Trial Outcomes & Findings for Eribulin Mesylate in Combination With Intermittent Erlotinib in Patients With Previously Treated, Advanced Non-Small Cell Lung Cancer (NCT NCT01104155)

NCT ID: NCT01104155

Last Updated: 2023-06-22

Results Overview

ORR was defined as the percentage of participants whose best overall response (BOR) was either a confirmed complete response (CR) or a partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria for target lesions assessed by computed tomography (CT) or magnetic resonance imaging (MRI) and based on investigator assessment. CRs and PRs had to be confirmed by a repeat assessment of response (CR or PR) separated by at least 4 weeks (28 days). CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to have a reduction in short axis to less than 10 millimeters. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR and the corresponding 95% two-sided confidence intervals (CI) were estimated for each treatment regimen using the Clopper-Pearson method for calculating the exact binomial CI. (CR + PR)

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 123 participants
• Primary outcome timeframe: From date of first dose of study drug until, or up to the date of data cutoff (07 Apr 2011)
• Results posted on: 2023-06-22

Participant Flow

164 participants were screened. Of these 164 participants, 41 were screening failures, and 123 were randomized into the study. Of the 41 screen failures, 31 participants failed to meet inclusion or exclusion criteria and 10 were excluded due to adverse events, withdrew consent, and other reasons.

Participant milestones

Measure	Eribulin Mesylate Plus Erlotinib, 21 Day Regimen Eribulin mesylate was given at a dose of 2 mg/m\^2 as a 2 to 5 min intravenous (IV) bolus on Day 1 and 150 mg of erlotinib was given orally once daily, one hour before or two hours after the ingestion of food, on Days 2 to 16 of a 21-day cycle.	Eribulin Mesylate Plus Erlotinib, 28 Day Regimen Eribulin mesylate was given at a dose of 1.4 mg/m\^2 as a 2 to 5 min IV bolus on Days 1 and 8, and 150 mg of erlotinib given orally once daily, one hour before or two hours after the ingestion of food, on Days 15 to 28 of a 28-day cycle.
Overall Study STARTED	63	60
Overall Study COMPLETED	38	42
Overall Study NOT COMPLETED	25	18

Reasons for withdrawal

Measure	Eribulin Mesylate Plus Erlotinib, 21 Day Regimen Eribulin mesylate was given at a dose of 2 mg/m\^2 as a 2 to 5 min intravenous (IV) bolus on Day 1 and 150 mg of erlotinib was given orally once daily, one hour before or two hours after the ingestion of food, on Days 2 to 16 of a 21-day cycle.	Eribulin Mesylate Plus Erlotinib, 28 Day Regimen Eribulin mesylate was given at a dose of 1.4 mg/m\^2 as a 2 to 5 min IV bolus on Days 1 and 8, and 150 mg of erlotinib given orally once daily, one hour before or two hours after the ingestion of food, on Days 15 to 28 of a 28-day cycle.
Overall Study Adverse Event	15	8
Overall Study Participant choice	6	5
Overall Study Withdrawal of consent	1	1
Overall Study Other	3	4

Baseline Characteristics

Eribulin Mesylate in Combination With Intermittent Erlotinib in Patients With Previously Treated, Advanced Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Measure	Eribulin Mesylate Plus Erlotinib, 21 Day Regimen n=63 Participants Eribulin mesylate was given at a dose of 2 mg/m\^2 as a 2 to 5 min intravenous (IV) bolus on Day 1 and 150 mg of erlotinib was given orally once daily, one hour before or two hours after the ingestion of food, on Days 2 to 16 of a 21-day cycle.	Eribulin Mesylate Plus Erlotinib, 28 Day Regimen n=60 Participants Eribulin mesylate was given at a dose of 1.4 mg/m\^2 as a 2 to 5 min IV bolus on Days 1 and 8, and 150 mg of erlotinib given orally once daily, one hour before or two hours after the ingestion of food, on Days 15 to 28 of a 28-day cycle.	Total n=123 Participants Total of all reporting groups
Age, Continuous	61.7 Years STANDARD_DEVIATION 11.08 • n=5 Participants	63.1 Years STANDARD_DEVIATION 10.05 • n=7 Participants	62.4 Years STANDARD_DEVIATION 10.57 • n=5 Participants
Sex/Gender, Customized Gender · Male	33 Participants n=5 Participants	33 Participants n=7 Participants	66 Participants n=5 Participants
Sex/Gender, Customized Gender · Female	30 Participants n=5 Participants	27 Participants n=7 Participants	57 Participants n=5 Participants

PRIMARY outcome

Timeframe: From date of first dose of study drug until, or up to the date of data cutoff (07 Apr 2011)

Population: Full analysis set (FAS) (Intent-to-treat population) included all participants who took at least one dose of study drug.

ORR was defined as the percentage of participants whose best overall response (BOR) was either a confirmed complete response (CR) or a partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria for target lesions assessed by computed tomography (CT) or magnetic resonance imaging (MRI) and based on investigator assessment. CRs and PRs had to be confirmed by a repeat assessment of response (CR or PR) separated by at least 4 weeks (28 days). CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to have a reduction in short axis to less than 10 millimeters. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR and the corresponding 95% two-sided confidence intervals (CI) were estimated for each treatment regimen using the Clopper-Pearson method for calculating the exact binomial CI. (CR + PR)

Outcome measures

Measure	Eribulin Mesylate Plus Erlotinib, 21 Day Regimen n=63 Participants Eribulin mesylate was given at a dose of 2 mg/m\^2 as a 2 to 5 min intravenous (IV) bolus on Day 1 and 150 mg of erlotinib was given orally once daily, one hour before or two hours after the ingestion of food, on Days 2 to 16 of a 21-day cycle.	Eribulin Mesylate Plus Erlotinib, 28 Day Regimen n=60 Participants Eribulin mesylate was given at a dose of 1.4 mg/m\^2 as a 2 to 5 min IV bolus on Days 1 and 8, and 150 mg of erlotinib given orally once daily, one hour before or two hours after the ingestion of food, on Days 15 to 28 of a 28-day cycle.
Objective Response Rate (ORR)	12.7 Percentage of participants Interval 5.6 to 23.5	16.7 Percentage of participants Interval 8.3 to 28.5

SECONDARY outcome

Timeframe: From date of first document CR or PR (whichever was recorded first) until first documentation of disease progression or death due to any cause, or up to data cutoff (31 May 2013) up to 3.25 years

Population: FAS

DOR was assessed for participants with a BOR of CR or PR, and was defined as the time from first documented evidence of CR or PR (whichever status was recorded first) until the first documented sign of disease progression or death (due to any cause), whichever was first. DOR was defined for participants with a confirmed CR or PR. For participants in the subset of responders who did not progress or die, duration of response was censored. DOR was analyzed using the Kaplan-Meier method.

Outcome measures

Measure	Eribulin Mesylate Plus Erlotinib, 21 Day Regimen n=63 Participants Eribulin mesylate was given at a dose of 2 mg/m\^2 as a 2 to 5 min intravenous (IV) bolus on Day 1 and 150 mg of erlotinib was given orally once daily, one hour before or two hours after the ingestion of food, on Days 2 to 16 of a 21-day cycle.	Eribulin Mesylate Plus Erlotinib, 28 Day Regimen n=60 Participants Eribulin mesylate was given at a dose of 1.4 mg/m\^2 as a 2 to 5 min IV bolus on Days 1 and 8, and 150 mg of erlotinib given orally once daily, one hour before or two hours after the ingestion of food, on Days 15 to 28 of a 28-day cycle.
Duration of Response (DOR)	9.4 Months Interval 2.7 to Not evaluable	9.7 Months Interval 5.6 to Not evaluable

SECONDARY outcome

Timeframe: From date of first dose of study drug until documentation of disease progression or death from any cause (whichever occurred first), or up to data cutoff (31 May 2013) up to 3.25 years

Population: FAS

PFS was measured as the time from the date of first administration of study treatment until the first documentation of disease progression or death (due to any cause), whichever occurred first, as determined by investigator assessment based on RECIST v1.1. Disease progression per RECIST v1.1 was defined as at least a 20% relative increase and 5 mm absolute increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. For participants who did not have an event (i.e. those who had not progressed, and were alive at the date of data cut-off or lost to Follow-up), progression-free survival was censored. Participants who did not progress in their disease were censored on the date of their last tumor assessment preceding the start of any additional anticancer therapy. PFS was analyzed using the Kaplan-Meier method.

Outcome measures

Measure	Eribulin Mesylate Plus Erlotinib, 21 Day Regimen n=63 Participants Eribulin mesylate was given at a dose of 2 mg/m\^2 as a 2 to 5 min intravenous (IV) bolus on Day 1 and 150 mg of erlotinib was given orally once daily, one hour before or two hours after the ingestion of food, on Days 2 to 16 of a 21-day cycle.	Eribulin Mesylate Plus Erlotinib, 28 Day Regimen n=60 Participants Eribulin mesylate was given at a dose of 1.4 mg/m\^2 as a 2 to 5 min IV bolus on Days 1 and 8, and 150 mg of erlotinib given orally once daily, one hour before or two hours after the ingestion of food, on Days 15 to 28 of a 28-day cycle.
Progression-Free Survival (PFS)	3.5 Months Interval 1.9 to 4.7	3.8 Months Interval 3.3 to 5.5

SECONDARY outcome

Timeframe: From date of first dose of study drug until documentation of disease progression or death from any cause (whichever occurred first) or up to data cutoff (31 May 2013), up to approximately 3.25 years

Population: FAS

DCR was defined as the percentage of participants who had a BOR of CR or PR, or stable disease (SD; duration of SD lasted for at least 7 weeks). To be assigned a BOR of SD, the time from the first administration of study drug until the date of documented SD was to be greater than or equal to 7 weeks (49 days). A participant's tumor assessment had to be at least 7 weeks following the randomization date to be consider SD. DCR and the corresponding exact Clopper-Pearson 95% CI were computed by treatment regimen. (CR + PR + SD)

Outcome measures

Measure	Eribulin Mesylate Plus Erlotinib, 21 Day Regimen n=63 Participants Eribulin mesylate was given at a dose of 2 mg/m\^2 as a 2 to 5 min intravenous (IV) bolus on Day 1 and 150 mg of erlotinib was given orally once daily, one hour before or two hours after the ingestion of food, on Days 2 to 16 of a 21-day cycle.	Eribulin Mesylate Plus Erlotinib, 28 Day Regimen n=60 Participants Eribulin mesylate was given at a dose of 1.4 mg/m\^2 as a 2 to 5 min IV bolus on Days 1 and 8, and 150 mg of erlotinib given orally once daily, one hour before or two hours after the ingestion of food, on Days 15 to 28 of a 28-day cycle.
Disease Control Rate (DCR)	47.6 Percentage of participants Interval 34.9 to 60.6	63.3 Percentage of participants Interval 49.9 to 75.4

SECONDARY outcome

Timeframe: From date of first dose of study drug until date of death from any cause or up to data cutoff (31 May 2013), up to approximately 3.25 years

Population: FAS

OS was defined as the length of time in months from the date of first administration of study drug until the date of death from any cause, and was based on the data cutoff date. In the absence of confirmation of death, participants were censored either at the date that the participant was last known to be alive or the date of study cutoff, whichever came first. OS and the corresponding 2-sided 95% CI was analyzed using the Kaplan-Meier method.

Outcome measures

Measure	Eribulin Mesylate Plus Erlotinib, 21 Day Regimen n=63 Participants Eribulin mesylate was given at a dose of 2 mg/m\^2 as a 2 to 5 min intravenous (IV) bolus on Day 1 and 150 mg of erlotinib was given orally once daily, one hour before or two hours after the ingestion of food, on Days 2 to 16 of a 21-day cycle.	Eribulin Mesylate Plus Erlotinib, 28 Day Regimen n=60 Participants Eribulin mesylate was given at a dose of 1.4 mg/m\^2 as a 2 to 5 min IV bolus on Days 1 and 8, and 150 mg of erlotinib given orally once daily, one hour before or two hours after the ingestion of food, on Days 15 to 28 of a 28-day cycle.
Overall Survival (OS)	7.6 Months Interval 6.3 to 11.0	8.5 Months Interval 6.2 to 13.1

Adverse Events

Eribulin Mesylate, 21 Day Cycle

Serious events: 38 serious events

Other events: 61 other events

Deaths: 59 deaths

Eribulin Mesylate, 28 Day Cycle

Serious events: 27 serious events

Other events: 60 other events

Deaths: 51 deaths

Serious adverse events

Measure	Eribulin Mesylate, 21 Day Cycle n=63 participants at risk Eribulin mesylate + Erlotinib: 21-day Regimen: Eribulin mesylate given at a dose of 2 mg/m2 as a 2-5 min intravenous (IV) bolus on Day 1 and 150 mg of erlotinib given orally once daily, one hour before or two hours after the ingestion of food, on Days 2-16 of a 21-day cycle.	Eribulin Mesylate, 28 Day Cycle n=60 participants at risk Eribulin mesylate + Erlotinib: 28-day Regimen: Eribulin mesylate given at a dose of 1.4 mg/m2 as a 2-5 min IV bolus on Days 1 and 8, and 150 mg of erlotinib given orally once daily, one hour before or two hours after the ingestion of food, on Days 15-28 of a 28-day cycle.
Blood and lymphatic system disorders Febrile neutropenia	14.3% 9/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	3.3% 2/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Blood and lymphatic system disorders Neutropenia	6.3% 4/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Cardiac disorders Atrial fibrillation	0.00% 0/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	3.3% 2/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Cardiac disorders Cardiac tamponade	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	0.00% 0/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Cardiac disorders Cardio-respiratory arrest	0.00% 0/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Cardiac disorders Pericardial effusion	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	0.00% 0/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Gastrointestinal disorders Diarrhoea	3.2% 2/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	0.00% 0/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Gastrointestinal disorders Enteritis	0.00% 0/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Gastrointestinal disorders Nausea	0.00% 0/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Gastrointestinal disorders Stomatitis	4.8% 3/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Gastrointestinal disorders Vomiting	4.8% 3/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
General disorders Fatigue	0.00% 0/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	3.3% 2/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
General disorders Non-cardiac chest pain	0.00% 0/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
General disorders Pyrexia	4.8% 3/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
General disorders Asthenia + Fatigue	0.00% 0/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	3.3% 2/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Hepatobiliary disorders Jaundice cholestatic	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	0.00% 0/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Infections and infestations Cellulitis	3.2% 2/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	0.00% 0/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Infections and infestations Gastroenteritis	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Infections and infestations Haematoma infection	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	0.00% 0/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Infections and infestations Neutropenic sepsis	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Infections and infestations Pneumonia	6.3% 4/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	5.0% 3/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Infections and infestations Sepsis	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Injury, poisoning and procedural complications Fall	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	0.00% 0/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Injury, poisoning and procedural complications Head injury	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	0.00% 0/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Injury, poisoning and procedural complications Laceration	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	0.00% 0/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Investigations Activated partial thromboplastin time prolonged	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	0.00% 0/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Investigations International normalised ratio increased	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	0.00% 0/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Investigations Neutrophil count decreased	6.3% 4/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	5.0% 3/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Investigations White blood cell count decreased	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	0.00% 0/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Metabolism and nutrition disorders Dehydration	4.8% 3/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	3.3% 2/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Metabolism and nutrition disorders Failure to thrive	0.00% 0/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Metabolism and nutrition disorders Hypoglycaemia	3.2% 2/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	0.00% 0/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Metabolism and nutrition disorders Hypokalaemia	3.2% 2/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	0.00% 0/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Metabolism and nutrition disorders Hyponatraemia	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	0.00% 0/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Metabolism and nutrition disorders Hypophosphataemia	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	0.00% 0/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Musculoskeletal and connective tissue disorders Bone pain	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	0.00% 0/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Musculoskeletal and connective tissue disorders Flank pain	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	0.00% 0/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Nervous system disorders Altered state of consciousness	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Nervous system disorders Cerebral ischaemia	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	0.00% 0/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Nervous system disorders Cerebrovascular accident	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	0.00% 0/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Nervous system disorders Convulsion	0.00% 0/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Nervous system disorders Grand mal convulsion	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	0.00% 0/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Nervous system disorders Partial seizures	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	0.00% 0/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Nervous system disorders Syncope	0.00% 0/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Renal and urinary disorders Renal failure acute	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Renal and urinary disorders Haematuria	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	0.00% 0/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	3.2% 2/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	4.8% 3/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	0.00% 0/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.9% 5/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	6.7% 4/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Respiratory, thoracic and mediastinal disorders Pleural effusion	4.8% 3/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	0.00% 0/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Respiratory, thoracic and mediastinal disorders Pneumothorax	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	0.00% 0/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.00% 0/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Respiratory, thoracic and mediastinal disorders Respiratory failure	3.2% 2/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Vascular disorders Deep vein thrombosis	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Nervous system disorders Generalised tonic-clonic seizure	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	0.00% 0/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Nervous system disorders Seizure	0.00% 0/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Renal and urinary disorders Acute kidney injury	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Respiratory, thoracic and mediastinal disorders Pulmonary mass	0.00% 0/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.00% 0/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Eye disorders Cataract	0.00% 0/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.

Other adverse events

Measure	Eribulin Mesylate, 21 Day Cycle n=63 participants at risk Eribulin mesylate + Erlotinib: 21-day Regimen: Eribulin mesylate given at a dose of 2 mg/m2 as a 2-5 min intravenous (IV) bolus on Day 1 and 150 mg of erlotinib given orally once daily, one hour before or two hours after the ingestion of food, on Days 2-16 of a 21-day cycle.	Eribulin Mesylate, 28 Day Cycle n=60 participants at risk Eribulin mesylate + Erlotinib: 28-day Regimen: Eribulin mesylate given at a dose of 1.4 mg/m2 as a 2-5 min IV bolus on Days 1 and 8, and 150 mg of erlotinib given orally once daily, one hour before or two hours after the ingestion of food, on Days 15-28 of a 28-day cycle.
Infections and infestations Paronychia	6.3% 4/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	3.3% 2/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Investigations Aspartate aminotransferase increased	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	8.3% 5/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Investigations Blood phosphorus decreased	0.00% 0/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	5.0% 3/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Blood and lymphatic system disorders Anaemia	30.2% 19/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	41.7% 25/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Blood and lymphatic system disorders Leukopenia	7.9% 5/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	13.3% 8/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Blood and lymphatic system disorders Neutropenia	46.0% 29/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	41.7% 25/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Blood and lymphatic system disorders Thrombocytopenia	6.3% 4/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	5.0% 3/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Cardiac disorders Tachycardia	6.3% 4/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	5.0% 3/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Gastrointestinal disorders Abdominal pain upper	3.2% 2/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	8.3% 5/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Gastrointestinal disorders Constipation	20.6% 13/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	35.0% 21/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Gastrointestinal disorders Diarrhoea	54.0% 34/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	43.3% 26/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Gastrointestinal disorders Dyspepsia	11.1% 7/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	10.0% 6/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Gastrointestinal disorders Nausea	31.7% 20/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	38.3% 23/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Gastrointestinal disorders Stomatitis	33.3% 21/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	18.3% 11/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Gastrointestinal disorders Vomiting	22.2% 14/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	26.7% 16/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
General disorders Asthenia	7.9% 5/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	10.0% 6/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
General disorders Asthenia + Fatigue	49.2% 31/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	55.0% 33/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
General disorders Chills	7.9% 5/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	3.3% 2/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
General disorders Fatigue	46.0% 29/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	50.0% 30/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
General disorders Mucosal inflammation	12.7% 8/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
General disorders Oedema peripheral	7.9% 5/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	8.3% 5/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
General disorders Pyrexia	19.0% 12/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	8.3% 5/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Infections and infestations Pneumonia	6.3% 4/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	3.3% 2/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Infections and infestations Upper respiratory tract infection	12.7% 8/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	11.7% 7/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Infections and infestations Urinary tract infection	9.5% 6/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	5.0% 3/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Investigations Neutrophil count decreased	12.7% 8/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	15.0% 9/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Investigations Weight decreased	11.1% 7/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	10.0% 6/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Investigations White blood cell count decreased	9.5% 6/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	11.7% 7/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Metabolism and nutrition disorders Decreased appetite	28.6% 18/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	40.0% 24/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Metabolism and nutrition disorders Dehydration	4.8% 3/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	11.7% 7/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Metabolism and nutrition disorders Hypokalaemia	25.4% 16/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	15.0% 9/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Metabolism and nutrition disorders Hyponatraemia	6.3% 4/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	11.7% 7/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Musculoskeletal and connective tissue disorders Arthralgia	11.1% 7/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	8.3% 5/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Musculoskeletal and connective tissue disorders Arthralgia + Myalgia	17.5% 11/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	13.3% 8/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Musculoskeletal and connective tissue disorders Back pain	11.1% 7/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	10.0% 6/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Musculoskeletal and connective tissue disorders Muscle spasms	6.3% 4/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	6.7% 4/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Musculoskeletal and connective tissue disorders Myalgia	6.3% 4/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	8.3% 5/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Musculoskeletal and connective tissue disorders Pain in extremity	3.2% 2/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	10.0% 6/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Respiratory, thoracic and mediastinal disorders Dysphonia	6.3% 4/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	8.3% 5/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Investigations Breath sounds abnormal	0.00% 0/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	6.7% 4/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	17.5% 11/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	23.3% 14/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Respiratory, thoracic and mediastinal disorders Epistaxis	15.9% 10/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	3.3% 2/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Respiratory, thoracic and mediastinal disorders Haemoptysis	7.9% 5/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	8.3% 5/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	11.1% 7/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	11.7% 7/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Respiratory, thoracic and mediastinal disorders Productive cough	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	10.0% 6/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	6.3% 4/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	6.7% 4/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Skin and subcutaneous tissue disorders Acne	4.8% 3/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	6.7% 4/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Skin and subcutaneous tissue disorders Alopecia	31.7% 20/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	20.0% 12/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Skin and subcutaneous tissue disorders Dermatitis acneiform	15.9% 10/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	18.3% 11/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Skin and subcutaneous tissue disorders Dry skin	14.3% 9/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	26.7% 16/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Skin and subcutaneous tissue disorders Pruritus	12.7% 8/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	13.3% 8/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Skin and subcutaneous tissue disorders Rash	44.4% 28/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	25.0% 15/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Nervous system disorders Dizziness	9.5% 6/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	15.0% 9/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Nervous system disorders Dysgeusia	6.3% 4/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	6.7% 4/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Nervous system disorders Headache	15.9% 10/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	11.7% 7/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Nervous system disorders Peripheral Neuropathy	7.9% 5/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	16.7% 10/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Nervous system disorders Peripheral sensory neuropathy	6.3% 4/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	10.0% 6/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Psychiatric disorders Insomnia	6.3% 4/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	15.0% 9/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Respiratory, thoracic and mediastinal disorders Cough	22.2% 14/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	23.3% 14/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Gastrointestinal disorders Dry mouth	3.2% 2/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	5.0% 3/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Gastrointestinal disorders Gastrooesophageal reflux disease	7.9% 5/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
General disorders Malaise	3.2% 2/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	5.0% 3/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
General disorders Pain	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	5.0% 3/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Infections and infestations Bronchitis	4.8% 3/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	5.0% 3/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Infections and infestations Nasopharyngitis	0.00% 0/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	5.0% 3/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Infections and infestations Oral candidiasis	3.2% 2/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	5.0% 3/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Metabolism and nutrition disorders Hyperglycaemia	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	8.3% 5/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Metabolism and nutrition disorders Hypomagnesaemia	3.2% 2/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	5.0% 3/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Musculoskeletal and connective tissue disorders Muscular weakness	6.3% 4/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	3.3% 2/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	3.2% 2/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	6.7% 4/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	6.3% 4/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	1.7% 1/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Musculoskeletal and connective tissue disorders Neuropathy based on broad MedDRA SMQ	6.3% 4/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	3.3% 2/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.00% 0/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	6.7% 4/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Nervous system disorders Hypoaesthesia	4.8% 3/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	5.0% 3/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Nervous system disorders Neuropathy based on broad MedDRA SMQ	12.7% 8/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	20.0% 12/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Nervous system disorders Neuropathy peripheral	3.2% 2/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	6.7% 4/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Psychiatric disorders Anxiety	6.3% 4/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	3.3% 2/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Renal and urinary disorders Renal failure	0.00% 0/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	5.0% 3/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Respiratory, thoracic and mediastinal disorders Hiccups	1.6% 1/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	5.0% 3/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	5.0% 3/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Skin and subcutaneous tissue disorders Rash maculo-papular	3.2% 2/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	5.0% 3/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.
Vascular disorders Hypotension	4.8% 3/63 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.	5.0% 3/60 • From date of administration of first dose up to 30 days after the last dose, or up to approximately 6 years 11 months Treatment-emergent adverse events (TEAEs) included adverse events that occurred from the first dose of study drug to 30 days after the last dose of study drug, or that were present prior to the first dose of study drug administration but worsened in severity during the study.

Additional Information

Eisai Medical Information

Eisai Inc.

Phone: 1-888-422-4743

Email: esi_oncmedinfo@eisai.com

Results disclosure agreements

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

Restriction type: OTHER