Trial Outcomes & Findings for Phase 3 Study to Treat Patients With Soft Tissue Sarcomas (NCT NCT02049905)

NCT ID: NCT02049905

Last Updated: 2024-06-13

Results Overview

PFS is defined as the time from the date of randomization to first documentation of objective tumor progression, according to RECIST 1.1 Criteria, or to death due to any cause in the absence of previous documentation of objective tumor progression. For subjects without documentation of objective tumor progression, who started other anti-tumor treatment, or lost to follow up/withdrew consent prior to confirmed progression, PFS is censored at the date of the last tumor assessment. PFS is defined as the interval from the date of randomization to the earliest date of documented evidence of recurrent or progressive disease, or the date of death due to any cause, whichever occurs first. PD is defined as: 20% increase in the sum of the longest diameter of target lesions from the smallest sum of the longest diameter recorded since the treatment started; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 new lesion is also considered PD.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

433 participants

Primary outcome timeframe

24 months

Results posted on

2024-06-13

Participant Flow

433 subjects were randomized in the intent to treat population, whereas 420 subjects were in the safety population. 13 subjects were discontinued prior to treatment start.

Participant milestones

Participant milestones
Measure	Aldoxorubicin Aldoxorubicin is administered at 350 mg/m2 (260 mg/m2 doxorubicin equivalent) intravenously on Day 1 every 21-day cycles until tumor progression or unacceptable toxicity occurs. Aldoxorubicin	Investigator's Choice of Treatment These treatments include: 1. Dacarbazine administered at 1000 mg/m2 by intravenous infusion (IVI), over 90±15 minutes on Day 1 every 21 days until tumor progression or unacceptable toxicity occurs; 2. Pazopanib, 800 mg orally each day until tumor progression or unacceptable toxicity occurs; 3. Gemcitabine, 900 mg/m2 by IVI over 90 minutes on Days 1 and 8, plus docetaxel, 100 mg/m2 by IVI over 1 hour on Day 8 of a 28 day cycle until tumor progression or unacceptable toxicity occurs; 4. Doxorubicin, 75 mg/m2 by IVI over 5 to 30 minutes every 21 days for a maximum cumulative dose of 550 mg/m2 or unacceptable toxicity occurs; or 5. Ifosfamide 2.0 g/m2 administered over 2 to 4 hours on Days 1-4 of a 21 day cycle + mesna per standard site administration regimen until tumor progression or unacceptable toxicity occurs. Investigator's Choice Treatment (Darcabazine, Pazopanib, Gemcitabine + Docetaxel, Doxorubicin, Ifosfamide)
Overall Study STARTED	218	215
Overall Study Safety Population	213	207
Overall Study COMPLETED	213	207
Overall Study NOT COMPLETED	5	8

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase 3 Study to Treat Patients With Soft Tissue Sarcomas

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Aldoxorubicin n=218 Participants Aldoxorubicin is administered at 350 mg/m2 (260 mg/m2 doxorubicin equivalent) intravenously on Day 1 every 21-day cycles until tumor progression or unacceptable toxicity occurs. Aldoxorubicin	Investigator's Choice of Treatment n=215 Participants These treatments include: 1. Dacarbazine administered at 1000 mg/m2 by intravenous infusion (IVI), over 90±15 minutes on Day 1 every 21 days until tumor progression or unacceptable toxicity occurs; 2. Pazopanib, 800 mg orally each day until tumor progression or unacceptable toxicity occurs; 3. Gemcitabine, 900 mg/m2 by IVI over 90 minutes on Days 1 and 8, plus docetaxel, 100 mg/m2 by IVI over 1 hour on Day 8 of a 28 day cycle until tumor progression or unacceptable toxicity occurs; 4. Doxorubicin, 75 mg/m2 by IVI over 5 to 30 minutes every 21 days for a maximum cumulative dose of 550 mg/m2 or unacceptable toxicity occurs; or 5. Ifosfamide 2.0 g/m2 administered over 2 to 4 hours on Days 1-4 of a 21 day cycle + mesna per standard site administration regimen until tumor progression or unacceptable toxicity occurs. Investigator's Choice Treatment (Darcabazine, Pazopanib, Gemcitabine + Docetaxel, Doxorubicin, Ifosfamide)	Total n=433 Participants Total of all reporting groups
Age, Continuous	56.6 years STANDARD_DEVIATION 11.68 • n=5 Participants	57.0 years STANDARD_DEVIATION 12.59 • n=7 Participants	56.8 years STANDARD_DEVIATION 12.13 • n=5 Participants
Sex: Female, Male Female	123 Participants n=5 Participants	128 Participants n=7 Participants	251 Participants n=5 Participants
Sex: Female, Male Male	95 Participants n=5 Participants	87 Participants n=7 Participants	182 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	25 Participants n=5 Participants	20 Participants n=7 Participants	45 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	178 Participants n=5 Participants	181 Participants n=7 Participants	359 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	15 Participants n=5 Participants	14 Participants n=7 Participants	29 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	13 Participants n=5 Participants	8 Participants n=7 Participants	21 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	18 Participants n=7 Participants	23 Participants n=5 Participants
Race (NIH/OMB) White	174 Participants n=5 Participants	174 Participants n=7 Participants	348 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	24 Participants n=5 Participants	14 Participants n=7 Participants	38 Participants n=5 Participants
Subjects with Metastatic, Locally Advanced, or Unresectable Soft Tissue Sarcomas Who Either Relapsed	218 Participants n=5 Participants	215 Participants n=7 Participants	433 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 months

Population: 5 patients were randomized, but not treated on Aldoxorubicin arm. 8 patients were randomized, but not treated on Investigator's Choice of Treatment.

Outcome measures

Outcome measures
Measure	Aldoxorubicin n=218 Participants Aldoxorubicin is administered at 350 mg/m\^2 (260 mg/m\^2 doxorubicin equivalent) intravenously on Day 1 every 21-day cycles until tumor progression or unacceptable toxicity occurs.	Investigator's Choice of Treatment n=215 Participants These treatments include: 1. Dacarbazine administered at 1000 mg/m2 by intravenous infusion (IVI), over 90±15 minutes on Day 1 every 21 days until tumor progression or unacceptable toxicity occurs; 2. Pazopanib, 800 mg orally each day until tumor progression or unacceptable toxicity occurs; 3. Gemcitabine, 900 mg/m2 by IVI over 90 minutes on Days 1 and 8, plus docetaxel, 100 mg/m2 by IVI over 1 hour on Day 8 of a 28 day cycle until tumor progression or unacceptable toxicity occurs; 4. Doxorubicin, 75 mg/m2 by IVI over 5 to 30 minutes every 21 days for a maximum cumulative dose of 550 mg/m2 or unacceptable toxicity occurs; or 5. Ifosfamide 2.0 g/m2 administered over 2 to 4 hours on Days 1-4 of a 21 day cycle + mesna per standard site administration regimen until tumor progression or unacceptable toxicity occurs. Investigator's Choice Treatment (Darcabazine, Pazopanib, Gemcitabine + Docetaxel, Doxorubicin, Ifosfamide)
Progression-Free Survival (PFS)	4.04 Months Interval 2.79 to 4.83	2.96 Months Interval 2.63 to 4.17

Adverse Events

Aldoxorubicin

Serious events: 91 serious events

Other events: 209 other events

Deaths: 148 deaths

Investigator's Choice of Treatment

Serious events: 68 serious events

Other events: 203 other events

Deaths: 131 deaths

Serious adverse events

Other adverse events

Additional Information

Sandeep Bobby Reddy, Chief Medical Officer

ImmunityBio

Phone: 855-797-9277

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Aldoxorubicin n=213 participants at risk Aldoxorubicin is administered at 350 mg/m\^2 (260 mg/m\^2 doxorubicin equivalent) intravenously on Day 1 every 21-day cycles until tumor progression or unacceptable toxicity occurs. Aldoxorubicin	Investigator's Choice of Treatment n=207 participants at risk These treatments include: 1. Dacarbazine administered at 1000 mg/m2 by intravenous infusion (IVI), over 90±15 minutes on Day 1 every 21 days until tumor progression or unacceptable toxicity occurs; 2. Pazopanib, 800 mg orally each day until tumor progression or unacceptable toxicity occurs; 3. Gemcitabine, 900 mg/m2 by IVI over 90 minutes on Days 1 and 8, plus docetaxel, 100 mg/m2 by IVI over 1 hour on Day 8 of a 28 day cycle until tumor progression or unacceptable toxicity occurs; 4. Doxorubicin, 75 mg/m2 by IVI over 5 to 30 minutes every 21 days for a maximum cumulative dose of 550 mg/m2 or unacceptable toxicity occurs; or 5. Ifosfamide 2.0 g/m2 administered over 2 to 4 hours on Days 1-4 of a 21 day cycle + mesna per standard site administration regimen until tumor progression or unacceptable toxicity occurs. Investigator's Choice Treatment (Darcabazine, Pazopanib, Gemcitabine + Docetaxel, Doxorubicin, Ifosfamide)
Gastrointestinal disorders Gastroesophageal reflux disease	0.47% 1/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.00% 0/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Gastrointestinal disorders Intestinal Obstruction	0.47% 1/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.00% 0/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.47% 1/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.00% 0/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Gastrointestinal disorders Malaena	0.47% 1/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.00% 0/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Gastrointestinal disorders Rectal heamorrhage	0.00% 0/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.48% 1/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.48% 1/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
General disorders Pyrexia	0.94% 2/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	2.4% 5/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
General disorders Asthenia	0.94% 2/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.00% 0/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
General disorders Death	0.94% 2/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.00% 0/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
General disorders Gait disturbance	0.47% 1/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.48% 1/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
General disorders General physical health deterioration	0.47% 1/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.48% 1/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
General disorders Pain	0.47% 1/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.48% 1/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
General disorders Hypothermia	0.47% 1/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.00% 0/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
General disorders Injection site reaction	0.47% 1/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.00% 0/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Nervous system disorders Cervial cord compression	0.00% 0/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.97% 2/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Nervous system disorders Peripheral motor neuropathy	0.94% 2/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.00% 0/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Nervous system disorders Peripheral sensory neuropathy	0.94% 2/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.00% 0/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Nervous system disorders Spinal cord compression	0.47% 1/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.48% 1/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Nervous system disorders Facial paralysis	0.00% 0/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.48% 1/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Nervous system disorders Facial paresis	0.47% 1/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.00% 0/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Nervous system disorders Hemiparesis	0.00% 0/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.48% 1/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Nervous system disorders Paraparesis	0.00% 0/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.48% 1/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Nervous system disorders Partial seizures	0.00% 0/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.48% 1/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Nervous system disorders Presyncope	0.00% 0/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.48% 1/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Nervous system disorders Seizure	0.47% 1/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.00% 0/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Nervous system disorders Somnolence	0.47% 1/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.00% 0/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Nervous system disorders Syncope	0.00% 0/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.48% 1/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Musculoskeletal and connective tissue disorders Back pain	0.94% 2/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	1.4% 3/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Musculoskeletal and connective tissue disorders Muscular weakness	1.4% 3/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.00% 0/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.97% 2/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Blood and lymphatic system disorders Febrile neutropenia	14.1% 30/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	2.9% 6/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Blood and lymphatic system disorders Neutropenia	5.2% 11/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.48% 1/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Blood and lymphatic system disorders Anaemia	2.8% 6/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	2.4% 5/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Blood and lymphatic system disorders Thrombocytopenia	1.4% 3/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	1.4% 3/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Blood and lymphatic system disorders Leukocytosis	0.47% 1/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.00% 0/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Blood and lymphatic system disorders Leukopenia	0.47% 1/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.00% 0/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Infections and infestations Sepsis	3.8% 8/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	1.9% 4/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Infections and infestations Pneumonia	1.4% 3/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	2.4% 5/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Infections and infestations Cellulitis	0.47% 1/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	1.9% 4/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Infections and infestations Bacteraemia	0.94% 2/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	0.00% 0/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.

Other adverse events
Measure	Aldoxorubicin n=213 participants at risk Aldoxorubicin is administered at 350 mg/m\^2 (260 mg/m\^2 doxorubicin equivalent) intravenously on Day 1 every 21-day cycles until tumor progression or unacceptable toxicity occurs. Aldoxorubicin	Investigator's Choice of Treatment n=207 participants at risk These treatments include: 1. Dacarbazine administered at 1000 mg/m2 by intravenous infusion (IVI), over 90±15 minutes on Day 1 every 21 days until tumor progression or unacceptable toxicity occurs; 2. Pazopanib, 800 mg orally each day until tumor progression or unacceptable toxicity occurs; 3. Gemcitabine, 900 mg/m2 by IVI over 90 minutes on Days 1 and 8, plus docetaxel, 100 mg/m2 by IVI over 1 hour on Day 8 of a 28 day cycle until tumor progression or unacceptable toxicity occurs; 4. Doxorubicin, 75 mg/m2 by IVI over 5 to 30 minutes every 21 days for a maximum cumulative dose of 550 mg/m2 or unacceptable toxicity occurs; or 5. Ifosfamide 2.0 g/m2 administered over 2 to 4 hours on Days 1-4 of a 21 day cycle + mesna per standard site administration regimen until tumor progression or unacceptable toxicity occurs. Investigator's Choice Treatment (Darcabazine, Pazopanib, Gemcitabine + Docetaxel, Doxorubicin, Ifosfamide)
Gastrointestinal disorders Nausea	50.7% 108/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	44.0% 91/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Gastrointestinal disorders Stomatitis	53.5% 114/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	15.0% 31/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Gastrointestinal disorders Diarrhoea	22.5% 48/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	30.0% 62/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Gastrointestinal disorders Vomiting	28.2% 60/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	21.3% 44/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Gastrointestinal disorders Constipation	29.6% 63/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	15.9% 33/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Gastrointestinal disorders Abdominal Pain	15.0% 32/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	17.9% 37/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Gastrointestinal disorders Abdominal Pain Upper	5.2% 11/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	4.8% 10/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Gastrointestinal disorders Dyspepsia	3.8% 8/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	4.8% 10/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Gastrointestinal disorders Gastroesophageal reflux disease	5.6% 12/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	2.9% 6/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Gastrointestinal disorders Oral pain	5.6% 12/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	2.9% 6/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
General disorders Fatigue	45.1% 96/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	38.2% 79/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
General disorders Pyrexia	16.0% 34/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	16.9% 35/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
General disorders Asthenia	12.2% 26/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	13.0% 27/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
General disorders Oedema pheripheral	10.3% 22/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	14.0% 29/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
General disorders Pain	5.2% 11/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	5.3% 11/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Blood and lymphatic system disorders Anaemia	45.1% 96/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	30.0% 62/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Blood and lymphatic system disorders Neutropenia	29.6% 63/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	18.8% 39/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Blood and lymphatic system disorders Thrombocytopenia	13.6% 29/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	14.5% 30/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Blood and lymphatic system disorders Febrile Neutropenia	15.0% 32/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	4.3% 9/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Blood and lymphatic system disorders Leukopenia	8.9% 19/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	4.8% 10/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Metabolism and nutrition disorders Decreased Appetite	28.2% 60/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	17.4% 36/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Metabolism and nutrition disorders Hypokalaemia	15.0% 32/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	11.1% 23/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Metabolism and nutrition disorders Dehydration	8.0% 17/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	7.7% 16/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Metabolism and nutrition disorders Hypophosphataemia	7.5% 16/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	5.8% 12/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Metabolism and nutrition disorders Hypoalbuminaemia	6.6% 14/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	5.8% 12/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Metabolism and nutrition disorders Hyperglycaemia	7.0% 15/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	4.8% 10/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Metabolism and nutrition disorders Hypomagnesaemia	8.5% 18/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	1.4% 3/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Metabolism and nutrition disorders Hyponatraemia	6.1% 13/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	3.9% 8/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Respiratory, thoracic and mediastinal disorders Cough	22.1% 47/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	12.6% 26/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Reproductive system and breast disorders Dyspnoea	14.1% 30/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	16.4% 34/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	10.8% 23/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	5.3% 11/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Respiratory, thoracic and mediastinal disorders Pleural effusion	4.2% 9/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	6.3% 13/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Investigations White blood cell count decreased	15.0% 32/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	9.7% 20/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Investigations Neutrophil count decreased	12.7% 27/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	9.2% 19/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Investigations Weight decreased	10.3% 22/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	10.6% 22/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Investigations Platelet count decreased	11.3% 24/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	8.7% 18/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Investigations Blood alkaline phosphatase increased	9.4% 20/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	6.8% 14/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Investigations Lymphocyte count decreased	10.8% 23/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	4.3% 9/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Investigations Alanine aminotransferase increased	3.8% 8/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	7.2% 15/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.
Investigations Aspartate aminotransferase increased	3.8% 8/213 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.	5.8% 12/207 • All AEs that occurred after any administration of the study medication were to be followed until the event resolves, until the subject began alternative treatment, or until 30 days after the last dose of study medication. The SAE reporting period ended if the subject began an alternative therapy or 30 days after the last administration of study drug, up to 640 days.