Trial Outcomes & Findings for Belinostat for Solid Tumors and Lymphomas in Patients With Varying Degrees of Hepatic Dysfunction (NCT NCT01273155)

Last Updated: 2019-03-26

Results Overview

A DLT was defined as an adverse event deemed possibly, probably, or definitely related to administration of study drugs and met the following criteria: grade≥3 non-hematological toxicity (except grade ≥3 diarrhea, nausea, vomiting responsive to supportive therapy);grade≥3 rise in creatinine (except grade 3 able to be corrected to grade 1 or baseline with intravenous fluids within 24hrs); grade≥3 electrolyte toxicities (except those able to be corrected to grade 1 or baseline within 48hrs); grade 4 thrombocytopenia; grade 4 neutropenia for \>5 days or febrile neutropenia; any neurotoxicity grade≥2 not reversible to grade 1 or baseline within 2wks; or any delay in treatment by ≥2wks due to treatment-related toxicity. Worsening liver function, as defined by a rise in serum bilirubin not related to tumor progression, was considered a DLT if a patient with mild dysfunction became severe for 1wk, or if a patient in either the moderate/severe groups had a \>1.5x increase in bilirubin for 1 wk.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

72 participants

Primary outcome timeframe

First cycle of therapy, 28 days.

Results posted on

2019-03-26

Participant Flow

Participant milestones

Participant milestones
Measure	Normal Function-Belinostat 1000 mg/m(2) Normal Liver Function was defined as bilirubin ≤Upper Limit of Normal (ULN) and aspartate aminotransferase (AST) ≤ ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 750 mg/m(2) Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 1000 mg/m(2) Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 500 mg/m(2) Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 750 mg/m(2) Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 250 mg/m(2) Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 350 mg/m(2) Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).
Overall Study STARTED	14	12	18	5	5	10	8
Overall Study COMPLETED	12	8	6	4	3	5	2
Overall Study NOT COMPLETED	2	4	12	1	2	5	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Normal Function-Belinostat 1000 mg/m(2) Normal Liver Function was defined as bilirubin ≤Upper Limit of Normal (ULN) and aspartate aminotransferase (AST) ≤ ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 750 mg/m(2) Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 1000 mg/m(2) Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 500 mg/m(2) Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 750 mg/m(2) Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 250 mg/m(2) Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 350 mg/m(2) Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).
Overall Study Off study trmt prior to end of C1/PD	2	3	8	0	0	2	3
Overall Study Change in liver function/no longer eval.	0	1	0	0	1	0	0
Overall Study Off study prior to C1/due to toxicity	0	0	2	0	0	0	1
Overall Study Died during Cycle 1	0	0	1	1	0	2	2
Overall Study Withdrew during C1/refused further trmt	0	0	1	0	1	1	0

Baseline Characteristics

Belinostat for Solid Tumors and Lymphomas in Patients With Varying Degrees of Hepatic Dysfunction

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Normal Function n=14 Participants Normal Liver Function was defined as bilirubin ≤Upper Limit of Normal (ULN) and aspartate aminotransferase (AST) ≤ ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction n=30 Participants Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction n=10 Participants Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction n=18 Participants Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Total n=72 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	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants	22 Participants n=7 Participants	6 Participants n=5 Participants	12 Participants n=4 Participants	47 Participants n=21 Participants
Age, Categorical >=65 years	7 Participants n=5 Participants	8 Participants n=7 Participants	4 Participants n=5 Participants	6 Participants n=4 Participants	25 Participants n=21 Participants
Age, Continuous	65 years n=5 Participants	59 years n=7 Participants	63.5 years n=5 Participants	57.5 years n=4 Participants	61 years n=21 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	11 Participants n=7 Participants	3 Participants n=5 Participants	8 Participants n=4 Participants	28 Participants n=21 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	19 Participants n=7 Participants	7 Participants n=5 Participants	10 Participants n=4 Participants	44 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	6 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=5 Participants	29 Participants n=7 Participants	9 Participants n=5 Participants	15 Participants n=4 Participants	66 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 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	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	8 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	16 Participants n=21 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants	19 Participants n=7 Participants	8 Participants n=5 Participants	15 Participants n=4 Participants	52 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Region of Enrollment United States	14 participants n=5 Participants	30 participants n=7 Participants	10 participants n=5 Participants	18 participants n=4 Participants	72 participants n=21 Participants
Eastern Cooperative Oncology Group Performance Status Grade 0	4 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	1 Participants n=4 Participants	10 Participants n=21 Participants
Eastern Cooperative Oncology Group Performance Status Grade 1	9 Participants n=5 Participants	26 Participants n=7 Participants	5 Participants n=5 Participants	13 Participants n=4 Participants	53 Participants n=21 Participants
Eastern Cooperative Oncology Group Performance Status Grade 2	1 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants	9 Participants n=21 Participants

PRIMARY outcome

Timeframe: First cycle of therapy, 28 days.

Population: Forty patients were evaluable for dose-limiting toxicity; others came off study prior to the end of Cycle 1 and were not evaluable.

Outcome measures

Outcome measures
Measure	Normal Function-Belinostat 1000 mg/m(2) n=12 Participants Normal Liver Function was defined as bilirubin ≤Upper Limit of Normal (ULN) and aspartate aminotransferase (AST) ≤ ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 750 mg/m(2) n=8 Participants Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 1000 mg/m(2) n=6 Participants Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 500 mg/m(2) n=4 Participants Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 750 mg/m(2) n=3 Participants Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 250 mg/m(2) n=5 Participants Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 350 mg/m(2) n=2 Participants Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).
Dose Limiting Toxicity (DLTs)	0 Toxicities	0 Toxicities	0 Toxicities	0 Toxicities	0 Toxicities	0 Toxicities	0 Toxicities

PRIMARY outcome

Timeframe: First cycle of therapy, 28 days

Population: Normal liver function patients were not eligible for dose escalation. Twenty-eight patients were evaluable for MTD; others came off study prior to the end of Cycle 1 and were not evaluable.

In order to maintain consistent dosing across the hepatic dysfunction groups, the dose recommended for cohorts with greater liver dysfunction could be no greater than the dose for cohorts of lesser dysfunction. In other words, it was assumed that a particular group would not tolerate a dose not tolerated by a group with lesser dysfunction and conversely, will tolerate a dose tolerated by a group with greater dysfunction. If a higher dose was tolerated in a group of greater dysfunction, but not in the group of lesser dysfunction, the lower dose would be recommended for both groups. The highest dose to be explored was no greater than the recommended dose for patients with normal liver function.

Outcome measures

Outcome measures
Measure	Normal Function-Belinostat 1000 mg/m(2) n=14 Participants Normal Liver Function was defined as bilirubin ≤Upper Limit of Normal (ULN) and aspartate aminotransferase (AST) ≤ ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 750 mg/m(2) n=7 Participants Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 1000 mg/m(2) n=7 Participants Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 500 mg/m(2) Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 750 mg/m(2) Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 250 mg/m(2) Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 350 mg/m(2) Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).
Maximum Tolerated Dose (MTD) of Belinostat According to Degree of Liver Dysfunction	1000 mg/m(2)	NA mg/m(2) The MTD was not established for the moderate and severe cohorts prior to study closure.	NA mg/m(2) The MTD was not established for the moderate and severe cohorts prior to study closure.	—	—	—	—

PRIMARY outcome

Timeframe: From Cycle 1 Day -7 up to 12 (21-day) cycles

Population: Total number of evaluable patients per cohort on the indicated dose level; only patients who received study drug were evaluable for assessment of toxicity (some patients were assigned to a dose level but did not receive study drug and are therefore not included).

The number of participants experiencing each adverse event by liver function cohort at each dose level. The grade refers to the severity of the Adverse Event. Grade 1 Mild; Grade 2 Moderate; Grade 3 Severe or medically significant but not immediately life-threatening; Grade 4 Life-threatening consequences; Grade 5 Death related to adverse event.

Outcome measures

Outcome measures
Measure	Normal Function-Belinostat 1000 mg/m(2) n=14 Participants Normal Liver Function was defined as bilirubin ≤Upper Limit of Normal (ULN) and aspartate aminotransferase (AST) ≤ ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 750 mg/m(2) n=10 Participants Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 1000 mg/m(2) n=15 Participants Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 500 mg/m(2) n=5 Participants Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 750 mg/m(2) n=6 Participants Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 250 mg/m(2) n=9 Participants Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 350 mg/m(2) n=5 Participants Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 2 Anemia	1 Participants	1 Participants	3 Participants	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 3 Anemia	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 2 Anorexia	1 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 2 Dyspepsia	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 2 Dyspnea	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 2 Edema (limbs)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 2 Fatigue	2 Participants	1 Participants	2 Participants	1 Participants	1 Participants	1 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 3 Fatigue	1 Participants	1 Participants	2 Participants	0 Participants	2 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 2 Hypertension	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 2 Hypophosphatemia	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 3 Hypophosphatemia	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 2 Infusion related reaction	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 2 infusion site extravasation	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 2 INR Increased	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 5 Lung Infection	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 2 Lymphocyte count decreased	1 Participants	0 Participants	4 Participants	1 Participants	1 Participants	0 Participants	1 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 3 Lymphocyte count decreased	3 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 2 Nausea	3 Participants	0 Participants	3 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 3 Pain in extremity	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 2 Peripheral nerve infection	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 2 Phlebitis	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 2 Rash maculo-papular	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 3 Syncope	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 2 Vomiting	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 3 Vomiting	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 2 Weight loss	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 2 White blood cell decreased	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 2 Abdominal distension	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 3 Alanine aminotransferase increased	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 3 Ascites	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 3 Blood bilirubin increased	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 4 Blood bilirubin increased	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 2 Chills	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 2 Constipation	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 2 Diarrhea	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 2 Fever	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 3 Generalized muscle weakness	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 2 Infections and infestations - Other	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 2 Malaise	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 2 Platelet count decreased	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 3 Aspartate aminotransferase increased	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug Grade 2 Blood bilirubin increased	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Cycle 1 Day -7 prior to infusion; 15 and 25 minutes after the start of infusion; and 5, 10, 15, 30, 60, and 90 minutes, and 2, 4, 6, 8, and 24 hours after the end of infusion.

Population: The number of patients in a given cohort that received Belinistat on Cycle 1 Day-7 and had blood samples successfully collected at the specified timepoints for PK analysis. There were 3 patients with Mild Liver Dysfunction who were not evaluable for Belinostat Cmax.

Maximum plasma concentrations (Cmax) for belinostat and five metabolites on Cycle 1 Day -7 as a function of degree of liver dysfunction.

Outcome measures

Outcome measures
Measure	Normal Function-Belinostat 1000 mg/m(2) n=14 Participants Normal Liver Function was defined as bilirubin ≤Upper Limit of Normal (ULN) and aspartate aminotransferase (AST) ≤ ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 750 mg/m(2) n=25 Participants Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 1000 mg/m(2) n=10 Participants Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 500 mg/m(2) n=15 Participants Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 750 mg/m(2) Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 250 mg/m(2) Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 350 mg/m(2) Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).
Pharmacokinetics (PK) of a Single-dose Belinostat (400 mg/m^2)) According to Degree of Liver Dysfunction: Maximum Plasma Concentrations (Cmax) Belinostat	21.9 µg/mL Standard Deviation 8.7	26.6 µg/mL Standard Deviation 9.5	22.1 µg/mL Standard Deviation 5.7	25.0 µg/mL Standard Deviation 7.4	—	—	—
Pharmacokinetics (PK) of a Single-dose Belinostat (400 mg/m^2)) According to Degree of Liver Dysfunction: Maximum Plasma Concentrations (Cmax) Belinostat glucuronide	80.8 µg/mL Standard Deviation 27.3	90.8 µg/mL Standard Deviation 19.2	67.2 µg/mL Standard Deviation 33.6	72.8 µg/mL Standard Deviation 28.2	—	—	—
Pharmacokinetics (PK) of a Single-dose Belinostat (400 mg/m^2)) According to Degree of Liver Dysfunction: Maximum Plasma Concentrations (Cmax) Methyl belinostat	2.10 µg/mL Standard Deviation 0.94	2.99 µg/mL Standard Deviation 1.15	3.26 µg/mL Standard Deviation 0.75	3.35 µg/mL Standard Deviation 0.90	—	—	—
Pharmacokinetics (PK) of a Single-dose Belinostat (400 mg/m^2)) According to Degree of Liver Dysfunction: Maximum Plasma Concentrations (Cmax) M21	1.26 µg/mL Standard Deviation 0.75	1.79 µg/mL Standard Deviation 0.70	1.64 µg/mL Standard Deviation 0.32	1.93 µg/mL Standard Deviation 0.59	—	—	—
Pharmacokinetics (PK) of a Single-dose Belinostat (400 mg/m^2)) According to Degree of Liver Dysfunction: Maximum Plasma Concentrations (Cmax) M24	2.56 µg/mL Standard Deviation 0.77	2.35 µg/mL Standard Deviation 0.96	1.82 µg/mL Standard Deviation 0.65	1.88 µg/mL Standard Deviation 0.96	—	—	—
Pharmacokinetics (PK) of a Single-dose Belinostat (400 mg/m^2)) According to Degree of Liver Dysfunction: Maximum Plasma Concentrations (Cmax) M26	1.68 µg/mL Standard Deviation 0.71	1.80 µg/mL Standard Deviation 0.64	1.83 µg/mL Standard Deviation 0.52	2.24 µg/mL Standard Deviation 1.65	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day-7 prior to infusion; 15 and 25 minutes after start of infusion; and 5, 10, 15, 60, 60, and 90 minutes, and 2, 4, 6, 8, and 24 hours after the end of infusion.

Population: The number of patients in a given cohort that received Belinostat on Cycle 1 day -7 and had blood samples successfully collected at the specified timepoints for PK analysis. One patient with Mild Liver Dysfunction was not evaluated for Belinostat AUC0-inf.

Area Under the Plasma Concentration Time Curve Extrapolated to Infinity (AUC0-inf) for belinostat and four metabolites on Cycle 1 Day -7 as a function of degree of liver dysfunction.

Outcome measures

Outcome measures
Measure	Normal Function-Belinostat 1000 mg/m(2) n=14 Participants Normal Liver Function was defined as bilirubin ≤Upper Limit of Normal (ULN) and aspartate aminotransferase (AST) ≤ ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 750 mg/m(2) n=25 Participants Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 1000 mg/m(2) n=10 Participants Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 500 mg/m(2) n=15 Participants Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 750 mg/m(2) Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 250 mg/m(2) Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 350 mg/m(2) Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Area Under the Plasma Concentration Time Curve Extrapolated to Infinity(AUC0-inf) Belinostat	719 µg*min/mL Standard Deviation 265	859 µg*min/mL Standard Deviation 270	834 µg*min/mL Standard Deviation 217	1012 µg*min/mL Standard Deviation 408	—	—	—
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Area Under the Plasma Concentration Time Curve Extrapolated to Infinity(AUC0-inf) Methyl belinostat	354 µg*min/mL Standard Deviation 305	483 µg*min/mL Standard Deviation 163	829 µg*min/mL Standard Deviation 471	930 µg*min/mL Standard Deviation 797	—	—	—
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Area Under the Plasma Concentration Time Curve Extrapolated to Infinity(AUC0-inf) M21	647 µg*min/mL Standard Deviation 884	840 µg*min/mL Standard Deviation 589	1058 µg*min/mL Standard Deviation 398	1295 µg*min/mL Standard Deviation 600	—	—	—
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Area Under the Plasma Concentration Time Curve Extrapolated to Infinity(AUC0-inf) M24	1009 µg*min/mL Standard Deviation 555	916 µg*min/mL Standard Deviation 450	885 µg*min/mL Standard Deviation 514	970 µg*min/mL Standard Deviation 693	—	—	—
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Area Under the Plasma Concentration Time Curve Extrapolated to Infinity(AUC0-inf) M26	361 µg*min/mL Standard Deviation 193	396 µg*min/mL Standard Deviation 164	600 µg*min/mL Standard Deviation 292	740 µg*min/mL Standard Deviation 576	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day -7 prior to infusion; 15 and 25 minutes after the start of infusion; and 5, 10, 15, 30, 60, and 90 minutes, and 2, 4, 6, 8, and 24 hours after the end of infusion.

Population: The number of patients in a given cohort that received Belinostat on Cycle 1 Day -7 and had blood samples successfully collected at the specified timepoints for PK analysis.

Area Under the Plasma Concentration Time Curve Extrapolated to Infinity(AUC0-inf) for Belinostat glucuronide, a Belinostat Metabolite on Cycle 1 Day-7 as a function of degree of liver dysfunction.

Outcome measures

Outcome measures
Measure	Normal Function-Belinostat 1000 mg/m(2) n=14 Participants Normal Liver Function was defined as bilirubin ≤Upper Limit of Normal (ULN) and aspartate aminotransferase (AST) ≤ ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 750 mg/m(2) n=25 Participants Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 1000 mg/m(2) n=10 Participants Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 500 mg/m(2) n=15 Participants Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 750 mg/m(2) Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 250 mg/m(2) Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 350 mg/m(2) Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Area Under the Plasma Concentration Time Curve Extrapolated to Infinity(AUC0-inf) of Belinostat	15.1 mg*min/mL Standard Deviation 10.4	18.4 mg*min/mL Standard Deviation 5.9	18.4 mg*min/mL Standard Deviation 13.4	23.4 mg*min/mL Standard Deviation 25.6	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day -7 prior to infusion; 15 and 25 minutes after the start of infusion; and 5, 10, 15, 30, 60, and 90 minutes, and 2, 4, 6, 8, and 24 hours after the end of infusion.

Population: The number of patients in a given cohort that received Belinostat on Cycle 1 Day -7 and had blood samples successfully collected at the specified timepoints for PK analysis.

Half-life Period (t1/2) of belinostat and five metabolites on Cycle 1 Day -7 as a function of degree of liver function.

Outcome measures

Outcome measures
Measure	Normal Function-Belinostat 1000 mg/m(2) n=14 Participants Normal Liver Function was defined as bilirubin ≤Upper Limit of Normal (ULN) and aspartate aminotransferase (AST) ≤ ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 750 mg/m(2) n=25 Participants Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 1000 mg/m(2) n=10 Participants Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 500 mg/m(2) n=15 Participants Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 750 mg/m(2) Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 250 mg/m(2) Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 350 mg/m(2) Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Half-Life (t1/2) Belinostat	118 min Standard Deviation 90	127 min Standard Deviation 57	144 min Standard Deviation 86	157 min Standard Deviation 118	—	—	—
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Half-Life (t1/2) Belinostat glucuronide	280 min Standard Deviation 55	246 min Standard Deviation 59	238 min Standard Deviation 128	267 min Standard Deviation 134	—	—	—
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Half-Life (t1/2) M21	305 min Standard Deviation 337	460 min Standard Deviation 324	486 min Standard Deviation 191	485 min Standard Deviation 205	—	—	—
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Half-Life (t1/2) M24	264 min Standard Deviation 106	253 min Standard Deviation 97	223 min Standard Deviation 119	260 min Standard Deviation 133	—	—	—
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Half-Life (t1/2) M26	131 min Standard Deviation 115	151 min Standard Deviation 194	177 min Standard Deviation 95	153 min Standard Deviation 83	—	—	—
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Half-Life (t1/2) Methyl belinostat	79.6 min Standard Deviation 38.9	80.3 min Standard Deviation 19.1	136.1 min Standard Deviation 96.0	133 min Standard Deviation 98	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day-7 prior to infusion; 15 and 25 minutes after the start of infusion; and 5, 10, 15, 30, 60, and 90 minutes, and 2, 4, 6, 8, and 24 hours after the end of infusion.

Population: The number of patients in a given cohort that received Belinistat on Cycle 1 Day-7 and had blood samples successfully collected at the specified timepoints for PK analysis.

Clearance (CL) of Belinostat on Cycle 1 Day-7 as a function of degree of liver dysfunction

Outcome measures

Outcome measures
Measure	Normal Function-Belinostat 1000 mg/m(2) n=14 Participants Normal Liver Function was defined as bilirubin ≤Upper Limit of Normal (ULN) and aspartate aminotransferase (AST) ≤ ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 750 mg/m(2) n=25 Participants Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 1000 mg/m(2) n=10 Participants Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 500 mg/m(2) n=15 Participants Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 750 mg/m(2) Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 250 mg/m(2) Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 350 mg/m(2) Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Clearance (CL)	661 mL/min/m^2 Standard Deviation 346	542 mL/min/m^2 Standard Deviation 214	505 mL/min/m^2 Standard Deviation 114	444 mL/min/m^2 Standard Deviation 137	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day-7 prior to infusion; 15 and 25 minutes after the start of infusion; and 5, 10, 15, 30, 60, and 90 minutes, and 2, 4, 6, 8, and 24 hours after the end of infusion.

Population: The number of patients in a given cohort that received Belinistat on Cycle 1 Day-7 and had blood samples successfully collected at the specified timepoints for PK analysis.

Belinostat Apparent volume of distribution at steady state (Vss) on Cycle 1 Day-7 as a function of degree of liver dysfunction.

Outcome measures

Outcome measures
Measure	Normal Function-Belinostat 1000 mg/m(2) n=14 Participants Normal Liver Function was defined as bilirubin ≤Upper Limit of Normal (ULN) and aspartate aminotransferase (AST) ≤ ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 750 mg/m(2) n=25 Participants Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 1000 mg/m(2) n=10 Participants Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 500 mg/m(2) n=15 Participants Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 750 mg/m(2) Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 250 mg/m(2) Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 350 mg/m(2) Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Volume of Distribution at Steady State (Vss)	30.1 L/m^2 Standard Deviation 16.1	25.7 L/m^2 Standard Deviation 17.4	38.1 L/m^2 Standard Deviation 40.4	29.6 L/m^2 Standard Deviation 15.4	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day-7 prior to infusion; 15 and 25 minutes after the start of infusion; and 5, 10, 15, 30, 60, and 90 minutes, and 2, 4, 6, 8, and 24 hours after the end of infusion.

Metabolic ratios of Maximum Plasma Concentrations (Cmax), reported as a geometric mean (geometric standard deviation), for the belinostat metabolic pathway on Cycle 1 Day-7 as a function of degree of liver dysfunction.

Outcome measures

Outcome measures
Measure	Normal Function-Belinostat 1000 mg/m(2) n=14 Participants Normal Liver Function was defined as bilirubin ≤Upper Limit of Normal (ULN) and aspartate aminotransferase (AST) ≤ ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 750 mg/m(2) n=25 Participants Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 1000 mg/m(2) n=10 Participants Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 500 mg/m(2) n=15 Participants Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 750 mg/m(2) Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 250 mg/m(2) Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 350 mg/m(2) Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Metabolic Ratios of Maximum Plasma Concentrations (Cmax) for the Belinostat Metabolic Pathway Belinostat glucuronide/belinostat	3.78 ratio Standard Deviation 1.47	3.57 ratio Standard Deviation 1.47	2.88 ratio Standard Deviation 1.54	2.85 ratio Standard Deviation 1.51	—	—	—
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Metabolic Ratios of Maximum Plasma Concentrations (Cmax) for the Belinostat Metabolic Pathway Methyl belinostat/belinostat	0.0948 ratio Standard Deviation 1.53	0.112 ratio Standard Deviation 1.52	0.149 ratio Standard Deviation 1.54	0.134 ratio Standard Deviation 1.38	—	—	—
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Metabolic Ratios of Maximum Plasma Concentrations (Cmax) for the Belinostat Metabolic Pathway M21/belinostat	0.0522 ratio Standard Deviation 1.69	0.0642 ratio Standard Deviation 1.50	0.0768 ratio Standard Deviation 1.54	0.0759 ratio Standard Deviation 1.43	—	—	—
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Metabolic Ratios of Maximum Plasma Concentrations (Cmax) for the Belinostat Metabolic Pathway M24/belinostat	0.117 ratio Standard Deviation 1.36	0.0870 ratio Standard Deviation 1.61	0.0738 ratio Standard Deviation 1.46	0.0710 ratio Standard Deviation 1.84	—	—	—
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Metabolic Ratios of Maximum Plasma Concentrations (Cmax) for the Belinostat Metabolic Pathway M26/belinostat	0.0752 ratio Standard Deviation 1.48	0.0666 ratio Standard Deviation 1.44	0.0824 ratio Standard Deviation 1.57	0.0806 ratio Standard Deviation 1.64	—	—	—
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Metabolic Ratios of Maximum Plasma Concentrations (Cmax) for the Belinostat Metabolic Pathway M24/M26	1.56 ratio Standard Deviation 1.46	1.32 ratio Standard Deviation 1.50	0.895 ratio Standard Deviation 1.88	0.611 ratio Standard Deviation 1.66	—	—	—
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Metabolic Ratios of Maximum Plasma Concentrations (Cmax) for the Belinostat Metabolic Pathway M26/M21	1.44 ratio Standard Deviation 1.88	0.96 ratio Standard Deviation 1.62	1.07 ratio Standard Deviation 1.50	1.06 ratio Standard Deviation 1.84	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day-7 prior to infusion; 15 and 25 minutes after the start of infusion; and 5, 10, 15, 30, 60, and 90 minutes, and 2, 4, 6, 8, and 24 hours after the end of infusion.

Population: The number of patients in a given cohort that received Belinistat on Cycle 1 Day-7 and had blood samples successfully collected at the specified timepoints for PK analysis. One patient with Mild Liver Dysfunction was not evaluable for Belinostat AUC0-inf.

Metabolic ratios of Area Under the Plasma Concentration Time Curve Extrapolated to Infinity (AUC0-inf), reported as geometric mean (geometric standard deviation), for the belinostat metabolic pathway on Cycle 1 Day-7 as a function of degree of liver dysfunction.

Outcome measures

Outcome measures
Measure	Normal Function-Belinostat 1000 mg/m(2) n=14 Participants Normal Liver Function was defined as bilirubin ≤Upper Limit of Normal (ULN) and aspartate aminotransferase (AST) ≤ ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 750 mg/m(2) n=25 Participants Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 1000 mg/m(2) n=10 Participants Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 500 mg/m(2) n=15 Participants Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 750 mg/m(2) Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 250 mg/m(2) Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 350 mg/m(2) Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Metabolic Ratios of Area Under the Plasma Concentration Time Curve Extrapolated to Infinity (AUC0-inf) for the Belinostat Metabolic Pathway Belinostat glucuronide/belinostat	18.7 ratio Standard Deviation 1.63	21.8 ratio Standard Deviation 1.63	18.1 ratio Standard Deviation 1.86	17.7 ratio Standard Deviation 1.91	—	—	—
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Metabolic Ratios of Area Under the Plasma Concentration Time Curve Extrapolated to Infinity (AUC0-inf) for the Belinostat Metabolic Pathway Methyl belinostat/belinostat	0.422 ratio Standard Deviation 1.56	0.574 ratio Standard Deviation 1.53	0.892 ratio Standard Deviation 1.65	0.759 ratio Standard Deviation 1.65	—	—	—
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Metabolic Ratios of Area Under the Plasma Concentration Time Curve Extrapolated to Infinity (AUC0-inf) for the Belinostat Metabolic Pathway M21/belinostat	0.901 ratio Standard Deviation 3.64	0.783 ratio Standard Deviation 2.30	1.24 ratio Standard Deviation 1.85	1.13 ratio Standard Deviation 2.13	—	—	—
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Metabolic Ratios of Area Under the Plasma Concentration Time Curve Extrapolated to Infinity (AUC0-inf) for the Belinostat Metabolic Pathway M24/belinostat	1.24 ratio Standard Deviation 1.55	1.01 ratio Standard Deviation 1.74	0.916 ratio Standard Deviation 1.62	0.825 ratio Standard Deviation 1.96	—	—	—
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Metabolic Ratios of Area Under the Plasma Concentration Time Curve Extrapolated to Infinity (AUC0-inf) for the Belinostat Metabolic Pathway M26/belinostat	0.452 ratio Standard Deviation 1.50	0.423 ratio Standard Deviation 1.49	0.666 ratio Standard Deviation 1.63	0.611 ratio Standard Deviation 1.66	—	—	—
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Metabolic Ratios of Area Under the Plasma Concentration Time Curve Extrapolated to Infinity (AUC0-inf) for the Belinostat Metabolic Pathway M24/M26	2.74 ratio Standard Deviation 1.72	2.35 ratio Standard Deviation 1.59	1.38 ratio Standard Deviation 1.91	1.35 ratio Standard Deviation 2.38	—	—	—
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Metabolic Ratios of Area Under the Plasma Concentration Time Curve Extrapolated to Infinity (AUC0-inf) for the Belinostat Metabolic Pathway M26/M21	1.15 ratio Standard Deviation 4.14	0.531 ratio Standard Deviation 2.26	0.539 ratio Standard Deviation 1.59	0.541 ratio Standard Deviation 2.63	—	—	—

SECONDARY outcome

Timeframe: at baseline and every two 21-day cycles of treatment, up to 12 cycles

Population: Patients were considered evaluable for response if they received at least one cycle of therapy and had their disease re-evaluated with a restaging scan, or exhibited objective disease progression prior ot the end of Cycle 1 but after receiving all Cycle 1 doses.

Radiologic response assessments by computed tomography (CT) scans were performed at baseline and every two cycles of treatment based on the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Per RECIST v1.1 Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum diameters; Stable Disease (SD), neither sufficient shrinkage to qualify for a PR nor sufficient increase to qualify for Progression of Disease (PD), taking as reference the smallest sum diameters while on study; PD, \>=20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) and an absolute increase of at least 5mm or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm.

Outcome measures

Outcome measures
Measure	Normal Function-Belinostat 1000 mg/m(2) n=14 Participants Normal Liver Function was defined as bilirubin ≤Upper Limit of Normal (ULN) and aspartate aminotransferase (AST) ≤ ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 750 mg/m(2) n=9 Participants Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 1000 mg/m(2) n=8 Participants Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 500 mg/m(2) n=4 Participants Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 750 mg/m(2) n=3 Participants Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 250 mg/m(2) n=6 Participants Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 350 mg/m(2) n=3 Participants Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).
Best Response Partial Response	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Best Response Stable Disease	6 Participants	3 Participants	1 Participants	2 Participants	1 Participants	0 Participants	0 Participants
Best Response Progressive Disease	8 Participants	6 Participants	7 Participants	2 Participants	2 Participants	6 Participants	3 Participants

SECONDARY outcome

Timeframe: From Cycle 1 Day -7 up to 12 (21-day) cycles.

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	Normal Function-Belinostat 1000 mg/m(2) n=14 Participants Normal Liver Function was defined as bilirubin ≤Upper Limit of Normal (ULN) and aspartate aminotransferase (AST) ≤ ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 750 mg/m(2) n=12 Participants Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 1000 mg/m(2) n=18 Participants Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 500 mg/m(2) n=5 Participants Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 750 mg/m(2) n=5 Participants Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 250 mg/m(2) n=10 Participants Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 350 mg/m(2) n=8 Participants Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0).	14 Participants	11 Participants	14 Participants	5 Participants	4 Participants	9 Participants	6 Participants

Adverse Events

Normal Function-Belinostat 1000 mg/m(2)

Serious events: 5 serious events

Other events: 14 other events

Deaths: 0 deaths

Mild Dysfunction-Belinostat 750 mg/m(2)

Serious events: 6 serious events

Other events: 11 other events

Deaths: 1 deaths

Mild Dysfunction-Belinostat 1000 mg/m(2)

Serious events: 7 serious events

Other events: 14 other events

Deaths: 3 deaths

Moderate Dysfunction-Belinostat 500 mg/m(2)

Serious events: 4 serious events

Other events: 5 other events

Deaths: 1 deaths

Moderate Dysfunction-Belinostat 750 mg/m(2)

Serious events: 3 serious events

Other events: 4 other events

Deaths: 1 deaths

Severe Dysfunction-Belinostat 250 mg/m(2)

Serious events: 7 serious events

Other events: 9 other events

Deaths: 6 deaths

Severe Dysfunction-Belinostat 350 mg/m(2)

Serious events: 4 serious events

Other events: 6 other events

Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure	Normal Function-Belinostat 1000 mg/m(2) n=14 participants at risk Normal Liver Function was defined as bilirubin ≤Upper Limit of Normal (ULN) and aspartate aminotransferase (AST) ≤ ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 750 mg/m(2) n=12 participants at risk Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 1000 mg/m(2) n=18 participants at risk Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 500 mg/m(2) n=5 participants at risk Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 750 mg/m(2) n=5 participants at risk Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 250 mg/m(2) n=10 participants at risk Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 350 mg/m(2) n=8 participants at risk Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).
Renal and urinary disorders Acute kidney injury	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Blood and lymphatic system disorders Anemia	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Metabolism and nutrition disorders Anorexia	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Gastrointestinal disorders Ascites	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Musculoskeletal and connective tissue disorders Back pain	7.1% 1/14 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, specify	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Investigations Blood bilirubin increased	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	30.0% 3/10 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Cardiac disorders Cardiac arrest	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Infections and infestations Catheter related infection	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
General disorders Chills	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Psychiatric disorders Confusion	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Gastrointestinal disorders Constipation	7.1% 1/14 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	10.0% 1/10 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Investigations Creatinine increased	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Metabolism and nutrition disorders Dehydration	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Infections and infestations Device related infection	7.1% 1/14 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Respiratory, thoracic and mediastinal disorders Dyspnea	7.1% 1/14 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Nervous system disorders Encephalopathy	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
General disorders Fatigue	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	10.0% 1/10 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
General disorders Fever	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Gastrointestinal disorders Gastric hemorrhage	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	10.0% 1/10 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Infections and infestations Hepatic infection	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Metabolism and nutrition disorders Hyperkalemia	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Vascular disorders Hypotension	7.1% 1/14 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Gastrointestinal disorders Ileus	7.1% 1/14 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Infections and infestations Infections and infestations - Other, specify	7.1% 1/14 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other, specify	7.1% 1/14 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Investigations INR increased	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Infections and infestations Lung infection	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	10.0% 1/10 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
General disorders Multi-organ failure	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Cardiac disorders Myocardial infarction	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Gastrointestinal disorders Nausea	7.1% 1/14 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	16.7% 3/18 • Number of events 5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	50.0% 5/10 • Number of events 6 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	37.5% 3/8 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Infections and infestations Sepsis	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Nervous system disorders Syncope	7.1% 1/14 • Number of events 4 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Infections and infestations Upper respiratory infection	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Gastrointestinal disorders Vomiting	7.1% 1/14 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	10.0% 1/10 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.

Other adverse events

Other adverse events
Measure	Normal Function-Belinostat 1000 mg/m(2) n=14 participants at risk Normal Liver Function was defined as bilirubin ≤Upper Limit of Normal (ULN) and aspartate aminotransferase (AST) ≤ ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 750 mg/m(2) n=12 participants at risk Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Mild Dysfunction-Belinostat 1000 mg/m(2) n=18 participants at risk Mild Liver Dysfunction was defined as bilirubin \>Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) \> ULN. Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 500 mg/m(2) n=5 participants at risk Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Moderate Dysfunction-Belinostat 750 mg/m(2) n=5 participants at risk Moderate Liver Dysfunction was defined as bilirubin \>1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 250 mg/m(2) n=10 participants at risk Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Severe Dysfunction-Belinostat 350 mg/m(2) n=8 participants at risk Severe Liver Dysfunction was defined as bilirubin \>3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Belinostat: Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).
Investigations Creatinine increased	14.3% 2/14 • Number of events 6 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	16.7% 3/18 • Number of events 5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	40.0% 2/5 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	25.0% 2/8 • Number of events 5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Metabolism and nutrition disorders Dehydration	7.1% 1/14 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Psychiatric disorders Depression	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Gastrointestinal disorders Diarrhea	14.3% 2/14 • Number of events 6 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	16.7% 2/12 • Number of events 4 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	11.1% 2/18 • Number of events 4 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	100.0% 5/5 • Number of events 5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	30.0% 3/10 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Nervous system disorders Dizziness	21.4% 3/14 • Number of events 13 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	11.1% 2/18 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Gastrointestinal disorders Dry mouth	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	10.0% 1/10 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	10.0% 1/10 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Nervous system disorders Dysesthesia	7.1% 1/14 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Nervous system disorders Dysgeusia	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	10.0% 1/10 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Gastrointestinal disorders Dyspepsia	7.1% 1/14 • Number of events 28 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	25.0% 3/12 • Number of events 11 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Gastrointestinal disorders Dysphagia	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Respiratory, thoracic and mediastinal disorders Dyspnea	7.1% 1/14 • Number of events 24 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	16.7% 3/18 • Number of events 5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	25.0% 2/8 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
General disorders Edema limbs	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	11.1% 2/18 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	40.0% 2/5 • Number of events 5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	40.0% 4/10 • Number of events 8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	25.0% 2/8 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
General disorders Edema trunk	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Investigations Electrocardiogram QT corrected interval prolonged	14.3% 2/14 • Number of events 15 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	16.7% 2/12 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	16.7% 3/18 • Number of events 6 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	40.0% 2/5 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	10.0% 1/10 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Nervous system disorders Encephalopathy	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 9 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Gastrointestinal disorders Abdominal distension	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	25.0% 2/8 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Gastrointestinal disorders Abdominal pain	14.3% 2/14 • Number of events 5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	40.0% 2/5 • Number of events 4 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	40.0% 2/5 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	25.0% 2/8 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Investigations Activated partial thromboplastin time prolonged	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Investigations Alanine aminotransferase increased	7.1% 1/14 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	50.0% 6/12 • Number of events 19 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	22.2% 4/18 • Number of events 8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	60.0% 3/5 • Number of events 6 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	40.0% 2/5 • Number of events 14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	37.5% 3/8 • Number of events 4 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Investigations Alkaline phosphatase increased	7.1% 1/14 • Number of events 4 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	25.0% 3/12 • Number of events 7 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	50.0% 9/18 • Number of events 17 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	40.0% 2/5 • Number of events 4 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	40.0% 2/5 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	30.0% 3/10 • Number of events 5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Immune system disorders Allergic reaction	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	7.1% 1/14 • Number of events 7 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Blood and lymphatic system disorders Anemia	42.9% 6/14 • Number of events 71 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	33.3% 4/12 • Number of events 7 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	27.8% 5/18 • Number of events 24 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	100.0% 5/5 • Number of events 27 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	40.0% 2/5 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	40.0% 4/10 • Number of events 7 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	50.0% 4/8 • Number of events 6 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Metabolism and nutrition disorders Anorexia	21.4% 3/14 • Number of events 43 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	33.3% 6/18 • Number of events 14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	60.0% 3/5 • Number of events 7 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	40.0% 2/5 • Number of events 6 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	10.0% 1/10 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	25.0% 2/8 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Psychiatric disorders Anxiety	14.3% 2/14 • Number of events 14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Gastrointestinal disorders Ascites	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	16.7% 2/12 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	30.0% 3/10 • Number of events 5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Investigations Aspartate aminotransferase increased	14.3% 2/14 • Number of events 6 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	58.3% 7/12 • Number of events 27 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	33.3% 6/18 • Number of events 17 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	40.0% 2/5 • Number of events 4 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	60.0% 3/5 • Number of events 8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	30.0% 3/10 • Number of events 7 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	50.0% 4/8 • Number of events 7 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Cardiac disorders Atrioventricular block first degree	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Musculoskeletal and connective tissue disorders Back pain	14.3% 2/14 • Number of events 5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 6 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	10.0% 1/10 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Gastrointestinal disorders Bloating	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Investigations Blood bilirubin increased	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	50.0% 6/12 • Number of events 12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	50.0% 9/18 • Number of events 18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	100.0% 5/5 • Number of events 17 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	60.0% 3/5 • Number of events 14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	40.0% 4/10 • Number of events 10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	25.0% 2/8 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	10.0% 1/10 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Injury, poisoning and procedural complications Bruising	7.1% 1/14 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Musculoskeletal and connective tissue disorders Chest wall pain	7.1% 1/14 • Number of events 12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
General disorders Chills	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	25.0% 3/12 • Number of events 10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	40.0% 2/5 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Nervous system disorders Cognitive disturbance	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Psychiatric disorders Confusion	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Gastrointestinal disorders Constipation	7.1% 1/14 • Number of events 14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	11.1% 2/18 • Number of events 4 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	60.0% 3/5 • Number of events 9 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	10.0% 1/10 • Number of events 4 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Respiratory, thoracic and mediastinal disorders Cough	7.1% 1/14 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	11.1% 2/18 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Skin and subcutaneous tissue disorders Erythema multiforme	14.3% 2/14 • Number of events 23 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Gastrointestinal disorders Esophageal hemorrhage	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	10.0% 1/10 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Nervous system disorders Extrapyramidal disorder	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Eye disorders Eye disorders - Other, specify	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Injury, poisoning and procedural complications Fall	7.1% 1/14 • Number of events 12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
General disorders Fatigue	57.1% 8/14 • Number of events 106 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	33.3% 4/12 • Number of events 11 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	38.9% 7/18 • Number of events 14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	40.0% 2/5 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	60.0% 3/5 • Number of events 7 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 2/10 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	25.0% 2/8 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
General disorders Fever	14.3% 2/14 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	25.0% 3/12 • Number of events 11 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	11.1% 2/18 • Number of events 4 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	60.0% 3/5 • Number of events 16 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	10.0% 1/10 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Gastrointestinal disorders Flatulence	7.1% 1/14 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
General disorders Flu like symptoms	7.1% 1/14 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Vascular disorders Flushing	7.1% 1/14 • Number of events 4 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	25.0% 3/12 • Number of events 12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Gastrointestinal disorders Gastroesophageal reflux disease	7.1% 1/14 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Metabolism and nutrition disorders Glucose intolerance	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 16 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Nervous system disorders Headache	14.3% 2/14 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	16.7% 2/12 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	11.1% 2/18 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	10.0% 1/10 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Renal and urinary disorders Hematuria	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Gastrointestinal disorders Hemorrhoidal hemorrhage	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Hepatobiliary disorders Hepatic failure	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Hepatobiliary disorders Hepatobiliary disorders - Other, specify	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Respiratory, thoracic and mediastinal disorders Hiccups	7.1% 1/14 • Number of events 24 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Vascular disorders Hot flashes	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	16.7% 3/18 • Number of events 6 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Metabolism and nutrition disorders Hypercalcemia	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	16.7% 2/12 • Number of events 4 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	11.1% 2/18 • Number of events 4 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Metabolism and nutrition disorders Hyperglycemia	14.3% 2/14 • Number of events 74 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 16 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Skin and subcutaneous tissue disorders Hyperhidrosis	7.1% 1/14 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Metabolism and nutrition disorders Hyperkalemia	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Metabolism and nutrition disorders Hypermagnesemia	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Metabolism and nutrition disorders Hypernatremia	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Vascular disorders Hypertension	21.4% 3/14 • Number of events 12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	11.1% 2/18 • Number of events 11 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	60.0% 3/5 • Number of events 15 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	37.5% 3/8 • Number of events 5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Metabolism and nutrition disorders Hyperuricemia	7.1% 1/14 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Metabolism and nutrition disorders Hypoalbuminemia	28.6% 4/14 • Number of events 32 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	33.3% 4/12 • Number of events 7 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	44.4% 8/18 • Number of events 29 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	40.0% 2/5 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	30.0% 3/10 • Number of events 7 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Metabolism and nutrition disorders Hypocalcemia	7.1% 1/14 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	16.7% 3/18 • Number of events 4 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	40.0% 2/5 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	10.0% 1/10 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Metabolism and nutrition disorders Hypoglycemia	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Metabolism and nutrition disorders Hypokalemia	21.4% 3/14 • Number of events 5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	50.0% 6/12 • Number of events 8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	27.8% 5/18 • Number of events 9 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	60.0% 3/5 • Number of events 9 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 2/10 • Number of events 6 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Metabolism and nutrition disorders Hypomagnesemia	7.1% 1/14 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	16.7% 2/12 • Number of events 9 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	11.1% 2/18 • Number of events 8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	40.0% 2/5 • Number of events 7 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Metabolism and nutrition disorders Hyponatremia	28.6% 4/14 • Number of events 26 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	33.3% 4/12 • Number of events 6 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	27.8% 5/18 • Number of events 11 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	60.0% 3/5 • Number of events 12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	30.0% 3/10 • Number of events 4 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	37.5% 3/8 • Number of events 6 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Metabolism and nutrition disorders Hypophosphatemia	14.3% 2/14 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	33.3% 4/12 • Number of events 27 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	11.1% 2/18 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	60.0% 3/5 • Number of events 6 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	60.0% 3/5 • Number of events 14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	30.0% 3/10 • Number of events 7 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	25.0% 2/8 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Vascular disorders Hypotension	7.1% 1/14 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	40.0% 2/5 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Infections and infestations Infections and infestations - Other, specify	14.3% 2/14 • Number of events 14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
General disorders Infusion related reaction	7.1% 1/14 • Number of events 7 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
General disorders Infusion site extravasation	7.1% 1/14 • Number of events 7 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
General disorders Injection site reaction	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Investigations INR increased	7.1% 1/14 • Number of events 4 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Psychiatric disorders Insomnia	14.3% 2/14 • Number of events 9 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	16.7% 2/12 • Number of events 9 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	11.1% 2/18 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Nervous system disorders Lethargy	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Investigations Lymphocyte count decreased	42.9% 6/14 • Number of events 25 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	25.0% 3/12 • Number of events 4 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	33.3% 6/18 • Number of events 26 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	100.0% 5/5 • Number of events 11 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 2/10 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	37.5% 3/8 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Investigations Lymphocyte count increased	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
General disorders Malaise	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other, specify	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Infections and infestations Mucosal infection	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	40.0% 2/5 • Number of events 7 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Gastrointestinal disorders Mucositis oral	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	11.1% 2/18 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Musculoskeletal and connective tissue disorders Myalgia	7.1% 1/14 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Gastrointestinal disorders Nausea	71.4% 10/14 • Number of events 50 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	58.3% 7/12 • Number of events 33 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	44.4% 8/18 • Number of events 15 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	100.0% 5/5 • Number of events 13 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	60.0% 3/5 • Number of events 8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	30.0% 3/10 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	37.5% 3/8 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 6 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Investigations Neutrophil count decreased	7.1% 1/14 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
General disorders Pain	14.3% 2/14 • Number of events 55 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	25.0% 2/8 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Musculoskeletal and connective tissue disorders Pain in extremity	7.1% 1/14 • Number of events 24 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Skin and subcutaneous tissue disorders Pain of skin	7.1% 1/14 • Number of events 7 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Cardiac disorders Palpitations	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Skin and subcutaneous tissue disorders Papulopustular rash	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Nervous system disorders Paresthesia	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Infections and infestations Peripheral nerve infection	7.1% 1/14 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	10.0% 1/10 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Infections and infestations Pharyngitis	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Infections and infestations Phlebitis	7.1% 1/14 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Investigations Platelet count decreased	7.1% 1/14 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	50.0% 6/12 • Number of events 24 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	11.1% 2/18 • Number of events 4 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	40.0% 2/5 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 2/10 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Respiratory, thoracic and mediastinal disorders Postnasal drip	7.1% 1/14 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Renal and urinary disorders Proteinuria	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Skin and subcutaneous tissue disorders Pruritus	7.1% 1/14 • Number of events 6 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	16.7% 2/12 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	40.0% 2/5 • Number of events 4 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	25.0% 2/8 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Psychiatric disorders Psychiatric disorders - Other, specify	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 66 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Skin and subcutaneous tissue disorders Rash acneiform	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Skin and subcutaneous tissue disorders Rash maculo-papular	7.1% 1/14 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Gastrointestinal disorders Rectal pain	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Renal and urinary disorders Renal and urinary disorders - Other, specify	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Cardiac disorders Sinus bradycardia	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Cardiac disorders Sinus tachycardia	14.3% 2/14 • Number of events 4 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	16.7% 2/12 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	16.7% 3/18 • Number of events 4 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	40.0% 2/5 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Infections and infestations Sinusitis	7.1% 1/14 • Number of events 7 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	11.1% 2/18 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Skin and subcutaneous tissue disorders Skin induration	7.1% 1/14 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Infections and infestations Skin infection	14.3% 2/14 • Number of events 4 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Gastrointestinal disorders Small intestinal obstruction	7.1% 1/14 • Number of events 4 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Nervous system disorders Somnolence	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Respiratory, thoracic and mediastinal disorders Sore throat	7.1% 1/14 • Number of events 12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Cardiac disorders Supraventricular tachycardia	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Nervous system disorders Tremor	7.1% 1/14 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	14.3% 2/14 • Number of events 5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Infections and infestations Upper respiratory infection	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Renal and urinary disorders Urinary frequency	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Renal and urinary disorders Urinary incontinence	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Infections and infestations Urinary tract infection	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Renal and urinary disorders Urinary tract pain	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Renal and urinary disorders Urinary urgency	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 2 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	8.3% 1/12 • Number of events 8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	20.0% 1/5 • Number of events 8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Gastrointestinal disorders Vomiting	50.0% 7/14 • Number of events 16 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	50.0% 6/12 • Number of events 24 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	38.9% 7/18 • Number of events 18 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	40.0% 2/5 • Number of events 4 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	40.0% 2/5 • Number of events 4 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	40.0% 4/10 • Number of events 5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Investigations Weight loss	7.1% 1/14 • Number of events 24 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 3 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	40.0% 2/5 • Number of events 8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/14 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	5.6% 1/18 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	12.5% 1/8 • Number of events 1 • From Cycle 1 Day -7 up to 12 (21-day) cycles.
Investigations White blood cell decreased	14.3% 2/14 • Number of events 15 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/12 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	11.1% 2/18 • Number of events 4 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/5 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/10 • From Cycle 1 Day -7 up to 12 (21-day) cycles.	0.00% 0/8 • From Cycle 1 Day -7 up to 12 (21-day) cycles.

Additional Information

Naoko Takebe, M.D., Ph.D.

National Cancer Institute

Phone: 240-781-3398

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place