Trial Outcomes & Findings for Quizartinib With Standard of Care Chemotherapy and as Continuation Therapy in Patients With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia (AML) (NCT NCT02668653)

NCT ID: NCT02668653

Last Updated: 2024-08-06

Results Overview

Overall survival is defined as the time from randomization until death from any cause.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 539 participants
• Primary outcome timeframe: Date of randomization to the date of death due to any cause, up to approximately 3 years after enrollment
• Results posted on: 2024-08-06

Participant Flow

A total of 539 participants who met all inclusion criteria and no exclusion criteria were randomized to treatment at 193 study sites in the following countries: Spain, Italy, Republic of Korea, Japan, China, US, France, Brazil, Germany, Russian Federation, Taiwan, Hungary, Czech Republic, Romania, Israel, Canada, Serbia, Poland, Portugal, Australia, Belgium, Bulgaria, Croatia, Ukraine, Singapore, and the UK. A total of 6 participants were randomized, but did not received treatment.

Participant milestones

Measure	Quizartinib Participants who were randomized to receive quizartinib treatment regimen.	Placebo Participants who were randomized to receive placebo treatment regimen.
Overall Study STARTED	268	271
Overall Study Safety Analysis Set	265	268
Overall Study COMPLETED	56	52
Overall Study NOT COMPLETED	212	219

Reasons for withdrawal

Measure	Quizartinib Participants who were randomized to receive quizartinib treatment regimen.	Placebo Participants who were randomized to receive placebo treatment regimen.
Overall Study Refractory disease	41	70
Overall Study Relapse	44	65
Overall Study Adverse Event	58	23
Overall Study Subject decision to stop study drug	25	23
Overall Study Other reasons not specified	16	11
Overall Study Non-protocol-specified AML therapy	12	6
Overall Study Investigator decision	10	7
Overall Study Failure to meet continuation criteria	5	12
Overall Study Lost to Follow-up	1	0
Overall Study Pregnancy	0	1
Overall Study Death	0	1

Baseline Characteristics

Quizartinib With Standard of Care Chemotherapy and as Continuation Therapy in Patients With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia (AML)

Baseline characteristics by cohort

Measure	Quizartinib n=268 Participants Participants who were randomized to receive the quizartinib treatment regimen.	Placebo n=271 Participants Participants who were randomized to receive placebo treatment regimen.	Total n=539 Participants Total of all reporting groups
Age, Continuous	53.6 years STANDARD_DEVIATION 13.07 • n=5 Participants	54.3 years STANDARD_DEVIATION 12.81 • n=7 Participants	54.0 years STANDARD_DEVIATION 12.93 • n=5 Participants
Age, Customized <60 years	161 Participants n=5 Participants	162 Participants n=7 Participants	323 Participants n=5 Participants
Age, Customized ≥60 years	107 Participants n=5 Participants	109 Participants n=7 Participants	216 Participants n=5 Participants
Sex: Female, Male Female	144 Participants n=5 Participants	150 Participants n=7 Participants	294 Participants n=5 Participants
Sex: Female, Male Male	124 Participants n=5 Participants	121 Participants n=7 Participants	245 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian	80 Participants n=5 Participants	78 Participants n=7 Participants	158 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized White	159 Participants n=5 Participants	163 Participants n=7 Participants	322 Participants n=5 Participants
Race/Ethnicity, Customized Other	27 Participants n=5 Participants	24 Participants n=7 Participants	51 Participants n=5 Participants
Race/Ethnicity, Customized Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Singapore	6 participants n=5 Participants	2 participants n=7 Participants	8 participants n=5 Participants
Region of Enrollment United States	8 participants n=5 Participants	13 participants n=7 Participants	21 participants n=5 Participants
Region of Enrollment Czechia	17 participants n=5 Participants	15 participants n=7 Participants	32 participants n=5 Participants
Region of Enrollment Portugal	3 participants n=5 Participants	6 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Russia	13 participants n=5 Participants	6 participants n=7 Participants	19 participants n=5 Participants
Region of Enrollment South Korea	36 participants n=5 Participants	34 participants n=7 Participants	70 participants n=5 Participants
Region of Enrollment China	9 participants n=5 Participants	11 participants n=7 Participants	20 participants n=5 Participants
Region of Enrollment Brazil	7 participants n=5 Participants	8 participants n=7 Participants	15 participants n=5 Participants
Region of Enrollment Poland	3 participants n=5 Participants	8 participants n=7 Participants	11 participants n=5 Participants
Region of Enrollment Bulgaria	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment France	13 participants n=5 Participants	12 participants n=7 Participants	25 participants n=5 Participants
Region of Enrollment Serbia	12 participants n=5 Participants	6 participants n=7 Participants	18 participants n=5 Participants
Region of Enrollment Croatia	5 participants n=5 Participants	10 participants n=7 Participants	15 participants n=5 Participants
Region of Enrollment Romania	6 participants n=5 Participants	11 participants n=7 Participants	17 participants n=5 Participants
Region of Enrollment Hungary	4 participants n=5 Participants	5 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Japan	16 participants n=5 Participants	13 participants n=7 Participants	29 participants n=5 Participants
Region of Enrollment Ukraine	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment United Kingdom	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment Spain	33 participants n=5 Participants	34 participants n=7 Participants	67 participants n=5 Participants
Region of Enrollment Canada	8 participants n=5 Participants	5 participants n=7 Participants	13 participants n=5 Participants
Region of Enrollment Belgium	4 participants n=5 Participants	3 participants n=7 Participants	7 participants n=5 Participants
Region of Enrollment Taiwan	12 participants n=5 Participants	17 participants n=7 Participants	29 participants n=5 Participants
Region of Enrollment Italy	31 participants n=5 Participants	29 participants n=7 Participants	60 participants n=5 Participants
Region of Enrollment Israel	5 participants n=5 Participants	9 participants n=7 Participants	14 participants n=5 Participants
Region of Enrollment Australia	3 participants n=5 Participants	5 participants n=7 Participants	8 participants n=5 Participants
Region of Enrollment Germany	10 participants n=5 Participants	7 participants n=7 Participants	17 participants n=5 Participants

PRIMARY outcome

Timeframe: Date of randomization to the date of death due to any cause, up to approximately 3 years after enrollment

Population: Overall survival was assessed in the Intent-to-Treat Analysis Set.

Overall survival is defined as the time from randomization until death from any cause.

Outcome measures

Measure	Quizartinib n=268 Participants Participants who were randomized to receive quizartinib treatment regimen.	Placebo n=271 Participants Participants who were randomized to receive placebo treatment regimen.
Overall Survival in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia	31.9 months Interval 21.0 to Due to insufficient number of events, an estimate of the upper limit of the confidence interval could not be determined	15.1 months Interval 13.2 to 26.2

SECONDARY outcome

Timeframe: Date of randomization to the date of refractory disease, relapse, or death, up to approximately 3 years after enrollment

Population: Event-free survival was assessed in the Intent-to-Treat Analysis Set.

Event-free survival (EFS) is the time from randomization to the earliest date of either refractory disease (or treatment failure [TF]), relapse, or death from any cause. Refractory disease is defined as complete remission never achieved during Induction (CR: >1000 neutrophils, >100,000 platelets, <5% blasts, and other [defined as absence of extramedullary disease [EMD], blasts with rods, and leukemic blasts]). For refractory disease, EFS event date is Day 1 (randomization). Relapse after CR is defined as ≥5% blasts, leukemic blasts, extramedullary leukemia, and presence of rods. This analysis is based on a response assessment with TF defined as not achieving response of CR, using a 42- day window from the start of the last cycle in Induction for CR evaluation.

Outcome measures

Measure	Quizartinib n=268 Participants Participants who were randomized to receive quizartinib treatment regimen.	Placebo n=271 Participants Participants who were randomized to receive placebo treatment regimen.
Event-free Survival in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia	0.03 months Interval 0.03 to 0.95	0.71 months Interval 0.03 to 3.42

SECONDARY outcome

Timeframe: Approximately Cycle 1 Day 21 (Induction) to end of Induction, up to approximately 120 days (each Induction cycle is up to 60 days)

Population: Complete remission was assessed in the Intent-to-Treat Analysis Set.

Complete remission (CR) rate is defined as the percentage of participants achieving CR, defined as <5% blasts, >1000 neutrophils, >100,000 platelets, and other [defined as absence of extramedullary disease [EMD], blasts with rods, and leukemic blasts], after induction

Outcome measures

Measure	Quizartinib n=268 Participants Participants who were randomized to receive quizartinib treatment regimen.	Placebo n=271 Participants Participants who were randomized to receive placebo treatment regimen.
Complete Remission (CR) Rate at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia	147 Participants	150 Participants

SECONDARY outcome

Timeframe: Approximately Cycle 1 Day 21 (Induction) to end of Induction, up to approximately 120 days (each Induction cycle is up to 60 days)

Population: Composite complete remission (CRc) rate was assessed in the Intent-to-Treat Analysis Set.

Composite complete remission (CRc) rate is defined as the percentage of participants whose best response is complete remission (CR), defined as <5% blasts, >1000 neutrophils, >100,000 platelets, and other [defined as absence of extramedullary disease [EMD], blasts with rods, and leukemic blasts], or CR with incomplete neutrophil or platelet recovery (CRi) at the end of first Induction cycle.

Outcome measures

Measure	Quizartinib n=268 Participants Participants who were randomized to receive quizartinib treatment regimen.	Placebo n=271 Participants Participants who were randomized to receive placebo treatment regimen.
Composite CR Rate at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia	192 Participants	176 Participants

SECONDARY outcome

Timeframe: Date of first dose up to 30 days after last dose, up to 36 cycles following continuation (approximately 6 years 11 months, each cycle is 28 days)

Population: Treatment-emergent adverse events were assessed in the Safety Analysis Set.

A treatment-emergent adverse event (TEAE) is defined as an adverse event that occur, having been absent before first dose of quizartinib or placebo, or have worsened in severity after initiating quizartinib or placebo. Adverse events collected more than 30 days after the last dose of quizartinib/placebo will not be considered TEAEs unless they are considered drug-related.

Outcome measures

Measure	Quizartinib n=265 Participants Participants who were randomized to receive quizartinib treatment regimen.	Placebo n=268 Participants Participants who were randomized to receive placebo treatment regimen.
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Anaemia	29 Participants	19 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Headache	73 Participants	53 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Any TEAE	264 Participants	265 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Gastrointestinal disorders	215 Participants	209 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Diarrhoea	98 Participants	94 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Nausea	90 Participants	84 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Vomiting	65 Participants	53 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Stomatitis	57 Participants	56 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Constipation	56 Participants	69 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Abdominal pain	46 Participants	38 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Dyspepsia	30 Participants	23 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Abdominal pain upper	29 Participants	25 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Infections and infestations	204 Participants	188 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Pneumonia	39 Participants	41 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Sepsis	15 Participants	28 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia General disorders and administration site disorders	177 Participants	173 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Pyrexia	112 Participants	109 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Oedema peripheral	30 Participants	37 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Fatigue	29 Participants	23 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Blood and lymphatic system disorders	168 Participants	143 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Febrile neutropenia	117 Participants	113 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Neutropenia	54 Participants	27 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Thrombocytopenia	30 Participants	30 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Metabolism and nutrition disorders	165 Participants	153 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Hypokalaemia	93 Participants	96 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Decreased appetite	46 Participants	36 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Hypomagnesaemia	30 Participants	30 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Hypophosphataemia	27 Participants	24 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Hypocalcaemia	26 Participants	29 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Skin and subcutaneous tissue disorders	152 Participants	158 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Rash	69 Participants	66 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Pruritus	35 Participants	40 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Investigations	140 Participants	105 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Alanine aminotransferase increased	42 Participants	27 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Electrocardiogram QT prolonged	36 Participants	11 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Aspartate aminotransferase increased	28 Participants	19 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Neutrophil count decreased	27 Participants	12 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Respiratory, thoracic, and mediastinal disorders	123 Participants	115 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Cough	50 Participants	44 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Epistaxis	40 Participants	29 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Oropharyngeal pain	27 Participants	18 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Nervous system disorders	103 Participants	97 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Musculoskeletal and connective tissue disorders	91 Participants	108 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Arthralgia	29 Participants	35 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Back pain	19 Participants	28 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Vascular disorders	71 Participants	70 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Hypertension	29 Participants	33 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Psychiatric disorders	57 Participants	50 Participants
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia Insomnia	37 Participants	30 Participants

SECONDARY outcome

Timeframe: Approximately Cycle 1 Day 21 (Induction phase) to end of Induction phase, up to approximately 120 days (each Induction cycle is up to 60 days)

Population: Complete remission was assessed in the Intent-to-Treat Analysis Set.

Complete remission (CR) is defined as participants achieving CR defined as <5% blasts, >1000 neutrophils, >100,000 platelets, and other [defined as absence of extramedullary disease [EMD], blasts with rods, and leukemic blasts]. Minimal or measurable residual disease is the presence of a small number of leukemic cells in the bone marrow of patients with AML below the level of detection using conventional morphologic assessment.

Outcome measures

Measure	Quizartinib n=268 Participants Participants who were randomized to receive quizartinib treatment regimen.	Placebo n=271 Participants Participants who were randomized to receive placebo treatment regimen.
Number of Participants Achieving CR With FLT3-ITD Minimal Residual Disease Negativity at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia	54 Participants	51 Participants

SECONDARY outcome

Timeframe: Approximately Cycle 1 Day 21 (Induction phase) to end of Induction phase, up to approximately 120 days (each Induction cycle is up to 60 days)

Population: Composite complete remission (CRc) rate was assessed in the Intent-to-Treat Analysis Set.

Composite complete remission (CRc) is defined as <5% blasts, >1000 neutrophils, >100,000 platelets, and other [defined as absence of extramedullary disease [EMD], blasts with rods, and leukemic blasts], or CR with incomplete neutrophil or platelet recovery (CRi). Minimal or measurable residual disease is the presence of a small number of leukemic cells in the bone marrow of patients with AML below the level of detection using conventional morphologic assessment.

Outcome measures

Measure	Quizartinib n=268 Participants Participants who were randomized to receive quizartinib treatment regimen.	Placebo n=271 Participants Participants who were randomized to receive placebo treatment regimen.
Number of Participants Achieving Composite CR With FLT3-ITD Minimal Residual Disease Negativity at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia	66 Participants	58 Participants

SECONDARY outcome

Timeframe: Induction Cycle 1: Day 8, predose, 2-4 hours (hr) postdose on Days 8, 15, 21; Consolidation Cycle 1: Day 6, predose, 2-4 hr postdose on Days 6, 13, 19; Continuation Cycle 1: 2-4 hr postdose, Days 1, 8, 15; Cycle 2 Days 1 and 15 (each cycle, 28 days)

Population: PK Parameters were assessed in the PK Analyses set, which includes all participants in the Intent-to-Treat Analysis Set who received at least 1 dose of quizartinib and had at least 1 PK sample assessed.

AUCss was assessed by population Pharmacokinetic (PK) analysis during Cycle 1 of each phase.

Outcome measures

Measure	Quizartinib n=259 Participants Participants who were randomized to receive quizartinib treatment regimen.	Placebo Participants who were randomized to receive placebo treatment regimen.
Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve at Steady State Induction Period	2680 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 84.9	—
Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve at Steady State Consolidation Period	3930 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 77.6	—
Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve at Steady State Continuation Period - Dose 1	5080 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 74.7	—
Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve at Steady State Continuation Period - Dose 2	10200 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 74.7	—

SECONDARY outcome

Timeframe: Induction Cycle 1: Day 8, predose, 2-4 hours (hr) postdose on Days 8, 15, 21; Consolidation Cycle 1: Day 6, predose, 2-4 hr postdose on Days 6, 13, 19; Continuation Cycle 1: 2-4 hr postdose, Days 1, 8, 15; Cycle 2 Days 1 and 15 (each cycle, 28 days)

Population: PK Parameters were assessed in the PK Analyses set, which includes all participants in the Intent-to-Treat Analysis Set who received at least 1 dose of quizartinib and had at least 1 PK sample assessed.

Css,max was assessed by population PK analysis during Cycle 1 of each phase.

Outcome measures

Measure	Quizartinib n=259 Participants Participants who were randomized to receive quizartinib treatment regimen.	Placebo Participants who were randomized to receive placebo treatment regimen.
Pharmacokinetic Parameter Steady State, Maximum Plasma Concentration (Css,Max) Induction Period	140 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 71.2	—
Pharmacokinetic Parameter Steady State, Maximum Plasma Concentration (Css,Max) Consolidation Period	204 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 63.5	—
Pharmacokinetic Parameter Steady State, Maximum Plasma Concentration (Css,Max) Continuation Period - Dose 1	265 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 59.7	—
Pharmacokinetic Parameter Steady State, Maximum Plasma Concentration (Css,Max) Continuation Period - Dose 2	529 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 59.7	—

SECONDARY outcome

Timeframe: Induction Cycle 1: Day 8, predose, 2-4 hours (hr) postdose on Days 8, 15, 21; Consolidation Cycle 1: Day 6, predose, 2-4 hr postdose on Days 6, 13, 19; Continuation Cycle 1: 2-4 hr postdose, Days 1, 8, 15; Cycle 2 Days 1 and 15 (each cycle, 28 days)

Population: PK Parameters were assessed in the PK Analyses set, which includes all participants in the Intent-to-Treat Analysis Set who received at least 1 dose of quizartinib and had at least 1 PK sample assessed.

Tmax,ss was assessed by population PK analysis during Cycle 1 of each phase.

Outcome measures

Measure	Quizartinib n=259 Participants Participants who were randomized to receive quizartinib treatment regimen.	Placebo Participants who were randomized to receive placebo treatment regimen.
Pharmacokinetic Parameter Time to Maximum Plasma Concentration Steady State (Tmax,ss) Induction Period	2.68 hours Interval 1.52 to 7.3	—
Pharmacokinetic Parameter Time to Maximum Plasma Concentration Steady State (Tmax,ss) Consolidation Period	2.70 hours Interval 1.74 to 5.95	—
Pharmacokinetic Parameter Time to Maximum Plasma Concentration Steady State (Tmax,ss) Continuation Period - Dose 1	2.73 hours Interval 1.74 to 5.95	—
Pharmacokinetic Parameter Time to Maximum Plasma Concentration Steady State (Tmax,ss) Continuation Period - Dose 2	2.73 hours Interval 1.74 to 5.95	—

Adverse Events

Quizartinib

Serious events: 146 serious events

Other events: 258 other events

Deaths: 130 deaths

Placebo

Serious events: 124 serious events

Other events: 258 other events

Deaths: 156 deaths

Serious adverse events

Measure	Quizartinib n=265 participants at risk Safety Analysis Set includes all subjects who received at least 1 dose of quizartinib/placebo.	Placebo n=268 participants at risk Safety Analysis Set includes all subjects who received at least 1 dose of quizartinib/placebo.
Blood and lymphatic system disorders Febrile neutropenia	10.9% 29/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	8.2% 22/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Blood and lymphatic system disorders Neutropenia	1.5% 4/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	1.9% 5/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Blood and lymphatic system disorders Myelosuppression	1.1% 3/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Blood and lymphatic system disorders Thrombocytopenia	0.75% 2/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	3.0% 8/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Blood and lymphatic system disorders Anaemia	0.75% 2/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.75% 2/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Blood and lymphatic system disorders Autoimmune haemolytic anaemia	0.75% 2/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Blood and lymphatic system disorders Leukopenia	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	1.1% 3/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Blood and lymphatic system disorders Lymphopenia	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Blood and lymphatic system disorders Pancytopenia	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Cardiac disorders Atrial fibrillation	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	1.1% 3/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Cardiac disorders Cardiac arrest	0.75% 2/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Cardiac disorders Cardiac failure	0.75% 2/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Cardiac disorders Cardiomyopathy	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Cardiac disorders Cardiotoxicity	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Cardiac disorders Left ventricular dysfunction	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Cardiac disorders Ventricular dysfunction	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Cardiac disorders Ventricular fibrillation	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Cardiac disorders Pericarditis	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	1.1% 3/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Cardiac disorders Myocardial infarction	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.75% 2/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Cardiac disorders Myocardial ischaemia	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Cardiac disorders Sinus tachycardia	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Cardiac disorders Ventricular arrhythmia	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Ear and labyrinth disorders Allergic otitis externa	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Anal fistula	1.5% 4/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Colitis	1.1% 3/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	1.1% 3/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Neutropenic colitis	0.75% 2/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.75% 2/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Vomiting	0.75% 2/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.75% 2/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Stomatitis	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.75% 2/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Dyspepsia	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Intestinal obstruction	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Dental caries	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Diarrhoea	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Gastrointestinal disorder	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Gastrointestinal haemorrhage	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Gastrooesophageal reflux disease	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Hemorrhoids	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Large intestinal ulcer	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Pancreatitis	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Colitis ischaemic	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Dysphagia	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Gastrointestinal inflammation	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Obstructive pancreatitis	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Oesophagitis	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Toothache	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
General disorders Pyrexia	3.0% 8/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	1.9% 5/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
General disorders Generalised oedema	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
General disorders Asthenia	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.75% 2/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
General disorders Cyst rupture	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
General disorders Death	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
General disorders Fat necrosis	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
General disorders Non-cardiac chest pain	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
General disorders General physical health deterioration	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.75% 2/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
General disorders Multiple organ dysfunction syndrome	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Hepatobiliary disorders Cholecystitis	0.75% 2/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Hepatobiliary disorders Drug-induced liver injury	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Hepatobiliary disorders Hepatic function abnormal	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Hepatobiliary disorders Hyperbilirubinaemia	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Hepatobiliary disorders Jaundice	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Hepatobiliary disorders Hepatic cytolysis	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.75% 2/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Hepatobiliary disorders Cholelithiasis	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Immune system disorders Graft versus host disease in gastrointestinal tract	1.5% 4/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Immune system disorders Graft versus host disease	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.75% 2/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Pneumonia	6.4% 17/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	5.6% 15/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Septic shock	4.2% 11/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	3.4% 9/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Sepsis	3.8% 10/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	5.2% 14/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Klebsiella sepsis	2.6% 7/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Herpes zoster	1.9% 5/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Pneumonia fungal	1.5% 4/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Urinary tract infection	1.1% 3/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.75% 2/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations COVID-19	1.1% 3/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Bacteraemia	0.75% 2/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Pseudomonas infection	0.75% 2/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Cellulitus	0.75% 2/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Klebsiella bacteraemia	0.75% 2/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Mucormycosis	0.75% 2/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Streptococcal sepsis	0.75% 2/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Upper respiratory tract infection	0.75% 2/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Staphylococcal sepsis	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	1.1% 3/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Endocarditis	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.75% 2/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Enterococcal sepsis	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.75% 2/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Escherichia sepsis	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.75% 2/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Respiratory tract infection	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.75% 2/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Abdominal infection	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Anal infection	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Aspergillus infection	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations BK virus infection	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Catheter site infection	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Diverticulitis	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Escherichia bacteraemia	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Influenza	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Lung abscess	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Oral herpes	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Pulmonary sepsis	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Staphylococcal bacteraemia	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Anal abscess	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Appendicitis	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Bronchitis	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Bronchopulmonary aspergillosis	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Clostridium colitis	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Clostridium difficile colitis	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Cytomegalovirus infection	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Gastrointestinal infection	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Hepatosplenic candidiasis	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Klebsiella infection	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Lower respiratory tract infection fungal	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Pseudomonal bacteraemia	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Subcutaneous abscess	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Varicella zoster virus infection	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Device related infection	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	1.1% 3/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Staphylococcal infection	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.75% 2/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Encephalitis	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.75% 2/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Bacterial sepsis	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Candida sepsis	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Catheter site cellulitis	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Cytomegalovirus chorioretinitis	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Dengue fever	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Disseminated varicella zoster virus infection	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Enterococcal bacteraemia	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Epstein-Barr virus infection reactivation	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Escherichia urinary tract infection	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Febrile infection	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Fungal sepsis	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Genital herpes	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Genitourinary tract infection	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Liver abscess	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Pneumonia influenzal	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Pneumonia klebsiella	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Pneumonia pseudomonal	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Pneumonia respiratory syncytial viral	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Pneumonia viral	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Rectal abscess	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Soft tissue infection	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Stenotrophomonas sepsis	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Systemic candida	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Systemic mycosis	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Vascular device infection	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Injury, poisoning and procedural complications Subdural haematoma	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Injury, poisoning and procedural complications Ankle fracture	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Injury, poisoning and procedural complications Femoral neck fracture	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Injury, poisoning and procedural complications Tendon rupture	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Injury, poisoning and procedural complications Toxicity to various agents	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Injury, poisoning and procedural complications Rib fracture	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Injury, poisoning and procedural complications Transfusion reaction	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Investigations Neutrophil count decreased	1.5% 4/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Investigations Blood alkaline phosphatase increased	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Investigations Blood bilirubin increased	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Investigations Electrocardiogram QT prolonged	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Investigations Gamma-glutamyltransferase increased	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Investigations Hepatic enzyme increased	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Investigations Platelet count decreased	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Investigations Transaminases increased	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Investigations Acid base balance abnormal	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Investigations Blood magnesium increased	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Investigations Blood pressure increased	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Investigations Alanine aminotransferase increased	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.75% 2/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Investigations Aspartate aminotransferase increased	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Investigations C-reactive protein increased	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Metabolism and nutrition disorders Dehydration	0.75% 2/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Metabolism and nutrition disorders Acid-base balance disorder mixed	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Metabolism and nutrition disorders Hyperkalaemia	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Metabolism and nutrition disorders Hypocalcaemia	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Metabolism and nutrition disorders Tumour lysis syndrome	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Musculoskeletal and connective tissue disorders Osteonecrosis	0.75% 2/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Musculoskeletal and connective tissue disorders Flank pain	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Musculoskeletal and connective tissue disorders Muscular weakness	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.75% 2/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Musculoskeletal and connective tissue disorders Haematoma muscle	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Musculoskeletal and connective tissue disorders Spinal pain	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma gastric	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast neoplasm	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix carcinoma	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acanthoma	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Post transplant lymphoproliferative disorder	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Nervous system disorders Brain oedema	0.75% 2/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Nervous system disorders Ischaemic stroke	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Nervous system disorders Cerebellar syndrome	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Nervous system disorders Cerebral haemorrhage	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Nervous system disorders Cerebral infarction	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Nervous system disorders Subarachnoid haemorrhage	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Nervous system disorders Cerebrovascular accident	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	1.1% 3/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Nervous system disorders Haemorrhage intracranial	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.75% 2/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Nervous system disorders Transient ischaemic attack	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.75% 2/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Nervous system disorders Cognitive disorder	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Nervous system disorders Haemorrhagic stroke	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Nervous system disorders Hemiplegia	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Nervous system disorders Seizure	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Psychiatric disorders Delirium	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Renal and urinary disorders Acute kidney injury	1.5% 4/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.75% 2/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Renal and urinary disorders Renal failure	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.75% 2/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Renal and urinary disorders Haematuria	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Renal and urinary disorders Urinary retention	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Reproductive system and breast disorders Vaginal haemorrhage	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.1% 3/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	1.1% 3/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.75% 2/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.75% 2/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Respiratory, thoracic and mediastinal disorders Cough	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Respiratory, thoracic and mediastinal disorders Epistaxis	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Respiratory, thoracic and mediastinal disorders Lung infiltration	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Respiratory, thoracic and mediastinal disorders Pneumomediastinum	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.75% 2/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.75% 2/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Skin and subcutaneous tissue disorders Subcutaneous emphysema	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Skin and subcutaneous tissue disorders Toxic skin eruption	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Skin and subcutaneous tissue disorders Rash papular	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Vascular disorders Deep vein thrombosis	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chloroma	0.00% 0/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.37% 1/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Skin and subcutaneous tissue disorders Acute febrile neutrophilic dermatosis	0.38% 1/265 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	0.00% 0/268 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).

Other adverse events

Measure	Quizartinib n=265 participants at risk Safety Analysis Set includes all subjects who received at least 1 dose of quizartinib/placebo.	Placebo n=268 participants at risk Safety Analysis Set includes all subjects who received at least 1 dose of quizartinib/placebo.
Blood and lymphatic system disorders Febrile neutropenia	37.0% 98/265 • Number of events 169 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	36.2% 97/268 • Number of events 178 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Blood and lymphatic system disorders Thrombocytopenia	11.7% 31/265 • Number of events 46 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	9.3% 25/268 • Number of events 37 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Blood and lymphatic system disorders Anaemia	10.2% 27/265 • Number of events 39 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	6.7% 18/268 • Number of events 35 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Blood and lymphatic system disorders Neutropenia	20.0% 53/265 • Number of events 130 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	8.2% 22/268 • Number of events 29 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Eye disorders Dry eye	8.3% 22/265 • Number of events 22 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	4.9% 13/268 • Number of events 17 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Diarrhoea	36.6% 97/265 • Number of events 146 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	35.1% 94/268 • Number of events 133 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Nausea	34.3% 91/265 • Number of events 168 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	31.3% 84/268 • Number of events 141 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Vomiting	23.8% 63/265 • Number of events 88 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	19.0% 51/268 • Number of events 76 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Stomatitis	21.1% 56/265 • Number of events 70 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	20.5% 55/268 • Number of events 66 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Abdominal pain	17.4% 46/265 • Number of events 59 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	14.2% 38/268 • Number of events 52 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Constipation	21.5% 57/265 • Number of events 77 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	25.7% 69/268 • Number of events 91 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Dyspepsia	10.9% 29/265 • Number of events 37 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	8.2% 22/268 • Number of events 27 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Hemorrhoids	9.8% 26/265 • Number of events 30 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	7.5% 20/268 • Number of events 24 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Abdominal pain upper	10.9% 29/265 • Number of events 36 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	9.3% 25/268 • Number of events 30 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Gastrointestinal disorders Gingival bleeding	5.3% 14/265 • Number of events 15 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	4.9% 13/268 • Number of events 18 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
General disorders Pyrexia	42.6% 113/265 • Number of events 203 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	39.6% 106/268 • Number of events 224 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
General disorders Oedema peripheral	11.3% 30/265 • Number of events 36 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	13.8% 37/268 • Number of events 40 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
General disorders Fatigue	11.7% 31/265 • Number of events 44 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	8.6% 23/268 • Number of events 35 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
General disorders Asthenia	5.7% 15/265 • Number of events 19 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	7.5% 20/268 • Number of events 29 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
General disorders Chills	3.0% 8/265 • Number of events 9 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	5.2% 14/268 • Number of events 19 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Pneumonia	9.4% 25/265 • Number of events 29 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	10.1% 27/268 • Number of events 30 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Upper respiratory tract infection	7.5% 20/265 • Number of events 38 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	5.6% 15/268 • Number of events 22 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Conjunctivitis	6.0% 16/265 • Number of events 19 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	3.0% 8/268 • Number of events 10 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Bacteraemia	5.3% 14/265 • Number of events 19 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	1.9% 5/268 • Number of events 5 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Sepsis	1.9% 5/265 • Number of events 5 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	5.2% 14/268 • Number of events 14 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Folliculitis	5.3% 14/265 • Number of events 19 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	1.5% 4/268 • Number of events 5 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Oral herpes	6.4% 17/265 • Number of events 18 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	4.1% 11/268 • Number of events 14 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Injury, poisoning and procedural complications Transfusion reaction	4.2% 11/265 • Number of events 14 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	7.1% 19/268 • Number of events 30 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Investigations Electrocardiogram QT prolonged	13.2% 35/265 • Number of events 70 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	4.1% 11/268 • Number of events 12 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Investigations Alanine aminotransferase increased	16.2% 43/265 • Number of events 64 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	9.7% 26/268 • Number of events 43 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Investigations Gamma-glutamyltransferase increased	8.7% 23/265 • Number of events 31 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	9.3% 25/268 • Number of events 33 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Investigations Aspartate aminotransferase increased	10.9% 29/265 • Number of events 41 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	7.1% 19/268 • Number of events 30 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Investigations Neutrophil count decreased	9.1% 24/265 • Number of events 73 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	4.5% 12/268 • Number of events 27 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Investigations Platelet count decreased	6.8% 18/265 • Number of events 34 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	2.6% 7/268 • Number of events 17 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Investigations Blood bilirubin increased	5.7% 15/265 • Number of events 21 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	4.9% 13/268 • Number of events 21 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Metabolism and nutrition disorders Hypokalaemia	35.1% 93/265 • Number of events 148 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	35.8% 96/268 • Number of events 162 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Metabolism and nutrition disorders Decreased appetite	17.4% 46/265 • Number of events 71 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	13.4% 36/268 • Number of events 44 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Metabolism and nutrition disorders Hypocalcaemia	9.4% 25/265 • Number of events 36 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	10.8% 29/268 • Number of events 39 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Metabolism and nutrition disorders Hypophosphataemia	10.2% 27/265 • Number of events 42 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	9.0% 24/268 • Number of events 32 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Metabolism and nutrition disorders Hypoalbuminaemia	8.7% 23/265 • Number of events 28 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	8.6% 23/268 • Number of events 31 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Metabolism and nutrition disorders Hypomagnesaemia	11.3% 30/265 • Number of events 44 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	11.2% 30/268 • Number of events 45 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Metabolism and nutrition disorders Hyponatraemia	3.8% 10/265 • Number of events 12 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	5.6% 15/268 • Number of events 20 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Metabolism and nutrition disorders Hyperglycaemia	4.5% 12/265 • Number of events 14 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	5.2% 14/268 • Number of events 15 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Musculoskeletal and connective tissue disorders Arthralgia	11.3% 30/265 • Number of events 37 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	13.1% 35/268 • Number of events 41 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Musculoskeletal and connective tissue disorders Back pain	7.5% 20/265 • Number of events 25 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	10.1% 27/268 • Number of events 32 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Musculoskeletal and connective tissue disorders Pain in extremity	6.8% 18/265 • Number of events 25 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	7.8% 21/268 • Number of events 21 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Musculoskeletal and connective tissue disorders Myalgia	6.0% 16/265 • Number of events 18 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	6.3% 17/268 • Number of events 19 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Nervous system disorders Headache	27.5% 73/265 • Number of events 120 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	20.1% 54/268 • Number of events 101 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Nervous system disorders Dizziness	6.4% 17/265 • Number of events 18 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	7.5% 20/268 • Number of events 22 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Psychiatric disorders Insomnia	14.3% 38/265 • Number of events 46 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	11.2% 30/268 • Number of events 36 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Psychiatric disorders Anxiety	5.7% 15/265 • Number of events 18 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	4.5% 12/268 • Number of events 13 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Respiratory, thoracic and mediastinal disorders Epistaxis	14.7% 39/265 • Number of events 45 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	10.9% 29/265 • Number of events 30 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Respiratory, thoracic and mediastinal disorders Cough	18.5% 49/265 • Number of events 56 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	16.4% 44/268 • Number of events 50 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	10.6% 28/265 • Number of events 35 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	6.7% 18/268 • Number of events 22 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.3% 14/265 • Number of events 17 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	7.5% 20/268 • Number of events 25 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Skin and subcutaneous tissue disorders Rash	26.0% 69/265 • Number of events 100 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	24.6% 66/268 • Number of events 102 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Skin and subcutaneous tissue disorders Pruritus	13.2% 35/265 • Number of events 49 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	14.9% 40/268 • Number of events 48 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Skin and subcutaneous tissue disorders Alopecia	6.8% 18/265 • Number of events 18 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	3.4% 9/268 • Number of events 9 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Skin and subcutaneous tissue disorders Erythema	6.8% 18/265 • Number of events 21 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	5.2% 14/268 • Number of events 15 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Skin and subcutaneous tissue disorders Urticaria	6.4% 17/265 • Number of events 23 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	4.1% 11/268 • Number of events 14 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Vascular disorders Hypertension	11.3% 30/265 • Number of events 35 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	12.3% 33/268 • Number of events 40 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Vascular disorders Hypotension	8.7% 23/265 • Number of events 27 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	6.3% 17/268 • Number of events 21 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).
Infections and infestations Nasopharyngitis	5.3% 14/265 • Number of events 20 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).	2.6% 7/268 • Number of events 8 • Treatment-emergent adverse events were collected from date of first dose up to 30 days after last dose, up to 36 cycles following continuation phase (approximately 6 years 11 months, each cycle is 28 days).

Additional Information

Contact for Clinical Trial Information

Daiichi Sankyo Inc.

Phone: 908-992-6400

Email: CTRinfo@dsi.com

Results disclosure agreements

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