Trial Outcomes & Findings for Pembrolizumab +/- Bevacizumab for Recurrent GBM (NCT NCT02337491)

NCT ID: NCT02337491

Last Updated: 2020-12-22

Results Overview

The MTD of pembrolizumab in combination with bevacizumab 10 mg/kg intravenously (IV) on days 1, 15 and 29 of each 42 day cycle is determined by the number of participants who experience a dose limiting toxicity (DLT) at the various regimens of dosing frequency of pembrolizumab 200 mg IV administered under evaluation. See subsequent primary outcome measure for the DLT definition. The MTD is defined as the pembrolizumab dose frequency regimen at which fewer than one-third of participants experience a DLT. If de-escalation does not occur per design, then the starting dose is the Recommended Phase II Dose (RP2D).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 80 participants
• Primary outcome timeframe: one cycle/42 days
• Results posted on: 2020-12-22

Participant Flow

Participants were enrolled between Feb 2015 and June 2016

Participant milestones

Measure	Cohort A: Pembrolizumab + Bevacizumab Pembrolizumab: 200 mg administered intravenously on days 1 and 22 of each 42 day cycle Bevacizumab: 10 mg/kg administered Intravenously on days 1, 15 and 29 of each 42 day cycle Participants were treated until disease progression or unacceptable toxicity up to 16 cycles.	Cohort B: Pembrolizumab Pembrolizumab: 200 mg administered intravenously on days 1 and 22 of each 42 day cycle Participants were treated until disease progression or unacceptable toxicity up to 16 cycles.
Overall Study STARTED	50	30
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	50	30

Reasons for withdrawal

Measure	Cohort A: Pembrolizumab + Bevacizumab Pembrolizumab: 200 mg administered intravenously on days 1 and 22 of each 42 day cycle Bevacizumab: 10 mg/kg administered Intravenously on days 1, 15 and 29 of each 42 day cycle Participants were treated until disease progression or unacceptable toxicity up to 16 cycles.	Cohort B: Pembrolizumab Pembrolizumab: 200 mg administered intravenously on days 1 and 22 of each 42 day cycle Participants were treated until disease progression or unacceptable toxicity up to 16 cycles.
Overall Study Death	1	1
Overall Study Adverse Event	0	1
Overall Study Withdrawal by Subject	3	0
Overall Study Progressive Disease	44	28
Overall Study On Treatment	2	0

Baseline Characteristics

Pembrolizumab +/- Bevacizumab for Recurrent GBM

Baseline characteristics by cohort

Measure	Cohort A: Pembrolizumab + Bevacizumab n=50 Participants Pembrolizumab: 200 mg administered intravenously on days 1 and 22 of each 42 day cycle Bevacizumab: 10 mg/kg administered Intravenously on days 1, 15 and 29 of each 42 day cycle Participants were treated until disease progression or unacceptable toxicity up to 16 cycles.	Cohort B: Pembrolizumab n=30 Participants Pembrolizumab: 200 mg administered intravenously on days 1 and 22 of each 42 day cycle Participants were treated until disease progression or unacceptable toxicity up to 16 cycles.	Total n=80 Participants Total of all reporting groups
Age, Continuous	50.7 years STANDARD_DEVIATION 12.7 • n=5 Participants	51.8 years STANDARD_DEVIATION 13.3 • n=7 Participants	51.1 years STANDARD_DEVIATION 12.9 • n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	11 Participants n=7 Participants	26 Participants n=5 Participants
Sex: Female, Male Male	35 Participants n=5 Participants	19 Participants n=7 Participants	54 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	41 Participants n=5 Participants	24 Participants n=7 Participants	65 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants

PRIMARY outcome

Timeframe: one cycle/42 days

Population: The analysis dataset is comprised of all participants who enrolled in the safety lead-in study. Only dose level 0 was evaluated and no de-escalation doses were evaluated.

The MTD of pembrolizumab in combination with bevacizumab 10 mg/kg intravenously (IV) on days 1, 15 and 29 of each 42 day cycle is determined by the number of participants who experience a dose limiting toxicity (DLT) at the various regimens of dosing frequency of pembrolizumab 200 mg IV administered under evaluation. See subsequent primary outcome measure for the DLT definition. The MTD is defined as the pembrolizumab dose frequency regimen at which fewer than one-third of participants experience a DLT. If de-escalation does not occur per design, then the starting dose is the Recommended Phase II Dose (RP2D).

Outcome measures

Measure	Cohort A Safety Lead-In: Pembrolizumab (DL 0) + Bevacizumab n=6 Participants Pembrolizumab (Dose Level 0): 200 mg administered intravenously on days 1 and 22 of each 42 day cycle Bevacizumab: 10 mg/kg administered Intravenously on days 1, 15 and 29 of each 42 day cycle Participants were treated until disease progression or unacceptable toxicity up to 16 cycles.	Cohort B: Pembrolizumab Pembrolizumab: 200 mg administered intravenously on days 1 and 22 of each 42 day cycle Participants were treated until disease progression or unacceptable toxicity up to 16 cycles.
Pembrolizumab Maximum Tolerated Dose (MTD) [Cohort A Safety Lead-In]	200 mg every 3 weeks	—

PRIMARY outcome

Timeframe: The evaluation for MTD occurred continuously through one cycle of treatment (42 days).

Population: The analysis dataset is comprised of all participants who enrolled in the safety lead-in study.

A DLT is defined as an adverse event (AE) that (a) is >= grade 3 and related to the pembrolizumab with an attribution of possible, probably or definite, and (b) occurs during and/or begins during the first 42 days of study treatment, and (c) does not meet any of the following exception criteria: grade 3 immune-related AE that downgrades to <= grade 2 within 5 days, or <= grade 1/baseline within 14 days of onset; grade 3 asymptomatic endocrinopathy; grade 3 inflammatory reaction attribution to anti-tumor response; grade 3 pneumonitis, neurologic event, or uveitis that downgrades to <=grade 1 within 3 days; liver transaminase elevation <= 8 times institutional upper limit of normal (ULN); total bilirubin <= 5 times institutional ULN; any pre-existing lab abnormality that deteriorates to grade 3/4 and determine not clinically significant by Investigator, Overall Principal Investigator and Sponsor.

Outcome measures

Measure	Cohort A Safety Lead-In: Pembrolizumab (DL 0) + Bevacizumab n=6 Participants Pembrolizumab (Dose Level 0): 200 mg administered intravenously on days 1 and 22 of each 42 day cycle Bevacizumab: 10 mg/kg administered Intravenously on days 1, 15 and 29 of each 42 day cycle Participants were treated until disease progression or unacceptable toxicity up to 16 cycles.	Cohort B: Pembrolizumab Pembrolizumab: 200 mg administered intravenously on days 1 and 22 of each 42 day cycle Participants were treated until disease progression or unacceptable toxicity up to 16 cycles.
Pembrolizumab Dose Limiting Toxicity (DLT) [Cohort A Safety Lead-In]	0 participants with DLT	—

PRIMARY outcome

Timeframe: Disease was assessed radiographically for response every cycle on treatment. Treatment duration in cycles (cycle=42 days) was a mean (SD) of 4.5 (4.4) for Cohort A and 2.5 (2.7) for Cohort B. Assessment at week 72/cycle 12 pertains to the 6-month PFS.

Population: The analysis dataset is comprised of all enrolled participants.

PFS6 is the proportion of patients remaining alive and progression-free at 6-months from study entry.

Progressive disease was established based on Response Assessment in Neuro-Oncology (RANO) criteria. PD is a >25% increase in sum of perpendicular diameters of all measurable enhancing lesions, significant increase of non-enhancing lesions, any new lesions, clear clinical deterioration, failure to return for evaluation due to death or deteriorating condition.

Outcome measures

Measure	Cohort A Safety Lead-In: Pembrolizumab (DL 0) + Bevacizumab n=50 Participants Pembrolizumab (Dose Level 0): 200 mg administered intravenously on days 1 and 22 of each 42 day cycle Bevacizumab: 10 mg/kg administered Intravenously on days 1, 15 and 29 of each 42 day cycle Participants were treated until disease progression or unacceptable toxicity up to 16 cycles.	Cohort B: Pembrolizumab n=30 Participants Pembrolizumab: 200 mg administered intravenously on days 1 and 22 of each 42 day cycle Participants were treated until disease progression or unacceptable toxicity up to 16 cycles.
6-Month Progression-Free Survival (PFS6)	0.26 proportion of participants Interval 0.146 to 0.403	0.067 proportion of participants Interval 0.009 to 0.221

SECONDARY outcome

Timeframe: Disease was assessed radiographically for response every cycle on treatment and every 6 weeks long-term. Median PFS follow-up (months) was 25 for Cohort A and 26 for Cohort B.

Population: The analysis dataset is comprised of all enrolled participants.

PFS based on Kaplan-Meier is defined as the time from study entry to the earliest documentation of disease progression (PD) or death. Participants alive without evidence of PD were censored at the date of last disease assessment. Per Response Assessment in Neuro-Oncology (RANO) criteria, PD is a >25% increase in sum of perpendicular diameters of all measurable enhancing lesions, significant increase of non-enhancing lesions, any new lesions, clear clinical deterioration, failure to return for evaluation due to death or deteriorating condition.

Outcome measures

Measure	Cohort A Safety Lead-In: Pembrolizumab (DL 0) + Bevacizumab n=50 Participants Pembrolizumab (Dose Level 0): 200 mg administered intravenously on days 1 and 22 of each 42 day cycle Bevacizumab: 10 mg/kg administered Intravenously on days 1, 15 and 29 of each 42 day cycle Participants were treated until disease progression or unacceptable toxicity up to 16 cycles.	Cohort B: Pembrolizumab n=30 Participants Pembrolizumab: 200 mg administered intravenously on days 1 and 22 of each 42 day cycle Participants were treated until disease progression or unacceptable toxicity up to 16 cycles.
Progression-Free Survival (PFS)	4.1 months Interval 2.8 to 5.5	1.4 months Interval 1.4 to 2.7

SECONDARY outcome

Timeframe: Participants were followed long-term for survival every 3 months from the end of treatment until death or lost to follow-up. Median survival follow-up was 25 months for each cohort.

Population: The analysis dataset is comprised of all enrolled participants.

OS based on Kaplan-Meier is defined as the time from study entry to death or date last known alive.

Outcome measures

Measure	Cohort A Safety Lead-In: Pembrolizumab (DL 0) + Bevacizumab n=50 Participants Pembrolizumab (Dose Level 0): 200 mg administered intravenously on days 1 and 22 of each 42 day cycle Bevacizumab: 10 mg/kg administered Intravenously on days 1, 15 and 29 of each 42 day cycle Participants were treated until disease progression or unacceptable toxicity up to 16 cycles.	Cohort B: Pembrolizumab n=30 Participants Pembrolizumab: 200 mg administered intravenously on days 1 and 22 of each 42 day cycle Participants were treated until disease progression or unacceptable toxicity up to 16 cycles.
Overall Survival (OS)	8.8 months Interval 7.7 to 14.2	10.3 months Interval 8.5 to 12.5

SECONDARY outcome

Timeframe: Disease was assessed radiographically for response every cycle on treatment. Treatment duration in cycles (each cycle=42 days) was a mean (SD) of 4.5 (4.4) for Cohort A and 2.5 (2.7) for Cohort B.

Population: The analysis dataset is comprised of all enrolled participants.

ORR was established based on Response Assessment in Neuro-Oncology (RANO) criteria. RANO criteria has 5 potential categories: Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive disease (PD) and Unknown. CR: disappearance of all enhancing lesions, stable or improved non-enhancing lesions, and stable or improved clinically. PR: >= 50% decrease in sum of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, stable or improved non-enhancing lesions, and stable or improved clinically. PD: >25% increase in sum of perpendicular diameters of all measurable enhancing lesions, significant increase of non-enhancing lesions, any new lesions, clear clinical deterioration, failure to return for evaluation due to death or deteriorating condition. SD: does not qualify for CR, PR or PD.

Outcome measures

Measure	Cohort A Safety Lead-In: Pembrolizumab (DL 0) + Bevacizumab n=50 Participants Pembrolizumab (Dose Level 0): 200 mg administered intravenously on days 1 and 22 of each 42 day cycle Bevacizumab: 10 mg/kg administered Intravenously on days 1, 15 and 29 of each 42 day cycle Participants were treated until disease progression or unacceptable toxicity up to 16 cycles.	Cohort B: Pembrolizumab n=30 Participants Pembrolizumab: 200 mg administered intravenously on days 1 and 22 of each 42 day cycle Participants were treated until disease progression or unacceptable toxicity up to 16 cycles.
Overall Radiographic Response (ORR)	0.20 percentage of participants Interval 0.11 to 0.32	0.0 percentage of participants Interval 0.0 to 0.095

Adverse Events

Cohort A: Pembrolizumab + Bevacizumab

Serious events: 22 serious events

Other events: 50 other events

Deaths: 3 deaths

Cohort B: Pembrolizumab

Serious events: 10 serious events

Other events: 29 other events

Deaths: 1 deaths

Serious adverse events

Measure	Cohort A: Pembrolizumab + Bevacizumab n=50 participants at risk Pembrolizumab: 200 mg administered intravenously on days 1 and 22 of each 42 day cycle Bevacizumab: 10 mg/kg administered Intravenously on days 1, 15 and 29 of each 42 day cycle Participants were treated until disease progression or unacceptable toxicity up to 16 cycles.	Cohort B: Pembrolizumab n=30 participants at risk Pembrolizumab (Dose Level 0): 200 mg administered intravenously on days 1 and 22 of each 42 day cycle Participants were treated until disease progression or unacceptable toxicity up to 16 cycles.
Infections and infestations Urinary tract infection	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Investigations Alanine aminotransferase increased	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Vascular disorders Vascular disorders - Other	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Blood and lymphatic system disorders Anemia	0.00% 0/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Psychiatric disorders Confusion	0.00% 0/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
General disorders Death NOS	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Gastrointestinal disorders Diarrhea	4.0% 2/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Nervous system disorders Dizziness	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Nervous system disorders Dysphasia	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Nervous system disorders Edema cerebral	0.00% 0/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Nervous system disorders Encephalopathy	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
General disorders Fatigue	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
General disorders Fever	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
General disorders Gait disturbance	4.0% 2/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Gastrointestinal disorders Gastric ulcer	0.00% 0/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Nervous system disorders Headache	12.0% 6/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Gastrointestinal disorders Hemorrhoids	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Vascular disorders Hypertension	4.0% 2/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Infections and infestations Infections and infestations - Other	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
General disorders Infusion related reaction	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Nervous system disorders Intracranial hemorrhage	6.0% 3/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Nervous system disorders Lethargy	0.00% 0/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Musculoskeletal and connective tissue disorders Muscle weakness left-sided	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Musculoskeletal and connective tissue disorders Muscle weakness right-sided	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Gastrointestinal disorders Nausea	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Nervous system disorders Nervous system disorders - Other	4.0% 2/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Cardiac disorders Palpitations	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Nervous system disorders Reversible posterior leukoencephalopathy syndrome	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Nervous system disorders Seizure	4.0% 2/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	6.7% 2/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Infections and infestations Skin infection	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Nervous system disorders Somnolence	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Nervous system disorders Stroke	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Surgical and medical procedures Surgical and medical procedures - Other	12.0% 6/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	6.7% 2/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Vascular disorders Thromboembolic event	0.00% 0/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	6.7% 2/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Renal and urinary disorders Urinary incontinence	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Gastrointestinal disorders Vomiting	4.0% 2/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.

Other adverse events

Measure	Cohort A: Pembrolizumab + Bevacizumab n=50 participants at risk Pembrolizumab: 200 mg administered intravenously on days 1 and 22 of each 42 day cycle Bevacizumab: 10 mg/kg administered Intravenously on days 1, 15 and 29 of each 42 day cycle Participants were treated until disease progression or unacceptable toxicity up to 16 cycles.	Cohort B: Pembrolizumab n=30 participants at risk Pembrolizumab (Dose Level 0): 200 mg administered intravenously on days 1 and 22 of each 42 day cycle Participants were treated until disease progression or unacceptable toxicity up to 16 cycles.
Gastrointestinal disorders Dysphagia	6.0% 3/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Nervous system disorders Dysphasia	22.0% 11/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	16.7% 5/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Respiratory, thoracic and mediastinal disorders Dyspnea	10.0% 5/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Ear and labyrinth disorders Ear pain	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
General disorders Edema face	4.0% 2/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
General disorders Edema limbs	6.0% 3/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	16.7% 5/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Endocrine disorders Endocrine disorders - Other	4.0% 2/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Nervous system disorders Dysarthria	4.0% 2/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Nervous system disorders Dysgeusia	4.0% 2/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Gastrointestinal disorders Dyspepsia	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Infections and infestations Urinary tract infection	10.0% 5/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	6.7% 2/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Renal and urinary disorders Urinary tract pain	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Renal and urinary disorders Urinary urgency	4.0% 2/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Vascular disorders Vascular disorders - Other	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Ear and labyrinth disorders Vertigo	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Gastrointestinal disorders Vomiting	14.0% 7/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	10.0% 3/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Investigations Weight loss	10.0% 5/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Respiratory, thoracic and mediastinal disorders Wheezing	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Investigations White blood cell decreased	24.0% 12/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Injury, poisoning and procedural complications Wound complication	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Infections and infestations Wound infection	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Gastrointestinal disorders Duodenal hemorrhage	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Gastrointestinal disorders Abdominal distension	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Gastrointestinal disorders Abdominal pain	12.0% 6/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Psychiatric disorders Agitation	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Investigations Alanine aminotransferase increased	16.0% 8/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	6.7% 2/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Investigations Alkaline phosphatase increased	6.0% 3/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	6.7% 2/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Immune system disorders Allergic reaction	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	6.0% 3/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Gastrointestinal disorders Anal hemorrhage	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Blood and lymphatic system disorders Anemia	12.0% 6/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	13.3% 4/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Metabolism and nutrition disorders Anorexia	10.0% 5/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	13.3% 4/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Psychiatric disorders Anorgasmia	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Psychiatric disorders Anxiety	16.0% 8/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	10.0% 3/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Musculoskeletal and connective tissue disorders Arthralgia	22.0% 11/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	6.7% 2/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Investigations Aspartate aminotransferase increased	18.0% 9/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Nervous system disorders Ataxia	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	13.3% 4/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Musculoskeletal and connective tissue disorders Back pain	10.0% 5/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Gastrointestinal disorders Bloating	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Investigations Blood bilirubin increased	4.0% 2/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Eye disorders Blurred vision	6.0% 3/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Musculoskeletal and connective tissue disorders Bone pain	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Infections and infestations Bronchial infection	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Respiratory, thoracic and mediastinal disorders Bronchospasm	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Injury, poisoning and procedural complications Bruising	4.0% 2/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	6.7% 2/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Skin and subcutaneous tissue disorders Bullous dermatitis	0.00% 0/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Injury, poisoning and procedural complications Burn	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Investigations Cardiac troponin T increased	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Investigations CD4 lymphocytes decreased	4.0% 2/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Cardiac disorders Chest pain - cardiac	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
General disorders Chills	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Nervous system disorders Cognitive disturbance	10.0% 5/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	6.7% 2/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Gastrointestinal disorders Colitis	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Nervous system disorders Concentration impairment	4.0% 2/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Psychiatric disorders Confusion	18.0% 9/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	23.3% 7/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Eye disorders Conjunctivitis	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Gastrointestinal disorders Constipation	14.0% 7/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Respiratory, thoracic and mediastinal disorders Cough	24.0% 12/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	10.0% 3/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Investigations Creatinine increased	8.0% 4/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Endocrine disorders Cushingoid	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Metabolism and nutrition disorders Dehydration	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	6.7% 2/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Gastrointestinal disorders Dental caries	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Psychiatric disorders Depression	10.0% 5/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Gastrointestinal disorders Diarrhea	24.0% 12/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Nervous system disorders Dizziness	14.0% 7/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Eye disorders Dry eye	6.0% 3/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	6.7% 2/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Gastrointestinal disorders Dry mouth	6.0% 3/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Skin and subcutaneous tissue disorders Dry skin	12.0% 6/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	6.7% 2/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Respiratory, thoracic and mediastinal disorders Epistaxis	18.0% 9/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Reproductive system and breast disorders Erectile dysfunction	4.0% 2/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Skin and subcutaneous tissue disorders Erythema multiforme	4.0% 2/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Nervous system disorders Extrapyramidal disorder	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Eye disorders Eye disorders - Other	12.0% 6/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	10.0% 3/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Infections and infestations Eye infection	0.00% 0/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Eye disorders Eye pain	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Nervous system disorders Facial muscle weakness	6.0% 3/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Injury, poisoning and procedural complications Fall	6.0% 3/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	16.7% 5/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
General disorders Fatigue	42.0% 21/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	40.0% 12/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Gastrointestinal disorders Fecal incontinence	0.00% 0/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
General disorders Fever	6.0% 3/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
General disorders Flu like symptoms	4.0% 2/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Vascular disorders Flushing	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
General disorders Gait disturbance	20.0% 10/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	30.0% 9/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Gastrointestinal disorders Gastroesophageal reflux disease	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Gastrointestinal disorders Gastrointestinal disorders - Other	10.0% 5/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
General disorders General disorders and administration site conditions - Other	0.00% 0/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	14.0% 7/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	6.7% 2/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Nervous system disorders Headache	42.0% 21/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	53.3% 16/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Ear and labyrinth disorders Hearing impaired	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Vascular disorders Hematoma	0.00% 0/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Renal and urinary disorders Hematuria	4.0% 2/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Gastrointestinal disorders Hemorrhoids	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Respiratory, thoracic and mediastinal disorders Hiccups	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Respiratory, thoracic and mediastinal disorders Hoarseness	22.0% 11/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Vascular disorders Hot flashes	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Metabolism and nutrition disorders Hypercalcemia	8.0% 4/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Metabolism and nutrition disorders Hyperglycemia	34.0% 17/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	23.3% 7/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Metabolism and nutrition disorders Hyperkalemia	4.0% 2/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Metabolism and nutrition disorders Hypermagnesemia	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Metabolism and nutrition disorders Hypernatremia	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Vascular disorders Hypertension	56.0% 28/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	6.7% 2/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Endocrine disorders Hyperthyroidism	10.0% 5/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Metabolism and nutrition disorders Hyperuricemia	6.0% 3/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Metabolism and nutrition disorders Hypoalbuminemia	10.0% 5/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	16.7% 5/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Metabolism and nutrition disorders Hypocalcemia	18.0% 9/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	10.0% 3/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Metabolism and nutrition disorders Hypoglycemia	6.0% 3/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Metabolism and nutrition disorders Hypokalemia	18.0% 9/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Metabolism and nutrition disorders Hypomagnesemia	8.0% 4/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Metabolism and nutrition disorders Hyponatremia	20.0% 10/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Metabolism and nutrition disorders Hypophosphatemia	10.0% 5/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Vascular disorders Hypotension	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Endocrine disorders Hypothyroidism	10.0% 5/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	6.7% 2/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Immune system disorders Immune system disorders - Other	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Psychiatric disorders Insomnia	0.00% 0/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Nervous system disorders Intracranial hemorrhage	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	6.7% 2/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Investigations Investigations - Other	0.00% 0/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Musculoskeletal and connective tissue disorders Joint range of motion decreased	6.0% 3/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Respiratory, thoracic and mediastinal disorders Laryngeal inflammation	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Blood and lymphatic system disorders Leukocytosis	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Psychiatric disorders Libido decreased	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
General disorders Localized edema	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Investigations Lymphocyte count decreased	14.0% 7/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	10.0% 3/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
General disorders Malaise	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Nervous system disorders Memory impairment	12.0% 6/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	13.3% 4/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Gastrointestinal disorders Mucositis oral	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Musculoskeletal and connective tissue disorders Muscle weakness left-sided	4.0% 2/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	6.7% 2/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	6.0% 3/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Musculoskeletal and connective tissue disorders Muscle weakness right-sided	6.0% 3/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	6.7% 2/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Musculoskeletal and connective tissue disorders Muscle weakness trunk	0.00% 0/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Musculoskeletal and connective tissue disorders Muscle weakness upper limb	0.00% 0/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other	8.0% 4/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	10.0% 3/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Musculoskeletal and connective tissue disorders Myalgia	22.0% 11/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Respiratory, thoracic and mediastinal disorders Nasal congestion	12.0% 6/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Gastrointestinal disorders Nausea	30.0% 15/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	20.0% 6/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Musculoskeletal and connective tissue disorders Neck pain	6.0% 3/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	6.7% 2/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Nervous system disorders Nervous system disorders - Other, specify	14.0% 7/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Nervous system disorders Nervous system disorders - Other	0.00% 0/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	20.0% 6/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Nervous system disorders Neuralgia	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Investigations Neutrophil count decreased	20.0% 10/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
General disorders Non-cardiac chest pain	6.0% 3/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Gastrointestinal disorders Oral hemorrhage	6.0% 3/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Gastrointestinal disorders Oral pain	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
General disorders Pain	10.0% 5/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Musculoskeletal and connective tissue disorders Pain in extremity	6.0% 3/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	13.3% 4/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Cardiac disorders Palpitations	6.0% 3/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Infections and infestations Papulopustular rash	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Nervous system disorders Paresthesia	12.0% 6/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	10.0% 3/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Infections and infestations Penile infection	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Investigations Platelet count decreased	20.0% 10/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	20.0% 6/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Infections and infestations Tooth infection	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Respiratory, thoracic and mediastinal disorders Postnasal drip	14.0% 7/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	6.7% 2/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Renal and urinary disorders Proteinuria	18.0% 9/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	10.0% 3/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Psychiatric disorders Psychiatric disorders - Other	4.0% 2/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Psychiatric disorders Psychosis	0.00% 0/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Skin and subcutaneous tissue disorders Purpura	0.00% 0/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Skin and subcutaneous tissue disorders Rash acneiform	4.0% 2/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Skin and subcutaneous tissue disorders Rash maculo-papular	8.0% 4/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Infections and infestations Rash pustular	0.00% 0/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Gastrointestinal disorders Rectal fistula	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Gastrointestinal disorders Rectal hemorrhage	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Reproductive system and breast disorders Reproductive system and breast disorders - Other	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other	6.0% 3/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Nervous system disorders Seizure	22.0% 11/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	13.3% 4/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Cardiac disorders Sinus bradycardia	6.0% 3/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Cardiac disorders Sinus tachycardia	4.0% 2/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Infections and infestations Sinusitis	4.0% 2/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other	26.0% 13/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Infections and infestations Skin infection	8.0% 4/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Skin and subcutaneous tissue disorders Skin ulceration	0.00% 0/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Respiratory, thoracic and mediastinal disorders Sore throat	12.0% 6/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Gastrointestinal disorders Stomach pain	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Surgical and medical procedures Surgical and medical procedures - Other	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Nervous system disorders Syncope	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Gastrointestinal disorders Toothache	6.0% 3/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Nervous system disorders Tremor	0.00% 0/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Infections and infestations Upper respiratory infection	12.0% 6/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Renal and urinary disorders Urinary frequency	4.0% 2/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	3.3% 1/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Renal and urinary disorders Urinary incontinence	0.00% 0/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	6.7% 2/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.
Renal and urinary disorders Urinary retention	2.0% 1/50 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.	0.00% 0/30 • Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months). SAEs defined per protocol and all remaining AEs categorized as Other AE without regard to treatment attribution.

Additional Information

David A. Reardon, MD

Dana-Farber Cancer Institute

Phone: 617-632-2166

Email: dreardon3@partners.org

Results disclosure agreements

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