Trial Outcomes & Findings for Safety Study of rhuMAb 2C4 to Treat Advanced Solid Tumors (NCT NCT00027027)

NCT ID: NCT00027027

Last Updated: 2015-07-27

Results Overview

For this protocol, an AE is defined any untoward medical occurrence (e.g., sign, symptom, disease, syndrome, intercurrent illness, abnormal laboratory finding) that emerges or worsens relative to pretreatment baseline during the treatment or post-treatment periods, regardless of the suspected cause. For this protocol an SAE was defined as any AE that occurred at any dose if: * It resulted in death (i.e., the AE caused or led to death), * It was life threatening, * It required or prolonged inpatient hospitalization, * It was disabling, * It resulted in a congenital anomaly/birth defect, * It may have jeopardized the participant or may have required medical or surgical intervention to prevent one of the outcomes listed above. The primary cause of death for all reported cases was disease progression, and all of the deaths occurred following study discontinuation, with one death occurring within 4 weeks of the last treatment day.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 21 participants
• Primary outcome timeframe: Days 1, 2, 5, 8, and 15 of Cycle 1; Days 1, 8, and Week 3, of Cycles 2 and beyond up to 1 year and at the follow-up visit (4 weeks after last infusion)
• Results posted on: 2015-07-27

Participant Flow

Participant milestones

Measure	rhuMAb 2C4: 0.5 Milligrams Per Kilogram (mg/kg) Recombinant Humanized Antibody to human epidermal growth factor receptor 2 (rhuMAb 2C4) 0.5 mg/kg was administered once every 3 weeks as an intravenous (IV) infusion until progressive disease (PD) or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 2 mg/kg rhuMAb 2C4 2 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 5 mg/kg rhuMAb 2C4 5 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 10 mg/kg rhuMAb 2C4 10 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 15 mg/kg rhuMAb 2C4 15 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.
Overall Study STARTED	3	3	4	3	8
Overall Study Discontinued Before 2 Treatment Cycles	0	0	1	0	1
Overall Study Completed 2 Cycles of Treatment	3	3	3	3	7
Overall Study Discontinued at Cycle 2	2	2	1	1	3
Overall Study Treated Beyond Cycle 2	1	1	2	2	4
Overall Study COMPLETED	0	0	0	0	0
Overall Study NOT COMPLETED	3	3	4	3	8

Reasons for withdrawal

Measure	rhuMAb 2C4: 0.5 Milligrams Per Kilogram (mg/kg) Recombinant Humanized Antibody to human epidermal growth factor receptor 2 (rhuMAb 2C4) 0.5 mg/kg was administered once every 3 weeks as an intravenous (IV) infusion until progressive disease (PD) or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 2 mg/kg rhuMAb 2C4 2 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 5 mg/kg rhuMAb 2C4 5 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 10 mg/kg rhuMAb 2C4 10 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 15 mg/kg rhuMAb 2C4 15 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.
Overall Study Adverse Event	0	0	1	0	1
Overall Study Admitted for Signs of PD	0	0	0	0	1
Overall Study Clinical Symptoms Progression not PD	1	0	0	0	0
Overall Study PD Requiring Surgery	0	0	1	0	0
Overall Study Physician Decision Due To PD	2	3	2	3	5
Overall Study Withdrawal by Subject	0	0	0	0	1

Baseline Characteristics

Safety Study of rhuMAb 2C4 to Treat Advanced Solid Tumors

Baseline characteristics by cohort

Measure	rhuMAb 2C4: 0.5 mg/kg n=3 Participants rhuMAb 2C4 0.5 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 2 mg/kg n=3 Participants rhuMAb 2C4 2 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 5 mg/kg n=4 Participants rhuMAb 2C4 5 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 10 mg/kg n=3 Participants rhuMAb 2C4 10 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 15 mg/kg n=8 Participants rhuMAb 2C4 15 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	Total n=21 Participants Total of all reporting groups
Age, Continuous	58 years STANDARD_DEVIATION 20.4 • n=5 Participants	55 years STANDARD_DEVIATION 13.6 • n=7 Participants	48 years STANDARD_DEVIATION 13.8 • n=5 Participants	61 years STANDARD_DEVIATION 17.1 • n=4 Participants	60 years STANDARD_DEVIATION 8.2 • n=21 Participants	56.7 years STANDARD_DEVIATION 12.7 • n=10 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	0 Participants n=4 Participants	6 Participants n=21 Participants	12 Participants n=10 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	2 Participants n=21 Participants	9 Participants n=10 Participants

PRIMARY outcome

Timeframe: Days 1, 2, 5, 8, and 15 of Cycle 1; Days 1, 8, and Week 3, of Cycles 2 and beyond up to 1 year and at the follow-up visit (4 weeks after last infusion)

Population: All enrolled participants

For this protocol, an AE is defined any untoward medical occurrence (e.g., sign, symptom, disease, syndrome, intercurrent illness, abnormal laboratory finding) that emerges or worsens relative to pretreatment baseline during the treatment or post-treatment periods, regardless of the suspected cause.

For this protocol an SAE was defined as any AE that occurred at any dose if:

• It resulted in death (i.e., the AE caused or led to death),
• It was life threatening,
• It required or prolonged inpatient hospitalization,
• It was disabling,
• It resulted in a congenital anomaly/birth defect,
• It may have jeopardized the participant or may have required medical or surgical intervention to prevent one of the outcomes listed above.

The primary cause of death for all reported cases was disease progression, and all of the deaths occurred following study discontinuation, with one death occurring within 4 weeks of the last treatment day.

Outcome measures

Measure	rhuMAb 2C4: 0.5 mg/kg n=3 Participants rhuMAb 2C4 0.5 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 2 mg/kg n=3 Participants rhuMAb 2C4 2 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 5 mg/kg n=4 Participants rhuMAb 2C4 5 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 10 mg/kg n=3 Participants rhuMAb 2C4 10 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 15 mg/kg n=8 Participants rhuMAb 2C4 15 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.
Number of Participants With an Adverse Event (AE), Serious Adverse Event (SAE), or Death Adverse events	3 participants	3 participants	4 participants	3 participants	8 participants
Number of Participants With an Adverse Event (AE), Serious Adverse Event (SAE), or Death Serious adverse events	3 participants	1 participants	2 participants	0 participants	5 participants
Number of Participants With an Adverse Event (AE), Serious Adverse Event (SAE), or Death Death	3 participants	1 participants	2 participants	0 participants	1 participants

PRIMARY outcome

Timeframe: Day 1 of Cycles 1 and 2, and 24 hours after Cycle 2 infusion

Population: All enrolled participants who completed at least 2 cycles of study treatment.

Incidence of DLTs defined as any Grade 3 or 4 major organ toxicity according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) Version 2 or any subjectively intolerable toxicity felt by the investigator to be related to rhuMAb 2C4.

One participant in the 15.0 mg/kg dose group experienced a gastrointestinal hemorrhage on Day 16. This event was judged by the investigator to be related to study drug. The participant recovered in 3 days and continued to receive rhuMAb 2C4 beyond Cycle 2.This was the only DLT reported during the first two treatment cycles.

Outcome measures

Measure	rhuMAb 2C4: 0.5 mg/kg n=3 Participants rhuMAb 2C4 0.5 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 2 mg/kg n=3 Participants rhuMAb 2C4 2 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 5 mg/kg n=3 Participants rhuMAb 2C4 5 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 10 mg/kg n=3 Participants rhuMAb 2C4 10 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 15 mg/kg n=7 Participants rhuMAb 2C4 15 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.
Number of Participants With Dose-Limiting Toxicities (DLTs)	3 participants	1 participants	2 participants	0 participants	6 participants

SECONDARY outcome

Timeframe: Days 1 (predose, 89 minutes following start of infusion and at 1.5, 4, and 8 hours postdose) 2, 5, 8 and 15 of Cycle 1; Days 1 (predose and 29 minutes following start of infusion) and 8 of Cycle 2

Population: All enrolled participants

Mean rhuMAb 2C4 serum concentrations versus nominal time profiles for the first two treatment cycles are presented for AUC micrograms per milliliters (ug/mL) by day. A one-compartment model was used for the 0.5 mg/kg dose group, and a two-compartment model was used for the 2-15 mg/kg dose groups.

Outcome measures

Measure	rhuMAb 2C4: 0.5 mg/kg n=3 Participants rhuMAb 2C4 0.5 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 2 mg/kg n=3 Participants rhuMAb 2C4 2 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 5 mg/kg n=4 Participants rhuMAb 2C4 5 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 10 mg/kg n=3 Participants rhuMAb 2C4 10 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 15 mg/kg n=8 Participants rhuMAb 2C4 15 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.
Pharmacokinetic Measurement of Area Under the Curve (AUC)	43.057 ug*hr/mL Standard Deviation 17.770	569.433 ug*hr/mL Standard Deviation 168.995	1478.000 ug*hr/mL Standard Deviation 349.396	3959.333 ug*hr/mL Standard Deviation 1110.113	4502.625 ug*hr/mL Standard Deviation 1245.289

SECONDARY outcome

Timeframe: Days 1 (predose, 89 minutes from infusion start, at 1.5, 4, and 8 hours postdose), 2, 5, 8 and 15 of Cycle 1; Days 1 (predose, 29 minutes from infusion start) and 8 of Cycles 2 and beyond until the follow-up visit (4 weeks after the last infusion)

Population: All enrolled participants

A one-compartment model was used for the 0.5 mg/kg dose group, and a two-compartment model was used for the 2-15 mg/kg dose groups.

Outcome measures

Measure	rhuMAb 2C4: 0.5 mg/kg n=3 Participants rhuMAb 2C4 0.5 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 2 mg/kg n=3 Participants rhuMAb 2C4 2 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 5 mg/kg n=4 Participants rhuMAb 2C4 5 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 10 mg/kg n=3 Participants rhuMAb 2C4 10 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 15 mg/kg n=8 Participants rhuMAb 2C4 15 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.
Pharmacokinetic Measurement of Systemic Clearance (CL)	13.1 mL/day/kg Standard Deviation 5.5	3.74 mL/day/kg Standard Deviation 1.28	3.52 mL/day/kg Standard Deviation 0.85	2.69 mL/day/kg Standard Deviation 0.92	3.68 mL/day/kg Standard Deviation 1.47

SECONDARY outcome

Timeframe: Days 1 (predose, 89 minutes from infusion start, at 1.5, 4, and 8 hours postdose), 2, 5, 8 and 15 of Cycle 1; Days 1 (predose, 29 minutes from infusion start) and 8 of Cycles 2 and beyond until the follow-up visit (4 weeks after the last infusion)

Population: All enrolled participants

A one-compartment model was used for the 0.5 mg/kg dose group, and a two-compartment model was used for the 2-15 mg/kg dose groups.

Outcome measures

Measure	rhuMAb 2C4: 0.5 mg/kg n=3 Participants rhuMAb 2C4 0.5 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 2 mg/kg n=3 Participants rhuMAb 2C4 2 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 5 mg/kg n=4 Participants rhuMAb 2C4 5 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 10 mg/kg n=3 Participants rhuMAb 2C4 10 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 15 mg/kg n=8 Participants rhuMAb 2C4 15 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.
Pharmacokinetic Measurement of Volume of Central Compartment (Vc)	43.6 mL/kg Standard Deviation 4.6	35.5 mL/kg Standard Deviation 3.5	39.7 mL/kg Standard Deviation 6.2	38.4 mL/kg Standard Deviation 5.3	42.8 mL/kg Standard Deviation 7.9

SECONDARY outcome

Timeframe: Days 1 (predose, 89 minutes from infusion start, at 1.5, 4, and 8 hours postdose), 2, 5, 8 and 15 of Cycle 1; Days 1 (predose, 29 minutes from infusion start) and 8 of Cycles 2 and beyond until the follow-up visit (4 weeks after the last infusion)

Population: Only participants in the measured treatment groups where a two-compartment model was used are included in the analysis.

A one-compartment model was used for the 0.5 mg/kg dose group, and a two-compartment model was used for the 2-15 mg/kg dose groups.

Outcome measures

Measure	rhuMAb 2C4: 0.5 mg/kg n=3 Participants rhuMAb 2C4 0.5 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 2 mg/kg n=4 Participants rhuMAb 2C4 2 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 5 mg/kg n=3 Participants rhuMAb 2C4 5 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 10 mg/kg n=8 Participants rhuMAb 2C4 10 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 15 mg/kg rhuMAb 2C4 15 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.
Pharmacokinetic Measurement of Steady-State Volume of Distribution (Vss)	69.5 mL/kg Standard Deviation 13.7	74.1 mL/kg Standard Deviation 30.4	73.4 mL/kg Standard Deviation 13.6	85.3 mL/kg Standard Deviation 36.7	—

SECONDARY outcome

Timeframe: Days 1 (predose, 89 minutes from infusion start, at 1.5, 4, and 8 hours postdose), 2, 5, 8 and 15 of Cycle 1; Days 1 (predose, 29 minutes from infusion start) and 8 of Cycles 2 and beyond until the follow-up visit (4 weeks after the last infusion)

Population: Only participants in the measured treatment groups where a two-compartment model was used are included in the analysis.

A one-compartment model was used for the 0.5 mg/kg dose group, and a two-compartment model was used for the 2-15 mg/kg dose groups.

Outcome measures

Measure	rhuMAb 2C4: 0.5 mg/kg n=3 Participants rhuMAb 2C4 0.5 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 2 mg/kg n=4 Participants rhuMAb 2C4 2 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 5 mg/kg n=3 Participants rhuMAb 2C4 5 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 10 mg/kg n=8 Participants rhuMAb 2C4 10 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 15 mg/kg rhuMAb 2C4 15 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.
Pharmacokinetic Measurement of Initial Distribution Half-Life (t1/2 Initial)	0.96 days Standard Deviation 0.99	1.09 days Standard Deviation 0.74	1.23 days Standard Deviation 0.90	1.50 days Standard Deviation 1.17	—

SECONDARY outcome

Timeframe: Days 1 (predose, 89 minutes from infusion start, at 1.5, 4, and 8 hours postdose), 2, 5, 8 and 15 of Cycle 1; Days 1 (predose, 29 minutes from infusion start) and 8 of Cycles 2 and beyond until the follow-up visit (4 weeks after the last infusion)

Population: All enrolled participants

A one-compartment model was used for the 0.5 mg/kg dose group, and a two-compartment model was used for the 2-15 mg/kg dose groups.

Outcome measures

Measure	rhuMAb 2C4: 0.5 mg/kg n=3 Participants rhuMAb 2C4 0.5 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 2 mg/kg n=3 Participants rhuMAb 2C4 2 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 5 mg/kg n=4 Participants rhuMAb 2C4 5 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 10 mg/kg n=3 Participants rhuMAb 2C4 10 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 15 mg/kg n=8 Participants rhuMAb 2C4 15 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.
Pharmacokinetic Measurement of Terminal Half-Life (t1/2 Terminal) in Days	2.6 days Standard Deviation 0.9	14.9 days Standard Deviation 1.1	17.2 days Standard Deviation 10.3	22.3 days Standard Deviation 9.9	18.6 days Standard Deviation 8.8

Adverse Events

rhuMAb 2C4: 0.5 mg/kg

Serious events: 3 serious events

Other events: 3 other events

Deaths: 0 deaths

rhuMAb 2C4: 2 mg/kg

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

rhuMAb 2C4: 5 mg/kg

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

rhuMAb 2C4: 10 mg/kg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

rhuMAb 2C4: 15 mg/kg

Serious events: 5 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Measure	rhuMAb 2C4: 0.5 mg/kg n=3 participants at risk rhuMAb 2C4 0.5 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 2 mg/kg n=3 participants at risk rhuMAb 2C4 2 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 5 mg/kg n=4 participants at risk rhuMAb 2C4 5 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 10 mg/kg n=3 participants at risk rhuMAb 2C4 10 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 15 mg/kg n=8 participants at risk rhuMAb 2C4 15 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Gastrointestinal disorders Diarrhoea	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Gastrointestinal disorders Gastric haemorrhage	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Gastrointestinal disorders Gastric varices haemorrhage	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Respiratory, thoracic and mediastinal disorders Pleural effusion	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Cardiac disorders Myocardial infarction	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Cardiac disorders Supraventricular tachycardia	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
General disorders Chest pain	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
General disorders Pain	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Psychiatric disorders Depression	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Psychiatric disorders Mental status changes	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Blood and lymphatic system disorders Anaemia	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Immune system disorders Drug hypersensitivity	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer metastatic	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Renal and urinary disorders Ureteric stenosis	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Vascular disorders Jugular vein thrombosis	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.

Other adverse events

Measure	rhuMAb 2C4: 0.5 mg/kg n=3 participants at risk rhuMAb 2C4 0.5 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 2 mg/kg n=3 participants at risk rhuMAb 2C4 2 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 5 mg/kg n=4 participants at risk rhuMAb 2C4 5 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 10 mg/kg n=3 participants at risk rhuMAb 2C4 10 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.	rhuMAb 2C4: 15 mg/kg n=8 participants at risk rhuMAb 2C4 15 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.
Metabolism and nutrition disorders Hyperglycaemia	66.7% 2/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Ear and labyrinth disorders Ear disorder	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor necrosis	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Gastrointestinal disorders Vomiting	100.0% 3/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	100.0% 4/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	37.5% 3/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Gastrointestinal disorders Nausea	100.0% 3/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	50.0% 2/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	66.7% 2/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 2/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Gastrointestinal disorders Diarrhoea	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	37.5% 3/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Gastrointestinal disorders Dyspepsia	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	37.5% 3/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Gastrointestinal disorders Constipation	66.7% 2/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 2/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	37.5% 3/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Gastrointestinal disorders Abdominal pain upper	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Gastrointestinal disorders Loose stools	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 2/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Gastrointestinal disorders Dry mouth	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	66.7% 2/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Gastrointestinal disorders Flatulence	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Gastrointestinal disorders Abdominal distension	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Gastrointestinal disorders Abdominal tenderness	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Gastrointestinal disorders Anal discomfort	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Gastrointestinal disorders Ascites	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Gastrointestinal disorders Faeces discoloured	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Gastrointestinal disorders Gastritis	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Gastrointestinal disorders Oral pain	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Gastrointestinal disorders Oral soft tissue disorder	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Gastrointestinal disorders Stomatitis	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
General disorders Fatigue	100.0% 3/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	62.5% 5/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
General disorders Pyrexia	66.7% 2/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 2/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
General disorders Oedema peripheral	66.7% 2/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 2/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
General disorders Rigors	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 2/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
General disorders Asthenia	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	50.0% 2/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
General disorders Gait abnormal	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	50.0% 2/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
General disorders Malaise	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	50.0% 2/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
General disorders Injection site pain	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
General disorders Mucosal inflammation	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
General disorders Pain	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Metabolism and nutrition disorders Anorexia	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 2/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 2/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	50.0% 2/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 2/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Metabolism and nutrition disorders Hyperkalaemia	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Metabolism and nutrition disorders Hypernatremia	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	66.7% 2/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Metabolism and nutrition disorders Hypocalcaemia	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Metabolism and nutrition disorders Hyponatremia	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Metabolism and nutrition disorders Gout	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Metabolism and nutrition disorders Hypercholesterolaemia	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Metabolism and nutrition disorders Hyperglyceridaemia	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Skin and subcutaneous tissue disorders Rash	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	66.7% 2/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	66.7% 2/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Skin and subcutaneous tissue disorders Pruritus	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	50.0% 2/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	50.0% 2/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Skin and subcutaneous tissue disorders Dermatitis	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Skin and subcutaneous tissue disorders Hypotrichosis	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Skin and subcutaneous tissue disorders Night sweats	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Skin and subcutaneous tissue disorders Onychorrhexis	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Skin and subcutaneous tissue disorders Rash erythematous	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Skin and subcutaneous tissue disorders Rash maculo-papular	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Skin and subcutaneous tissue disorders Skin discolouration	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Skin and subcutaneous tissue disorders Skin lesion	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Skin and subcutaneous tissue disorders Subcutaneous nodule	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Respiratory, thoracic and mediastinal disorders Cough	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	50.0% 2/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Respiratory, thoracic and mediastinal disorders Dyspnoea	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 2/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	66.7% 2/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Respiratory, thoracic and mediastinal disorders Breath sounds decreased	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Respiratory, thoracic and mediastinal disorders Nasal congestion	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Respiratory, thoracic and mediastinal disorders Nasal dryness	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Respiratory, thoracic and mediastinal disorders Nasal passage irritation	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Respiratory, thoracic and mediastinal disorders Sinus congestion	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Nervous system disorders Headache	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	50.0% 2/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Nervous system disorders Dizziness	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Nervous system disorders Hypoaesthesia	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 2/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Nervous system disorders Amnesia	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Nervous system disorders Cognitive disorder	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Nervous system disorders Disturbance in attention	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Nervous system disorders Dysarthria	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Nervous system disorders Dysguesia	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Nervous system disorders Dysgraphia	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Nervous system disorders Hypoguesia	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Nervous system disorders Paraesthesia	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Nervous system disorders Somnolence	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Nervous system disorders Speech disorder	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Eye disorders Eye pruritus	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Investigations Blood alkaline phosphatase increased	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 2/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Investigations Alanine aminotranseferase increased	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	66.7% 2/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Investigations Aspertate aminotransferase increased	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Investigations Troponin T increased	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Investigations Weight decreased	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 2/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Investigations Blood bilirubin increased	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Investigations Blood creatine phosphokinase MB increased	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Investigations Protein urine	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Investigations Troponin I increased	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Investigations Weight increased	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Musculoskeletal and connective tissue disorders Back pain	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 2/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Musculoskeletal and connective tissue disorders Myalgia	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	50.0% 2/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 2/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Musculoskeletal and connective tissue disorders Joint stiffness	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Musculoskeletal and connective tissue disorders Muscle spasms	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Musculoskeletal and connective tissue disorders Muscle twitching	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Renal and urinary disorders Chromaturia	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	50.0% 2/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Renal and urinary disorders Dysuria	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Renal and urinary disorders Haematuria	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Renal and urinary disorders Micturition urgency	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Renal and urinary disorders Urinary retension	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 2/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Renal and urinary disorders Bladder pain	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Renal and urinary disorders Calculus urethral	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Eye disorders Keratoconjunctivitis sicca	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Renal and urinary disorders Pollakiuria	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Renal and urinary disorders Proteinuria	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Renal and urinary disorders Urethral stricture	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Renal and urinary disorders Urine odour abnormal	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Blood and lymphatic system disorders Anaemia	66.7% 2/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	66.7% 2/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 2/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Blood and lymphatic system disorders Coagulopathy	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Infections and infestations Urinary tract infection	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 2/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Infections and infestations Nasopharyngitis	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Infections and infestations Upper respiratory tract infection	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Infections and infestations Herpes zoster	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Infections and infestations Lower respiratory tract infection	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Infections and infestations Pneumonia	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Infections and infestations Sinusitis	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Injury, poisoning and procedural complications Contusion	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	66.7% 2/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Injury, poisoning and procedural complications Back injury	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Injury, poisoning and procedural complications Blister	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Injury, poisoning and procedural complications Foot fracture	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Injury, poisoning and procedural complications Foreign body trauma	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Injury, poisoning and procedural complications Muscle strain	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Injury, poisoning and procedural complications Post procedural pain	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Psychiatric disorders Depression	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	50.0% 2/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Psychiatric disorders Anxiety	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Psychiatric disorders Confusional state	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	50.0% 2/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Psychiatric disorders Agitation	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Psychiatric disorders Insomnia	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Psychiatric disorders Libido decreased	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Psychiatric disorders Sleep disorder	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Eye disorders Blindness	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Eye disorders Conjunctivitis	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Eye disorders Madarosis	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Eye disorders Ocular icterus	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Vascular disorders Hot flush	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Vascular disorders Hypertension	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Vascular disorders Hypotension	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Cardiac disorders Tachycardia	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	12.5% 1/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Reproductive system and breast disorders Scrotal oedema	33.3% 1/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.
Surgical and medical procedures Nasal sinus drainage	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	25.0% 1/4 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/3 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.	0.00% 0/8 • From baseline through 4 weeks after the last infusion of study drug, up to 56 weeks.

Additional Information

Medical Communications

Hoffmann-LaRoche

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