Trial Outcomes & Findings for A Study of Pertuzumab in Participants With Prostate Cancer (NCT NCT02480010)

Last Updated: 2015-09-18

Results Overview

Objective PSA response rate was determined according to Prostate Specific Antigen Working Group (PSAWG) guidelines. All participants achieving a drop in PSA of greater than or equal to (≥) 50 percent (%) from baseline (confirmed with a second value at least 4 weeks later) fulfilled the criteria of a PSA response. The confirmatory second value had to be at least 50% lower than baseline, but could be higher than the first drop in PSA. Confirmatory value could not be 50% higher compared to first drop in PSA. The date of response was the date the first 50% (or greater) decline was observed. Progressive disease (PD) was defined by a minimum of three consecutive serum PSA measurements obtained at least 7 days apart within the previous 3 months of start of trial, which documented progressively increasing values. Non-response was defined as neither PD nor Response.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

68 participants

Primary outcome timeframe

Screening, Every 3 weeks up to Week 24

Results posted on

2015-09-18

Participant Flow

Participant milestones

Participant milestones
Measure	Pertuzumab 420 Milligrams (mg) - Cohort A Participants in Cohort A received an intravenous (IV) loading dose of 840 mg pertuzumab on Day 1 of Cycle 1 (3-week cycles); from Cycle 2 onwards, participants received IV infusions of 420 mg on Day 1. Treatment continued for a maximum of 36 cycles or until study termination.	Pertuzumab 1050 mg - Cohort B Participants in Cohort B received 1050 mg pertuzumab as an IV infusion on Day 1 of each 3-week cycle for a maximum of 36 cycles or until study termination.
Overall Study STARTED	35	33
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	35	33

Reasons for withdrawal

Reasons for withdrawal
Measure	Pertuzumab 420 Milligrams (mg) - Cohort A Participants in Cohort A received an intravenous (IV) loading dose of 840 mg pertuzumab on Day 1 of Cycle 1 (3-week cycles); from Cycle 2 onwards, participants received IV infusions of 420 mg on Day 1. Treatment continued for a maximum of 36 cycles or until study termination.	Pertuzumab 1050 mg - Cohort B Participants in Cohort B received 1050 mg pertuzumab as an IV infusion on Day 1 of each 3-week cycle for a maximum of 36 cycles or until study termination.
Overall Study Adverse Event	3	1
Overall Study Death	1	0
Overall Study Insufficient therapeutic response	31	29
Overall Study Refused Treatment	0	3

Baseline Characteristics

A Study of Pertuzumab in Participants With Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pertuzumab 420 mg - Cohort A n=35 Participants Participants in Cohort A received an IV loading dose of 840 mg pertuzumab on Day 1 of Cycle 1 (3-week cycles); from Cycle 2 onwards, participants received IV infusions of 420 mg on Day 1. Treatment continued for a maximum of 36 cycles or until study termination.	Pertuzumab 1050 mg - Cohort B n=33 Participants Participants in Cohort B received 1050 mg pertuzumab as an IV infusion on Day 1 of each 3-week cycle for a maximum of 36 cycles or until study termination.	Total n=68 Participants Total of all reporting groups
Age, Continuous	70.8 years STANDARD_DEVIATION 7.45 • n=5 Participants	71.2 years STANDARD_DEVIATION 6.01 • n=7 Participants	71.0 years STANDARD_DEVIATION 6.74 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	35 Participants n=5 Participants	33 Participants n=7 Participants	68 Participants n=5 Participants

PRIMARY outcome

Timeframe: Screening, Every 3 weeks up to Week 24

Population: ITT population

Outcome measures

Outcome measures
Measure	Pertuzumab 420 mg - Cohort A n=35 Participants Participants in Cohort A received an IV loading dose of 840 mg pertuzumab on Day 1 of Cycle 1 (3-week cycles); from Cycle 2 onwards, participants received IV infusions of 420 mg on Day 1. Treatment continued for a maximum of 36 cycles or until study termination.	Pertuzumab 1050 mg - Cohort B n=33 Participants Participants in Cohort B received 1050 mg pertuzumab as an IV infusion on Day 1 of each 3-week cycle for a maximum of 36 cycles or until study termination.
Percentage of Participants With Confirmed, Objective Response, Non-Response or Progressive Disease by PSA Levels Within the First 24 Weeks of Treatment With Pertuzumab Objective response	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Confirmed, Objective Response, Non-Response or Progressive Disease by PSA Levels Within the First 24 Weeks of Treatment With Pertuzumab Non-response	34.3 percentage of participants	30.3 percentage of participants
Percentage of Participants With Confirmed, Objective Response, Non-Response or Progressive Disease by PSA Levels Within the First 24 Weeks of Treatment With Pertuzumab PD	65.7 percentage of participants	66.7 percentage of participants
Percentage of Participants With Confirmed, Objective Response, Non-Response or Progressive Disease by PSA Levels Within the First 24 Weeks of Treatment With Pertuzumab Missing	0.0 percentage of participants	3.0 percentage of participants

SECONDARY outcome

Timeframe: Screening, Every 3 weeks up to a maximum of 18 months

Population: ITT population

Time to disease progression was defined by time in weeks from start of therapy to the onset of the earliest of the following events. 1) PSA progression as defined by the PSAWG, 2) Evidence of disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria 3) One bone scan at least 6 months subsequent to baseline demonstrating 2 or more new skeletal lesions and 4) An event due to metastatic prostate cancer requiring intervention.

Outcome measures

Outcome measures
Measure	Pertuzumab 420 mg - Cohort A n=34 Participants Participants in Cohort A received an IV loading dose of 840 mg pertuzumab on Day 1 of Cycle 1 (3-week cycles); from Cycle 2 onwards, participants received IV infusions of 420 mg on Day 1. Treatment continued for a maximum of 36 cycles or until study termination.	Pertuzumab 1050 mg - Cohort B n=30 Participants Participants in Cohort B received 1050 mg pertuzumab as an IV infusion on Day 1 of each 3-week cycle for a maximum of 36 cycles or until study termination.
Time to Disease Progression	5.6 weeks Interval 2.8 to 20.9	6.1 weeks Interval 2.7 to 17.9

SECONDARY outcome

Timeframe: Screening, Weeks 6, 12, 24, 36 and 48

Population: This analysis was only planned if either cohort went to full recruitment. Analysis of this outcome in a small number of participants would have high variability and also unlikely to be relevant if safety and tolerability criteria were not met.

Overall objective response by RECIST criteria (CR or PR) was to be defined for participants who had measurable disease at baseline or developed new lesions post-baseline. The longest diameter only for all target lesions was measured and the following responses recorded: CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of the longest diameter as compared to the baseline sum longest diameter.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Screening, Every 3 weeks for a maximum of 18 months

Time to response was the date of the first documentation of PSA response.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Every 3 weeks for a maximum of 18 months

Duration of PSA Response was measured from first 50% decline in PSA compared to baseline until the time at which there was an increase of ≥50% from the PSA nadir, provided the absolute increase was at least 5 nanograms per milliliter (ng/ml). The increase must have been confirmed by a second consecutive measurement that was at least 50% above the nadir.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Weeks 6, 12, 24, 36 and 48

For participants with measurable disease, duration of response was defined as first documentation of tumor response, either a PR or CR, to first documentation of PD or death. Participants who never progressed or died were censored at their last tumor measurement.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Screening, Weeks 3, 6, 9 and 12

Population: ITT population

Disease progression was defined as the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Non-progression included participants who had responded plus those who had not responded and not progressed within the first 3 cycles.

Outcome measures

Outcome measures
Measure	Pertuzumab 420 mg - Cohort A n=35 Participants Participants in Cohort A received an IV loading dose of 840 mg pertuzumab on Day 1 of Cycle 1 (3-week cycles); from Cycle 2 onwards, participants received IV infusions of 420 mg on Day 1. Treatment continued for a maximum of 36 cycles or until study termination.	Pertuzumab 1050 mg - Cohort B n=33 Participants Participants in Cohort B received 1050 mg pertuzumab as an IV infusion on Day 1 of each 3-week cycle for a maximum of 36 cycles or until study termination.
Percentage of Participants Without Progression	20.0 percentage of participants	18.2 percentage of participants

SECONDARY outcome

Timeframe: Every 3 weeks up to a maximum of 18 weeks

Time to disease progression was defined by time in weeks from start of therapy to the onset of the earliest of the following events: 1) Opioid therapy, 2) Radiation therapy, 3) Glucocorticoid therapy, 4) Radionuclide therapy or 5) Chemotherapy.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Screening, Every 3 weeks up to a maximum of 18 months

Population: Data were not analyzed due to early termination of the study.

Overall survival was defined as the interval of time in weeks between start of treatment and day of death. Participants who did not die while being followed were censored at the last time that they were known to be alive.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Every 3 weeks up to a maximum of 18 weeks

Population: ITT Population

Time to Treatment Failure was time to the first documentation of progressive disease, day of death while on study (or 30 days after withdrawing from the trial) or day of early discontinuation due to toxicity (adverse events or abnormal laboratory value), refusal of treatment/refusing to cooperate/withdrawing consent, insufficient therapeutic response, or failure to return, whichever is earliest, after the start of treatment. Participants who did not experience any of the above events while on study were censored on the day of their last PSA or tumor measurement, whichever was later.

Outcome measures

Outcome measures
Measure	Pertuzumab 420 mg - Cohort A n=35 Participants Participants in Cohort A received an IV loading dose of 840 mg pertuzumab on Day 1 of Cycle 1 (3-week cycles); from Cycle 2 onwards, participants received IV infusions of 420 mg on Day 1. Treatment continued for a maximum of 36 cycles or until study termination.	Pertuzumab 1050 mg - Cohort B n=33 Participants Participants in Cohort B received 1050 mg pertuzumab as an IV infusion on Day 1 of each 3-week cycle for a maximum of 36 cycles or until study termination.
Time to Treatment Failure	6.1 days Interval 2.8 to 20.9	6.1 days Interval 2.7 to 17.9

SECONDARY outcome

Timeframe: Screening, Weeks 6, 12, 24, 36 and 48

Population: Data were not analyzed to due to early termination of the study.

Bone alkaline phosphatase (BAP) is the bone-specific isoform of alkaline phosphatase. Serum Bone alkaline phosphatase is used to measure osteoporosis and is measured as units per liter (u/L).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Screening, Weeks 6, 12, 24, 36 and 48

Population: Data were not analyzed to due to early termination of the study.

In bone physiology, the N-terminal telopeptide (or more formally, amino-terminal collagen crosslinks, and known by the acronym NTX) is a telopeptide that can be used as a biomarker to measure the rate of bone turnover. NTX can be measured in the urine (uNTX) or serum (serum NTX).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cycles 1 and 2 (Weeks 3 and 6): predose (immediately prior to infusion) and within 15 minutes following the end of the infusion on Day 1, Day 8, and Day 15. Cycle 3 (Week 9) and beyond: predose and within 15 minutes following end of infusion on Day 1

Population: ITT Population; Only participants with non-missing data were included in the analysis.

The area under the plot of plasma concentration of drug against time after drug administration is defined as the area under the curve (AUC). The AUC0-infinity is calculated from time 0 (prior to administration of medication) to infinity (the time of complete elimination of the drug). The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. AUC is measured as micrograms times days per milliliter (µg\*day/mL)

Outcome measures

Outcome measures
Measure	Pertuzumab 420 mg - Cohort A n=35 Participants Participants in Cohort A received an IV loading dose of 840 mg pertuzumab on Day 1 of Cycle 1 (3-week cycles); from Cycle 2 onwards, participants received IV infusions of 420 mg on Day 1. Treatment continued for a maximum of 36 cycles or until study termination.	Pertuzumab 1050 mg - Cohort B n=31 Participants Participants in Cohort B received 1050 mg pertuzumab as an IV infusion on Day 1 of each 3-week cycle for a maximum of 36 cycles or until study termination.
Area Under the Concentration Curve Extrapolated to Infinity (AUC0-Inf) of Pertuzumab	3488 µg*day/mL Geometric Coefficient of Variation 44	5097 µg*day/mL Geometric Coefficient of Variation 71

SECONDARY outcome

Population: ITT Population

The AUC0-last is calculated from time 0 (prior to administration of medication) to last measured data point. The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption.

Outcome measures

Outcome measures
Measure	Pertuzumab 420 mg - Cohort A n=35 Participants Participants in Cohort A received an IV loading dose of 840 mg pertuzumab on Day 1 of Cycle 1 (3-week cycles); from Cycle 2 onwards, participants received IV infusions of 420 mg on Day 1. Treatment continued for a maximum of 36 cycles or until study termination.	Pertuzumab 1050 mg - Cohort B n=33 Participants Participants in Cohort B received 1050 mg pertuzumab as an IV infusion on Day 1 of each 3-week cycle for a maximum of 36 cycles or until study termination.
AUC to Last Measurable Concentration (AUC0-last) of Pertuzumab	2305 µg*day/mL Geometric Coefficient of Variation 22	2626 µg*day/mL Geometric Coefficient of Variation 28

SECONDARY outcome

Population: ITT Population

Cmax is the maximum (or peak) plasma concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered and prior to the administration of a second dose. Cmax is measured as micrograms per mL (μg/mL).

Outcome measures

Outcome measures
Measure	Pertuzumab 420 mg - Cohort A n=35 Participants Participants in Cohort A received an IV loading dose of 840 mg pertuzumab on Day 1 of Cycle 1 (3-week cycles); from Cycle 2 onwards, participants received IV infusions of 420 mg on Day 1. Treatment continued for a maximum of 36 cycles or until study termination.	Pertuzumab 1050 mg - Cohort B n=33 Participants Participants in Cohort B received 1050 mg pertuzumab as an IV infusion on Day 1 of each 3-week cycle for a maximum of 36 cycles or until study termination.
Maximum Plasma Concentration of Pertuzumab	255 μg/mL Geometric Coefficient of Variation 23	294 μg/mL Geometric Coefficient of Variation 24

SECONDARY outcome

Timeframe: Cycles 1 and 2 (Weeks 3 and 6): predose (immediately prior to infusion) and within 15 minutes following the end of the infusion on Day 1 and on Days 8 and 15, Cycle 3 (Week 9) and beyond: predose and within 15 minutes following end of infusion on Day 1

Population: ITT Population

Cmax refers to the maximum (or peak) plasma concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered and prior to the administration of a second dose. tmax is the time at which the Cmax is observed.

Outcome measures

Outcome measures
Measure	Pertuzumab 420 mg - Cohort A n=35 Participants Participants in Cohort A received an IV loading dose of 840 mg pertuzumab on Day 1 of Cycle 1 (3-week cycles); from Cycle 2 onwards, participants received IV infusions of 420 mg on Day 1. Treatment continued for a maximum of 36 cycles or until study termination.	Pertuzumab 1050 mg - Cohort B n=33 Participants Participants in Cohort B received 1050 mg pertuzumab as an IV infusion on Day 1 of each 3-week cycle for a maximum of 36 cycles or until study termination.
Time to Maximum Plasma Concentration (Tmax) of Pertuzumab	0.073 days Geometric Coefficient of Variation 11	0.074 days Geometric Coefficient of Variation 6

SECONDARY outcome

Population: ITT Population; Only participants with non-missing data were included in the analysis.

t1/2 is the time in days required for the concentration of the drug to reach half of its original value

Outcome measures

Outcome measures
Measure	Pertuzumab 420 mg - Cohort A n=35 Participants Participants in Cohort A received an IV loading dose of 840 mg pertuzumab on Day 1 of Cycle 1 (3-week cycles); from Cycle 2 onwards, participants received IV infusions of 420 mg on Day 1. Treatment continued for a maximum of 36 cycles or until study termination.	Pertuzumab 1050 mg - Cohort B n=31 Participants Participants in Cohort B received 1050 mg pertuzumab as an IV infusion on Day 1 of each 3-week cycle for a maximum of 36 cycles or until study termination.
Terminal Elimination Half-Life (t1/2) of Pertuzumab	13.7 days Geometric Coefficient of Variation 39	19.3 days Geometric Coefficient of Variation 69

SECONDARY outcome

Population: ITT Population; Only participants with non-missing data were included in the analysis.

Clearance (expressed as volume/time) describes the removal of drug from a volume of plasma in a given unit of time (drug loss from the body). It is measured as milliliters per day (mL/day).

Outcome measures

Outcome measures
Measure	Pertuzumab 420 mg - Cohort A n=35 Participants Participants in Cohort A received an IV loading dose of 840 mg pertuzumab on Day 1 of Cycle 1 (3-week cycles); from Cycle 2 onwards, participants received IV infusions of 420 mg on Day 1. Treatment continued for a maximum of 36 cycles or until study termination.	Pertuzumab 1050 mg - Cohort B n=31 Participants Participants in Cohort B received 1050 mg pertuzumab as an IV infusion on Day 1 of each 3-week cycle for a maximum of 36 cycles or until study termination.
Serum Clearance of Pertuzumab	270 mL/day Geometric Coefficient of Variation 29	253 mL/day Geometric Coefficient of Variation 35

SECONDARY outcome

Population: ITT Population; Only participants with non-missing data were included in the analysis.

The volume of distribution at steady state (Vss), also known as apparent volume of distribution, is a pharmacological, theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it currently is in blood plasma.

Outcome measures

Outcome measures
Measure	Pertuzumab 420 mg - Cohort A n=35 Participants Participants in Cohort A received an IV loading dose of 840 mg pertuzumab on Day 1 of Cycle 1 (3-week cycles); from Cycle 2 onwards, participants received IV infusions of 420 mg on Day 1. Treatment continued for a maximum of 36 cycles or until study termination.	Pertuzumab 1050 mg - Cohort B n=31 Participants Participants in Cohort B received 1050 mg pertuzumab as an IV infusion on Day 1 of each 3-week cycle for a maximum of 36 cycles or until study termination.
Volume of Distribution at Steady State of Pertuzumab	4452 mL Geometric Coefficient of Variation 26	5227 mL Geometric Coefficient of Variation 24

SECONDARY outcome

Population: ITT Population; Only participants with non-missing data were included in the analysis.

MRT is the average time that pertuzumab is present in the systemic circulation and is measured in days.

Outcome measures

Outcome measures
Measure	Pertuzumab 420 mg - Cohort A n=35 Participants Participants in Cohort A received an IV loading dose of 840 mg pertuzumab on Day 1 of Cycle 1 (3-week cycles); from Cycle 2 onwards, participants received IV infusions of 420 mg on Day 1. Treatment continued for a maximum of 36 cycles or until study termination.	Pertuzumab 1050 mg - Cohort B n=31 Participants Participants in Cohort B received 1050 mg pertuzumab as an IV infusion on Day 1 of each 3-week cycle for a maximum of 36 cycles or until study termination.
Mean Residence Time (MRT) of Pertuzumab	18.1 days Geometric Coefficient of Variation 42	25.7 days Geometric Coefficient of Variation 77

Adverse Events

Pertuzumab 420 mg - Cohort A

Serious events: 9 serious events

Other events: 28 other events

Deaths: 0 deaths

Pertuzumab 1050 mg - Cohort B

Serious events: 6 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER

Measure	Pertuzumab 420 mg - Cohort A n=35 participants at risk Participants in Cohort A received an IV loading dose of 840 mg pertuzumab on Day 1 of Cycle 1 (3-week cycles); from Cycle 2 onwards, participants received IV infusions of 420 mg on Day 1. Treatment continued for a maximum of 36 cycles or until study termination.	Pertuzumab 1050 mg - Cohort B n=33 participants at risk Participants in Cohort B received 1050 mg pertuzumab as an IV infusion on Day 1 of each 3-week cycle for a maximum of 36 cycles or until study termination.
Renal and urinary disorders Urinary retention	8.6% 3/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	0.00% 0/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Renal and urinary disorders Renal Failure	2.9% 1/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	0.00% 0/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Blood and lymphatic system disorders Anemia	2.9% 1/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	0.00% 0/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Blood and lymphatic system disorders Hematolytic Uremic Syndrome	2.9% 1/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	0.00% 0/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Cardiac disorders Atrial Fibrillation	2.9% 1/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	0.00% 0/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
General disorders Oedema Peripheral	2.9% 1/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	0.00% 0/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Investigations Electrocardiogram wave Inversions	2.9% 1/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	0.00% 0/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Metabolism and nutrition disorders Hypoglycemia	2.9% 1/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	0.00% 0/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Nervous system disorders Cauda Equina Syndrome	2.9% 1/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	0.00% 0/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.9% 1/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	0.00% 0/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Gastrointestinal disorders Abdominal Pain	0.00% 0/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	3.0% 1/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Gastrointestinal disorders Hemastemisis	0.00% 0/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	3.0% 1/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Gastrointestinal disorders Ileus Paralytic	0.00% 0/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	3.0% 1/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Gastrointestinal disorders Nausea	0.00% 0/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	3.0% 1/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Infections and infestations Central Line Infection	0.00% 0/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	3.0% 1/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Infections and infestations Sepsis	0.00% 0/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	3.0% 1/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic Pain	0.00% 0/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	3.0% 1/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Vascular disorders Deep Vein Thrombosis	0.00% 0/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	3.0% 1/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.

Measure	Pertuzumab 420 mg - Cohort A n=35 participants at risk Participants in Cohort A received an IV loading dose of 840 mg pertuzumab on Day 1 of Cycle 1 (3-week cycles); from Cycle 2 onwards, participants received IV infusions of 420 mg on Day 1. Treatment continued for a maximum of 36 cycles or until study termination.	Pertuzumab 1050 mg - Cohort B n=33 participants at risk Participants in Cohort B received 1050 mg pertuzumab as an IV infusion on Day 1 of each 3-week cycle for a maximum of 36 cycles or until study termination.
Gastrointestinal disorders Diarrhoea	51.4% 18/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	51.5% 17/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Gastrointestinal disorders Nausea	31.4% 11/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	6.1% 2/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Gastrointestinal disorders Constipation	8.6% 3/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	3.0% 1/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Gastrointestinal disorders Flatulence	8.6% 3/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	3.0% 1/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Gastrointestinal disorders Vomiting	11.4% 4/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	0.00% 0/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Gastrointestinal disorders Abdominal Pain Upper	5.7% 2/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	3.0% 1/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
General disorders Fatigue	42.9% 15/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	12.1% 4/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
General disorders Asthenia	8.6% 3/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	6.1% 2/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
General disorders Pyrexia	8.6% 3/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	3.0% 1/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
General disorders Influenza Like Illnes	5.7% 2/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	0.00% 0/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	8.6% 3/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	12.1% 4/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Respiratory, thoracic and mediastinal disorders Cough	11.4% 4/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	0.00% 0/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Respiratory, thoracic and mediastinal disorders Epistaxis	5.7% 2/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	3.0% 1/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Respiratory, thoracic and mediastinal disorders Dysponea	5.7% 2/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	0.00% 0/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Respiratory, thoracic and mediastinal disorders Pharyngnolaryngeal Pain	5.7% 2/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	0.00% 0/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Respiratory, thoracic and mediastinal disorders Rhinitis Allergic	5.7% 2/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	0.00% 0/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Musculoskeletal and connective tissue disorders Backpain	14.3% 5/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	6.1% 2/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Musculoskeletal and connective tissue disorders Pain in Extremity	8.6% 3/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	12.1% 4/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Musculoskeletal and connective tissue disorders Arhralgia	5.7% 2/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	6.1% 2/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Musculoskeletal and connective tissue disorders Bone Pain	5.7% 2/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	0.00% 0/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Musculoskeletal and connective tissue disorders Buttock Pain	5.7% 2/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	0.00% 0/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Nervous system disorders Dysguesia	11.4% 4/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	3.0% 1/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Nervous system disorders Headache	8.6% 3/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	3.0% 1/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Nervous system disorders Hypoaesthesia	5.7% 2/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	6.1% 2/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Nervous system disorders Paraesthesia	5.7% 2/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	3.0% 1/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Infections and infestations Rhinitis	8.6% 3/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	6.1% 2/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Infections and infestations Nasopharyngitis	8.6% 3/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	0.00% 0/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Infections and infestations Urinary Tract Infection	5.7% 2/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	3.0% 1/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Metabolism and nutrition disorders Anorexia	22.9% 8/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	6.1% 2/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Skin and subcutaneous tissue disorders Rash	8.6% 3/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	12.1% 4/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Skin and subcutaneous tissue disorders Onychorrhexis	5.7% 2/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	0.00% 0/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Renal and urinary disorders Haematuria	11.4% 4/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	0.00% 0/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Renal and urinary disorders Dysuria	5.7% 2/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	0.00% 0/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Renal and urinary disorders Urinary Retention	5.7% 2/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	0.00% 0/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Blood and lymphatic system disorders Anaemia	11.4% 4/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	0.00% 0/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.
Investigations Ejection Fraction Decreased	5.7% 2/35 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.	3.0% 1/33 • Adverse Events were recorded from the date of Screening until 7 weeks after the last infusion of study treatment.