Trial Outcomes & Findings for Safety Study to Evaluate Monoclonal Antibody KW-0761 in Subjects With Peripheral T-cell Lymphoma (NCT NCT00888927)

Last Updated: 2024-04-25

Results Overview

The objective was to find the maximum tolerated dose (MTD). In the dose escalation phase (Phase 1), the starting dose was 0.1 mg/kg administered intravenously once every week for four weeks, followed by a 2-week observation period in the first treatment course. Succeeding dose levels included 0.3 and 1.0 mg/kg. Standard 3+3 cohorts for safety and DLT detection were utilized. Each cohort consisted of at least three subjects. If Dose-Limiting Toxicity (DLT) was observed in 0/3 subjects, escalation to the next dose level occurred.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

42 participants

Primary outcome timeframe

6 weeks

Results posted on

2024-04-25

Participant Flow

Participant milestones

Participant milestones
Measure	Phase 1 Cohort 1 First course: 0.1 mg/kg once a week over 1 hour for 4 weeks Subsequent courses: 0.1 mg/kg over 1 hour every other week KW-0761: The starting dose will be 0.1 mg/kg administered i.v. once every week for four weeks, followed by a 2-week observation period in the first treatment course. If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.	Phase 1 Cohort 2 First course: 0.3 mg/kg once a week over 1 hour for 4 weeks Subsequent courses: 0.3 mg/kg over 1 hour every other week KW-0761: The starting dose will be 0.3 mg/kg administered i.v. once every week for four weeks, followed by a 2-week observation period in the first treatment course. If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.	Phase 1 Cohort 3 First course: 1.0 mg/kg once a week over 1 hour for 4 weeks Subsequent courses: 1.0 mg/kg over 1 hour every other week KW-0761: The starting dose will be 1.0 mg/kg administered i.v. once every week for four weeks, followed by a 2-week observation period in the first treatment course. If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.	Phase 2 First course: Maximum tolerated dose once a week over 1 hour for 4 weeks Subsequent courses: Maximum tolerated dose over 1 hour every other week If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.
Overall Study STARTED	3	3	3	33
Overall Study COMPLETED	3	3	3	31
Overall Study NOT COMPLETED	0	0	0	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase 1 Cohort 1 First course: 0.1 mg/kg once a week over 1 hour for 4 weeks Subsequent courses: 0.1 mg/kg over 1 hour every other week KW-0761: The starting dose will be 0.1 mg/kg administered i.v. once every week for four weeks, followed by a 2-week observation period in the first treatment course. If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.	Phase 1 Cohort 2 First course: 0.3 mg/kg once a week over 1 hour for 4 weeks Subsequent courses: 0.3 mg/kg over 1 hour every other week KW-0761: The starting dose will be 0.3 mg/kg administered i.v. once every week for four weeks, followed by a 2-week observation period in the first treatment course. If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.	Phase 1 Cohort 3 First course: 1.0 mg/kg once a week over 1 hour for 4 weeks Subsequent courses: 1.0 mg/kg over 1 hour every other week KW-0761: The starting dose will be 1.0 mg/kg administered i.v. once every week for four weeks, followed by a 2-week observation period in the first treatment course. If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.	Phase 2 First course: Maximum tolerated dose once a week over 1 hour for 4 weeks Subsequent courses: Maximum tolerated dose over 1 hour every other week If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.
Overall Study Adverse Event	0	0	0	1
Overall Study Withdrawal of consent	0	0	0	1

Baseline Characteristics

Safety Study to Evaluate Monoclonal Antibody KW-0761 in Subjects With Peripheral T-cell Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1 Cohort 1 n=3 Participants First course: 0.1 mg/kg once a week over 1 hour for 4 weeks Subsequent courses: 0.1 mg/kg over 1 hour every other week KW-0761: The starting dose will be 0.1 mg/kg administered i.v. once every week for four weeks, followed by a 2-week observation period in the first treatment course. If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.	Phase 1 Cohort 2 n=3 Participants First course: 0.3 mg/kg once a week over 1 hour for 4 weeks Subsequent courses: 0.3 mg/kg over 1 hour every other week KW-0761: The starting dose will be 0.3 mg/kg administered i.v. once every week for four weeks, followed by a 2-week observation period in the first treatment course. If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.	Phase 1 Cohort 3 n=3 Participants First course: 1.0 mg/kg once a week over 1 hour for 4 weeks Subsequent courses: 1.0 mg/kg over 1 hour every other week KW-0761: The starting dose will be 1.0 mg/kg administered i.v. once every week for four weeks, followed by a 2-week observation period in the first treatment course. If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.	Phase 2 n=33 Participants First course: Maximum tolerated dose once a week over 1 hour for 4 weeks Subsequent courses: Maximum tolerated dose over 1 hour every other week If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.	Total n=42 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	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	12 Participants n=4 Participants	16 Participants n=21 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	21 Participants n=4 Participants	26 Participants n=21 Participants
Age, Continuous	66 years n=5 Participants	72.3 years n=7 Participants	63.3 years n=5 Participants	66.7 years n=4 Participants	66.8 years n=21 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	15 Participants n=4 Participants	18 Participants n=21 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	18 Participants n=4 Participants	24 Participants n=21 Participants
Race/Ethnicity, Customized Race/Ethnicity · Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	3 Participants n=21 Participants
Race/Ethnicity, Customized Race/Ethnicity · White/Caucasian, Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	2 Participants n=21 Participants
Race/Ethnicity, Customized Race/Ethnicity · White/Caucasian, Not Hispanic or Latino	1 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	24 Participants n=4 Participants	31 Participants n=21 Participants
Race/Ethnicity, Customized Race/Ethnicity · White/Caucasian, Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants	4 Participants n=21 Participants
Race/Ethnicity, Customized Race/Ethnicity · Other, Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized Race/Ethnicity · Not Reported, Not Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Region of Enrollment United States	3 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	33 participants n=4 Participants	42 participants n=21 Participants

PRIMARY outcome

Timeframe: 6 weeks

Population: Safety Analysis set - Included all subjects who received at least one dose of KW-0761 (even a partial dose)

Outcome measures

Outcome measures
Measure	Phase 1 Cohort 1 n=3 Participants First course: 0.1 mg/kg once a week over 1 hour for 4 weeks Subsequent courses: 0.1 mg/kg over 1 hour every other week KW-0761: The starting dose will be 0.1 mg/kg administered i.v. once every week for four weeks, followed by a 2-week observation period in the first treatment course. If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.	Phase 1 Cohort 2 n=3 Participants First course: 0.3 mg/kg once a week over 1 hour for 4 weeks Subsequent courses: 0.3 mg/kg over 1 hour every other week KW-0761: The starting dose will be 0.3 mg/kg administered i.v. once every week for four weeks, followed by a 2-week observation period in the first treatment course. If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.	Phase 1 Cohort 3 n=3 Participants First course: 1.0 mg/kg once a week over 1 hour for 4 weeks Subsequent courses: 1.0 mg/kg over 1 hour every other week KW-0761: The starting dose will be 1.0 mg/kg administered i.v. once every week for four weeks, followed by a 2-week observation period in the first treatment course. If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.	Phase 2 n=33 Participants First course: Maximum tolerated dose once a week over 1 hour for 4 weeks Subsequent courses: Maximum tolerated dose over 1 hour every other week If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.
Maximum Tolerated Dose Subjects with any Dose-Limiting Toxicity (DLT)	0 Participants	0 Participants	0 Participants	0 Participants
Maximum Tolerated Dose Subjects with any treatment emergent adverse event (TEAE)	3 Participants	3 Participants	3 Participants	32 Participants
Maximum Tolerated Dose Subjects with any treatment-emergent serious adverse event	0 Participants	1 Participants	1 Participants	8 Participants
Maximum Tolerated Dose Subjects with any TEAE(s) leading to discontinuation	0 Participants	1 Participants	0 Participants	7 Participants

SECONDARY outcome

Timeframe: one year

Population: Efficacy Analysis Set: all subjects who received at least four doses of KW-0761 and had at least one on-study assessment for response.

Overall Response Rate was determined based on the response in all compartments (lymph nodes, skin, and viscera) as follows: Complete Response (CR) = complete disappearance of all clinical evidence of disease; Partial Response (PR) = regression of measurable disease; Stable Disease (SD) = failure to attain CR, PR, or PD; Progressive Disease (PD) = PD in any compartment; Relapse = recurrence of disease in prior CR in any compartment.

Outcome measures

Outcome measures
Measure	Phase 1 Cohort 1 n=3 Participants First course: 0.1 mg/kg once a week over 1 hour for 4 weeks Subsequent courses: 0.1 mg/kg over 1 hour every other week KW-0761: The starting dose will be 0.1 mg/kg administered i.v. once every week for four weeks, followed by a 2-week observation period in the first treatment course. If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.	Phase 1 Cohort 2 n=3 Participants First course: 0.3 mg/kg once a week over 1 hour for 4 weeks Subsequent courses: 0.3 mg/kg over 1 hour every other week KW-0761: The starting dose will be 0.3 mg/kg administered i.v. once every week for four weeks, followed by a 2-week observation period in the first treatment course. If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.	Phase 1 Cohort 3 n=3 Participants First course: 1.0 mg/kg once a week over 1 hour for 4 weeks Subsequent courses: 1.0 mg/kg over 1 hour every other week KW-0761: The starting dose will be 1.0 mg/kg administered i.v. once every week for four weeks, followed by a 2-week observation period in the first treatment course. If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.	Phase 2 n=30 Participants First course: Maximum tolerated dose once a week over 1 hour for 4 weeks Subsequent courses: Maximum tolerated dose over 1 hour every other week If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.
Overall Response Rate (ORR)	2 Participants	2 Participants	1 Participants	9 Participants

Adverse Events

Phase 1 Cohort 1

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Phase 1 Cohort 2

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Phase 1 Cohort 3

Serious events: 1 serious events

Other events: 3 other events

Deaths: 1 deaths

Phase 2

Serious events: 8 serious events

Other events: 32 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Kyowa Kirin Pharmaceutical Development

Phone: 609-919-1100

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Phase 1 Cohort 1 n=3 participants at risk First course: 0.1 mg/kg once a week over 1 hour for 4 weeks Subsequent courses: 0.1 mg/kg over 1 hour every other week KW-0761: The starting dose will be 0.1 mg/kg administered i.v. once every week for four weeks, followed by a 2-week observation period in the first treatment course. If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.	Phase 1 Cohort 2 n=3 participants at risk First course: 0.3 mg/kg once a week over 1 hour for 4 weeks Subsequent courses: 0.3 mg/kg over 1 hour every other week KW-0761: The starting dose will be 0.3 mg/kg administered i.v. once every week for four weeks, followed by a 2-week observation period in the first treatment course. If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.	Phase 1 Cohort 3 n=3 participants at risk First course: 1.0 mg/kg once a week over 1 hour for 4 weeks Subsequent courses: 1.0 mg/kg over 1 hour every other week KW-0761: The starting dose will be 1.0 mg/kg administered i.v. once every week for four weeks, followed by a 2-week observation period in the first treatment course. If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.	Phase 2 n=33 participants at risk First course: Maximum tolerated dose once a week over 1 hour for 4 weeks Subsequent courses: Maximum tolerated dose over 1 hour every other week If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.
Gastrointestinal disorders Nausea	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	6.1% 2/33 • Number of events 2 • Between the date of first dose and within 30 days after the last dose, up to one year
Gastrointestinal disorders Diarrhoea	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	3.0% 1/33 • Number of events 1 • Between the date of first dose and within 30 days after the last dose, up to one year
Gastrointestinal disorders Vomiting	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	6.1% 2/33 • Number of events 2 • Between the date of first dose and within 30 days after the last dose, up to one year
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	3.0% 1/33 • Number of events 1 • Between the date of first dose and within 30 days after the last dose, up to one year
General disorders Disease progression	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	33.3% 1/3 • Number of events 1 • Between the date of first dose and within 30 days after the last dose, up to one year	3.0% 1/33 • Number of events 1 • Between the date of first dose and within 30 days after the last dose, up to one year
General disorders Chest pain	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	3.0% 1/33 • Number of events 1 • Between the date of first dose and within 30 days after the last dose, up to one year
Infections and infestations Bronchopneumonia	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	3.0% 1/33 • Number of events 1 • Between the date of first dose and within 30 days after the last dose, up to one year
Infections and infestations Staphylococcal skin infection	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	3.0% 1/33 • Number of events 1 • Between the date of first dose and within 30 days after the last dose, up to one year
Infections and infestations Skin infection	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	3.0% 1/33 • Number of events 1 • Between the date of first dose and within 30 days after the last dose, up to one year
Infections and infestations Escherichia urinary tract infection	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	3.0% 1/33 • Number of events 1 • Between the date of first dose and within 30 days after the last dose, up to one year
Injury, poisoning and procedural complications Radiation necrosis	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	33.3% 1/3 • Number of events 1 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/33 • Between the date of first dose and within 30 days after the last dose, up to one year
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	33.3% 1/3 • Number of events 1 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/33 • Between the date of first dose and within 30 days after the last dose, up to one year
Injury, poisoning and procedural complications Graft haemorrhage	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	3.0% 1/33 • Number of events 1 • Between the date of first dose and within 30 days after the last dose, up to one year
Investigations Liver function test abnormal	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	3.0% 1/33 • Number of events 1 • Between the date of first dose and within 30 days after the last dose, up to one year
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	3.0% 1/33 • Number of events 1 • Between the date of first dose and within 30 days after the last dose, up to one year
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm malignant	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	6.1% 2/33 • Number of events 2 • Between the date of first dose and within 30 days after the last dose, up to one year
Psychiatric disorders Confusional state	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	3.0% 1/33 • Number of events 1 • Between the date of first dose and within 30 days after the last dose, up to one year
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	33.3% 1/3 • Number of events 1 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/33 • Between the date of first dose and within 30 days after the last dose, up to one year
Vascular disorders Hypotension	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	0.00% 0/3 • Between the date of first dose and within 30 days after the last dose, up to one year	6.1% 2/33 • Number of events 2 • Between the date of first dose and within 30 days after the last dose, up to one year