Trial Outcomes & Findings for Tivozanib in Treating Patients With Liver Cancer That Is Metastatic or Cannot Be Removed by Surgery (NCT NCT01835223)

NCT ID: NCT01835223

Last Updated: 2020-10-28

Results Overview

Will be descriptively analyzed using standard Kaplan-Meier estimation along with the corresponding descriptive statistics and 95% confidence intervals.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 33 participants
• Primary outcome timeframe: 24 weeks
• Results posted on: 2020-10-28

Participant Flow

Participant milestones

Measure	Treatment (Tivozanib 1mg) Patients receive tivozanib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Tivozanib: Given PO	Treatment (Tivozanib 1.5mg) Patients receive tivozanib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Overall Study STARTED	30	3
Overall Study COMPLETED	21	2
Overall Study NOT COMPLETED	9	1

Reasons for withdrawal

Measure	Treatment (Tivozanib 1mg) Patients receive tivozanib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Tivozanib: Given PO	Treatment (Tivozanib 1.5mg) Patients receive tivozanib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Overall Study Adverse Event	1	0
Overall Study Withdrawal by Subject	2	0
Overall Study Disease progression	2	1
Overall Study Became Inelligible	4	0

Baseline Characteristics

Tivozanib in Treating Patients With Liver Cancer That Is Metastatic or Cannot Be Removed by Surgery

Baseline characteristics by cohort

Measure	Treatment (Tivozanib 1mg) n=24 Participants Patients receive tivozanib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Tivozanib: Given PO	Treatment (Tivozanib 1.5mg) n=3 Participants Patients receive tivozanib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Tivozanib: Given PO	Total n=27 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	9 Participants n=5 Participants	1 Participants n=7 Participants	10 Participants n=5 Participants
Age, Categorical >=65 years	15 Participants n=5 Participants	2 Participants n=7 Participants	17 Participants n=5 Participants
Age, Continuous	66.2 years STANDARD_DEVIATION 5.5 • n=5 Participants	65.5 years STANDARD_DEVIATION 11.4 • n=7 Participants	65.6 years STANDARD_DEVIATION 10.8 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Male	23 Participants n=5 Participants	3 Participants n=7 Participants	26 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	22 Participants n=5 Participants	3 Participants n=7 Participants	25 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	24 participants n=5 Participants	3 participants n=7 Participants	27 participants n=5 Participants
ECOG Performance Status 0:Fully active, able to carry on all pre-disease performance without restriction.	14 participants n=5 Participants	2 participants n=7 Participants	16 participants n=5 Participants
ECOG Performance Status 1: Restricted in physically strenuous, but able for work of light or sedentary nature	9 participants n=5 Participants	1 participants n=7 Participants	10 participants n=5 Participants

PRIMARY outcome

Timeframe: 24 weeks

Population: This outcome was only assessed as part of the Phase II study - which was conducted on the Tivozanib 1mg arm.

Will be descriptively analyzed using standard Kaplan-Meier estimation along with the corresponding descriptive statistics and 95% confidence intervals.

Outcome measures

Measure	Treatment (Tivozanib 1mg) n=19 Participants Patients receive tivozanib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Tivozanib: Given PO	Treatment (Tivozanib 1.5mg) Patients receive tivozanib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Tivozanib: Given PO
PFS, Assessed Using Standard RECIST Criteria	58 percentage of participants Interval 33.0 to 76.0	—

SECONDARY outcome

Timeframe: Up to 3 years

Population: This outcome was only assessed as part of the Phase II study - which was conducted on the Tivozanib 1mg arm. Only 19 subjects were evaluable for the primary or secondary end-points.

The number of patients achieving clinical benefit (CR, PR, or SD by RECIST).

Outcome measures

Measure	Treatment (Tivozanib 1mg) n=19 Participants Patients receive tivozanib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Tivozanib: Given PO	Treatment (Tivozanib 1.5mg) Patients receive tivozanib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Tivozanib: Given PO
Clinical Benefit Rate (CR, PR, and SD) by RECIST	12 Participants	—

SECONDARY outcome

Timeframe: Up to 3 years

Population: This outcome was only assessed as part of the Phase II study - which was conducted on the Tivozanib 1mg arm. Only 19 subjects were evaluable for the primary or secondary end-points.

Toxicity frequency will be tabulated by grade across all dose levels and cycles for all patients in the safety sample and for the subset treated at the recommended phase 2 dose.

Outcome measures

Measure	Treatment (Tivozanib 1mg) n=19 Participants Patients receive tivozanib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Tivozanib: Given PO	Treatment (Tivozanib 1.5mg) Patients receive tivozanib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Tivozanib: Given PO
Incidence of Adverse Events and Toxicities, Assessed Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4	19 Participants	—

SECONDARY outcome

Timeframe: Up to 3 years

Population: This outcome was only assessed as part of the Phase II study - which was conducted on the Tivozanib 1mg arm. Only 19 subjects were evaluable for the primary or secondary end-points.

Overall survival is defined as the time from treatment until death or last follow-up.

Outcome measures

Measure	Treatment (Tivozanib 1mg) n=19 Participants Patients receive tivozanib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Tivozanib: Given PO	Treatment (Tivozanib 1.5mg) Patients receive tivozanib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Tivozanib: Given PO
Overall Survival Rate	0.40 percent probability Interval 0.19 to 0.6	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 3 years

Population: This outcome was only assessed as part of the Phase II study - which was conducted on the Tivozanib 1mg arm. Only 19 subjects were evaluable for the primary or secondary end-points.

Defined as an AFP decrease greater than 50%.

Outcome measures

Measure	Treatment (Tivozanib 1mg) n=19 Participants Patients receive tivozanib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Tivozanib: Given PO	Treatment (Tivozanib 1.5mg) Patients receive tivozanib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Tivozanib: Given PO
AFP Response	4 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 3 years

Population: Due to funding limitations, this outcome was not assessed.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 3 years

Population: Due to funding issues, data were not completed.

Associations between drug exposure and response/survival and toxicity by quartiles of drug exposure.

Outcome measures

Outcome data not reported

Adverse Events

Treatment (Tivozanib 1mg)

Serious events: 15 serious events

Other events: 24 other events

Deaths: 18 deaths

Treatment (Tivozanib 1.5mg)

Serious events: 3 serious events

Other events: 3 other events

Deaths: 3 deaths

Serious adverse events

Measure	Treatment (Tivozanib 1mg) n=24 participants at risk Patients receive tivozanib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Tivozanib: Given PO	Treatment (Tivozanib 1.5mg) n=3 participants at risk Patients receive tivozanib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Tivozanib: Given PO
Cardiac disorders Acute myocardial infarction	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Cardiac disorders Cardiac failure congestive	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Gastrointestinal disorders Abdominal pain upper	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Gastrointestinal disorders Colitis	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Gastrointestinal disorders Gastrointestinal haemorrhage	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Gastrointestinal disorders Oesophageal ulcer haemorrhage	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Gastrointestinal disorders Pancreatitis	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Gastrointestinal disorders Stomatitis	0.00% 0/24 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	33.3% 1/3 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
General disorders Pyrexia	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	33.3% 1/3 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Hepatobiliary disorders Cholecystitis	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Hepatobiliary disorders Hepatic failure	8.3% 2/24 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Infections and infestations Bacteraemia	0.00% 0/24 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	33.3% 1/3 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Infections and infestations Enterocolitis infectious	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Infections and infestations Infection	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Infections and infestations Pneumonia	0.00% 0/24 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	33.3% 1/3 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Infections and infestations Staphylococcal infection	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Investigations Blood bilirubin increased	8.3% 2/24 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Metabolism and nutrition disorders Dehydration	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm malignant	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Nervous system disorders Cerebrovascular accident	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Nervous system disorders Encephalopathy	4.2% 1/24 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Renal and urinary disorders Acute kidney injury	4.2% 1/24 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	8.3% 2/24 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Vascular disorders Hypertension	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	33.3% 1/3 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Vascular disorders Hypotension	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.

Other adverse events

Measure	Treatment (Tivozanib 1mg) n=24 participants at risk Patients receive tivozanib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Tivozanib: Given PO	Treatment (Tivozanib 1.5mg) n=3 participants at risk Patients receive tivozanib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Tivozanib: Given PO
Blood and lymphatic system disorders Increased tendency to bruise	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Cardiac disorders Palpitations	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Ear and labyrinth disorders Hypoacusis	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Endocrine disorders Hypothyroidism	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Eye disorders Vision blurred	0.00% 0/24 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	33.3% 1/3 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Gastrointestinal disorders Abdominal distension	12.5% 3/24 • Number of events 3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Gastrointestinal disorders Abdominal pain	29.2% 7/24 • Number of events 7 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	66.7% 2/3 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Gastrointestinal disorders Abdominal pain upper	16.7% 4/24 • Number of events 4 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Gastrointestinal disorders Ascites	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Gastrointestinal disorders Constipation	25.0% 6/24 • Number of events 7 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Gastrointestinal disorders Diarrhoea	58.3% 14/24 • Number of events 27 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	66.7% 2/3 • Number of events 7 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Gastrointestinal disorders Dyspepsia	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Gastrointestinal disorders Faeces discoloured	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Gastrointestinal disorders Flatulence	8.3% 2/24 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Gastrointestinal disorders Gastrooesophageal reflux disease	12.5% 3/24 • Number of events 3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	66.7% 2/3 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Gastrointestinal disorders Large intestinal haemorrhage	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Gastrointestinal disorders Lip swelling	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Gastrointestinal disorders Nausea	45.8% 11/24 • Number of events 23 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	33.3% 1/3 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Gastrointestinal disorders Rectal haemorrhage	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Gastrointestinal disorders Stomatitis	20.8% 5/24 • Number of events 12 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	33.3% 1/3 • Number of events 4 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Gastrointestinal disorders Varices oesophageal	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Gastrointestinal disorders Vomiting	37.5% 9/24 • Number of events 17 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	33.3% 1/3 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
General disorders Chest pain	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	33.3% 1/3 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
General disorders Chills	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
General disorders Fatigue	79.2% 19/24 • Number of events 45 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	66.7% 2/3 • Number of events 3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
General disorders Infusion site extravasation	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
General disorders Oedema	8.3% 2/24 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
General disorders Oedema peripheral	20.8% 5/24 • Number of events 5 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
General disorders Pain	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
General disorders Pyrexia	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
General disorders Thirst	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Hepatobiliary disorders Cholangitis	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Hepatobiliary disorders Hepatic failure	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Hepatobiliary disorders Jaundice	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Hepatobiliary disorders Portal vein thrombosis	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Immune system disorders Hypersensitivity	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Infections and infestations Bronchitis	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Infections and infestations Candida infection	8.3% 2/24 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Infections and infestations Cellulitis	8.3% 2/24 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Infections and infestations Fungal skin infection	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Infections and infestations Nasopharyngitis	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Infections and infestations Oral candidiasis	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Infections and infestations Perichondritis	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Infections and infestations Pneumonia	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Infections and infestations Rhinitis	8.3% 2/24 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Infections and infestations Sinusitis	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Infections and infestations Urinary tract infection	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Infections and infestations Viral infection	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Injury, poisoning and procedural complications Contusion	8.3% 2/24 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	33.3% 1/3 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Injury, poisoning and procedural complications Fall	8.3% 2/24 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Investigations Activated partial thromboplastin time prolonged	0.00% 0/24 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	33.3% 1/3 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Investigations Alanine aminotransferase increased	25.0% 6/24 • Number of events 7 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	66.7% 2/3 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Investigations Ammonia increased	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Investigations Aspartate aminotransferase increased	20.8% 5/24 • Number of events 6 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	66.7% 2/3 • Number of events 5 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Investigations Blood alkaline phosphatase increased	20.8% 5/24 • Number of events 8 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	66.7% 2/3 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Investigations Blood bilirubin decreased	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Investigations Blood bilirubin increased	25.0% 6/24 • Number of events 14 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	100.0% 3/3 • Number of events 6 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Investigations Blood creatinine increased	0.00% 0/24 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	66.7% 2/3 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Investigations Haemoglobin decreased	8.3% 2/24 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	33.3% 1/3 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Investigations Lipase increased	4.2% 1/24 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Investigations Lymphocyte count decreased	12.5% 3/24 • Number of events 4 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	100.0% 3/3 • Number of events 8 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Investigations Platelet count decreased	16.7% 4/24 • Number of events 5 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	66.7% 2/3 • Number of events 3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Investigations Urine viscosity increased	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Investigations Weight decreased	33.3% 8/24 • Number of events 10 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Metabolism and nutrition disorders Cachexia	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Metabolism and nutrition disorders Decreased appetite	62.5% 15/24 • Number of events 28 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	33.3% 1/3 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Metabolism and nutrition disorders Dehydration	16.7% 4/24 • Number of events 4 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	66.7% 2/3 • Number of events 3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Metabolism and nutrition disorders Hypercalcaemia	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Metabolism and nutrition disorders Hyperkalaemia	8.3% 2/24 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	100.0% 3/3 • Number of events 4 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Metabolism and nutrition disorders Hypernatraemia	0.00% 0/24 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	66.7% 2/3 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Metabolism and nutrition disorders Hypoalbuminaemia	16.7% 4/24 • Number of events 7 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	100.0% 3/3 • Number of events 5 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Metabolism and nutrition disorders Hypoglycaemia	8.3% 2/24 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Metabolism and nutrition disorders Hypokalaemia	8.3% 2/24 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Metabolism and nutrition disorders Hypomagnesaemia	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	33.3% 1/3 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Metabolism and nutrition disorders Hyponatraemia	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	66.7% 2/3 • Number of events 4 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Musculoskeletal and connective tissue disorders Arthralgia	12.5% 3/24 • Number of events 4 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Musculoskeletal and connective tissue disorders Back pain	12.5% 3/24 • Number of events 3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Musculoskeletal and connective tissue disorders Flank pain	12.5% 3/24 • Number of events 4 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Musculoskeletal and connective tissue disorders Groin pain	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Musculoskeletal and connective tissue disorders Muscle spasms	8.3% 2/24 • Number of events 3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	33.3% 1/3 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Musculoskeletal and connective tissue disorders Muscular weakness	12.5% 3/24 • Number of events 4 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	16.7% 4/24 • Number of events 5 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Musculoskeletal and connective tissue disorders Myalgia	8.3% 2/24 • Number of events 3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Musculoskeletal and connective tissue disorders Neck pain	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	8.3% 2/24 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Musculoskeletal and connective tissue disorders Spinal pain	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Musculoskeletal and connective tissue disorders Spinal stenosis	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Nervous system disorders Amnesia	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Nervous system disorders Balance disorder	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Nervous system disorders Cognitive disorder	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Nervous system disorders Dizziness	41.7% 10/24 • Number of events 12 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	33.3% 1/3 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Nervous system disorders Dysgeusia	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Nervous system disorders Encephalopathy	16.7% 4/24 • Number of events 5 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Nervous system disorders Headache	20.8% 5/24 • Number of events 6 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	33.3% 1/3 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Nervous system disorders Hepatic encephalopathy	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Nervous system disorders Posterior reversible encephalopathy syndrome	0.00% 0/24 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	33.3% 1/3 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Nervous system disorders Somnolence	8.3% 2/24 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Nervous system disorders Taste disorder	8.3% 2/24 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Psychiatric disorders Anxiety	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Psychiatric disorders Confusional state	8.3% 2/24 • Number of events 3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Psychiatric disorders Delirium	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Psychiatric disorders Depressed mood	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Psychiatric disorders Depression	8.3% 2/24 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Psychiatric disorders Disorientation	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Psychiatric disorders Insomnia	12.5% 3/24 • Number of events 3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Psychiatric disorders Nightmare	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Renal and urinary disorders Haematuria	8.3% 2/24 • Number of events 3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Renal and urinary disorders Nephrolithiasis	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Renal and urinary disorders Pollakiuria	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Renal and urinary disorders Proteinuria	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Renal and urinary disorders Renal disorder	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Renal and urinary disorders Renal failure	0.00% 0/24 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	33.3% 1/3 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Renal and urinary disorders Urinary incontinence	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Renal and urinary disorders Urinary retention	0.00% 0/24 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	33.3% 1/3 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Respiratory, thoracic and mediastinal disorders Cough	16.7% 4/24 • Number of events 7 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	33.3% 1/3 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Respiratory, thoracic and mediastinal disorders Dysphonia	33.3% 8/24 • Number of events 13 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	66.7% 2/3 • Number of events 4 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	20.8% 5/24 • Number of events 6 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	66.7% 2/3 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Respiratory, thoracic and mediastinal disorders Epistaxis	12.5% 3/24 • Number of events 4 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	33.3% 1/3 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Respiratory, thoracic and mediastinal disorders Hiccups	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Respiratory, thoracic and mediastinal disorders Nasal congestion	12.5% 3/24 • Number of events 4 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	4.2% 1/24 • Number of events 3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Respiratory, thoracic and mediastinal disorders Productive cough	8.3% 2/24 • Number of events 3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	8.3% 2/24 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract congestion	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Skin and subcutaneous tissue disorders Dry skin	20.8% 5/24 • Number of events 5 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Skin and subcutaneous tissue disorders Erythema	8.3% 2/24 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Skin and subcutaneous tissue disorders Nail discolouration	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Skin and subcutaneous tissue disorders Nail ridging	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Skin and subcutaneous tissue disorders Night sweats	0.00% 0/24 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	33.3% 1/3 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	12.5% 3/24 • Number of events 6 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	33.3% 1/3 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Skin and subcutaneous tissue disorders Pruritus	16.7% 4/24 • Number of events 7 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Skin and subcutaneous tissue disorders Rash	8.3% 2/24 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	33.3% 1/3 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Skin and subcutaneous tissue disorders Rash generalised	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Skin and subcutaneous tissue disorders Rash papular	8.3% 2/24 • Number of events 4 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Skin and subcutaneous tissue disorders Skin discolouration	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Skin and subcutaneous tissue disorders Skin exfoliation	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Skin and subcutaneous tissue disorders Skin necrosis	4.2% 1/24 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Skin and subcutaneous tissue disorders Urticaria	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Vascular disorders Hot flush	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Vascular disorders Hypertension	16.7% 4/24 • Number of events 5 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	33.3% 1/3 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Vascular disorders Hypotension	8.3% 2/24 • Number of events 2 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Vascular disorders Pelvic venous thrombosis	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Vascular disorders Peripheral coldness	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.
Vascular disorders Thrombophlebitis	4.2% 1/24 • Number of events 1 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.	0.00% 0/3 • Phase 1: Cycle 1 Day 15, Day 1 of Each Cycle After Cycle 1, Cycle 3 Day 1 (for phase 1 only), and to the End of Treatment. Phase II: From start of treatment until end of treatment.

Additional Information

Katy Wang, Statistician, M.A.

Roswell Park Cancer Institute

Phone: 716-845-1300

Email: katy.wang@roswellpark.org

Results disclosure agreements

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