Trial Outcomes & Findings for Phase II Anti-PD1 Epigenetic Therapy Study in NSCLC. (NCT NCT01928576)

NCT ID: NCT01928576

Last Updated: 2024-05-03

Results Overview

Percentage of participants with response to combination Nivolumab and epigenetic therapy. Response will be assessed by RECIST 1.1 criteria, where complete response (CR)= disappearance of all target lesions, partial response (PR) is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

143 participants

Primary outcome timeframe

2 years

Results posted on

2024-05-03

Participant Flow

43 patients were not eligible. The list of reasons for subjects not being eligible include Subject had did not have disease amenable to biopsy, Disease Progression, elevated creatinine, COVID-19, hyponatremia, patient declined, patient sent to hospice, deceased, history of pneumonitis, not have enough tissue for biopsy, central nervous system involvement, pericardial effusion, brain metastasis, and Hypoxemia.

Participant milestones

Participant milestones
Measure	ARM A Anti-PD-1/PD-L1 treatment naïve patients only Every 28 days for 2 cycles Azacitidine 40mg/m2 subcutaneous days 1-6 and 8-10 Entinostat 7mg by mouth Days 3 and 10 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg.	ARM B Every 28 days for 2 cycles CC-486 300 mg by mouth days 1 - 21 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg.	Arm C Nivolumab 3mg/kg every 2 weeks until progression Nivolumab	Arm D Anti-PD-1/PD-L1 treatment naïve patients only Every 28 days for 6 cycles Azacitidine 40mg/m2 days 1-5 and 8-10 Entinostat 5mg Days 3 and 10 Nivolumab 3mg/kg Days 1 and 15 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg. Azacitidine Entinostat Nivolumab	Arm E Patients must have had refractory (Arm E=less than 24 weeks from first dose of anti-PD-1/PD-L1) disease during or after anti-PD-1 or anti-PD-L1 therapy and, in the opinion of the investigator, must be unlikely to benefit from nivolumab monotherapy. Every 28 days for 6 cycles Azacitidine 40mg/m2 days 1-5 and 8-10 Entinostat 5mg Days 3 and 10 Nivolumab 3mg/kg Days 1 and 15 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg. Azacitidine Entinostat Nivolumab	Arm F Patients must have had recurrent (Arm F=more than 24 weeks from first dose of anti-PD1/PD-L1) disease during or after anti-PD-1 or anti-PD-L1 therapy and, in the opinion of the investigator, must be unlikely to benefit from nivolumab monotherapy. Every 28 days for 6 cycles Azacitidine 40mg/m2 days 1-5 and 8-10 Entinostat 5mg Days 3 and 10 Nivolumab 3mg/kg Days 1 and 15 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg. Azacitidine Entinostat Nivolumab
Overall Study STARTED	32	7	21	14	7	19
Overall Study COMPLETED	32	7	21	14	7	19
Overall Study NOT COMPLETED	0	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

age data was missing for 1 participant in Arm F.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ARM A n=32 Participants Anti-PD-1/PD-L1 treatment naïve patients only Every 28 days for 2 cycles Azacitidine 40mg/m2 subcutaneous days 1-6 and 8-10 Entinostat 7mg by mouth Days 3 and 10 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg.	ARM B n=7 Participants Every 28 days for 2 cycles CC-486 300 mg by mouth days 1 - 21 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg.	Arm C n=21 Participants Nivolumab 3mg/kg every 2 weeks until progression Nivolumab	Arm D n=14 Participants Anti-PD-1/PD-L1 treatment naïve patients only Every 28 days for 6 cycles Azacitidine 40mg/m2 days 1-5 and 8-10 Entinostat 5mg Days 3 and 10 Nivolumab 3mg/kg Days 1 and 15 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg. Azacitidine Entinostat Nivolumab	Arm E n=7 Participants Patients must have had refractory (Arm E=less than 24 weeks from first dose of anti-PD-1/PD-L1) disease during or after anti-PD-1 or anti-PD-L1 therapy and, in the opinion of the investigator, must be unlikely to benefit from nivolumab monotherapy. Every 28 days for 6 cycles Azacitidine 40mg/m2 days 1-5 and 8-10 Entinostat 5mg Days 3 and 10 Nivolumab 3mg/kg Days 1 and 15 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg. Azacitidine Entinostat Nivolumab	Arm F n=19 Participants Patients must have had recurrent (Arm F=more than 24 weeks from first dose of anti-PD1/PD-L1) disease during or after anti-PD-1 or anti-PD-L1 therapy and, in the opinion of the investigator, must be unlikely to benefit from nivolumab monotherapy. Every 28 days for 6 cycles Azacitidine 40mg/m2 days 1-5 and 8-10 Entinostat 5mg Days 3 and 10 Nivolumab 3mg/kg Days 1 and 15 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg. Azacitidine Entinostat Nivolumab	Total n=100 Participants Total of all reporting groups
Age, Continuous	63.5 years n=32 Participants • age data was missing for 1 participant in Arm F	67 years n=7 Participants • age data was missing for 1 participant in Arm F	62 years n=21 Participants • age data was missing for 1 participant in Arm F	65.5 years n=14 Participants • age data was missing for 1 participant in Arm F	70 years n=7 Participants • age data was missing for 1 participant in Arm F	66.6 years n=18 Participants • age data was missing for 1 participant in Arm F	70 years n=99 Participants • age data was missing for 1 participant in Arm F
Sex/Gender, Customized Unknown	0 Participants n=32 Participants	0 Participants n=7 Participants	0 Participants n=21 Participants	0 Participants n=14 Participants	0 Participants n=7 Participants	1 Participants n=19 Participants	1 Participants n=100 Participants
Sex/Gender, Customized Female	16 Participants n=32 Participants	4 Participants n=7 Participants	9 Participants n=21 Participants	5 Participants n=14 Participants	3 Participants n=7 Participants	8 Participants n=19 Participants	45 Participants n=100 Participants
Sex/Gender, Customized Male	16 Participants n=32 Participants	3 Participants n=7 Participants	12 Participants n=21 Participants	9 Participants n=14 Participants	4 Participants n=7 Participants	10 Participants n=19 Participants	54 Participants n=100 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=32 Participants	0 Participants n=7 Participants	0 Participants n=21 Participants	0 Participants n=14 Participants	0 Participants n=7 Participants	0 Participants n=19 Participants	0 Participants n=100 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	31 Participants n=32 Participants	6 Participants n=7 Participants	19 Participants n=21 Participants	14 Participants n=14 Participants	6 Participants n=7 Participants	18 Participants n=19 Participants	94 Participants n=100 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=32 Participants	1 Participants n=7 Participants	2 Participants n=21 Participants	0 Participants n=14 Participants	1 Participants n=7 Participants	1 Participants n=19 Participants	6 Participants n=100 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=32 Participants	0 Participants n=7 Participants	0 Participants n=21 Participants	0 Participants n=14 Participants	0 Participants n=7 Participants	0 Participants n=19 Participants	0 Participants n=100 Participants
Race (NIH/OMB) Asian	5 Participants n=32 Participants	2 Participants n=7 Participants	3 Participants n=21 Participants	1 Participants n=14 Participants	0 Participants n=7 Participants	0 Participants n=19 Participants	11 Participants n=100 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=32 Participants	0 Participants n=7 Participants	0 Participants n=21 Participants	0 Participants n=14 Participants	0 Participants n=7 Participants	0 Participants n=19 Participants	0 Participants n=100 Participants
Race (NIH/OMB) Black or African American	5 Participants n=32 Participants	1 Participants n=7 Participants	3 Participants n=21 Participants	3 Participants n=14 Participants	0 Participants n=7 Participants	1 Participants n=19 Participants	13 Participants n=100 Participants
Race (NIH/OMB) White	21 Participants n=32 Participants	4 Participants n=7 Participants	14 Participants n=21 Participants	9 Participants n=14 Participants	6 Participants n=7 Participants	15 Participants n=19 Participants	69 Participants n=100 Participants
Race (NIH/OMB) More than one race	1 Participants n=32 Participants	0 Participants n=7 Participants	1 Participants n=21 Participants	1 Participants n=14 Participants	1 Participants n=7 Participants	1 Participants n=19 Participants	5 Participants n=100 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=32 Participants	0 Participants n=7 Participants	0 Participants n=21 Participants	0 Participants n=14 Participants	0 Participants n=7 Participants	2 Participants n=19 Participants	2 Participants n=100 Participants
Region of Enrollment United States	32 Participants n=32 Participants	7 Participants n=7 Participants	21 Participants n=21 Participants	14 Participants n=14 Participants	7 Participants n=7 Participants	19 Participants n=19 Participants	100 Participants n=100 Participants

PRIMARY outcome

Timeframe: 2 years

Population: 1 patient from ARM A and 1 patient from ARM C did not have documentation of resict reads to analysis.

Outcome measures

Outcome measures
Measure	ARM A n=31 Participants Anti-PD-1/PD-L1 treatment naïve patients only Every 28 days for 2 cycles Azacitidine 40mg/m2 subcutaneous days 1-6 and 8-10 Entinostat 7mg by mouth Days 3 and 10 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg.	ARM B n=7 Participants Every 28 days for 2 cycles CC-486 300 mg by mouth days 1 - 21 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg.	Arm C n=20 Participants Nivolumab 3mg/kg every 2 weeks until progression Nivolumab	Arm D n=14 Participants Anti-PD-1/PD-L1 treatment naïve patients only Every 28 days for 6 cycles Azacitidine 40mg/m2 days 1-5 and 8-10 Entinostat 5mg Days 3 and 10 Nivolumab 3mg/kg Days 1 and 15 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg. Azacitidine Entinostat Nivolumab	Arm E n=7 Participants Patients must have had refractory (Arm E=less than 24 weeks from first dose of anti-PD-1/PD-L1) disease during or after anti-PD-1 or anti-PD-L1 therapy and, in the opinion of the investigator, must be unlikely to benefit from nivolumab monotherapy. Every 28 days for 6 cycles Azacitidine 40mg/m2 days 1-5 and 8-10 Entinostat 5mg Days 3 and 10 Nivolumab 3mg/kg Days 1 and 15 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg. Azacitidine Entinostat Nivolumab	Arm F n=19 Participants Patients must have had recurrent (Arm F=more than 24 weeks from first dose of anti-PD1/PD-L1) disease during or after anti-PD-1 or anti-PD-L1 therapy and, in the opinion of the investigator, must be unlikely to benefit from nivolumab monotherapy. Every 28 days for 6 cycles Azacitidine 40mg/m2 days 1-5 and 8-10 Entinostat 5mg Days 3 and 10 Nivolumab 3mg/kg Days 1 and 15 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg. Azacitidine Entinostat Nivolumab
Objective Response	4 Participants	1 Participants	5 Participants	3 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: 2 years

Number of months from the time of randomization until radiologic (per RECIST 1.1) or clinical progression or death, whichever comes first.

Outcome measures

Outcome measures
Measure	ARM A n=32 Participants Anti-PD-1/PD-L1 treatment naïve patients only Every 28 days for 2 cycles Azacitidine 40mg/m2 subcutaneous days 1-6 and 8-10 Entinostat 7mg by mouth Days 3 and 10 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg.	ARM B n=7 Participants Every 28 days for 2 cycles CC-486 300 mg by mouth days 1 - 21 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg.	Arm C n=21 Participants Nivolumab 3mg/kg every 2 weeks until progression Nivolumab	Arm D n=14 Participants Anti-PD-1/PD-L1 treatment naïve patients only Every 28 days for 6 cycles Azacitidine 40mg/m2 days 1-5 and 8-10 Entinostat 5mg Days 3 and 10 Nivolumab 3mg/kg Days 1 and 15 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg. Azacitidine Entinostat Nivolumab	Arm E n=7 Participants Patients must have had refractory (Arm E=less than 24 weeks from first dose of anti-PD-1/PD-L1) disease during or after anti-PD-1 or anti-PD-L1 therapy and, in the opinion of the investigator, must be unlikely to benefit from nivolumab monotherapy. Every 28 days for 6 cycles Azacitidine 40mg/m2 days 1-5 and 8-10 Entinostat 5mg Days 3 and 10 Nivolumab 3mg/kg Days 1 and 15 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg. Azacitidine Entinostat Nivolumab	Arm F n=19 Participants Patients must have had recurrent (Arm F=more than 24 weeks from first dose of anti-PD1/PD-L1) disease during or after anti-PD-1 or anti-PD-L1 therapy and, in the opinion of the investigator, must be unlikely to benefit from nivolumab monotherapy. Every 28 days for 6 cycles Azacitidine 40mg/m2 days 1-5 and 8-10 Entinostat 5mg Days 3 and 10 Nivolumab 3mg/kg Days 1 and 15 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg. Azacitidine Entinostat Nivolumab
Progression Free Survival	4.6 months Interval 3.7 to 13.7	3.7 months Interval 0.9 to not estimable because the upper confidence limits for the survivor function in this cohort was never less than 50%	5.7 months Interval 2.1 to 14.7	7.8 months Interval 3.2 to not estimable because the upper confidence limits for the survivor function in this cohort was never less than 50%	4.9 months Interval 1.4 to not estimable because the upper confidence limits for the survivor function in this cohort was never less than 50%	3.8 months Interval 2.9 to 6.64

SECONDARY outcome

Timeframe: 2 years

Number of months from the time nivolumab begins until radiologic (per RECIST 1.1) or clinical progression is noted.

Outcome measures

Outcome measures
Measure	ARM A n=32 Participants Anti-PD-1/PD-L1 treatment naïve patients only Every 28 days for 2 cycles Azacitidine 40mg/m2 subcutaneous days 1-6 and 8-10 Entinostat 7mg by mouth Days 3 and 10 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg.	ARM B n=7 Participants Every 28 days for 2 cycles CC-486 300 mg by mouth days 1 - 21 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg.	Arm C n=21 Participants Nivolumab 3mg/kg every 2 weeks until progression Nivolumab	Arm D n=14 Participants Anti-PD-1/PD-L1 treatment naïve patients only Every 28 days for 6 cycles Azacitidine 40mg/m2 days 1-5 and 8-10 Entinostat 5mg Days 3 and 10 Nivolumab 3mg/kg Days 1 and 15 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg. Azacitidine Entinostat Nivolumab	Arm E n=7 Participants Patients must have had refractory (Arm E=less than 24 weeks from first dose of anti-PD-1/PD-L1) disease during or after anti-PD-1 or anti-PD-L1 therapy and, in the opinion of the investigator, must be unlikely to benefit from nivolumab monotherapy. Every 28 days for 6 cycles Azacitidine 40mg/m2 days 1-5 and 8-10 Entinostat 5mg Days 3 and 10 Nivolumab 3mg/kg Days 1 and 15 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg. Azacitidine Entinostat Nivolumab	Arm F n=19 Participants Patients must have had recurrent (Arm F=more than 24 weeks from first dose of anti-PD1/PD-L1) disease during or after anti-PD-1 or anti-PD-L1 therapy and, in the opinion of the investigator, must be unlikely to benefit from nivolumab monotherapy. Every 28 days for 6 cycles Azacitidine 40mg/m2 days 1-5 and 8-10 Entinostat 5mg Days 3 and 10 Nivolumab 3mg/kg Days 1 and 15 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg. Azacitidine Entinostat Nivolumab
Time to Progression	4.6 months Interval 3.4 to 13.7	3.7 months Interval 0.9 to not estimable because the upper confidence limits for the survivor function in this cohort was never less than 50%	5.7 months Interval 2.1 to 14.7	7.8 months Interval 3.2 to not estimable because the upper confidence limits for the survivor function in this cohort was never less than 50%	4.9 months Interval 1.4 to not estimable because the upper confidence limits for the survivor function in this cohort was never less than 50%	3.8 months Interval 2.9 to 21.8

SECONDARY outcome

Timeframe: 2 years

Number of months from the time of randomization until death. Estimation will be by the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	ARM A n=32 Participants Anti-PD-1/PD-L1 treatment naïve patients only Every 28 days for 2 cycles Azacitidine 40mg/m2 subcutaneous days 1-6 and 8-10 Entinostat 7mg by mouth Days 3 and 10 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg.	ARM B n=7 Participants Every 28 days for 2 cycles CC-486 300 mg by mouth days 1 - 21 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg.	Arm C n=21 Participants Nivolumab 3mg/kg every 2 weeks until progression Nivolumab	Arm D n=14 Participants Anti-PD-1/PD-L1 treatment naïve patients only Every 28 days for 6 cycles Azacitidine 40mg/m2 days 1-5 and 8-10 Entinostat 5mg Days 3 and 10 Nivolumab 3mg/kg Days 1 and 15 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg. Azacitidine Entinostat Nivolumab	Arm E n=7 Participants Patients must have had refractory (Arm E=less than 24 weeks from first dose of anti-PD-1/PD-L1) disease during or after anti-PD-1 or anti-PD-L1 therapy and, in the opinion of the investigator, must be unlikely to benefit from nivolumab monotherapy. Every 28 days for 6 cycles Azacitidine 40mg/m2 days 1-5 and 8-10 Entinostat 5mg Days 3 and 10 Nivolumab 3mg/kg Days 1 and 15 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg. Azacitidine Entinostat Nivolumab	Arm F n=19 Participants Patients must have had recurrent (Arm F=more than 24 weeks from first dose of anti-PD1/PD-L1) disease during or after anti-PD-1 or anti-PD-L1 therapy and, in the opinion of the investigator, must be unlikely to benefit from nivolumab monotherapy. Every 28 days for 6 cycles Azacitidine 40mg/m2 days 1-5 and 8-10 Entinostat 5mg Days 3 and 10 Nivolumab 3mg/kg Days 1 and 15 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg. Azacitidine Entinostat Nivolumab
Overall Survival	10.5 months Interval 7.7 to 25.1	4 months Interval 1.3 to not estimable because the upper confidence limits for the survivor function in this cohort was never less than 50%	16.9 months Interval 12.9 to 57.4	14 months Interval 7.9 to not estimable because the upper confidence limits for the survivor function in this cohort was never less than 50%	5 months Interval 3.2 to not estimable because the upper confidence limits for the survivor function in this cohort was never less than 50%	12.1 months Interval 7.7 to 25.6

SECONDARY outcome

Timeframe: 2 years

Number of participants who experience adverse events as defined by CTCAE v4.0 that require a dose reduction.

Outcome measures

Outcome measures
Measure	ARM A n=32 Participants Anti-PD-1/PD-L1 treatment naïve patients only Every 28 days for 2 cycles Azacitidine 40mg/m2 subcutaneous days 1-6 and 8-10 Entinostat 7mg by mouth Days 3 and 10 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg.	ARM B n=7 Participants Every 28 days for 2 cycles CC-486 300 mg by mouth days 1 - 21 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg.	Arm C n=21 Participants Nivolumab 3mg/kg every 2 weeks until progression Nivolumab	Arm D n=14 Participants Anti-PD-1/PD-L1 treatment naïve patients only Every 28 days for 6 cycles Azacitidine 40mg/m2 days 1-5 and 8-10 Entinostat 5mg Days 3 and 10 Nivolumab 3mg/kg Days 1 and 15 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg. Azacitidine Entinostat Nivolumab	Arm E n=7 Participants Patients must have had refractory (Arm E=less than 24 weeks from first dose of anti-PD-1/PD-L1) disease during or after anti-PD-1 or anti-PD-L1 therapy and, in the opinion of the investigator, must be unlikely to benefit from nivolumab monotherapy. Every 28 days for 6 cycles Azacitidine 40mg/m2 days 1-5 and 8-10 Entinostat 5mg Days 3 and 10 Nivolumab 3mg/kg Days 1 and 15 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg. Azacitidine Entinostat Nivolumab	Arm F n=19 Participants Patients must have had recurrent (Arm F=more than 24 weeks from first dose of anti-PD1/PD-L1) disease during or after anti-PD-1 or anti-PD-L1 therapy and, in the opinion of the investigator, must be unlikely to benefit from nivolumab monotherapy. Every 28 days for 6 cycles Azacitidine 40mg/m2 days 1-5 and 8-10 Entinostat 5mg Days 3 and 10 Nivolumab 3mg/kg Days 1 and 15 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg. Azacitidine Entinostat Nivolumab
Safety and Tolerability as Assessed by Number of Participants With Dose-limiting Toxicities	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants

Adverse Events

ARM A

Serious events: 4 serious events

Other events: 32 other events

Deaths: 22 deaths

ARM B

Serious events: 1 serious events

Other events: 7 other events

Deaths: 6 deaths

Arm C

Serious events: 1 serious events

Other events: 21 other events

Deaths: 12 deaths

Arm D

Serious events: 0 serious events

Other events: 14 other events

Deaths: 5 deaths

Arm E

Serious events: 2 serious events

Other events: 7 other events

Deaths: 7 deaths

Arm F

Serious events: 0 serious events

Other events: 19 other events

Deaths: 12 deaths

Serious adverse events

Serious adverse events
Measure	ARM A n=32 participants at risk Anti-PD-1/PD-L1 treatment naïve patients only Every 28 days for 2 cycles Azacitidine 40mg/m2 subcutaneous days 1-6 and 8-10 Entinostat 7mg by mouth Days 3 and 10 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg.	ARM B n=7 participants at risk Every 28 days for 2 cycles CC-486 300 mg by mouth days 1 - 21 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg.	Arm C n=21 participants at risk Nivolumab 3mg/kg every 2 weeks until progression Nivolumab	Arm D n=14 participants at risk Anti-PD-1/PD-L1 treatment naïve patients only Every 28 days for 6 cycles Azacitidine 40mg/m2 days 1-5 and 8-10 Entinostat 5mg Days 3 and 10 Nivolumab 3mg/kg Days 1 and 15 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg. Azacitidine Entinostat Nivolumab	Arm E n=7 participants at risk Patients must have had refractory (Arm E=less than 24 weeks from first dose of anti-PD-1/PD-L1) disease during or after anti-PD-1 or anti-PD-L1 therapy and, in the opinion of the investigator, must be unlikely to benefit from nivolumab monotherapy. Every 28 days for 6 cycles Azacitidine 40mg/m2 days 1-5 and 8-10 Entinostat 5mg Days 3 and 10 Nivolumab 3mg/kg Days 1 and 15 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg. Azacitidine Entinostat Nivolumab	Arm F n=19 participants at risk Patients must have had recurrent (Arm F=more than 24 weeks from first dose of anti-PD1/PD-L1) disease during or after anti-PD-1 or anti-PD-L1 therapy and, in the opinion of the investigator, must be unlikely to benefit from nivolumab monotherapy. Every 28 days for 6 cycles Azacitidine 40mg/m2 days 1-5 and 8-10 Entinostat 5mg Days 3 and 10 Nivolumab 3mg/kg Days 1 and 15 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg. Azacitidine Entinostat Nivolumab
Gastrointestinal disorders Constipation	0.00% 0/32 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	4.8% 1/21 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/14 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/19 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Gastrointestinal disorders Abdominal Pain	0.00% 0/32 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	4.8% 1/21 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/14 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/19 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	3.1% 1/32 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/21 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/14 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/19 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Investigations White blood cell decreased	0.00% 0/32 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/21 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/14 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/19 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Respiratory, thoracic and mediastinal disorders Dyspnea	6.2% 2/32 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/21 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/14 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/19 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Psychiatric disorders confusion	3.1% 1/32 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/21 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/14 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/19 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/32 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/21 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/14 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/19 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/32 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/21 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/14 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/19 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Gastrointestinal disorders vomiting	0.00% 0/32 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/21 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/14 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/19 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
General disorders Fever	3.1% 1/32 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/21 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/14 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/19 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Cardiac disorders Cardiac troponin T increased	3.1% 1/32 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/21 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/14 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/19 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.

Other adverse events

Other adverse events
Measure	ARM A n=32 participants at risk Anti-PD-1/PD-L1 treatment naïve patients only Every 28 days for 2 cycles Azacitidine 40mg/m2 subcutaneous days 1-6 and 8-10 Entinostat 7mg by mouth Days 3 and 10 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg.	ARM B n=7 participants at risk Every 28 days for 2 cycles CC-486 300 mg by mouth days 1 - 21 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg.	Arm C n=21 participants at risk Nivolumab 3mg/kg every 2 weeks until progression Nivolumab	Arm D n=14 participants at risk Anti-PD-1/PD-L1 treatment naïve patients only Every 28 days for 6 cycles Azacitidine 40mg/m2 days 1-5 and 8-10 Entinostat 5mg Days 3 and 10 Nivolumab 3mg/kg Days 1 and 15 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg. Azacitidine Entinostat Nivolumab	Arm E n=7 participants at risk Patients must have had refractory (Arm E=less than 24 weeks from first dose of anti-PD-1/PD-L1) disease during or after anti-PD-1 or anti-PD-L1 therapy and, in the opinion of the investigator, must be unlikely to benefit from nivolumab monotherapy. Every 28 days for 6 cycles Azacitidine 40mg/m2 days 1-5 and 8-10 Entinostat 5mg Days 3 and 10 Nivolumab 3mg/kg Days 1 and 15 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg. Azacitidine Entinostat Nivolumab	Arm F n=19 participants at risk Patients must have had recurrent (Arm F=more than 24 weeks from first dose of anti-PD1/PD-L1) disease during or after anti-PD-1 or anti-PD-L1 therapy and, in the opinion of the investigator, must be unlikely to benefit from nivolumab monotherapy. Every 28 days for 6 cycles Azacitidine 40mg/m2 days 1-5 and 8-10 Entinostat 5mg Days 3 and 10 Nivolumab 3mg/kg Days 1 and 15 Followed by: Nivolumab 3mg/kg every 2 weeks until progression After a patient has completed 6 months of nivolumab, they can receive nivolumab every 4 weeks instead of every 2 weeks. The dose for Nivolumab every 4 weeks is 480mg. Azacitidine Entinostat Nivolumab
Gastrointestinal disorders Abdominal pain	12.5% 4/32 • Number of events 6 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	19.0% 4/21 • Number of events 5 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	21.4% 3/14 • Number of events 7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	10.5% 2/19 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Investigations Absolute Lymphocytes Decreased	9.4% 3/32 • Number of events 6 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	9.5% 2/21 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/14 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	10.5% 2/19 • Number of events 6 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Investigations Absolute neutrophil Count (ANC)decreased	6.2% 2/32 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	28.6% 2/7 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	9.5% 2/21 • Number of events 4 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	7.1% 1/14 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	5.3% 1/19 • Number of events 4 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Investigations Alanine Aminotransferase Increased	9.4% 3/32 • Number of events 6 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	23.8% 5/21 • Number of events 14 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 2/14 • Number of events 14 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/19 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Investigations albumin decreased	12.5% 4/32 • Number of events 5 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/21 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/14 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/19 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Investigations alkaline phosphae increased	31.2% 10/32 • Number of events 12 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	28.6% 2/7 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	19.0% 4/21 • Number of events 4 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	64.3% 9/14 • Number of events 41 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	85.7% 6/7 • Number of events 18 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	5.3% 1/19 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
General disorders Alopecia	15.6% 5/32 • Number of events 5 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	4.8% 1/21 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 2/14 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/19 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Investigations Anemia	53.1% 17/32 • Number of events 31 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	57.1% 4/7 • Number of events 9 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	47.6% 10/21 • Number of events 22 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	50.0% 7/14 • Number of events 29 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	28.6% 2/7 • Number of events 6 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	21.1% 4/19 • Number of events 8 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Metabolism and nutrition disorders Anorexia	59.4% 19/32 • Number of events 34 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	71.4% 5/7 • Number of events 8 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	38.1% 8/21 • Number of events 12 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 2/14 • Number of events 5 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	42.9% 3/7 • Number of events 4 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	26.3% 5/19 • Number of events 8 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Psychiatric disorders Anxiety	12.5% 4/32 • Number of events 9 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	33.3% 7/21 • Number of events 10 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	21.4% 3/14 • Number of events 5 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	10.5% 2/19 • Number of events 4 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Musculoskeletal and connective tissue disorders Arthralgia	6.2% 2/32 • Number of events 5 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	19.0% 4/21 • Number of events 7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	7.1% 1/14 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	5.3% 1/19 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Investigations Aspartate aminotransferase increased	18.8% 6/32 • Number of events 9 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	28.6% 2/7 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 3/21 • Number of events 8 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 2/14 • Number of events 9 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	5.3% 1/19 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Musculoskeletal and connective tissue disorders Back Pain	25.0% 8/32 • Number of events 14 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	42.9% 3/7 • Number of events 4 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	19.0% 4/21 • Number of events 4 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	7.1% 1/14 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	21.1% 4/19 • Number of events 6 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Eye disorders Blurred Vision	3.1% 1/32 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	9.5% 2/21 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 2/14 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	5.3% 1/19 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Musculoskeletal and connective tissue disorders Chest Pain (Non-Cardiac)	15.6% 5/32 • Number of events 9 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	9.5% 2/21 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	7.1% 1/14 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	10.5% 2/19 • Number of events 4 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
General disorders Chills	3.1% 1/32 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 3/21 • Number of events 4 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 2/14 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/19 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Psychiatric disorders Confusion	0.00% 0/32 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	9.5% 2/21 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	7.1% 1/14 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	28.6% 2/7 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/19 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Gastrointestinal disorders Constipation	46.9% 15/32 • Number of events 30 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	71.4% 5/7 • Number of events 14 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	33.3% 7/21 • Number of events 12 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	78.6% 11/14 • Number of events 14 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	42.9% 3/7 • Number of events 4 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	26.3% 5/19 • Number of events 7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Respiratory, thoracic and mediastinal disorders Cough	50.0% 16/32 • Number of events 27 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	57.1% 4/7 • Number of events 8 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	76.2% 16/21 • Number of events 32 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	21.4% 3/14 • Number of events 14 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	42.9% 3/7 • Number of events 6 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	31.6% 6/19 • Number of events 10 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Investigations creatine increased	6.2% 2/32 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	9.5% 2/21 • Number of events 5 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	7.1% 1/14 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	5.3% 1/19 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
General disorders Dehydration	15.6% 5/32 • Number of events 5 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	28.6% 2/7 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	4.8% 1/21 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 2/14 • Number of events 8 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	5.3% 1/19 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Psychiatric disorders Depression	6.2% 2/32 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/21 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	7.1% 1/14 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	15.8% 3/19 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Gastrointestinal disorders Diarrhea	25.0% 8/32 • Number of events 9 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	42.9% 9/21 • Number of events 13 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	7.1% 1/14 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	21.1% 4/19 • Number of events 4 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Nervous system disorders Dizziness	21.9% 7/32 • Number of events 10 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 4 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 3/21 • Number of events 4 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	28.6% 4/14 • Number of events 4 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/19 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Gastrointestinal disorders Dry Mouth	15.6% 5/32 • Number of events 7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 3/21 • Number of events 4 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	21.4% 3/14 • Number of events 5 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	15.8% 3/19 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Skin and subcutaneous tissue disorders Dry Skin	9.4% 3/32 • Number of events 4 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 3/21 • Number of events 4 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	7.1% 1/14 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/19 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Gastrointestinal disorders Dysguesia	21.9% 7/32 • Number of events 11 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	4.8% 1/21 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 2/14 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/19 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Respiratory, thoracic and mediastinal disorders Dyspepsia	28.1% 9/32 • Number of events 12 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	42.9% 3/7 • Number of events 4 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	19.0% 4/21 • Number of events 5 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 2/14 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	28.6% 2/7 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	5.3% 1/19 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Skin and subcutaneous tissue disorders Edema	28.1% 9/32 • Number of events 13 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 3/21 • Number of events 4 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 2/14 • Number of events 6 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	42.9% 3/7 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	5.3% 1/19 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
General disorders Fatigue	81.2% 26/32 • Number of events 54 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	100.0% 7/7 • Number of events 16 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	76.2% 16/21 • Number of events 33 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	64.3% 9/14 • Number of events 16 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	71.4% 5/7 • Number of events 6 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	42.1% 8/19 • Number of events 18 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Musculoskeletal and connective tissue disorders Generalized weakness	0.00% 0/32 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	19.0% 4/21 • Number of events 5 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	7.1% 1/14 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	5.3% 1/19 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Nervous system disorders Headache	18.8% 6/32 • Number of events 8 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 3/21 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	50.0% 7/14 • Number of events 15 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	21.1% 4/19 • Number of events 7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Respiratory, thoracic and mediastinal disorders Hoarseness	6.2% 2/32 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	4.8% 1/21 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/14 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/19 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Metabolism and nutrition disorders Hyperglycemia	21.9% 7/32 • Number of events 11 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	57.1% 12/21 • Number of events 83 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	42.9% 6/14 • Number of events 13 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	10.5% 2/19 • Number of events 5 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Metabolism and nutrition disorders Hyperkalemia	6.2% 2/32 • Number of events 9 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 3/21 • Number of events 21 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 2/14 • Number of events 4 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/19 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Vascular disorders Hypertension	21.9% 7/32 • Number of events 17 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	33.3% 7/21 • Number of events 65 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	42.9% 6/14 • Number of events 19 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	10.5% 2/19 • Number of events 8 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Respiratory, thoracic and mediastinal disorders Dyspnea	71.9% 23/32 • Number of events 35 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	71.4% 5/7 • Number of events 9 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	47.6% 10/21 • Number of events 14 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	35.7% 5/14 • Number of events 15 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	57.1% 4/7 • Number of events 4 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	15.8% 3/19 • Number of events 7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Skin and subcutaneous tissue disorders Rash acneiform	12.5% 4/32 • Number of events 7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	28.6% 2/7 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	23.8% 5/21 • Number of events 24 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	35.7% 5/14 • Number of events 13 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/19 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Injury, poisoning and procedural complications fall	0.00% 0/32 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	4.8% 1/21 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	7.1% 1/14 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	5.3% 1/19 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
General disorders Fever	3.1% 1/32 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	23.8% 5/21 • Number of events 5 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 2/14 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	5.3% 1/19 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Gastrointestinal disorders Heartburn	3.1% 1/32 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	42.9% 3/7 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/21 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/14 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	5.3% 1/19 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Respiratory, thoracic and mediastinal disorders Laryngeal hemorrhage	0.00% 0/32 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	23.8% 5/21 • Number of events 5 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/14 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/19 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Metabolism and nutrition disorders Hypoalbumenia	59.4% 19/32 • Number of events 58 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	28.6% 2/7 • Number of events 5 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	71.4% 15/21 • Number of events 183 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	50.0% 7/14 • Number of events 46 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	10.5% 2/19 • Number of events 13 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Metabolism and nutrition disorders hypocalcemia	21.9% 7/32 • Number of events 10 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	28.6% 6/21 • Number of events 18 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	28.6% 4/14 • Number of events 10 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	28.6% 2/7 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	10.5% 2/19 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/32 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 3/21 • Number of events 5 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 2/14 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	28.6% 2/7 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	5.3% 1/19 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Metabolism and nutrition disorders Hypomagnesemia	12.5% 4/32 • Number of events 8 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	28.6% 6/21 • Number of events 14 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/14 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	5.3% 1/19 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Metabolism and nutrition disorders Hyponatrema	18.8% 6/32 • Number of events 7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	28.6% 6/21 • Number of events 9 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	28.6% 4/14 • Number of events 7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	28.6% 2/7 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	10.5% 2/19 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Metabolism and nutrition disorders Hypophosphatemia	21.9% 7/32 • Number of events 8 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	28.6% 2/7 • Number of events 4 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 3/21 • Number of events 5 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	28.6% 4/14 • Number of events 12 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	10.5% 2/19 • Number of events 8 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Vascular disorders Hypotension	9.4% 3/32 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	4.8% 1/21 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 2/14 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	28.6% 2/7 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	5.3% 1/19 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Infections and infestations Injection site reaction	71.9% 23/32 • Number of events 33 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	4.8% 1/21 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	28.6% 4/14 • Number of events 6 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	21.1% 4/19 • Number of events 16 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Psychiatric disorders Insomnia	28.1% 9/32 • Number of events 12 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 3/21 • Number of events 9 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	7.1% 1/14 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	28.6% 2/7 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	10.5% 2/19 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Gastrointestinal disorders Oral Mucositis	12.5% 4/32 • Number of events 4 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/21 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	7.1% 1/14 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/19 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Musculoskeletal and connective tissue disorders Myalgia	9.4% 3/32 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	4.8% 1/21 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/14 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/19 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Gastrointestinal disorders Nasal Congestion	3.1% 1/32 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	4.8% 1/21 • Number of events 6 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	7.1% 1/14 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	10.5% 2/19 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Gastrointestinal disorders Nasuea	53.1% 17/32 • Number of events 28 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	57.1% 4/7 • Number of events 8 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	33.3% 7/21 • Number of events 8 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	57.1% 8/14 • Number of events 12 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	42.9% 3/7 • Number of events 5 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	42.1% 8/19 • Number of events 24 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Investigations Neutrophil count decreased	18.8% 6/32 • Number of events 7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	28.6% 2/7 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	9.5% 2/21 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 2/14 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	5.3% 1/19 • Number of events 4 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
General disorders Pain	25.0% 8/32 • Number of events 17 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	28.6% 2/7 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	38.1% 8/21 • Number of events 24 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	42.9% 6/14 • Number of events 11 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	71.4% 5/7 • Number of events 8 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	15.8% 3/19 • Number of events 9 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Nervous system disorders neuropathy	6.2% 2/32 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	9.5% 2/21 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	7.1% 1/14 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/19 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Investigations Platelet Count Decreased	12.5% 4/32 • Number of events 4 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 4 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	9.5% 2/21 • Number of events 5 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	35.7% 5/14 • Number of events 8 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	42.9% 3/7 • Number of events 4 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	5.3% 1/19 • Number of events 5 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Respiratory, thoracic and mediastinal disorders Pneumonitis	6.2% 2/32 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/21 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 2/14 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/19 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Skin and subcutaneous tissue disorders Pruritis	21.9% 7/32 • Number of events 17 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	23.8% 5/21 • Number of events 27 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	21.4% 3/14 • Number of events 6 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	36.8% 7/19 • Number of events 9 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Gastrointestinal disorders Sore throat	6.2% 2/32 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/21 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	7.1% 1/14 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/19 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Gastrointestinal disorders Voice Hoarseness	3.1% 1/32 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 3/21 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/14 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/19 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Gastrointestinal disorders vomiting	21.9% 7/32 • Number of events 11 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	28.6% 2/7 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	9.5% 2/21 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	21.4% 3/14 • Number of events 5 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	28.6% 2/7 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	21.1% 4/19 • Number of events 7 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Investigations Weight loss	28.1% 9/32 • Number of events 14 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 3/21 • Number of events 4 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	21.4% 3/14 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	5.3% 1/19 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Respiratory, thoracic and mediastinal disorders Wheeze	9.4% 3/32 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	14.3% 1/7 • Number of events 1 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	9.5% 2/21 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	0.00% 0/14 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	28.6% 2/7 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	5.3% 1/19 • Number of events 3 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.
Investigations White Blood Cell Decreased	50.0% 16/32 • Number of events 34 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	57.1% 4/7 • Number of events 19 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	33.3% 7/21 • Number of events 14 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	50.0% 7/14 • Number of events 15 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	28.6% 2/7 • Number of events 2 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.	10.5% 2/19 • Number of events 10 • All Adverse events and Serious Adverse events data was collected during the treatment phase of the study and then at a 30 day follow up visit, up to 2 years. Death assessed up to 5 years post treatment.

Additional Information

Amber Michalik

Johns Hopkins

Phone: 667-306-8336

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place