Trial Outcomes & Findings for ONO-4538 Study in Patients With Advanced Non-Small Cell Lung Cancer (NCT NCT02175017)

NCT ID: NCT02175017

Last Updated: 2024-12-09

Results Overview

Response rate (%) = (Number of subjects whose confirmed best overall response was complete response (CR) or partial response (PR) / Total number of FAS)\*100. 95% Confidence interval (CI) was calculated by Wilson method.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 104 participants
• Primary outcome timeframe: Screening phase: Up to 14 days before enrollment.Treatment phase: Day 43 of each cycle or end of treatment phase (up to approximately 10 months).Follow-up phase: 28 days after final dose or for discontinuation occurring 28 or fewer days after final dose.
• Results posted on: 2024-12-09

Participant Flow

Of 104 subjects determined eligible, 1 had an unknown histological type and excluded.

Participant milestones

Measure	Squamous Non-small Cell Lung Cancer (NSCLC) In each treatment cycle, patients received an intravenous infusion of nivolumab (ONO-4538) at a dose of 3 mg/kg with 2-week dosing intervals for 6 weeks. Radiological assessments (computed tomography/ magnetic resonance imaging) were conducted every 6 weeks. Patients entered subsequent treatment cycles unless they met discontinuation criteria, including disease progression, unacceptable adverse events, and consent withdrawal. Patients who were discontinued for any of these reasons entered the follow-up phase.	Non-squamous Non-small Cell Lung Cancer (NSCLC) In each treatment cycle, patients received an intravenous infusion of nivolumab (ONO-4538) at a dose of 3 mg/kg with 2-week dosing intervals for 6 weeks. Radiological assessments (computed tomography/ magnetic resonance imaging) were conducted every 6 weeks. Patients entered subsequent treatment cycles unless they met discontinuation criteria, including disease progression, unacceptable adverse events, and consent withdrawal. Patients who were discontinued for any of these reasons entered the follow-up phase.
Overall Study STARTED	45	58
Overall Study COMPLETED	12	15
Overall Study NOT COMPLETED	33	43

Reasons for withdrawal

Measure	Squamous Non-small Cell Lung Cancer (NSCLC) In each treatment cycle, patients received an intravenous infusion of nivolumab (ONO-4538) at a dose of 3 mg/kg with 2-week dosing intervals for 6 weeks. Radiological assessments (computed tomography/ magnetic resonance imaging) were conducted every 6 weeks. Patients entered subsequent treatment cycles unless they met discontinuation criteria, including disease progression, unacceptable adverse events, and consent withdrawal. Patients who were discontinued for any of these reasons entered the follow-up phase.	Non-squamous Non-small Cell Lung Cancer (NSCLC) In each treatment cycle, patients received an intravenous infusion of nivolumab (ONO-4538) at a dose of 3 mg/kg with 2-week dosing intervals for 6 weeks. Radiological assessments (computed tomography/ magnetic resonance imaging) were conducted every 6 weeks. Patients entered subsequent treatment cycles unless they met discontinuation criteria, including disease progression, unacceptable adverse events, and consent withdrawal. Patients who were discontinued for any of these reasons entered the follow-up phase.
Overall Study Did not receive the investigational product	1	2
Overall Study Withdrawal by Subject	6	3
Overall Study Met an exclusion criteria	0	1
Overall Study Adverse Event	3	10
Overall Study Disease progression	20	27
Overall Study Other than above reasons	3	0

Baseline Characteristics

ONO-4538 Study in Patients With Advanced Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Measure	Squamous Non-small Cell Lung Cancer (NSCLC) n=44 Participants Refer to "Participant Flow".	Non-squamous Non-small Cell Lung Cancer (NSCLC) n=56 Participants Refer to "Participant Flow".	Total n=100 Participants Total of all reporting groups
Age, Continuous	69.5 years n=5 Participants	63.5 years n=7 Participants	66.5 years n=5 Participants
Age, Customized <65 years	14 Participants n=5 Participants	30 Participants n=7 Participants	44 Participants n=5 Participants
Age, Customized 65-<75 years	21 Participants n=5 Participants	20 Participants n=7 Participants	41 Participants n=5 Participants
Age, Customized >=75 years	9 Participants n=5 Participants	6 Participants n=7 Participants	15 Participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	22 Participants n=7 Participants	22 Participants n=5 Participants
Sex: Female, Male Male	44 Participants n=5 Participants	34 Participants n=7 Participants	78 Participants n=5 Participants
Region of Enrollment South Korea	44 Participants n=5 Participants	56 Participants n=7 Participants	100 Participants n=5 Participants
Histology Squamous	44 Participants n=5 Participants	0 Participants n=7 Participants	44 Participants n=5 Participants
Histology Adenocarcinoma	0 Participants n=5 Participants	50 Participants n=7 Participants	50 Participants n=5 Participants
Histology Large cell carcinoma	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Histology Other	0 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants
Disease stage IIIB	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants
Disease stage IV	37 Participants n=5 Participants	54 Participants n=7 Participants	91 Participants n=5 Participants
Disease stage Recurrent	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Prior treatment for NSCLC: Surgery Yes	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Prior treatment for NSCLC: Surgery No	35 Participants n=5 Participants	47 Participants n=7 Participants	82 Participants n=5 Participants
Prior treatment for NSCLC: Radiotherapy Yes	11 Participants n=5 Participants	13 Participants n=7 Participants	24 Participants n=5 Participants
Prior treatment for NSCLC: Radiotherapy No	33 Participants n=5 Participants	43 Participants n=7 Participants	76 Participants n=5 Participants
Prior treatment for NSCLC-Medication: Platinum-based chemotherapy Yes	44 Participants n=5 Participants	56 Participants n=7 Participants	100 Participants n=5 Participants
Prior treatment for NSCLC-Medication: Platinum-based chemotherapy No	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Prior treatment for NSCLC-Medication: EGFR-TKI therapy Yes	1 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants
Prior treatment for NSCLC-Medication: EGFR-TKI therapy No	43 Participants n=5 Participants	49 Participants n=7 Participants	92 Participants n=5 Participants
Number of treatment regimens for NSCLC 1	42 Participants n=5 Participants	49 Participants n=7 Participants	91 Participants n=5 Participants
Number of treatment regimens for NSCLC 2	2 Participants n=5 Participants	7 Participants n=7 Participants	9 Participants n=5 Participants
Smoking history Never smoker	1 Participants n=5 Participants	21 Participants n=7 Participants	22 Participants n=5 Participants
Smoking history Current/former smoker	43 Participants n=5 Participants	35 Participants n=7 Participants	78 Participants n=5 Participants
Eastern Cooperative Oncology Group performance status 0	6 Participants n=5 Participants	8 Participants n=7 Participants	14 Participants n=5 Participants
Eastern Cooperative Oncology Group performance status 1	38 Participants n=5 Participants	48 Participants n=7 Participants	86 Participants n=5 Participants
Brain metastasis Yes	10 Participants n=5 Participants	16 Participants n=7 Participants	26 Participants n=5 Participants
Brain metastasis No	34 Participants n=5 Participants	40 Participants n=7 Participants	74 Participants n=5 Participants
EGFR status Positive	1 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants
EGFR status Negative	13 Participants n=5 Participants	43 Participants n=7 Participants	56 Participants n=5 Participants
EGFR status Unknown	30 Participants n=5 Participants	6 Participants n=7 Participants	36 Participants n=5 Participants

PRIMARY outcome

Timeframe: Screening phase: Up to 14 days before enrollment.Treatment phase: Day 43 of each cycle or end of treatment phase (up to approximately 10 months).Follow-up phase: 28 days after final dose or for discontinuation occurring 28 or fewer days after final dose.

Population: Full analysis set（FAS): This set was defined as a full group of subjects who were included in safety analysis set, which was defined as group of subjects who were enrolled and received at least one dose of the study drug. This set was used in the primary efficacy evaluation.

Response rate (%) = (Number of subjects whose confirmed best overall response was complete response (CR) or partial response (PR) / Total number of FAS)*100. 95% Confidence interval (CI) was calculated by Wilson method.

Outcome measures

Measure	Squamous Non-small Cell Lung Cancer (NSCLC) n=44 Participants Refer to "Participant Flow".	Non-squamous Non-small Cell Lung Cancer (NSCLC) n=56 Participants Refer to "Participant Flow".
Response Rate (Centrally Assessed)	13.6 percentage of participants Interval 6.4 to 26.7	19.6 percentage of participants Interval 11.3 to 31.8

SECONDARY outcome

Timeframe: Screening phase: Up to 14 days before enrollment.Treatment phase: Day 43 of each cycle or end of treatment phase (up to approximately 10 months).Follow-up phase: 28 days after final dose or for discontinuation occurring 28 or fewer days after final dose.

Population: FAS

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Outcome measures

Measure	Squamous Non-small Cell Lung Cancer (NSCLC) n=44 Participants Refer to "Participant Flow".	Non-squamous Non-small Cell Lung Cancer (NSCLC) n=56 Participants Refer to "Participant Flow".
Response Rate (Investigator-assessed)	18.2 percentage of participants Interval 9.5 to 32.0	19.6 percentage of participants Interval 11.3 to 31.8

SECONDARY outcome

Timeframe: Follow-up phase: Every 6 months after the first day of treatment of the last subject enrolled in the study, until death or study completion.

Population: FAS

Overall survival (days) = (the date of death due to any cause) - (the first dose date of investigational product) + 1. 95% CI was calculated by Kaplan-Meier method.

Outcome measures

Measure	Squamous Non-small Cell Lung Cancer (NSCLC) n=44 Participants Refer to "Participant Flow".	Non-squamous Non-small Cell Lung Cancer (NSCLC) n=56 Participants Refer to "Participant Flow".
Overall Survival	NA days Interval 249.0 to During the period up to the cut-off, 27 (27.0%) out of 100 subjects in the FAS died (fatal) \[squamous NSCLC 12 subjects (27.3%), non-squamous NSCLC 15 subjects (26.8%)\] and median overall survival could not be estimated. And the upper limit of the 95% CI for the median could not be obtained. There was an insufficient number of participants with events.	NA days Interval 291.0 to During the period up to the cut-off, 27 (27.0%) out of 100 subjects in the FAS died (fatal) \[squamous NSCLC 12 subjects (27.3%), non-squamous NSCLC 15 subjects (26.8%)\] and median overall survival could not be estimated. And the upper limit of the 95% CI for the median could not be obtained. There was an insufficient number with events.

SECONDARY outcome

Timeframe: Screening phase: Up to 14 days before enrollment.Treatment phase: Day 43 of each cycle or until central PD was confirmed or data cut-off point.Follow-up phase: Until beginning subsequent treatment for non-small cell lung cancer or PD or recurrence.

Population: FAS

Progression free survival (days) = (the earlier date of the first documented progressive disease (PD) or death due to any cause) - (the first dose date of investigational product) + 1. 95% CI was calculated by Kaplan-Meier method.

Outcome measures

Measure	Squamous Non-small Cell Lung Cancer (NSCLC) n=44 Participants Refer to "Participant Flow".	Non-squamous Non-small Cell Lung Cancer (NSCLC) n=56 Participants Refer to "Participant Flow".
Progression Free Survival (Centrally Assessed)	67.0 days Interval 41.0 to 182.0	162.0 days Interval 43.0 to 216.0

SECONDARY outcome

Timeframe: Screening phase: Up to 14 days before enrollment.Treatment phase: Day 43 of each cycle or end of treatment phase(up to approximately 10 months).Follow-up phase: Until beginning subsequent treatment for non-small cell lung cancer or PD or recurrence.

Population: FAS

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Duration of response (days) = (the date of the first documented PD or death due to any cause after response was confirmed) - (the date of the first confirmed CR or PR) + 1. Median (95% CI) was calculated by Kaplan-Meier method.

Outcome measures

Measure	Squamous Non-small Cell Lung Cancer (NSCLC) n=44 Participants Refer to "Participant Flow".	Non-squamous Non-small Cell Lung Cancer (NSCLC) n=56 Participants Refer to "Participant Flow".
Duration of Response (Centrally Assessed)	NA days Interval 145.0 to Median duration of response could not be estimated and the upper limit of the 95% CI for the median could not be obtained. There was an insufficient number of participants with events.	NA days Interval 85.0 to Median duration of response could not be estimated and the upper limit of the 95% CI for the median could not be obtained. There was an insufficient number of participants with events.

Adverse Events

Squamous Non-small Cell Lung Cancer (NSCLC)

Serious events: 20 serious events

Other events: 24 other events

Deaths: 12 deaths

Non-squamous Non-small Cell Lung Cancer (NSCLC)

Serious events: 17 serious events

Other events: 36 other events

Deaths: 15 deaths

Serious adverse events

Measure	Squamous Non-small Cell Lung Cancer (NSCLC) n=44 participants at risk Refer to "Participant Flow".	Non-squamous Non-small Cell Lung Cancer (NSCLC) n=56 participants at risk Refer to "Participant Flow".
Cardiac disorders Angina unstable	2.3% 1/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	0.00% 0/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Cardiac disorders Cardiac failure	0.00% 0/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	1.8% 1/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Gastrointestinal disorders Diarrhoea	2.3% 1/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	0.00% 0/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	1.8% 1/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Gastrointestinal disorders Ileus	0.00% 0/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	1.8% 1/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Gastrointestinal disorders Inguinal hernia	2.3% 1/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	0.00% 0/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
General disorders Asthenia	0.00% 0/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	1.8% 1/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
General disorders Pyrexia	4.5% 2/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	0.00% 0/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Infections and infestations Pneumonia	11.4% 5/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	7.1% 4/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Infections and infestations Sialoadenitis	0.00% 0/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	1.8% 1/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Infections and infestations Lung infection	2.3% 1/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	1.8% 1/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Injury, poisoning and procedural complications Subdural haemorrhage	2.3% 1/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	0.00% 0/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Metabolism and nutrition disorders Diabetes mellitus	2.3% 1/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	0.00% 0/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Metabolism and nutrition disorders Hypercalcaemia	6.8% 3/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	0.00% 0/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	1.8% 1/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Metabolism and nutrition disorders Decreased appetite	2.3% 1/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	0.00% 0/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	1.8% 1/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Musculoskeletal and connective tissue disorders Myalgia	2.3% 1/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	0.00% 0/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Musculoskeletal and connective tissue disorders Pain in extremity	2.3% 1/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	0.00% 0/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to spine	0.00% 0/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	1.8% 1/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.00% 0/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	1.8% 1/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm progression	2.3% 1/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	1.8% 1/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Nervous system disorders Cerebral infarction	2.3% 1/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	0.00% 0/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Nervous system disorders Dizziness	0.00% 0/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	1.8% 1/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Nervous system disorders Hemiparesis	2.3% 1/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	0.00% 0/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Nervous system disorders Vocal cord paralysis	0.00% 0/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	1.8% 1/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Nervous system disorders Partial seizures	0.00% 0/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	1.8% 1/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Psychiatric disorders Major depression	2.3% 1/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	0.00% 0/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.3% 1/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	5.4% 3/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Respiratory, thoracic and mediastinal disorders Emphysema	2.3% 1/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	0.00% 0/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	1.8% 1/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Respiratory, thoracic and mediastinal disorders Pneumonitis	2.3% 1/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	3.6% 2/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	1.8% 1/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Vascular disorders Infarction	0.00% 0/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	1.8% 1/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.

Other adverse events

Measure	Squamous Non-small Cell Lung Cancer (NSCLC) n=44 participants at risk Refer to "Participant Flow".	Non-squamous Non-small Cell Lung Cancer (NSCLC) n=56 participants at risk Refer to "Participant Flow".
Gastrointestinal disorders Constipation	18.2% 8/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	19.6% 11/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Gastrointestinal disorders Diarrhoea	13.6% 6/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	3.6% 2/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Gastrointestinal disorders Dyspepsia	11.4% 5/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	8.9% 5/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Gastrointestinal disorders Nausea	13.6% 6/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	10.7% 6/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
General disorders Asthenia	6.8% 3/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	7.1% 4/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
General disorders Chest discomfort	2.3% 1/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	5.4% 3/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
General disorders Chest pain	13.6% 6/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	8.9% 5/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
General disorders Chills	4.5% 2/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	7.1% 4/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
General disorders Fatigue	15.9% 7/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	19.6% 11/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
General disorders Influenza like illness	4.5% 2/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	5.4% 3/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
General disorders Pain	9.1% 4/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	5.4% 3/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
General disorders Pyrexia	15.9% 7/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	14.3% 8/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Infections and infestations Upper respiratory tract infection	2.3% 1/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	5.4% 3/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	5.4% 3/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	5.4% 3/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Metabolism and nutrition disorders Decreased appetite	40.9% 18/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	35.7% 20/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Musculoskeletal and connective tissue disorders Back pain	2.3% 1/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	10.7% 6/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	7.1% 4/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	6.8% 3/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	5.4% 3/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Musculoskeletal and connective tissue disorders Myalgia	9.1% 4/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	8.9% 5/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Nervous system disorders Dizziness	9.1% 4/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	10.7% 6/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Nervous system disorders Headache	4.5% 2/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	10.7% 6/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Psychiatric disorders Anxiety	2.3% 1/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	5.4% 3/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Psychiatric disorders Insomnia	9.1% 4/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	8.9% 5/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Renal and urinary disorders Dysuria	0.00% 0/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	7.1% 4/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Respiratory, thoracic and mediastinal disorders Cough	27.3% 12/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	26.8% 15/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Respiratory, thoracic and mediastinal disorders Dyspnoea	25.0% 11/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	26.8% 15/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Respiratory, thoracic and mediastinal disorders Productive cough	20.5% 9/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	16.1% 9/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	4.5% 2/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	7.1% 4/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Skin and subcutaneous tissue disorders Pruritus	13.6% 6/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	21.4% 12/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.
Skin and subcutaneous tissue disorders Rash	4.5% 2/44 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.	8.9% 5/56 • From the start of the first dose of the investigational product to 28 days after the final dose or discontinuation, occurring 28 or fewer days after the final dose, or data cut-off point (June 2, 2015), whichever occurs first. Adverse events will be monitored and assessed before each dose and as needed based on clinical symptoms. Total assessment period: up to 10 months per participant. The analysis was performed on SAS, which was defined as group of subjects who received at least one dose of the study drug. Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of study drug that first appeared following exposure to study drug or any event already presented that worsened relative to the pre-treatment state following the treatment. All-Cause Mortality was defined as incidence of TEAEs leading to death.

Additional Information

Medical Information Center

Ono Pharmaceutical Co., Ltd.

Email: clinical_trial@ono-pharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this tiral prior to submission for publication/presentation.
• Publication restrictions are in place

Restriction type: OTHER