Trial Outcomes & Findings for A Multiple-Dose Study of RhuMab 2C4 and Docetaxel in the Treatment of Advanced Solid Tumors (NCT NCT02490475)

NCT ID: NCT02490475

Last Updated: 2017-05-17

Results Overview

A prior dose level was defined as an MTD if at a certain dose level, there were greater than or equal to (≥) 2 out of 6 participants who had Dose Limiting Toxicities (DLTs). If there were no DLTs or DLTs were seen in less than (\<) 2 participants in the highest dose level, that was considered as MTD. Participants received escalating doses of docetaxel and pertuzumab until DLTs were observed. DLTs were defined as any of the following: 1) Any non-hematological toxicity ≥ Grade 3 according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 except for fever, chills and flu-like symptoms, in spite of adequate toxicity management, 2) Grade 4 neutropenia lasting greater than (\>) 7 days, 3) Febrile neutropenia, 4) Thrombocytopenia Grade 4 or any thrombocytopenia requiring platelet transfusion or 5) Any subjectively intolerable toxicity felt by the investigator to be related to either one of the compounds.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 19 participants
• Primary outcome timeframe: Cycle 1 Up to Day 15
• Results posted on: 2017-05-17

Participant Flow

Participant milestones

Measure	Docetaxel 60 Plus (+) Pertuzumab 1050 Participants received 60 milligrams per square meter (mg/m\^2) docetaxel and 1050 mg of pertuzumab as an intravenous (IV) infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 docetaxel was administered on Day 1 and pertuzumab was administered at least 24 hours (h) apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 75 + Pertuzumab 1050 Participants received 75 mg/m\^2 docetaxel and 1050 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 75 + Pertuzumab 420 Participants received 75 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 100 + Pertuzumab 420 Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.
Period 1: First 6 Cycles STARTED	6	2	6	5
Period 1: First 6 Cycles COMPLETED	0	0	0	0
Period 1: First 6 Cycles NOT COMPLETED	6	2	6	5
Period 2: Extension Phase STARTED	1	0	3	1
Period 2: Extension Phase COMPLETED	0	0	0	0
Period 2: Extension Phase NOT COMPLETED	1	0	3	1

Reasons for withdrawal

Measure	Docetaxel 60 Plus (+) Pertuzumab 1050 Participants received 60 milligrams per square meter (mg/m\^2) docetaxel and 1050 mg of pertuzumab as an intravenous (IV) infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 docetaxel was administered on Day 1 and pertuzumab was administered at least 24 hours (h) apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 75 + Pertuzumab 1050 Participants received 75 mg/m\^2 docetaxel and 1050 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 75 + Pertuzumab 420 Participants received 75 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 100 + Pertuzumab 420 Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.
Period 1: First 6 Cycles Adverse Event	2	1	0	1
Period 1: First 6 Cycles Insufficient Therapeutic Response	2	0	2	2
Period 1: First 6 Cycles Refused Treatment	1	0	0	0
Period 1: First 6 Cycles Completed 6 Cycles of Therapy	1	1	4	2
Period 2: Extension Phase Insufficient Therapeutic Response	1	0	2	0
Period 2: Extension Phase Refused Treatment	0	0	0	1
Period 2: Extension Phase Adverse Event	0	0	1	0

Baseline Characteristics

A Multiple-Dose Study of RhuMab 2C4 and Docetaxel in the Treatment of Advanced Solid Tumors

Baseline characteristics by cohort

Measure	Docetaxel 60 Plus (+) Pertuzumab 1050 n=6 Participants Participants received 60 mg/m\^2 docetaxel and 1050 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 75 + Pertuzumab 1050 n=2 Participants Participants received 75 mg/m\^2 docetaxel and 1050 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 75 + Pertuzumab 420 n=6 Participants Participants received 75 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 100 + Pertuzumab 420 n=5 Participants Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Total n=19 Participants Total of all reporting groups
Age, Continuous	58.2 years STANDARD_DEVIATION 5.38 • n=93 Participants	62.5 years STANDARD_DEVIATION 9.19 • n=4 Participants	59.5 years STANDARD_DEVIATION 6.06 • n=27 Participants	45.0 years STANDARD_DEVIATION 20.21 • n=483 Participants	55.6 years STANDARD_DEVIATION 12.55 • n=36 Participants
Sex: Female, Male Female	2 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	3 Participants n=483 Participants	6 Participants n=36 Participants
Sex: Female, Male Male	4 Participants n=93 Participants	2 Participants n=4 Participants	5 Participants n=27 Participants	2 Participants n=483 Participants	13 Participants n=36 Participants

PRIMARY outcome

Timeframe: Cycle 1 Up to Day 15

Population: Safety Population: included all participants who received any amount of study medication and who had at least one post-baseline safety follow-up.

A prior dose level was defined as an MTD if at a certain dose level, there were greater than or equal to (≥) 2 out of 6 participants who had Dose Limiting Toxicities (DLTs). If there were no DLTs or DLTs were seen in less than (<) 2 participants in the highest dose level, that was considered as MTD. Participants received escalating doses of docetaxel and pertuzumab until DLTs were observed. DLTs were defined as any of the following: 1) Any non-hematological toxicity ≥ Grade 3 according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 except for fever, chills and flu-like symptoms, in spite of adequate toxicity management, 2) Grade 4 neutropenia lasting greater than (>) 7 days, 3) Febrile neutropenia, 4) Thrombocytopenia Grade 4 or any thrombocytopenia requiring platelet transfusion or 5) Any subjectively intolerable toxicity felt by the investigator to be related to either one of the compounds.

Outcome measures

Measure	Docetaxel 75 + Pertuzumab 420 Participants received 75 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 100 Alone Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Entire Study Population n=19 Participants Participants received escalating dose levels of combination of docetaxel and pertuzumab. Participants received docetaxel 60 mg/m\^2 and pertuzumab 1050 mg at dose level 1, docetaxel 75 mg/m\^2 and pertuzumab 1050 mg at dose level 2, docetaxel 75 mg/m\^2 and pertuzumab 420 mg at dose level 3 or 100 mg/m\^2 and pertuzumab 420 mg at dose level 4 until DLTs were observed.	Pertuzumab 840 Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Pertuzumab 420 Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Docetaxel 100 + Pertuzumab 420 Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.
Maximum Tolerated Dose (MTD) of Docetaxel in Combination of Pertuzumab	—	—	75.0 mg/m^2	—	—	—

SECONDARY outcome

Timeframe: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22

Population: ITT population; Participants in any cohort infused with the specified dose of pertuzumab were included in analysis. number (n) equals (=) number of participants analyzed at the specified timepoint for each arm, respectively.

The biological half-life or terminal half-life of pertuzumab is the time in days it takes for it to lose half of its pharmacologic activity.

Outcome measures

Measure	Docetaxel 75 + Pertuzumab 420 Participants received 75 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 100 Alone Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Entire Study Population n=8 Participants Participants received escalating dose levels of combination of docetaxel and pertuzumab. Participants received docetaxel 60 mg/m\^2 and pertuzumab 1050 mg at dose level 1, docetaxel 75 mg/m\^2 and pertuzumab 1050 mg at dose level 2, docetaxel 75 mg/m\^2 and pertuzumab 420 mg at dose level 3 or 100 mg/m\^2 and pertuzumab 420 mg at dose level 4 until DLTs were observed.	Pertuzumab 840 n=11 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Pertuzumab 420 n=10 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Docetaxel 100 + Pertuzumab 420 Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.
Plasma Decay Half Life (t1/2) for Pertuzumab in Combination With Docetaxel Cycle 1 (n=8,11,0)	—	—	12.65 days Interval 7.8 to 19.59	11.65 days Interval 6.95 to 25.96	NA days Participants received 420 mg of pertuzumab only in Cycle 2 per dose regimen.	—
Plasma Decay Half Life (t1/2) for Pertuzumab in Combination With Docetaxel Cycle 2 (n=7,0,10)	—	—	19.02 days Interval 9.02 to 49.63	NA days Participants received 840 mg of pertuzumab only in Cycle 1 per dose regimen.	18.46 days Interval 8.85 to 42.0	—

SECONDARY outcome

Timeframe: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22

Population: ITT population; Participants in any cohort infused with the specified dose of pertuzumab were included in analysis. n = number of participants analyzed at the specified timepoint for each arm, respectively.

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

Outcome measures

Measure	Docetaxel 75 + Pertuzumab 420 Participants received 75 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 100 Alone Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Entire Study Population n=8 Participants Participants received escalating dose levels of combination of docetaxel and pertuzumab. Participants received docetaxel 60 mg/m\^2 and pertuzumab 1050 mg at dose level 1, docetaxel 75 mg/m\^2 and pertuzumab 1050 mg at dose level 2, docetaxel 75 mg/m\^2 and pertuzumab 420 mg at dose level 3 or 100 mg/m\^2 and pertuzumab 420 mg at dose level 4 until DLTs were observed.	Pertuzumab 840 n=11 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Pertuzumab 420 n=10 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Docetaxel 100 + Pertuzumab 420 Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.
Maximum Observed Plasma Concentration (Cmax) for Pertuzumab in Combination With Docetaxel Cycle 1 (n=8,11,0)	—	—	301.0 μg/mL Standard Deviation 93.0	255.0 μg/mL Standard Deviation 84.0	NA μg/mL Standard Deviation NA Participants received 420 mg of pertuzumab only in Cycle 2 per dose regimen.	—
Maximum Observed Plasma Concentration (Cmax) for Pertuzumab in Combination With Docetaxel Cycle 2 (n=7,0,10)	—	—	368.0 μg/mL Standard Deviation 79.0	NA μg/mL Standard Deviation NA Participants received 840 mg of pertuzumab only in Cycle 1 per dose regimen.	150.0 μg/mL Standard Deviation 43.0	—

SECONDARY outcome

Timeframe: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22

Population: ITT population; Participants in any cohort infused with the specified dose of pertuzumab were included in analysis. n = number of participants analyzed at the specified timepoint for each arm, respectively.

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-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. AUC is measured as micrograms times days per milliliter (μg*day/mL).

Outcome measures

Measure	Docetaxel 75 + Pertuzumab 420 Participants received 75 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 100 Alone Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Entire Study Population n=8 Participants Participants received escalating dose levels of combination of docetaxel and pertuzumab. Participants received docetaxel 60 mg/m\^2 and pertuzumab 1050 mg at dose level 1, docetaxel 75 mg/m\^2 and pertuzumab 1050 mg at dose level 2, docetaxel 75 mg/m\^2 and pertuzumab 420 mg at dose level 3 or 100 mg/m\^2 and pertuzumab 420 mg at dose level 4 until DLTs were observed.	Pertuzumab 840 n=11 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Pertuzumab 420 n=10 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Docetaxel 100 + Pertuzumab 420 Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.
Area Under the Concentration Curve From Time Zero to the Last Visit (AUC [0-last]) for Pertuzumab in Combination With Docetaxel Cycle 1 (n=8,11,0)	—	—	2390 μg*day/mL Standard Deviation 584	1749 μg*day/mL Standard Deviation 543	NA μg*day/mL Standard Deviation NA Participants received 420 mg of pertuzumab only in Cycle 2 per dose regimen.	—
Area Under the Concentration Curve From Time Zero to the Last Visit (AUC [0-last]) for Pertuzumab in Combination With Docetaxel Cycle 2 (n=7,0,10)	—	—	3500 μg*day/mL Standard Deviation 551	NA μg*day/mL Standard Deviation NA Participants received 840 mg of pertuzumab only in Cycle 1 per dose regimen.	1491 μg*day/mL Standard Deviation 472	—

SECONDARY outcome

Timeframe: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22

Population: ITT population; Participants in any cohort infused with the specified dose of pertuzumab were included in analysis. n = number of participants analyzed at the specified timepoint for each arm, respectively.

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 μg*day/mL.

Outcome measures

Measure	Docetaxel 75 + Pertuzumab 420 Participants received 75 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 100 Alone Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Entire Study Population n=8 Participants Participants received escalating dose levels of combination of docetaxel and pertuzumab. Participants received docetaxel 60 mg/m\^2 and pertuzumab 1050 mg at dose level 1, docetaxel 75 mg/m\^2 and pertuzumab 1050 mg at dose level 2, docetaxel 75 mg/m\^2 and pertuzumab 420 mg at dose level 3 or 100 mg/m\^2 and pertuzumab 420 mg at dose level 4 until DLTs were observed.	Pertuzumab 840 n=11 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Pertuzumab 420 n=10 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Docetaxel 100 + Pertuzumab 420 Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.
AUC From Time Zero to Infinity (AUC [0-infinity]) for Pertuzumab in Combination With Docetaxel Cycle 1 (n=8,11,0)	—	—	3951 μg*day/mL Standard Deviation 919	2796 μg*day/mL Standard Deviation 967	NA μg*day/mL Standard Deviation NA Participants received 420 mg of pertuzumab only in Cycle 2 per dose regimen	—
AUC From Time Zero to Infinity (AUC [0-infinity]) for Pertuzumab in Combination With Docetaxel Cycle 2 (n=7,0,10)	—	—	6856 μg*day/mL Standard Deviation 2335	NA μg*day/mL Standard Deviation NA Participants received 840 mg of pertuzumab only in Cycle 1 per dose regimen.	2762 μg*day/mL Standard Deviation 892	—

SECONDARY outcome

Timeframe: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22

Population: ITT population; Participants in any cohort infused with the specified dose of pertuzumab were included in analysis. n = number of participants analyzed at the specified timepoint for each arm, respectively.

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

Measure	Docetaxel 75 + Pertuzumab 420 Participants received 75 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 100 Alone Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Entire Study Population n=8 Participants Participants received escalating dose levels of combination of docetaxel and pertuzumab. Participants received docetaxel 60 mg/m\^2 and pertuzumab 1050 mg at dose level 1, docetaxel 75 mg/m\^2 and pertuzumab 1050 mg at dose level 2, docetaxel 75 mg/m\^2 and pertuzumab 420 mg at dose level 3 or 100 mg/m\^2 and pertuzumab 420 mg at dose level 4 until DLTs were observed.	Pertuzumab 840 n=11 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Pertuzumab 420 n=10 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Docetaxel 100 + Pertuzumab 420 Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.
Clearance (Cl) of Pertuzimab in Combination With Docetaxel Cycle 2 (n=7,0,10)	—	—	167 mL/day Standard Deviation 49	NA mL/day Standard Deviation NA Participants received 840 mg of pertuzumab only in Cycle 1 per dose regimen.	169 mL/day Standard Deviation 60	—
Clearance (Cl) of Pertuzimab in Combination With Docetaxel Cycle 1 (n=8,11,0)	—	—	282 mL/day Standard Deviation 83	329 mL/day Standard Deviation 97	NA mL/day Standard Deviation NA Participants received 420 mg of pertuzumab only in Cycle 2 per dose regimen.	—

SECONDARY outcome

Timeframe: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22

Population: ITT population; Participants in any cohort infused with the specified dose of pertuzumab were included in analysis. n = number of participants analyzed at the specified timepoint for each arm, respectively.

The volume of distribution at steady state (Vz), 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

Measure	Docetaxel 75 + Pertuzumab 420 Participants received 75 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 100 Alone Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Entire Study Population n=8 Participants Participants received escalating dose levels of combination of docetaxel and pertuzumab. Participants received docetaxel 60 mg/m\^2 and pertuzumab 1050 mg at dose level 1, docetaxel 75 mg/m\^2 and pertuzumab 1050 mg at dose level 2, docetaxel 75 mg/m\^2 and pertuzumab 420 mg at dose level 3 or 100 mg/m\^2 and pertuzumab 420 mg at dose level 4 until DLTs were observed.	Pertuzumab 840 n=11 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Pertuzumab 420 n=10 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Docetaxel 100 + Pertuzumab 420 Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.
Volume of Distribution (Vz) at Steady State of Pertuzumab in Combination With Docetaxel Cycle 1 (n=8,11,0)	—	—	5214 mL Standard Deviation 1386	5355 mL Standard Deviation 1680	NA mL Standard Deviation NA Participants received 420 mg of pertuzumab only in Cycle 2 per dose regimen.	—
Volume of Distribution (Vz) at Steady State of Pertuzumab in Combination With Docetaxel Cycle 2 (n=7,0,10)	—	—	4672 mL Standard Deviation 1221	NA mL Standard Deviation NA Participants received 840 mg of pertuzumab only in Cycle 1 per dose regimen.	4233 mL Standard Deviation 1555	—

SECONDARY outcome

Timeframe: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22

Population: ITT population; Participants in any cohort infused with the specified dose of pertuzumab were included in analysis. n = number of participants analyzed at the specified timepoint for each arm, respectively.

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

Outcome measures

Measure	Docetaxel 75 + Pertuzumab 420 Participants received 75 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 100 Alone Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Entire Study Population n=8 Participants Participants received escalating dose levels of combination of docetaxel and pertuzumab. Participants received docetaxel 60 mg/m\^2 and pertuzumab 1050 mg at dose level 1, docetaxel 75 mg/m\^2 and pertuzumab 1050 mg at dose level 2, docetaxel 75 mg/m\^2 and pertuzumab 420 mg at dose level 3 or 100 mg/m\^2 and pertuzumab 420 mg at dose level 4 until DLTs were observed.	Pertuzumab 840 n=11 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Pertuzumab 420 n=10 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Docetaxel 100 + Pertuzumab 420 Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.
Mean Residence Time (MRT) of Pertuzumab Cycle 1 (n=8,11,0)	—	—	17.8 days Standard Deviation 5.8	15.8 days Standard Deviation 6.7	NA days Standard Deviation NA Participants received 420 mg of pertuzumab only in Cycle 2 per dose regimen.	—
Mean Residence Time (MRT) of Pertuzumab Cycle 2 (n=7,0,10)	—	—	29.5 days Standard Deviation 18.5	NA days Standard Deviation NA Participants received 840 mg of pertuzumab only in Cycle 1 per dose regimen.	25.8 days Standard Deviation 13.2	—

SECONDARY outcome

Timeframe: Weeks 7 (Cycle 2),13 (Cycle 4) and Final Visit Up to 22 weeks

Population: ITT population; n = number of participants still receiving treatment at the specified cycle for each arm respectively.

Best Overall response was evaluated as Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progressive Disease (PD). CR: complete disappearance of all target lesions. PR: at least a 30 percent (%) decrease in the sum of the longest diameters. SD: neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum of the longest diameters since the treatment started. PD: at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters of the target lesions recorded since the treatment started, including screening, or the appearance of one or more new lesions. If participants withdrew due to insufficient therapeutic response or death and had no tumor measurements at the final visit, they were counted under progressive disease for final visit.

Outcome measures

Measure	Docetaxel 75 + Pertuzumab 420 n=5 Participants Participants received 75 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 100 Alone Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Entire Study Population n=6 Participants Participants received escalating dose levels of combination of docetaxel and pertuzumab. Participants received docetaxel 60 mg/m\^2 and pertuzumab 1050 mg at dose level 1, docetaxel 75 mg/m\^2 and pertuzumab 1050 mg at dose level 2, docetaxel 75 mg/m\^2 and pertuzumab 420 mg at dose level 3 or 100 mg/m\^2 and pertuzumab 420 mg at dose level 4 until DLTs were observed.	Pertuzumab 840 n=2 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Pertuzumab 420 n=6 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Docetaxel 100 + Pertuzumab 420 Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.
Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Cycle 2: CR (n=6,1,6,4)	0.0 percentage of participants	—	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—
Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Cycle 2:PR (n=6,1,6,4)	0.0 percentage of participants	—	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—
Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Cycle 2:SD (n=6,1,6,4)	75.0 percentage of participants	—	83.3 percentage of participants	100.0 percentage of participants	83.3 percentage of participants	—
Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Cycle 2:PD (n=6,1,6,4)	25.0 percentage of participants	—	16.7 percentage of participants	0 percentage of participants	16.7 percentage of participants	—
Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Cycle 2:Missing (n=6,1,6,4)	0.0 percentage of participants	—	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—
Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Cycle 4:CR (n=5,1,5,3)	0.0 percentage of participants	—	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—
Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Cycle 4:PR (n=5,1,5,3)	0 percentage of participants	—	0.0 percentage of participants	0.0 percentage of participants	20.0 percentage of participants	—
Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Cycle 4:SD (n=5,1,5,3)	66.7 percentage of participants	—	80.0 percentage of participants	100.0 percentage of participants	40.0 percentage of participants	—
Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Cycle 4:PD (n=5,1,5,3)	33.3 percentage of participants	—	20.0 percentage of participants	0.0 percentage of participants	40.0 percentage of participants	—
Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Cycle 4:Missing (n=5,1,5,3)	0.0 percentage of participants	—	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—
Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Final visit:CR (n=6,2,6,5)	0.0 percentage of participants	—	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—
Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Final visit:PR (n=6,2,6,5)	0.0 percentage of participants	—	0.0 percentage of participants	0.0 percentage of participants	16.7 percentage of participants	—
Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Final visit:SD (n=6,2,6,5)	20.0 percentage of participants	—	33.3 percentage of participants	50.0 percentage of participants	33.3 percentage of participants	—
Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Final visit:PD (n=6,2,6,5)	60.0 percentage of participants	—	50.0 percentage of participants	0.0 percentage of participants	50.0 percentage of participants	—
Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Final visit:Missing (n=6,2,6,5)	20.0 percentage of participants	—	16.7 percentage of participants	50.0 percentage of participants	0.0 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline, Weeks 7(Cycle 2), 13 (Cycle 4) and Final Visit Up to Week 22

Population: ITT population; n = number of participants still receiving treatment at the specified cycle for each arm, respectively.

Ejection fraction (EF) is the fraction of outbound blood pumped from the heart with each heartbeat. It is commonly measured by echocardiogram and serves as a general measure of a person's cardiac function. Changes in LVEF were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 criteria. The decrease in LVEF has been categorized as follows: A) Increase, no change, decrease from baseline less than (<) 10%; B) Absolute value <50% and decrease from baseline greater than or equal to (≥) 10%; C) Absolute value <50% and decrease from baseline≥15% ; D) Other. If participants withdrew due to insufficient therapeutic response or death and had no tumor measurements at the final visit, they were counted under progressive disease for final visit.

Outcome measures

Measure	Docetaxel 75 + Pertuzumab 420 n=5 Participants Participants received 75 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 100 Alone Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Entire Study Population n=6 Participants Participants received escalating dose levels of combination of docetaxel and pertuzumab. Participants received docetaxel 60 mg/m\^2 and pertuzumab 1050 mg at dose level 1, docetaxel 75 mg/m\^2 and pertuzumab 1050 mg at dose level 2, docetaxel 75 mg/m\^2 and pertuzumab 420 mg at dose level 3 or 100 mg/m\^2 and pertuzumab 420 mg at dose level 4 until DLTs were observed.	Pertuzumab 840 n=2 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Pertuzumab 420 n=6 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Docetaxel 100 + Pertuzumab 420 Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.
Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint Cycle 2: A (n=6,1,6,4)	100.0 percentage of participants	—	83.3 percentage of participants	100.0 percentage of participants	100.0 percentage of participants	—
Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint Cycle 2: B (n=6,1,6,4)	0.0 percentage of participants	—	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—
Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint Cycle 2: C (n=6,1,6,4)	0.0 percentage of participants	—	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—
Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint Cycle 2: D (n=6,1,6,4)	0.0 percentage of participants	—	16.7 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—
Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint Cycle 4: A (n=5,1,4,3)	100.0 percentage of participants	—	100.0 percentage of participants	100.0 percentage of participants	75.0 percentage of participants	—
Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint Cycle 4: B (n=5,1,4,3)	0.0 percentage of participants	—	0.0 percentage of participants	0.0 percentage of participants	25.0 percentage of participants	—
Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint Cycle 4: C (n=5,1,4,3)	0.0 percentage of participants	—	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—
Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint Cycle 4: D (n=5,1,4,3)	0.0 percentage of participants	—	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—
Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint Final Visit: A (n=3,1,5,2)	100.0 percentage of participants	—	66.7 percentage of participants	100.0 percentage of participants	80.0 percentage of participants	—
Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint Final Visit: B (n=3,1,5,2)	0.0 percentage of participants	—	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—
Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint Final Visit: C (n=3,1,5,2)	0.0 percentage of participants	—	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—
Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint Final Visit: D (n=3,1,5,2)	0.0 percentage of participants	—	33.3 percentage of participants	0.0 percentage of participants	20.0 percentage of participants	—

SECONDARY outcome

Timeframe: Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose

Population: ITT population; Data from Cohort 2 (docetaxel 75 mg/m\^2 and pertuzumab 1050 mg) were excluded because there were only 2 participant data. It was planned not to report PK data, if less than or equal to 2 participants were analyzed. n= number of participants analyzed at the specified cycle.

The biological half-life or terminal half-life of docetaxel is the time in hours it takes for it to lose half of its pharmacologic activity. Data for "docetaxel alone" arms were analyzed for the timepoints on Day 1 prior to the administration of pertuzumab. The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1.

Outcome measures

Measure	Docetaxel 75 + Pertuzumab 420 n=6 Participants Participants received 75 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 100 Alone n=5 Participants Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Entire Study Population n=6 Participants Participants received escalating dose levels of combination of docetaxel and pertuzumab. Participants received docetaxel 60 mg/m\^2 and pertuzumab 1050 mg at dose level 1, docetaxel 75 mg/m\^2 and pertuzumab 1050 mg at dose level 2, docetaxel 75 mg/m\^2 and pertuzumab 420 mg at dose level 3 or 100 mg/m\^2 and pertuzumab 420 mg at dose level 4 until DLTs were observed.	Pertuzumab 840 n=6 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Pertuzumab 420 n=6 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Docetaxel 100 + Pertuzumab 420 n=4 Participants Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.
t1/2 for Docetaxel Alone and in Combination With Pertuzumab Cycle 1 (n=6,0,6,0,5,0)	NA days In Cycle 1 analysis was performed for docetaxel alone data on pertuzumab naive participants only.	8.92 days Interval 7.49 to 13.5	17.7 days Interval 7.31 to 22.7	NA days In Cycle 1 analysis was performed for docetaxel alone data on pertuzumab naive participants only.	12.0 days Interval 9.56 to 19.4	NA days In Cycle 1 analysis was performed for docetaxel alone data on pertuzumab naive participants only.
t1/2 for Docetaxel Alone and in Combination With Pertuzumab Cycle 2(n=0,6,0,6,0,4)	13.8 days Interval 9.62 to 23.8	NA days Data were not analyzed for docetaxel alone since participants were already exposed to pertuzumab in Cycle 1.	NA days Data were not analyzed for docetaxel alone since participants were already exposed to pertuzumab in Cycle 1.	19.7 days Interval 12.5 to 27.1	NA days Data were not analyzed for docetaxel alone since participants were already exposed to pertuzumab in Cycle 1.	11.8 days Interval 8.04 to 21.4

SECONDARY outcome

Timeframe: Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose

Population: ITT population; Data from Cohort 2 (docetaxel 75 mg/m\^2 and pertuzumab 1050 mg) were excluded because there were only 2 participant data. It was planned not to report PK data, if less than or equal to 2 participants were analyzed. n= number of participants analyzed at the specified cycle.

Tmax is defined as the time after administration of a drug when the maximum plasma concentration is reached; Data for "docetaxel alone" arms were analyzed for the timepoints on Day 1 prior to the administration of pertuzumab. When the rate of absorption equals the rate of elimination. The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1.

Outcome measures

Measure	Docetaxel 75 + Pertuzumab 420 n=6 Participants Participants received 75 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 100 Alone n=5 Participants Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Entire Study Population n=6 Participants Participants received escalating dose levels of combination of docetaxel and pertuzumab. Participants received docetaxel 60 mg/m\^2 and pertuzumab 1050 mg at dose level 1, docetaxel 75 mg/m\^2 and pertuzumab 1050 mg at dose level 2, docetaxel 75 mg/m\^2 and pertuzumab 420 mg at dose level 3 or 100 mg/m\^2 and pertuzumab 420 mg at dose level 4 until DLTs were observed.	Pertuzumab 840 n=6 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Pertuzumab 420 n=6 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Docetaxel 100 + Pertuzumab 420 n=4 Participants Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.
Tmax for Docetaxel Alone and in Combination With Pertuzumab Cycle 1 (n=6,0,6,0,5,0)	NA days In Cycle 1 analysis was performed for docetaxel alone data on pertuzumab naive participants only.	0.90 days Interval 0.9 to 0.9	0.50 days Interval 0.5 to 0.9	NA days In Cycle 1 analysis was performed for docetaxel alone data on pertuzumab naive participants only.	0.50 days Interval 0.5 to 0.9	NA days In Cycle 1 analysis was performed for docetaxel alone data on pertuzumab naive participants only.
Tmax for Docetaxel Alone and in Combination With Pertuzumab Cycle 2 (n=0,6,0,6,0,4)	0.90 days Interval 0.5 to 0.9	NA days Data were not analyzed for docetaxel alone since participants were already exposed to pertuzumab in Cycle 1.	NA days Data were not analyzed for docetaxel alone since participants were already exposed to pertuzumab in Cycle 1.	0.90 days Interval 0.5 to 1.25	NA days Data were not analyzed for docetaxel alone since participants were already exposed to pertuzumab in Cycle 1.	0.70 days Interval 0.5 to 0.9

SECONDARY outcome

Timeframe: Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose

Population: ITT population; Data from Cohort 2 (docetaxel 75 mg/m\^2 and pertuzumab 1050 mg) were excluded because there were only 2 participant data. It was planned not to report PK data, if less than or equal to 2 participants were analyzed. n= number of participants analyzed at the specified cycle.

Cmax refers to the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and prior to the administration of a second dose and is measures as nanograms per milliliter (ng/mL). The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1.

Outcome measures

Measure	Docetaxel 75 + Pertuzumab 420 n=6 Participants Participants received 75 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 100 Alone n=5 Participants Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Entire Study Population n=6 Participants Participants received escalating dose levels of combination of docetaxel and pertuzumab. Participants received docetaxel 60 mg/m\^2 and pertuzumab 1050 mg at dose level 1, docetaxel 75 mg/m\^2 and pertuzumab 1050 mg at dose level 2, docetaxel 75 mg/m\^2 and pertuzumab 420 mg at dose level 3 or 100 mg/m\^2 and pertuzumab 420 mg at dose level 4 until DLTs were observed.	Pertuzumab 840 n=6 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Pertuzumab 420 n=6 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Docetaxel 100 + Pertuzumab 420 n=4 Participants Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.
Cmax for Docetaxel Alone and in Combination With Pertuzumab Cycle 1 (n=6,0,6,0,5,0)	NA ng/mL Standard Deviation NA In Cycle 1 analysis was performed for docetaxel alone data on pertuzumab naive participants only.	5450 ng/mL Standard Deviation 1867	1642 ng/mL Standard Deviation 274	NA ng/mL Standard Deviation NA In Cycle 1 analysis was performed for docetaxel alone data on pertuzumab naive participants only.	3128 ng/mL Standard Deviation 895	NA ng/mL Standard Deviation NA In Cycle 1 analysis was performed for docetaxel alone data on pertuzumab naive participants only.
Cmax for Docetaxel Alone and in Combination With Pertuzumab Cycle 2 (n=0,6,0,6,0,4)	2722 ng/mL Standard Deviation 912	NA ng/mL Standard Deviation NA Data were not analyzed for docetaxel alone since participants were already exposed to pertuzumab in Cycle 1.	NA ng/mL Standard Deviation NA Data were not analyzed for docetaxel alone since participants were already exposed to pertuzumab in Cycle 1.	1695 ng/mL Standard Deviation 331	NA ng/mL Standard Deviation NA Data were not analyzed for docetaxel alone since participants were already exposed to pertuzumab in Cycle 1.	4705 ng/mL Standard Deviation 1871

SECONDARY outcome

Timeframe: Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose

Population: ITT population; Data from Cohort 2 (docetaxel 75 mg/m\^2 and pertuzumab 1050 mg) were excluded because there were only 2 participant data. It was planned not to report PK data, if less than or equal to 2 participants were analyzed. n= number of participants analyzed at the specified cycle.

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 ng*h/mL. The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1.

Outcome measures

Measure	Docetaxel 75 + Pertuzumab 420 n=6 Participants Participants received 75 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 100 Alone n=5 Participants Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Entire Study Population n=6 Participants Participants received escalating dose levels of combination of docetaxel and pertuzumab. Participants received docetaxel 60 mg/m\^2 and pertuzumab 1050 mg at dose level 1, docetaxel 75 mg/m\^2 and pertuzumab 1050 mg at dose level 2, docetaxel 75 mg/m\^2 and pertuzumab 420 mg at dose level 3 or 100 mg/m\^2 and pertuzumab 420 mg at dose level 4 until DLTs were observed.	Pertuzumab 840 n=6 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Pertuzumab 420 n=6 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Docetaxel 100 + Pertuzumab 420 n=4 Participants Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.
AUC(0-∞) for Docetaxel Alone and in Combination With Pertuzumab Cycle 1 (n=6,0,6,0,5,0)	NA ng*h/mL Standard Deviation NA In Cycle 1 analysis was performed for docetaxel alone data on pertuzumab naive participants only.	5930 ng*h/mL Standard Deviation 2137	1838 ng*h/mL Standard Deviation 244	NA ng*h/mL Standard Deviation NA In Cycle 1 analysis was performed for docetaxel alone data on pertuzumab naive participants only.	3744 ng*h/mL Standard Deviation 1304	NA ng*h/mL Standard Deviation NA In Cycle 1 analysis was performed for docetaxel alone data on pertuzumab naive participants only.
AUC(0-∞) for Docetaxel Alone and in Combination With Pertuzumab Cycle 2 (n=0,6,0,6,0,4)	3496 ng*h/mL Standard Deviation 1211	NA ng*h/mL Standard Deviation NA Data were not analyzed for docetaxel alone since participants were already exposed to pertuzumab in Cycle 1.	NA ng*h/mL Standard Deviation NA Data were not analyzed for docetaxel alone since participants were already exposed to pertuzumab in Cycle 1.	1734 ng*h/mL Standard Deviation 409	NA ng*h/mL Standard Deviation NA Data were not analyzed for docetaxel alone since participants were already exposed to pertuzumab in Cycle 1.	5218 ng*h/mL Standard Deviation 2216

SECONDARY outcome

Timeframe: Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose

Population: ITT population; Data from Cohort 2 (docetaxel 75 mg/m\^2 and pertuzumab 1050 mg) were excluded because there were only 2 participant data. It was planned not to report PK data, if less than or equal to 2 participants were analyzed. n= number of participants analyzed at the specified cycle.

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. The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1.

Outcome measures

Measure	Docetaxel 75 + Pertuzumab 420 n=6 Participants Participants received 75 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 100 Alone n=5 Participants Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Entire Study Population n=6 Participants Participants received escalating dose levels of combination of docetaxel and pertuzumab. Participants received docetaxel 60 mg/m\^2 and pertuzumab 1050 mg at dose level 1, docetaxel 75 mg/m\^2 and pertuzumab 1050 mg at dose level 2, docetaxel 75 mg/m\^2 and pertuzumab 420 mg at dose level 3 or 100 mg/m\^2 and pertuzumab 420 mg at dose level 4 until DLTs were observed.	Pertuzumab 840 n=6 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Pertuzumab 420 n=6 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Docetaxel 100 + Pertuzumab 420 n=4 Participants Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.
Vss for Docetaxel Alone and in Combination With Pertuzumab Cycle 1 (n=6,0,6,0,5,0)	NA mL/m^2 Standard Deviation NA In Cycle 1 analysis was performed for docetaxel alone data on pertuzumab naive participants only.	254233 mL/m^2 Standard Deviation 85054	786981 mL/m^2 Standard Deviation 218139	NA mL/m^2 Standard Deviation NA In Cycle 1 analysis was performed for docetaxel alone data on pertuzumab naive participants only.	410174 mL/m^2 Standard Deviation 184216	NA mL/m^2 Standard Deviation NA In Cycle 1 analysis was performed for docetaxel alone data on pertuzumab naive participants only.
Vss for Docetaxel Alone and in Combination With Pertuzumab Cycle 2 (n=0,6,0,6,0,4)	566759 mL/m^2 Standard Deviation 361946	NA mL/m^2 Standard Deviation NA Data were not analyzed for docetaxel alone since participants were already exposed to pertuzumab in Cycle 1.	NA mL/m^2 Standard Deviation NA Data were not analyzed for docetaxel alone since participants were already exposed to pertuzumab in Cycle 1.	1023569 mL/m^2 Standard Deviation 335711	NA mL/m^2 Standard Deviation NA Data were not analyzed for docetaxel alone since participants were already exposed to pertuzumab in Cycle 1.	428863 mL/m^2 Standard Deviation 283977

SECONDARY outcome

Timeframe: Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose

Population: ITT population; Data from Cohort 2 (docetaxel 75 mg/m\^2 and pertuzumab 1050 mg) were excluded because there were only 2 participant data. It was planned not to report PK data, if less than or equal to 2 participants were analyzed. n= number of participants analyzed at the specified cycle.

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 hour per meter squared (mL/h/m^2). The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1.

Outcome measures

Measure	Docetaxel 75 + Pertuzumab 420 n=6 Participants Participants received 75 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 100 Alone n=5 Participants Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Entire Study Population n=6 Participants Participants received escalating dose levels of combination of docetaxel and pertuzumab. Participants received docetaxel 60 mg/m\^2 and pertuzumab 1050 mg at dose level 1, docetaxel 75 mg/m\^2 and pertuzumab 1050 mg at dose level 2, docetaxel 75 mg/m\^2 and pertuzumab 420 mg at dose level 3 or 100 mg/m\^2 and pertuzumab 420 mg at dose level 4 until DLTs were observed.	Pertuzumab 840 n=6 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Pertuzumab 420 n=6 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Docetaxel 100 + Pertuzumab 420 n=4 Participants Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.
CL for Docetaxel Alone and in Combination With Pertuzumab Cycle 1 (n=6,0,6,0,5,0)	NA mL/h/m^2 Standard Deviation NA In Cycle 1 analysis was performed for docetaxel alone data on pertuzumab naive participants only.	18913 mL/h/m^2 Standard Deviation 7245	33128 mL/h/m^2 Standard Deviation 4396	NA mL/h/m^2 Standard Deviation NA In Cycle 1 analysis was performed for docetaxel alone data on pertuzumab naive participants only.	22013 mL/h/m^2 Standard Deviation 7031	NA mL/h/m^2 Standard Deviation NA In Cycle 1 analysis was performed for docetaxel alone data on pertuzumab naive participants only.
CL for Docetaxel Alone and in Combination With Pertuzumab Cycle 2 (n=0,6,0,6,0,4)	23747 mL/h/m^2 Standard Deviation 8175	NA mL/h/m^2 Standard Deviation NA Data were not analyzed for docetaxel alone since participants were already exposed to pertuzumab in Cycle 1.	NA mL/h/m^2 Standard Deviation NA Data were not analyzed for docetaxel alone since participants were already exposed to pertuzumab in Cycle 1.	35813 mL/h/m^2 Standard Deviation 6216	NA mL/h/m^2 Standard Deviation NA Data were not analyzed for docetaxel alone since participants were already exposed to pertuzumab in Cycle 1.	22976 mL/h/m^2 Standard Deviation 12679

SECONDARY outcome

Timeframe: From Baseline until 4 weeks after the end of treatment

Population: Safety Population

DLTs were defined as any of the following: 1) Any non-hematological toxicity greter than or equal to (≥) Grade 3 according t0 CTCAE version 3.0 except for fever, chills and flu-like symptoms, in spite of adequate toxicity management, 2) Grade 4 neutropenia lasting greater than (>) 7 days, 3) Febrile neutropenia, 4) Thrombocytopenia Grade 4 or any thrombocytopenia requiring platelet transfusion or 5) Any subjectively intolerable toxicity felt by the investigator to be related to either one of the compounds.

Outcome measures

Measure	Docetaxel 75 + Pertuzumab 420 n=5 Participants Participants received 75 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 100 Alone Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Entire Study Population n=6 Participants Participants received escalating dose levels of combination of docetaxel and pertuzumab. Participants received docetaxel 60 mg/m\^2 and pertuzumab 1050 mg at dose level 1, docetaxel 75 mg/m\^2 and pertuzumab 1050 mg at dose level 2, docetaxel 75 mg/m\^2 and pertuzumab 420 mg at dose level 3 or 100 mg/m\^2 and pertuzumab 420 mg at dose level 4 until DLTs were observed.	Pertuzumab 840 n=2 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Pertuzumab 420 n=6 Participants Participants received pertuzumab 840 mg by IV infusion over approximately 90 minutes in Cycle 1 followed by a three weekly dose (Cycle 2) of 420 mg by IV infusion over approximately 30 minutes.	Docetaxel 100 + Pertuzumab 420 Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.
Number of Participants With DLTs	2 number of participants	—	0 number of participants	2 number of participants	0 number of participants	—

Adverse Events

Docetaxel 60 Plus (+) Pertuzumab 1050

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

Docetaxel 75 + Pertuzumab 1050

Serious events: 2 serious events

Other events: 2 other events

Deaths: 0 deaths

Docetaxel 75 + Pertuzumab 420

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Docetaxel 100 + Pertuzumab 420

Serious events: 3 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Measure	Docetaxel 60 Plus (+) Pertuzumab 1050 n=6 participants at risk Participants received 60 mg/m\^2 docetaxel and 1050 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 75 + Pertuzumab 1050 n=2 participants at risk Participants received 75 mg/m\^2 docetaxel and 1050 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 75 + Pertuzumab 420 n=6 participants at risk Participants received 75 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 100 + Pertuzumab 420 n=5 participants at risk Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.
Gastrointestinal disorders Diarrhoea	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	50.0% 1/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Gastrointestinal disorders Nausea	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Gastrointestinal disorders Vomiting	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	50.0% 1/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
General disorders Fatigue	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	50.0% 1/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
General disorders Pyrexia	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Infections and infestations Lower respiratory tract infection	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Infections and infestations Urinary tract infection	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Nervous system disorders Paralysis	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Vascular disorders Hypertension	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.

Other adverse events

Measure	Docetaxel 60 Plus (+) Pertuzumab 1050 n=6 participants at risk Participants received 60 mg/m\^2 docetaxel and 1050 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 75 + Pertuzumab 1050 n=2 participants at risk Participants received 75 mg/m\^2 docetaxel and 1050 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 75 + Pertuzumab 420 n=6 participants at risk Participants received 75 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.	Docetaxel 100 + Pertuzumab 420 n=5 participants at risk Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication.
Musculoskeletal and connective tissue disorders Back pain	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Musculoskeletal and connective tissue disorders Chest wall pain	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Musculoskeletal and connective tissue disorders Limb discomfort	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Musculoskeletal and connective tissue disorders Shoulder pain	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Psychiatric disorders Insomnia	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	33.3% 2/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Psychiatric disorders Depression	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Psychiatric disorders Anxiety	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Psychiatric disorders Confusional state	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	50.0% 1/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Metabolism and nutrition disorders Anorexia	33.3% 2/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	33.3% 2/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Vascular disorders Hypertension	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	50.0% 1/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Vascular disorders Flushing	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Vascular disorders Hot flush	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Vascular disorders Lymphoedema	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Vascular disorders Phlebitis	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Eye disorders Lacrimation	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	33.3% 2/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Eye disorders Conjunctivitis	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Eye disorders Diplopia	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Eye disorders Dry eye	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Eye disorders Visual acuity reduced	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Blood and lymphatic system disorders Anaemia	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Blood and lymphatic system disorders Lymph node pain	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Investigations Alanine aminotransferase increased	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	50.0% 1/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Investigations Weight decreased	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Renal and urinary disorders Dysuria	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Renal and urinary disorders Urinary incontinence	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Cardiac disorders Ventricular disfunction	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Injury, poisoning and procedural complications Contusion	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Reproductive system and breast disorders Gential Haemorrhage	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Gastrointestinal disorders Diarrhoea	83.3% 5/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	100.0% 2/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	83.3% 5/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	80.0% 4/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Gastrointestinal disorders Nausea	83.3% 5/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	100.0% 2/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	83.3% 5/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	80.0% 4/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Gastrointestinal disorders Abdominal pain	66.7% 4/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	40.0% 2/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Gastrointestinal disorders Dyspepsia	33.3% 2/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	33.3% 2/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	40.0% 2/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Gastrointestinal disorders Mouth ulceration	33.3% 2/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	50.0% 3/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Gastrointestinal disorders Stomatitis	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	60.0% 3/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Gastrointestinal disorders Vomiting	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	40.0% 2/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Gastrointestinal disorders Constipation	33.3% 2/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Gastrointestinal disorders Abdominal pain upper	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Gastrointestinal disorders Haemorrhoids	33.3% 2/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Gastrointestinal disorders Proctalgia	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Gastrointestinal disorders Abdominal pain lower	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Gastrointestinal disorders Anal fissure	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Gastrointestinal disorders Ascites	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Gastrointestinal disorders Gastrooesophageal reflux disease	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Gastrointestinal disorders Gingivitis	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Gastrointestinal disorders Glossitis	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Gastrointestinal disorders Oesophagitis	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Gastrointestinal disorders Proctitis	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Gastrointestinal disorders Tongue ulceration	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	50.0% 1/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Gastrointestinal disorders Toothache	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
General disorders Fatigue	83.3% 5/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	100.0% 2/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	100.0% 6/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	100.0% 5/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
General disorders Mucosal inflammation	33.3% 2/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	33.3% 2/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
General disorders Malaise	33.3% 2/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
General disorders Oedema peripheral	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
General disorders Chest pain	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
General disorders Chills	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	40.0% 2/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
General disorders Extravasation	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	50.0% 1/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
General disorders Pyrexia	33.3% 2/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
General disorders Injection site haemorrhage	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
General disorders Pain	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
General disorders Suprapubic pain	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	50.0% 1/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Nervous system disorders Dysgeusia	66.7% 4/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	50.0% 1/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	66.7% 4/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Nervous system disorders Headache	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	33.3% 2/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	40.0% 2/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Nervous system disorders Paraesthesia	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Nervous system disorders Ageusia	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Nervous system disorders Dizziness	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Nervous system disorders Hypoaesthesia	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Nervous system disorders Neuropathy	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Nervous system disorders Neuropathy peripheral	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Nervous system disorders Somnolence	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Nervous system disorders Syncope	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	83.3% 5/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	80.0% 4/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Skin and subcutaneous tissue disorders Rash	66.7% 4/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	33.3% 2/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	40.0% 2/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Skin and subcutaneous tissue disorders Nail disorder	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	33.3% 2/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Skin and subcutaneous tissue disorders Erythema	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Skin and subcutaneous tissue disorders Acne	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Skin and subcutaneous tissue disorders Drug eruption	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Skin and subcutaneous tissue disorders Erythema multiforme	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Skin and subcutaneous tissue disorders Periorbital oedema	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Skin and subcutaneous tissue disorders Rash follicular	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Skin and subcutaneous tissue disorders Rash papular	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Skin and subcutaneous tissue disorders Skin disorder	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Infections and infestations Lower respiratory tract infection	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	50.0% 1/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	40.0% 2/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Infections and infestations Nasopharyngitis	33.3% 2/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Infections and infestations Oral candidiasis	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Infections and infestations Upper respiratory tract infection	33.3% 2/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Infections and infestations Candidiasis	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	50.0% 1/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Infections and infestations Cystitis	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Infections and infestations Eye infection	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Infections and infestations Localised infection	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Infections and infestations Respiratory tract infection	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Infections and infestations Urinary tract infection	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Respiratory, thoracic and mediastinal disorders Epistaxis	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	83.3% 5/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Respiratory, thoracic and mediastinal disorders Cough	33.3% 2/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	40.0% 2/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	40.0% 2/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	33.3% 2/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Respiratory, thoracic and mediastinal disorders Throat irritation	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Respiratory, thoracic and mediastinal disorders Nasal mucosal disorder	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Musculoskeletal and connective tissue disorders Arthralgia	33.3% 2/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	66.7% 4/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	20.0% 1/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	0.00% 0/2 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	16.7% 1/6 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.	40.0% 2/5 • Adverse events were continuously monitored from Screening until 4 weeks after the final visit.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: genentech@druginfo.com

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