Trial Outcomes & Findings for Efficacy Study of Pharmacokinetic(PK)/Pharmacodynamic(PD) Relationship of Monotherapy MORAb-004 in Metastatic Melanoma (NCT NCT01335009)

NCT ID: NCT01335009

Last Updated: 2021-09-01

Results Overview

PFS was defined as the time (in weeks) from the date of randomization to the date of the first sign of disease progression (PD) based on Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, or date of death, regardless of cause. PD greater than or equal to (\>=) 20 percent (%) increase in the nadir of total tumor burden (TTB) (minimum 5 millimeter \[mm\]). Participants who were alive with no disease progression had their PFS time censored at the date of their last tumor assessment. Participants who received a new anti-cancer therapy before disease progression had their PFS time censored at the date of their last tumor assessment before the new anti-cancer therapy was started. PFS was analyzed using Kaplan Meier method.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 76 participants
• Primary outcome timeframe: Week 24
• Results posted on: 2021-09-01

Participant Flow

Participants took part in the study at 29 sites in 4 countries (the United States, Australia, Germany, and the United Kingdom), 20 of which enrolled participants.

A total of 76 participants were randomized to treatment with MORAb-004 (40 participants in the 2 milligram per kilogram [mg/kg] group and 36 participants in the 4 mg/kg group).

Participant milestones

Measure	MORAb-004 2 mg/kg Participants received one cycle of treatment with MORAb-004 2 mg/kg, administered intravenously on Days 1, 8, 15, and 22 of the 28-day cycle (4 administrations per cycle). Participants who completed Cycle 1 continued with additional cycles without interruption or dose escalation until disease progression, using computed tomography/magnetic resonance imaging (CT/MRI) or until they discontinued the study for any reason. Participants were assessed for disease progression by CT/MRI every 8 weeks from the date of first study treatment (that is, Cycle 1 Day 1), regardless of delays in treatment.	MORAb-004 4 mg/kg Participants received one cycle of treatment with MORAb-004 4 mg/kg, administered intravenously on Days 1, 8, 15, and 22 of the 28-day cycle (4 administrations per cycle). Participants who completed Cycle 1 continued with additional cycles without interruption or dose escalation until disease progression, using CT/MRI or until they discontinued the study for any reason. Participants were assessed for disease progression by CT/MRI every 8 weeks from the date of first study treatment (that is, Cycle 1 Day 1), regardless of delays in treatment.
Overall Study STARTED	40	36
Overall Study COMPLETED	9	3
Overall Study NOT COMPLETED	31	33

Reasons for withdrawal

Measure	MORAb-004 2 mg/kg Participants received one cycle of treatment with MORAb-004 2 mg/kg, administered intravenously on Days 1, 8, 15, and 22 of the 28-day cycle (4 administrations per cycle). Participants who completed Cycle 1 continued with additional cycles without interruption or dose escalation until disease progression, using computed tomography/magnetic resonance imaging (CT/MRI) or until they discontinued the study for any reason. Participants were assessed for disease progression by CT/MRI every 8 weeks from the date of first study treatment (that is, Cycle 1 Day 1), regardless of delays in treatment.	MORAb-004 4 mg/kg Participants received one cycle of treatment with MORAb-004 4 mg/kg, administered intravenously on Days 1, 8, 15, and 22 of the 28-day cycle (4 administrations per cycle). Participants who completed Cycle 1 continued with additional cycles without interruption or dose escalation until disease progression, using CT/MRI or until they discontinued the study for any reason. Participants were assessed for disease progression by CT/MRI every 8 weeks from the date of first study treatment (that is, Cycle 1 Day 1), regardless of delays in treatment.
Overall Study Too ill to travel to study sites	1	0
Overall Study Death	28	32
Overall Study Withdrawal by Subject	1	1
Overall Study Lost to Follow-up	1	0

Baseline Characteristics

Efficacy Study of Pharmacokinetic(PK)/Pharmacodynamic(PD) Relationship of Monotherapy MORAb-004 in Metastatic Melanoma

Baseline characteristics by cohort

Measure	MORAb-004 2 mg/kg n=40 Participants Participants received one cycle of treatment with MORAb-004 2 mg/kg, administered intravenously on Days 1, 8, 15, and 22 of the 28-day cycle (4 administrations per cycle). Participants who completed Cycle 1 continued with additional cycles without interruption or dose escalation until disease progression, using CT/MRI or until they discontinued the study for any reason. Participants were assessed for disease progression by CT/MRI every 8 weeks from the date of first study treatment (that is, Cycle 1 Day 1), regardless of delays in treatment.	MORAb-004 4 mg/kg n=36 Participants Participants received one cycle of treatment with MORAb-004 4 mg/kg, administered intravenously on Days 1, 8, 15, and 22 of the 28-day cycle (4 administrations per cycle). Participants who completed Cycle 1 continued with additional cycles without interruption or dose escalation until disease progression, using CT/MRI or until they discontinued the study for any reason. Participants were assessed for disease progression by CT/MRI every 8 weeks from the date of first study treatment (that is, Cycle 1 Day 1), regardless of delays in treatment.	Total n=76 Participants Total of all reporting groups
Age, Continuous	65.1 years STANDARD_DEVIATION 12.22 • n=93 Participants	61.2 years STANDARD_DEVIATION 12.15 • n=4 Participants	63.3 years STANDARD_DEVIATION 12.26 • n=27 Participants
Sex: Female, Male Female	18 Participants n=93 Participants	9 Participants n=4 Participants	27 Participants n=27 Participants
Sex: Female, Male Male	22 Participants n=93 Participants	27 Participants n=4 Participants	49 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=93 Participants	4 Participants n=4 Participants	5 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	39 Participants n=93 Participants	32 Participants n=4 Participants	71 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) White	39 Participants n=93 Participants	34 Participants n=4 Participants	73 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants

PRIMARY outcome

Timeframe: Week 24

Population: Primary efficacy population included all participants in the safety population who meet all key eligibility criteria (including measurable disease at baseline after at least 1 systemic treatment) analyzed by the dose level to which they were randomized.

PFS was defined as the time (in weeks) from the date of randomization to the date of the first sign of disease progression (PD) based on Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, or date of death, regardless of cause. PD greater than or equal to (>=) 20 percent (%) increase in the nadir of total tumor burden (TTB) (minimum 5 millimeter [mm]). Participants who were alive with no disease progression had their PFS time censored at the date of their last tumor assessment. Participants who received a new anti-cancer therapy before disease progression had their PFS time censored at the date of their last tumor assessment before the new anti-cancer therapy was started. PFS was analyzed using Kaplan Meier method.

Outcome measures

Measure	MORAb-004 2 mg/kg n=39 Participants Participants received one cycle of treatment with MORAb-004 2 mg/kg, administered intravenously on Days 1, 8, 15, and 22 of the 28-day cycle (4 administrations per cycle). Participants who completed Cycle 1 continued with additional cycles without interruption or dose escalation until disease progression, using CT/MRI or until they discontinued the study for any reason. Participants were assessed for disease progression by CT/MRI every 8 weeks from the date of first study treatment (that is, Cycle 1 Day 1), regardless of delays in treatment.	MORAb-004 4 mg/kg n=36 Participants Participants received one cycle of treatment with MORAb-004 4 mg/kg, administered intravenously on Days 1, 8, 15, and 22 of the 28-day cycle (4 administrations per cycle). Participants who completed Cycle 1 continued with additional cycles without interruption or dose escalation until disease progression, using CT/MRI or until they discontinued the study for any reason. Participants were assessed for disease progression by CT/MRI every 8 weeks from the date of first study treatment (that is, Cycle 1 Day 1), regardless of delays in treatment.
Percentage of Participants With Progression-free Survival (PFS) at Week 24	13.5 percentage of participants Interval 5.0 to 26.4	8.9 percentage of participants Interval 2.3 to 21.3

SECONDARY outcome

Timeframe: Week 16 and Week 52

Population: Primary efficacy population included all participants in the safety population who meet all key eligibility criteria (including measurable disease at baseline after at least 1 systemic treatment) analyzed by the dose level to which they were randomized.

PFS was defined as the time (in weeks) from the date of randomization to the date of the first observation of PD (RECIST version 1.1) or date of death, regardless of the cause. PD >=20% increase in the nadir of TTB (minimum 5 mm). Participants who were alive with no disease progression had their PFS time censored at the date of their last tumor assessment. Participants who received new anti-cancer therapy before disease progression had their PFS time censored at the date of their last tumor assessment before the new anti-cancer therapy was initiated. PFS was based on the Kaplan-Meier method.

Outcome measures

Measure	MORAb-004 2 mg/kg n=39 Participants Participants received one cycle of treatment with MORAb-004 2 mg/kg, administered intravenously on Days 1, 8, 15, and 22 of the 28-day cycle (4 administrations per cycle). Participants who completed Cycle 1 continued with additional cycles without interruption or dose escalation until disease progression, using CT/MRI or until they discontinued the study for any reason. Participants were assessed for disease progression by CT/MRI every 8 weeks from the date of first study treatment (that is, Cycle 1 Day 1), regardless of delays in treatment.	MORAb-004 4 mg/kg n=36 Participants Participants received one cycle of treatment with MORAb-004 4 mg/kg, administered intravenously on Days 1, 8, 15, and 22 of the 28-day cycle (4 administrations per cycle). Participants who completed Cycle 1 continued with additional cycles without interruption or dose escalation until disease progression, using CT/MRI or until they discontinued the study for any reason. Participants were assessed for disease progression by CT/MRI every 8 weeks from the date of first study treatment (that is, Cycle 1 Day 1), regardless of delays in treatment.
Percentage of Participants With PFS at Weeks 16 and 52 Week 16	32.5 percentage of participants Interval 18.3 to 47.6	20.8 percentage of participants Interval 9.2 to 35.7
Percentage of Participants With PFS at Weeks 16 and 52 Week 52	NA percentage of participants Data from pre-specified Kaplan Meier estimation was inestimable, because of no available participants with events at Week 52.	8.9 percentage of participants Interval 2.3 to 21.3

SECONDARY outcome

Timeframe: Date of first study treatment (Day 1) to date of death or up to approximately 2 years 7 months

Population: Primary efficacy population included all participants in the safety population who meet all key eligibility criteria (including measurable disease at baseline after at least 1 systemic treatment) analyzed by the dose level to which they were randomized. Participants without documentation of death at the time of analysis were censored at the date last known to be alive.

OS was defined as the time (in weeks) from the date of randomization to the date of death, regardless of cause. In the absence of death confirmation, or for participants alive at the time of analysis, the survival time was censored at the date of the last study follow-up. OS was calculated using the Kaplan-Meier method. As per planned analysis, efficacy outcomes was planned to be analyzed until cut-off date (02 December 2013).

Outcome measures

Measure	MORAb-004 2 mg/kg n=39 Participants Participants received one cycle of treatment with MORAb-004 2 mg/kg, administered intravenously on Days 1, 8, 15, and 22 of the 28-day cycle (4 administrations per cycle). Participants who completed Cycle 1 continued with additional cycles without interruption or dose escalation until disease progression, using CT/MRI or until they discontinued the study for any reason. Participants were assessed for disease progression by CT/MRI every 8 weeks from the date of first study treatment (that is, Cycle 1 Day 1), regardless of delays in treatment.	MORAb-004 4 mg/kg n=36 Participants Participants received one cycle of treatment with MORAb-004 4 mg/kg, administered intravenously on Days 1, 8, 15, and 22 of the 28-day cycle (4 administrations per cycle). Participants who completed Cycle 1 continued with additional cycles without interruption or dose escalation until disease progression, using CT/MRI or until they discontinued the study for any reason. Participants were assessed for disease progression by CT/MRI every 8 weeks from the date of first study treatment (that is, Cycle 1 Day 1), regardless of delays in treatment.
Overall Survival (OS)	40.9 weeks Interval 29.0 to 53.3	29.3 weeks Interval 22.9 to 35.4

SECONDARY outcome

Timeframe: Date of first study treatment (Day 1) to complete response or partial response, assessed up to approximately 2 years 7 months

Population: ORR population included a subset of participants from the primary efficacy population who had at least 1 on-study radiologic evaluation performed (in addition to their baseline evaluation), analyzed by the dose level received.

ORR was defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) that occurred (defined by RECIST version 1.1) using CT/MRI. Per RECIST 1.1, CR= disappearance of all lesions; PR greater than or equal to (>=) 30percent (%) decrease from baseline in TTB. As per planned analysis, efficacy outcomes was planned to be analyzed until cut-off date (02 December 2013).

Outcome measures

Measure	MORAb-004 2 mg/kg n=34 Participants Participants received one cycle of treatment with MORAb-004 2 mg/kg, administered intravenously on Days 1, 8, 15, and 22 of the 28-day cycle (4 administrations per cycle). Participants who completed Cycle 1 continued with additional cycles without interruption or dose escalation until disease progression, using CT/MRI or until they discontinued the study for any reason. Participants were assessed for disease progression by CT/MRI every 8 weeks from the date of first study treatment (that is, Cycle 1 Day 1), regardless of delays in treatment.	MORAb-004 4 mg/kg n=32 Participants Participants received one cycle of treatment with MORAb-004 4 mg/kg, administered intravenously on Days 1, 8, 15, and 22 of the 28-day cycle (4 administrations per cycle). Participants who completed Cycle 1 continued with additional cycles without interruption or dose escalation until disease progression, using CT/MRI or until they discontinued the study for any reason. Participants were assessed for disease progression by CT/MRI every 8 weeks from the date of first study treatment (that is, Cycle 1 Day 1), regardless of delays in treatment.
Percentage of Participants With Overall Response	NA percentage of participants Data was inestimable, because of no available participants with events at Week 52.	3.1 percentage of participants Interval 0.0 to 9.2

SECONDARY outcome

Timeframe: Day 1 Cycle 1 (Cycle length = 28 days)

Population: All participants in the safety population who receive at least one dose of MORAb-004 and who had at least one on-treatment PK/PD assessment performed that is sufficient to evaluate the endpoint of interest. Here "overall number of participants analyzed" are participants who were available for this outcome measure.

OBD is defined as the dose level/exposure level at which three parameters are met: 1) adequate pharmacokinetic (PK) profile with a serum half-life (t1/2) of >=48 hours, 2) at least minimal demonstration of antitumor efficacy (50% or greater PFS rate at 16 weeks), and 3) change of 25% or greater from baseline value in any of the pharmacodynamic (PD) parameters assessed in the study in 30% of participants at that dose level.

Outcome measures

Measure	MORAb-004 2 mg/kg n=39 Participants Participants received one cycle of treatment with MORAb-004 2 mg/kg, administered intravenously on Days 1, 8, 15, and 22 of the 28-day cycle (4 administrations per cycle). Participants who completed Cycle 1 continued with additional cycles without interruption or dose escalation until disease progression, using CT/MRI or until they discontinued the study for any reason. Participants were assessed for disease progression by CT/MRI every 8 weeks from the date of first study treatment (that is, Cycle 1 Day 1), regardless of delays in treatment.	MORAb-004 4 mg/kg n=36 Participants Participants received one cycle of treatment with MORAb-004 4 mg/kg, administered intravenously on Days 1, 8, 15, and 22 of the 28-day cycle (4 administrations per cycle). Participants who completed Cycle 1 continued with additional cycles without interruption or dose escalation until disease progression, using CT/MRI or until they discontinued the study for any reason. Participants were assessed for disease progression by CT/MRI every 8 weeks from the date of first study treatment (that is, Cycle 1 Day 1), regardless of delays in treatment.
Optimal Biologic Dosing (OBD) of Morab-004	NA milligram(s) Here 'NA' signifies that OBD was not evaluated due to minimal antitumor efficacy (less than 50%) and percentage of participants with response was too low hence, was not demonstrated.	NA milligram(s) Here 'NA' signifies that OBD was not evaluated due to minimal antitumor efficacy (less than 50%) and percentage of participants with response was too low hence, was not demonstrated.

Adverse Events

MORAb-004 2 mg/kg

Serious events: 17 serious events

Other events: 40 other events

Deaths: 28 deaths

MORAb-004 4 mg/kg

Serious events: 16 serious events

Other events: 36 other events

Deaths: 32 deaths

Serious adverse events

Measure	MORAb-004 2 mg/kg n=40 participants at risk Participants received one cycle of treatment with MORAb-004 2 mg/kg, administered intravenously on Days 1, 8, 15, and 22 of the 28-day cycle (4 administrations per cycle). Participants who completed Cycle 1 continued with additional cycles without interruption or dose escalation until disease progression, using CT/MRI or until they discontinued the study for any reason. Participants were assessed for disease progression by CT/MRI every 8 weeks from the date of first study treatment (that is, Cycle 1 Day 1), regardless of delays in treatment.	MORAb-004 4 mg/kg n=36 participants at risk Participants received one cycle of treatment with MORAb-004 4 mg/kg, administered intravenously on Days 1, 8, 15, and 22 of the 28-day cycle (4 administrations per cycle). Participants who completed Cycle 1 continued with additional cycles without interruption or dose escalation until disease progression, using CT/MRI or until they discontinued the study for any reason. Participants were assessed for disease progression by CT/MRI every 8 weeks from the date of first study treatment (that is, Cycle 1 Day 1), regardless of delays in treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic malignant melanoma	7.5% 3/40 • Number of events 3 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine carcinoma of the skin	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Infections and infestations Cellulitis	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	8.3% 3/36 • Number of events 3 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Infections and infestations Sepsis	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Infections and infestations Septic shock	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Infections and infestations Urosepsis	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Infections and infestations Wound infection	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
General disorders Infusion related reaction	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	5.6% 2/36 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
General disorders Pyrexia	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	5.6% 2/36 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
General disorders Chills	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
General disorders Fatigue	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Cardiac disorders Acute myocardial infarction	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Cardiac disorders Atrial fibrillation	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Cardiac disorders Bradycardia	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Cardiac disorders Pericardial effusion	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	5.0% 2/40 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Blood and lymphatic system disorders Anaemia	5.0% 2/40 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Gastrointestinal disorders Abdominal pain	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Gastrointestinal disorders Nausea	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Nervous system disorders Brain oedema	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Nervous system disorders Syncope	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Nervous system disorders Toxic encephalopathy	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Psychiatric disorders Confusional state	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Hepatobiliary disorders Cholecystitis acute	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Immune system disorders Hypersensitivity	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Musculoskeletal and connective tissue disorders Pain in extremity	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Renal and urinary disorders Hydronephrosis	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Vascular disorders Lymphoedema	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Vascular disorders Deep vein thrombosis	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	8.3% 3/36 • Number of events 3 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Infections and infestations Tumour haemorrhage	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
General disorders Delirium	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Psychiatric disorders Mental status changes	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Injury, poisoning and procedural complications Tibia fracture	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Infections and infestations Pneumonia	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.

Other adverse events

Measure	MORAb-004 2 mg/kg n=40 participants at risk Participants received one cycle of treatment with MORAb-004 2 mg/kg, administered intravenously on Days 1, 8, 15, and 22 of the 28-day cycle (4 administrations per cycle). Participants who completed Cycle 1 continued with additional cycles without interruption or dose escalation until disease progression, using CT/MRI or until they discontinued the study for any reason. Participants were assessed for disease progression by CT/MRI every 8 weeks from the date of first study treatment (that is, Cycle 1 Day 1), regardless of delays in treatment.	MORAb-004 4 mg/kg n=36 participants at risk Participants received one cycle of treatment with MORAb-004 4 mg/kg, administered intravenously on Days 1, 8, 15, and 22 of the 28-day cycle (4 administrations per cycle). Participants who completed Cycle 1 continued with additional cycles without interruption or dose escalation until disease progression, using CT/MRI or until they discontinued the study for any reason. Participants were assessed for disease progression by CT/MRI every 8 weeks from the date of first study treatment (that is, Cycle 1 Day 1), regardless of delays in treatment.
General disorders Fatigue	45.0% 18/40 • Number of events 28 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	50.0% 18/36 • Number of events 28 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
General disorders Chills	32.5% 13/40 • Number of events 13 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	50.0% 18/36 • Number of events 20 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
General disorders Pyrexia	22.5% 9/40 • Number of events 11 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	33.3% 12/36 • Number of events 17 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
General disorders Infusion related reaction	10.0% 4/40 • Number of events 4 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 3 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
General disorders Oedema peripheral	10.0% 4/40 • Number of events 4 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	8.3% 3/36 • Number of events 6 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
General disorders Influenza like illness	7.5% 3/40 • Number of events 3 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Gastrointestinal disorders Nausea	32.5% 13/40 • Number of events 18 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	41.7% 15/36 • Number of events 21 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Gastrointestinal disorders Constipation	22.5% 9/40 • Number of events 11 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	25.0% 9/36 • Number of events 9 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Gastrointestinal disorders Vomiting	7.5% 3/40 • Number of events 3 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	25.0% 9/36 • Number of events 12 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Gastrointestinal disorders Abdominal pain	12.5% 5/40 • Number of events 5 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	13.9% 5/36 • Number of events 6 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Gastrointestinal disorders Diarrhoea	10.0% 4/40 • Number of events 4 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	16.7% 6/36 • Number of events 10 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Gastrointestinal disorders Dyspepsia	10.0% 4/40 • Number of events 4 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	8.3% 3/36 • Number of events 4 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Nervous system disorders Headache	52.5% 21/40 • Number of events 35 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	58.3% 21/36 • Number of events 31 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Nervous system disorders Dizziness	7.5% 3/40 • Number of events 4 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	11.1% 4/36 • Number of events 4 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Nervous system disorders Tremor	5.0% 2/40 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	5.6% 2/36 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Musculoskeletal and connective tissue disorders Arthralgia	22.5% 9/40 • Number of events 10 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	13.9% 5/36 • Number of events 6 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Musculoskeletal and connective tissue disorders Back pain	12.5% 5/40 • Number of events 5 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	25.0% 9/36 • Number of events 9 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Musculoskeletal and connective tissue disorders Pain in extremity	10.0% 4/40 • Number of events 5 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	8.3% 3/36 • Number of events 3 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Musculoskeletal and connective tissue disorders Myalgia	2.5% 1/40 • Number of events 3 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	8.3% 3/36 • Number of events 3 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Metabolism and nutrition disorders Decreased appetite	22.5% 9/40 • Number of events 14 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	30.6% 11/36 • Number of events 12 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Metabolism and nutrition disorders Hyponatraemia	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	11.1% 4/36 • Number of events 5 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Respiratory, thoracic and mediastinal disorders Cough	12.5% 5/40 • Number of events 9 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	22.2% 8/36 • Number of events 9 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.0% 4/40 • Number of events 6 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	16.7% 6/36 • Number of events 7 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	10.0% 4/40 • Number of events 4 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	5.6% 2/36 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Blood and lymphatic system disorders Anaemia	20.0% 8/40 • Number of events 16 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	27.8% 10/36 • Number of events 22 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Infections and infestations Urinary tract infection	5.0% 2/40 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	13.9% 5/36 • Number of events 5 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Infections and infestations Cellulitis	5.0% 2/40 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract infection	7.5% 3/40 • Number of events 3 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Skin and subcutaneous tissue disorders Erythema	5.0% 2/40 • Number of events 3 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	8.3% 3/36 • Number of events 4 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Skin and subcutaneous tissue disorders Pruritus	7.5% 3/40 • Number of events 4 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	5.6% 2/36 • Number of events 3 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Skin and subcutaneous tissue disorders Night sweats	5.0% 2/40 • Number of events 3 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	5.6% 2/36 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Skin and subcutaneous tissue disorders Rash	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	8.3% 3/36 • Number of events 3 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Psychiatric disorders Anxiety	5.0% 2/40 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	11.1% 4/36 • Number of events 4 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Psychiatric disorders Confusional state	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	11.1% 4/36 • Number of events 6 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Injury, poisoning and procedural complications Procedural pain	7.5% 3/40 • Number of events 3 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Vascular disorders Hypertension	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	8.3% 3/36 • Number of events 3 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Skin and subcutaneous tissue disorders Rash generalised	2.5% 1/40 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Skin and subcutaneous tissue disorders Rash macular	2.5% 1/40 • Number of events 3 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Blood and lymphatic system disorders Lymph node pain	5.0% 2/40 • Number of events 5 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Cardiac disorders Arrhythmia supraventricular	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Cardiac disorders Sinus bradycardia	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Cardiac disorders Sinus tachycardia	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Eye disorders Diabetic retinopathy	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Eye disorders Eye discharge	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Eye disorders Eye pain	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Eye disorders Macular oedema	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Eye disorders Vision blurred	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Eye disorders Vitreous haemorrhage	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Gastrointestinal disorders Abdominal discomfort	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Gastrointestinal disorders Abdominal pain lower	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Gastrointestinal disorders Abdominal pain upper	5.0% 2/40 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 3 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Gastrointestinal disorders Abdominal tenderness	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Gastrointestinal disorders Colitis	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Gastrointestinal disorders Dental caries	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Gastrointestinal disorders Dry mouth	5.0% 2/40 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Gastrointestinal disorders Frequent bowel movements	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	5.6% 2/36 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Gastrointestinal disorders Gingival bleeding	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Gastrointestinal disorders Haematochezia	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Gastrointestinal disorders Intussusception	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Gastrointestinal disorders Stomatitis	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Gastrointestinal disorders Toothache	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	5.6% 2/36 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
General disorders Feeling cold	5.0% 2/40 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
General disorders Feeling hot	5.0% 2/40 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
General disorders Hernia	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
General disorders Infusion site extravasation	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	5.6% 2/36 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
General disorders Localised oedema	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
General disorders Pain	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
General disorders Swelling	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Immune system disorders Drug hypersensitivity	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Immune system disorders Hypersensitivity	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Immune system disorders Seasonal allergy	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Infections and infestations Cystitis	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Infections and infestations Folliculitis	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Infections and infestations Fungal skin infection	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Infections and infestations Gastroenteritis	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Infections and infestations Herpes zoster	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Infections and infestations Infection	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Infections and infestations Influenza	5.0% 2/40 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Infections and infestations Lung infection	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Infections and infestations Nasopharyngitis	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Infections and infestations Oral candidiasis	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Infections and infestations Oral herpes	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Infections and infestations Pneumonia	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Infections and infestations Rhinitis	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Infections and infestations Sinusitis	5.0% 2/40 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Injury, poisoning and procedural complications Contusion	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Injury, poisoning and procedural complications Excoriation	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Injury, poisoning and procedural complications Incision site pain	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Injury, poisoning and procedural complications Joint dislocation	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Injury, poisoning and procedural complications Joint sprain	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Injury, poisoning and procedural complications Skin laceration	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Infections and infestations Skin infection	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	5.6% 2/36 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Infections and infestations Upper respiratory tract infection	7.5% 3/40 • Number of events 3 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Injury, poisoning and procedural complications Tongue injury	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Investigations Alanine aminotransferase increased	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	5.6% 2/36 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Investigations Aspartate aminotransferase increased	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	5.6% 2/36 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Investigations Blood alkaline phosphatase increased	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Investigations Blood bilirubin increased	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Investigations Blood creatinine increased	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Investigations Blood glucose increased	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Investigations Blood pressure increased	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Investigations Blood urea increased	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Investigations Blood uric acid increased	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Investigations Blood urine present	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Investigations Breath sounds abnormal	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Investigations Electrocardiogram QT prolonged	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Investigations Electrocardiogram RR interval prolonged	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Investigations Eosinophil count increased	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Investigations International normalised ratio increased	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Investigations Lipase increased	2.5% 1/40 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Investigations Lymphocyte count decreased	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Investigations Protein urine present	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Investigations Prothrombin time prolonged	2.5% 1/40 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Investigations QRS axis abnormal	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Investigations Respiratory rate increased	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	5.6% 2/36 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Investigations Specific gravity urine increased	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Investigations Weight decreased	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Investigations Weight increased	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Investigations White blood cell count increased	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Investigations White blood cells urine positive	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Metabolism and nutrition disorders Dehydration	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Metabolism and nutrition disorders Hyperglycaemia	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Metabolism and nutrition disorders Hyperlipidaemia	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Metabolism and nutrition disorders Hypocalcaemia	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Metabolism and nutrition disorders Hypoalbuminaemia	5.0% 2/40 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Metabolism and nutrition disorders Hypokalaemia	5.0% 2/40 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	5.6% 2/36 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Metabolism and nutrition disorders Hypophosphataemia	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Musculoskeletal and connective tissue disorders Arthritis	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Musculoskeletal and connective tissue disorders Joint stiffness	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Musculoskeletal and connective tissue disorders Muscle spasms	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Musculoskeletal and connective tissue disorders Muscular weakness	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	13.9% 5/36 • Number of events 5 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	5.6% 2/36 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Musculoskeletal and connective tissue disorders Osteoarthritis	5.0% 2/40 • Number of events 3 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	15.0% 6/40 • Number of events 10 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Nervous system disorders Aphasia	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Nervous system disorders Balance disorder	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Nervous system disorders Brain oedema	2.5% 1/40 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Nervous system disorders Coma	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Nervous system disorders Disturbance in attention	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Nervous system disorders Dysgeusia	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	5.6% 2/36 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Nervous system disorders Dyskinesia	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Nervous system disorders Hypoaesthesia	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Nervous system disorders Memory impairment	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Nervous system disorders Neuralgia	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Nervous system disorders Paraesthesia	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Nervous system disorders Peripheral sensory neuropathy	5.0% 2/40 • Number of events 4 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Nervous system disorders Sciatica	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Nervous system disorders Sinus headache	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Nervous system disorders Somnolence	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	5.6% 2/36 • Number of events 4 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Psychiatric disorders Agitation	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Psychiatric disorders Depression	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	5.6% 2/36 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Psychiatric disorders Disorientation	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Psychiatric disorders Insomnia	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	5.6% 2/36 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Psychiatric disorders Mood altered	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Psychiatric disorders Nightmare	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Renal and urinary disorders Dysuria	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Renal and urinary disorders Haematuria	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Renal and urinary disorders Hypertonic bladder	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Renal and urinary disorders Proteinuria	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Renal and urinary disorders Urinary retention	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Reproductive system and breast disorders Balanitis	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Reproductive system and breast disorders Scrotal oedema	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Respiratory, thoracic and mediastinal disorders Nasal congestion	7.5% 3/40 • Number of events 3 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.0% 2/40 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Respiratory, thoracic and mediastinal disorders Postnasal drip	2.5% 1/40 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Respiratory, thoracic and mediastinal disorders Productive cough	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Respiratory, thoracic and mediastinal disorders Pulmonary congestion	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Respiratory, thoracic and mediastinal disorders Rhonchi	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Skin and subcutaneous tissue disorders Alopecia	2.5% 1/40 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Skin and subcutaneous tissue disorders Blister	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Skin and subcutaneous tissue disorders Dry skin	5.0% 2/40 • Number of events 4 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Skin and subcutaneous tissue disorders Fungating wound	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Skin and subcutaneous tissue disorders Hyperhidrosis	5.0% 2/40 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Skin and subcutaneous tissue disorders Intertrigo	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Skin and subcutaneous tissue disorders Skin discolouration	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Skin and subcutaneous tissue disorders Skin disorder	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Skin and subcutaneous tissue disorders Skin exfoliation	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Skin and subcutaneous tissue disorders Skin haemorrhage	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Skin and subcutaneous tissue disorders Subcutaneous nodule	2.5% 1/40 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Skin and subcutaneous tissue disorders Swelling face	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Skin and subcutaneous tissue disorders Vitiligo	5.0% 2/40 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Vascular disorders Deep vein thrombosis	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Vascular disorders Flushing	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Vascular disorders Hot flush	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Vascular disorders Hypotension	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	5.6% 2/36 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Vascular disorders Orthostatic hypotension	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Vascular disorders Vena cava thrombosis	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Vascular disorders Lymphoedema	5.0% 2/40 • Number of events 3 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Blood and lymphatic system disorders Lymphopenia	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	5.6% 2/36 • Number of events 5 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Blood and lymphatic system disorders Atrial flutter	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Ear and labyrinth disorders Vertigo	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Eye disorders Conjunctival oedema	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Gastrointestinal disorders Dysphagia	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Gastrointestinal disorders Flatulence	5.0% 2/40 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	0.00% 0/36 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
General disorders Asthenia	2.5% 1/40 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 1 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.
Gastrointestinal disorders Abdominal distension	0.00% 0/40 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.	2.8% 1/36 • Number of events 2 • From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months) Safety population included all randomized participants who received at least 1 dose of study drug, analyzed by the actual treatment received. The severity of AE toxicities was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, v4.03, where applicable.

Additional Information

Eisai Medical Information

Eisai Inc.

Phone: 18882742378

Email: esi_medinfo@eisai.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place