Trial Outcomes & Findings for AMG 386 and Abiraterone for Advanced Prostate Cancer (NCT NCT01553188)

Last Updated: 2019-03-05

Results Overview

PFS is defined as the duration of time from start of treatment to time of progression or death, whichever comes first. Clinical progression is assessed by the Response Criteria in Solid Tumors (RECIST) and is at least a 20% increase in the sum of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

36 participants

Primary outcome timeframe

Median potential follow-up of 50.3 months

Results posted on

2019-03-05

Participant Flow

An initial run-I phase of AMG 386 will be conducted with 15mg/kg weekly escalating to 30mg/kg weekly to establish the maximum tolerated dose.

Participant milestones

Participant milestones
Measure	DL 1 Run in - 15mg/kg Dose escalation phase to determine MTD of AMG AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg). Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily DL 1 AMG is 15 mg/kg DL 2 AMG is 30 mg/kg The randomized portion is 30 mg/kg.	DL 2 Run in - 30mg/kg Dose escalation phase to determine MTD of AMG AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg). Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily DL 1 AMG is 15 mg/kg DL 2 AMG is 30 mg/kg The randomized portion is 30 mg/kg.	Abiraterone, Prednisone and AMG Abiraterone and prednisone will be given with maximum tolerated dose (MTD) of Trebananib (AMG) AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg). Supplied in 240 mg v will be administered as an intravenous (IV) infusion using an intravenous infusion pump given over a 60-minute period. Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily Prednisone: Prednisone should be taken orally either, at 5mg twice a day for each dose or 10 mg once a day a patients preference.	Abiraterone and Prednisone Only Abiraterone and prednisone only Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily Prednisone: Prednisone should be taken orally either, at 5mg twice a day for each dose or 10 mg once a day a patients preference.
Overall Study STARTED	3	6	16	11
Overall Study COMPLETED	2	5	14	11
Overall Study NOT COMPLETED	1	1	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	DL 1 Run in - 15mg/kg Dose escalation phase to determine MTD of AMG AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg). Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily DL 1 AMG is 15 mg/kg DL 2 AMG is 30 mg/kg The randomized portion is 30 mg/kg.	DL 2 Run in - 30mg/kg Dose escalation phase to determine MTD of AMG AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg). Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily DL 1 AMG is 15 mg/kg DL 2 AMG is 30 mg/kg The randomized portion is 30 mg/kg.	Abiraterone, Prednisone and AMG Abiraterone and prednisone will be given with maximum tolerated dose (MTD) of Trebananib (AMG) AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg). Supplied in 240 mg v will be administered as an intravenous (IV) infusion using an intravenous infusion pump given over a 60-minute period. Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily Prednisone: Prednisone should be taken orally either, at 5mg twice a day for each dose or 10 mg once a day a patients preference.	Abiraterone and Prednisone Only Abiraterone and prednisone only Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily Prednisone: Prednisone should be taken orally either, at 5mg twice a day for each dose or 10 mg once a day a patients preference.
Overall Study Patient choice	1	0	0	0
Overall Study Intercurrent illness and adverse event	0	1	2	0

Baseline Characteristics

AMG 386 and Abiraterone for Advanced Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	DL 1 Run in - 15mg/kg n=3 Participants Dose escalation phase to determine MTD of AMG AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg). Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily DL 1 AMG is 15 mg/kg DL 2 AMG is 30 mg/kg The randomized portion is 30 mg/kg.	DL 2 Run in - 30mg/kg n=6 Participants Dose escalation phase to determine MTD of AMG AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg). Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily DL 1 AMG is 15 mg/kg DL 2 AMG is 30 mg/kg The randomized portion is 30 mg/kg.	Abiraterone, Prednisone and AMG n=16 Participants Abiraterone and prednisone will be given with maximum tolerated dose (MTD) of Trebananib (AMG) AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg). Supplied in 240 mg v will be administered as an intravenous (IV) infusion using an intravenous infusion pump given over a 60-minute period. Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily Prednisone: Prednisone should be taken orally either, at 5mg twice a day for each dose or 10 mg once a day a patients preference.	Abiraterone and Prednisone Only n=11 Participants Abiraterone and prednisone only Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily Prednisone: Prednisone should be taken orally either, at 5mg twice a day for each dose or 10 mg once a day a patients preference.	Total n=36 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=93 Participants	6 Participants n=4 Participants	2 Participants n=27 Participants	3 Participants n=483 Participants	14 Participants n=36 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	14 Participants n=27 Participants	8 Participants n=483 Participants	22 Participants n=36 Participants
Age, Continuous	62.4 years STANDARD_DEVIATION 1.8 • n=93 Participants	62.9 years STANDARD_DEVIATION 8.7 • n=4 Participants	74.85 years STANDARD_DEVIATION 7.44 • n=27 Participants	66.05 years STANDARD_DEVIATION 9.87 • n=483 Participants	69.13 years STANDARD_DEVIATION 9.56 • n=36 Participants
Sex: Female, Male Female	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Sex: Female, Male Male	3 Participants n=93 Participants	6 Participants n=4 Participants	16 Participants n=27 Participants	11 Participants n=483 Participants	36 Participants n=36 Participants
Race/Ethnicity, Customized Not meeting definition for Hispanic or Latino	3 Participants n=93 Participants	6 Participants n=4 Participants	16 Participants n=27 Participants	10 Participants n=483 Participants	35 Participants n=36 Participants
Race/Ethnicity, Customized Mexican, Puerto Rican, Cuban, Central or So Amer.	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	1 Participants n=36 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=93 Participants	4 Participants n=4 Participants	5 Participants n=27 Participants	0 Participants n=483 Participants	9 Participants n=36 Participants
Race/Ethnicity, Customized White	3 Participants n=93 Participants	2 Participants n=4 Participants	10 Participants n=27 Participants	11 Participants n=483 Participants	26 Participants n=36 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	1 Participants n=36 Participants
Region of Enrollment United States	3 Participants n=93 Participants	6 Participants n=4 Participants	16 Participants n=27 Participants	11 Participants n=483 Participants	36 Participants n=36 Participants
OnStudy Prostatic Specific Antigen (PSA) >4.0 mg/mL	3 Participants n=93 Participants	6 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	9 Participants n=36 Participants
OnStudy Prostatic Specific Antigen (PSA) <4.0 mg/mL	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	2 Participants n=483 Participants	2 Participants n=36 Participants

PRIMARY outcome

Timeframe: Median potential follow-up of 50.3 months

Population: One patient of the 9 (i.e., Run-in in Participant Flow) was not evaluable for responses as we previously defined through the document. Thus, it cannot be included in the PFS assessment. Patient came off the trial early for other reasons.

Outcome measures

Outcome measures
Measure	DL 1 Run in - 15mg/kg n=2 Participants Dose escalation phase to determine MTD of AMG AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg). Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily DL 1 AMG is 15 mg/kg DL 2 AMG is 30 mg/kg The randomized portion is 30 mg/kg.	DL 2 Run in - 30mg/kg n=6 Participants Dose escalation phase to determine MTD of AMG AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg). Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily DL 1 AMG is 15 mg/kg DL 2 AMG is 30 mg/kg The randomized portion is 30 mg/kg.	Abiraterone, Prednisone and AMG n=16 Participants Abiraterone and prednisone will be given with maximum tolerated dose (MTD) of Trebananib (AMG) AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg). Supplied in 240 mg v will be administered as an intravenous (IV) infusion using an intravenous infusion pump given over a 60-minute period. Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily Prednisone: Prednisone should be taken orally either, at 5mg twice a day for each dose or 10 mg once a day a patients preference.	Abiraterone and Prednisone Only n=11 Participants Abiraterone and prednisone only Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily Prednisone: Prednisone should be taken orally either, at 5mg twice a day for each dose or 10 mg once a day a patients preference.
Progression Free Survival (PFS)	2.8 Months Interval 1.9 to 3.6	9.0 Months Interval 1.8 to 29.1	11.5 Months Interval 5.5 to 19.2	10.1 Months Interval 2.7 to 13.7

SECONDARY outcome

Timeframe: Median potential follow-up of 50.3 months

Radiographic progression free survival is defined as the duration of time from start of treatment to time of radiographic progression by computed tomography (CT) scan (or magnetic resonance imaging (MRI)) or bone scan. Progression is a minimum of two new lesions observed on bone scan. The minimum size for a measurable lesion on CY and MRI should be twice the slice thickness based on the assumption that CT slice thickness is 500 or less.

Outcome measures

Outcome measures
Measure	DL 1 Run in - 15mg/kg n=2 Participants Dose escalation phase to determine MTD of AMG AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg). Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily DL 1 AMG is 15 mg/kg DL 2 AMG is 30 mg/kg The randomized portion is 30 mg/kg.	DL 2 Run in - 30mg/kg n=6 Participants Dose escalation phase to determine MTD of AMG AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg). Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily DL 1 AMG is 15 mg/kg DL 2 AMG is 30 mg/kg The randomized portion is 30 mg/kg.	Abiraterone, Prednisone and AMG n=16 Participants Abiraterone and prednisone will be given with maximum tolerated dose (MTD) of Trebananib (AMG) AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg). Supplied in 240 mg v will be administered as an intravenous (IV) infusion using an intravenous infusion pump given over a 60-minute period. Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily Prednisone: Prednisone should be taken orally either, at 5mg twice a day for each dose or 10 mg once a day a patients preference.	Abiraterone and Prednisone Only n=11 Participants Abiraterone and prednisone only Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily Prednisone: Prednisone should be taken orally either, at 5mg twice a day for each dose or 10 mg once a day a patients preference.
Radiographic Progression Free Survival	2.7 Months Interval 1.8 to 3.6	9.0 Months Interval 1.8 to The undefined value is because of the small numbers and the data. It is not estimable.	13.7 Months Interval 8.2 to 19.2	10.6 Months Interval 2.7 to 20.1

SECONDARY outcome

Timeframe: Time between the first day of treatment to the day of death, approximately 50.3 months.

Overall Survival is the time between the first day of treatment to the day of death.

Outcome measures

Outcome measures
Measure	DL 1 Run in - 15mg/kg n=2 Participants Dose escalation phase to determine MTD of AMG AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg). Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily DL 1 AMG is 15 mg/kg DL 2 AMG is 30 mg/kg The randomized portion is 30 mg/kg.	DL 2 Run in - 30mg/kg n=6 Participants Dose escalation phase to determine MTD of AMG AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg). Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily DL 1 AMG is 15 mg/kg DL 2 AMG is 30 mg/kg The randomized portion is 30 mg/kg.	Abiraterone, Prednisone and AMG n=16 Participants Abiraterone and prednisone will be given with maximum tolerated dose (MTD) of Trebananib (AMG) AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg). Supplied in 240 mg v will be administered as an intravenous (IV) infusion using an intravenous infusion pump given over a 60-minute period. Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily Prednisone: Prednisone should be taken orally either, at 5mg twice a day for each dose or 10 mg once a day a patients preference.	Abiraterone and Prednisone Only n=11 Participants Abiraterone and prednisone only Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily Prednisone: Prednisone should be taken orally either, at 5mg twice a day for each dose or 10 mg once a day a patients preference.
Overall Survival	11.1 Months Interval 5.4 to 16.8	27.9 Months Interval 10.7 to The undefined value is because of the small numbers and the data. It is not estimable.	31.1 Months Interval 18.8 to 43.2	25.5 Months Interval 8.1 to 34.8

SECONDARY outcome

Timeframe: Date treatment consent signed to date off study, approximately 65 months and 7 days

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	DL 1 Run in - 15mg/kg n=3 Participants Dose escalation phase to determine MTD of AMG AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg). Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily DL 1 AMG is 15 mg/kg DL 2 AMG is 30 mg/kg The randomized portion is 30 mg/kg.	DL 2 Run in - 30mg/kg n=6 Participants Dose escalation phase to determine MTD of AMG AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg). Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily DL 1 AMG is 15 mg/kg DL 2 AMG is 30 mg/kg The randomized portion is 30 mg/kg.	Abiraterone, Prednisone and AMG n=16 Participants Abiraterone and prednisone will be given with maximum tolerated dose (MTD) of Trebananib (AMG) AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg). Supplied in 240 mg v will be administered as an intravenous (IV) infusion using an intravenous infusion pump given over a 60-minute period. Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily Prednisone: Prednisone should be taken orally either, at 5mg twice a day for each dose or 10 mg once a day a patients preference.	Abiraterone and Prednisone Only n=11 Participants Abiraterone and prednisone only Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily Prednisone: Prednisone should be taken orally either, at 5mg twice a day for each dose or 10 mg once a day a patients preference.
Count of Participants With Serious and Non-serious Adverse Events	3 Participants	6 Participants	16 Participants	11 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: First 28 days of treatment

The MTD is defined as the highest dose studied for which the incidence of dose limiting toxicity was less than 33%.

Outcome measures

Outcome measures
Measure	DL 1 Run in - 15mg/kg n=36 Participants Dose escalation phase to determine MTD of AMG AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg). Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily DL 1 AMG is 15 mg/kg DL 2 AMG is 30 mg/kg The randomized portion is 30 mg/kg.	DL 2 Run in - 30mg/kg Dose escalation phase to determine MTD of AMG AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg). Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily DL 1 AMG is 15 mg/kg DL 2 AMG is 30 mg/kg The randomized portion is 30 mg/kg.	Abiraterone, Prednisone and AMG Abiraterone and prednisone will be given with maximum tolerated dose (MTD) of Trebananib (AMG) AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg). Supplied in 240 mg v will be administered as an intravenous (IV) infusion using an intravenous infusion pump given over a 60-minute period. Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily Prednisone: Prednisone should be taken orally either, at 5mg twice a day for each dose or 10 mg once a day a patients preference.	Abiraterone and Prednisone Only Abiraterone and prednisone only Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily Prednisone: Prednisone should be taken orally either, at 5mg twice a day for each dose or 10 mg once a day a patients preference.
Maximum Tolerated Dose (MTD)	30 mg/kg	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: First 28 days of treatment

Population: Per protocol, only participants in the Run-in phase were evaluated for DLT.

DLTs are defined as any grade 3 or higher hematologic (excluding anemia) or non-hematologic toxicity considered to be possible related to AMG 386. Any treatment related adverse events that lead tor reduction of dose exposure of either agent (duration or dose) by \>50% in cycle 1 will be considered a DLT.

Outcome measures

Outcome measures
Measure	DL 1 Run in - 15mg/kg n=3 Participants Dose escalation phase to determine MTD of AMG AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg). Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily DL 1 AMG is 15 mg/kg DL 2 AMG is 30 mg/kg The randomized portion is 30 mg/kg.	DL 2 Run in - 30mg/kg n=6 Participants Dose escalation phase to determine MTD of AMG AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg). Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily DL 1 AMG is 15 mg/kg DL 2 AMG is 30 mg/kg The randomized portion is 30 mg/kg.	Abiraterone, Prednisone and AMG Abiraterone and prednisone will be given with maximum tolerated dose (MTD) of Trebananib (AMG) AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg). Supplied in 240 mg v will be administered as an intravenous (IV) infusion using an intravenous infusion pump given over a 60-minute period. Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily Prednisone: Prednisone should be taken orally either, at 5mg twice a day for each dose or 10 mg once a day a patients preference.	Abiraterone and Prednisone Only Abiraterone and prednisone only Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily Prednisone: Prednisone should be taken orally either, at 5mg twice a day for each dose or 10 mg once a day a patients preference.
Dose Limiting Toxicity (DLT)	0 Participants	1 Participants	—	—

Adverse Events

DL 1 Run in - 15mg/kg

Serious events: 3 serious events

Other events: 3 other events

Deaths: 0 deaths

DL 2 Run in - 30mg/kg

Serious events: 6 serious events

Other events: 6 other events

Deaths: 1 deaths

Abiraterone, Prednisone and AMG

Serious events: 14 serious events

Other events: 16 other events

Deaths: 4 deaths

Abiraterone and Prednisone Only

Serious events: 11 serious events

Other events: 11 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Ravi Madan

National Cancer Institute

Phone: 301-480-7168

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	DL 1 Run in - 15mg/kg n=3 participants at risk Dose escalation phase to determine MTD of AMG AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg). Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily DL 1 AMG is 15 mg/kg DL 2 AMG is 30 mg/kg The randomized portion is 30 mg/kg.	DL 2 Run in - 30mg/kg n=6 participants at risk Dose escalation phase to determine MTD of AMG AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg). Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily DL 1 AMG is 15 mg/kg DL 2 AMG is 30 mg/kg The randomized portion is 30 mg/kg.	Abiraterone, Prednisone and AMG n=16 participants at risk Abiraterone and prednisone will be given with maximum tolerated dose (MTD) of Trebananib (AMG) AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg). Supplied in 240 mg v will be administered as an intravenous (IV) infusion using an intravenous infusion pump given over a 60-minute period. Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily Prednisone: Prednisone should be taken orally either, at 5mg twice a day for each dose or 10 mg once a day a patients preference.	Abiraterone and Prednisone Only n=11 participants at risk Abiraterone and prednisone only Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily Prednisone: Prednisone should be taken orally either, at 5mg twice a day for each dose or 10 mg once a day a patients preference.
Nervous system disorders Ataxia	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/16 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/11 • Date treatment consent signed to date off study, approximately 65 months and 7 days.
Nervous system disorders Dizziness	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/11 • Date treatment consent signed to date off study, approximately 65 months and 7 days.
General disorders Fatigue	0.00% 0/3 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/16 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/11 • Date treatment consent signed to date off study, approximately 65 months and 7 days.
General disorders Gait disturbance	0.00% 0/3 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/16 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/11 • Date treatment consent signed to date off study, approximately 65 months and 7 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, progressive disease	66.7% 2/3 • Number of events 2 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	50.0% 3/6 • Number of events 3 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	37.5% 6/16 • Number of events 6 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	72.7% 8/11 • Number of events 8 • Date treatment consent signed to date off study, approximately 65 months and 7 days.
Nervous system disorders Nervous system disorders - Other, specify	33.3% 1/3 • Number of events 2 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/16 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/11 • Date treatment consent signed to date off study, approximately 65 months and 7 days.
Psychiatric disorders Confusion	0.00% 0/3 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	16.7% 1/6 • Number of events 2 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/16 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/11 • Date treatment consent signed to date off study, approximately 65 months and 7 days.
General disorders Death NOS	0.00% 0/3 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	25.0% 4/16 • Number of events 4 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	27.3% 3/11 • Number of events 3 • Date treatment consent signed to date off study, approximately 65 months and 7 days.
Eye disorders Glaucoma	0.00% 0/3 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/11 • Date treatment consent signed to date off study, approximately 65 months and 7 days.
Nervous system disorders Presyncope	0.00% 0/3 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/16 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/11 • Date treatment consent signed to date off study, approximately 65 months and 7 days.
Infections and infestations Sepsis	0.00% 0/3 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	12.5% 2/16 • Number of events 2 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/11 • Date treatment consent signed to date off study, approximately 65 months and 7 days.
Renal and urinary disorders Acute kidney injury	0.00% 0/3 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/11 • Date treatment consent signed to date off study, approximately 65 months and 7 days.
Respiratory, thoracic and mediastinal disorders Bronchopulmonary hemorrhage	0.00% 0/3 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/11 • Date treatment consent signed to date off study, approximately 65 months and 7 days.
Infections and infestations Lung infection	0.00% 0/3 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	12.5% 2/16 • Number of events 2 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	9.1% 1/11 • Number of events 1 • Date treatment consent signed to date off study, approximately 65 months and 7 days.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/3 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/11 • Date treatment consent signed to date off study, approximately 65 months and 7 days.
Nervous system disorders Syncope	0.00% 0/3 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/11 • Date treatment consent signed to date off study, approximately 65 months and 7 days.
Vascular disorders Thromboembolic event	0.00% 0/3 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	9.1% 1/11 • Number of events 1 • Date treatment consent signed to date off study, approximately 65 months and 7 days.
Renal and urinary disorders Urinary tract obstruction	0.00% 0/3 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/11 • Date treatment consent signed to date off study, approximately 65 months and 7 days.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/16 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	9.1% 1/11 • Number of events 1 • Date treatment consent signed to date off study, approximately 65 months and 7 days.
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/16 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	9.1% 1/11 • Number of events 1 • Date treatment consent signed to date off study, approximately 65 months and 7 days.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/3 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/16 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	18.2% 2/11 • Number of events 2 • Date treatment consent signed to date off study, approximately 65 months and 7 days.
Cardiac disorders Supraventricular tachycardia	0.00% 0/3 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	0.00% 0/16 • Date treatment consent signed to date off study, approximately 65 months and 7 days.	9.1% 1/11 • Number of events 1 • Date treatment consent signed to date off study, approximately 65 months and 7 days.