 102 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Infections and infestations Upper respiratory tract infection	9.2% 30/325 • Number of events 42 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	10.7% 35/327 • Number of events 52 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Infections and infestations Pneumonia	5.2% 17/325 • Number of events 18 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	7.3% 24/327 • Number of events 26 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.
Respiratory, thoracic and mediastinal disorders Cough	10.2% 33/325 • Number of events 60 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.	9.8% 32/327 • Number of events 44 • Adverse events were assessed from the date the informed consent form is signed and no later than 30 (+2) days after the last dose, up to 14 months.All-Cause Mortality was assessed up to 36 months.