Trial Outcomes & Findings for Trial of TRC105 and Pazopanib Versus Pazopanib Alone in Patients With Advanced Angiosarcoma (NCT NCT02979899)

Last Updated: 2020-05-12

Results Overview

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Progression free survival is defined as time from randomization to either first disease progression (per independent radiology review of images by RECIST 1.1) or death from any cause.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

128 participants

Primary outcome timeframe

from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to cut off date of interim analysis (25 months)

Results posted on

2020-05-12

Participant Flow

Participant milestones

Participant milestones
Measure	TRC105 + Votrient Weekly TRC105 i.v. in combination with standard dose votrient by mouth, once daily TRC105: TRC105 antibody Votrient: pazopanib	Votrient Standard dose votrient by mouth, once daily Votrient: pazopanib
Overall Study STARTED	64	64
Overall Study COMPLETED	64	64
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Trial of TRC105 and Pazopanib Versus Pazopanib Alone in Patients With Advanced Angiosarcoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TRC105 + Votrient n=64 Participants Weekly TRC105 i.v. in combination with standard dose votrient by mouth, once daily TRC105: TRC105 antibody Votrient: pazopanib	Votrient n=64 Participants Standard dose votrient by mouth, once daily Votrient: pazopanib	Total n=128 Participants Total of all reporting groups
Age, Continuous	69 years n=5 Participants	67 years n=7 Participants	68 years n=5 Participants
Sex: Female, Male Female	35 Participants n=5 Participants	42 Participants n=7 Participants	77 Participants n=5 Participants
Sex: Female, Male Male	29 Participants n=5 Participants	22 Participants n=7 Participants	51 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	55 Participants n=5 Participants	56 Participants n=7 Participants	111 Participants n=5 Participants
Race/Ethnicity, Customized Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment United States	50 participants n=5 Participants	46 participants n=7 Participants	96 participants n=5 Participants
Region of Enrollment Poland	0 participants n=5 Participants	4 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment United Kingdom	8 participants n=5 Participants	9 participants n=7 Participants	17 participants n=5 Participants
Region of Enrollment France	6 participants n=5 Participants	5 participants n=7 Participants	11 participants n=5 Participants
ECOG Performance Status ECOG Grade 0	30 Participants n=5 Participants	27 Participants n=7 Participants	57 Participants n=5 Participants
ECOG Performance Status ECOG Grade 1	32 Participants n=5 Participants	36 Participants n=7 Participants	68 Participants n=5 Participants
ECOG Performance Status Not Available	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to cut off date of interim analysis (25 months)

Population: All patients randomized onto study by cut off date of interim analysis

Outcome measures

Outcome measures
Measure	TRC105 + Votrient n=62 Participants Weekly TRC105 i.v. in combination with standard dose votrient by mouth, once daily TRC105: TRC105 antibody Votrient: pazopanib	Votrient n=61 Participants Standard dose votrient by mouth, once daily Votrient: pazopanib
Progression Free Survival of Patients With Unresectable Angiosarcoma PFS by RECIST 1.1	4.2 months Interval 2.8 to 8.3	4.3 months Interval 2.9 to Confidence interval not estimable because not enough events to estimate a standard error
Progression Free Survival of Patients With Unresectable Angiosarcoma PFS by Investigator Assessment	3.5 months Interval 2.6 to 5.5	2.9 months Interval 2.6 to 4.1

SECONDARY outcome

Timeframe: from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to cut off date of interim analysis (25 months)

Population: All patients randomized onto study by cut off date of interim analysis

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions: Complete Response (CR) is disappearance of all target lesions; Partial Response (PR) is \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Overall response rate is defined as the number of patients with a best response designation of complete response or partial response recorded between the date of randomization and the date of documented progression.

Outcome measures

Outcome measures
Measure	TRC105 + Votrient n=62 Participants Weekly TRC105 i.v. in combination with standard dose votrient by mouth, once daily TRC105: TRC105 antibody Votrient: pazopanib	Votrient n=61 Participants Standard dose votrient by mouth, once daily Votrient: pazopanib
Objective Response Rate of Patients With Unresectable Angiosarcoma	3 Participants	8 Participants

SECONDARY outcome

Timeframe: from beginning of study to cut off date of interim analysis (25 months)

Population: All patients randomized onto study by cut off date of interim analysis

Overall survival is the number of death events at 25 months, including all on-study and off-study deaths (past post-treatment 28-day follow up visit)

Outcome measures

Outcome measures
Measure	TRC105 + Votrient n=62 Participants Weekly TRC105 i.v. in combination with standard dose votrient by mouth, once daily TRC105: TRC105 antibody Votrient: pazopanib	Votrient n=61 Participants Standard dose votrient by mouth, once daily Votrient: pazopanib
Overall Survival of Patients With Unresectable Angiosarcoma	17 Participants	19 Participants

SECONDARY outcome

Timeframe: Screening and 9 weeks (Cycle 3 Day 1)

Population: All patients who completed the questionnaire during specified intervals listed below

Patient reported outcomes as measured by the EuroQol five dimensions questionnaire (EQ-5D-5L) and the European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30). The EORTC QLQ-C30 health scale is on a scale of 1 to 7, with 1 being poor health and 7 being excellent health. The EQ-5D-5L scale is on a scale of 0 to 100, with 0 being the worst health one can imagine, and 100 being the best health one can imagine.

Outcome measures

Outcome measures
Measure	TRC105 + Votrient n=64 Participants Weekly TRC105 i.v. in combination with standard dose votrient by mouth, once daily TRC105: TRC105 antibody Votrient: pazopanib	Votrient n=62 Participants Standard dose votrient by mouth, once daily Votrient: pazopanib
To Characterize Patient Reported Outcomes Between the Two Arms of the Study EORTC QLQ-C30 Health Score at Screening	5 units on a scale Interval 1.0 to 7.0	5 units on a scale Interval 1.0 to 7.0
To Characterize Patient Reported Outcomes Between the Two Arms of the Study EQ-5D-5L Health Score at Screening	75 units on a scale Interval 5.0 to 100.0	75 units on a scale Interval 20.0 to 100.0
To Characterize Patient Reported Outcomes Between the Two Arms of the Study EORTC QLQ-C30 Health Score at Cycle 3 Day 1	4 units on a scale Interval 1.0 to 6.0	5 units on a scale Interval 1.0 to 6.0
To Characterize Patient Reported Outcomes Between the Two Arms of the Study EQ-5D-5L Health Score at Cycle 3 Day 1	70 units on a scale Interval 20.0 to 100.0	70 units on a scale Interval 20.0 to 97.0

Adverse Events

TRC105 + Votrient

Serious events: 27 serious events

Other events: 63 other events

Deaths: 23 deaths

Votrient

Serious events: 12 serious events

Other events: 57 other events

Deaths: 20 deaths

Serious adverse events

Other adverse events

Additional Information

Charles Theuer, Medical Monitor

TRACON Pharmaceuticals Inc

Phone: 8585500780

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	TRC105 + Votrient n=63 participants at risk All patients that received at least one dose of TRC105 in combination with pazopanib	Votrient n=57 participants at risk All patients that received at least one dose of pazopanib alone.
General disorders Disease Progression	6.3% 4/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	0.00% 0/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Vascular disorders Embolism	4.8% 3/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	0.00% 0/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Infections and infestations Wound infection	3.2% 2/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	1.8% 1/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Infections and infestations Sepsis	0.00% 0/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	5.3% 3/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
General disorders Fatigue	4.8% 3/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	0.00% 0/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Gastrointestinal disorders Pyrexia	1.6% 1/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	1.8% 1/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	1.6% 1/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	0.00% 0/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Respiratory, thoracic and mediastinal disorders Respiratory Distress	1.6% 1/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	0.00% 0/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.6% 1/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	0.00% 0/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	1.6% 1/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	0.00% 0/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.6% 1/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	0.00% 0/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Respiratory, thoracic and mediastinal disorders Hydropneumothorax	0.00% 0/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	1.8% 1/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Respiratory, thoracic and mediastinal disorders Dyspnea	1.6% 1/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	0.00% 0/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Psychiatric disorders Mental Status Change	0.00% 0/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	1.8% 1/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Nervous system disorders Headache	1.6% 1/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	0.00% 0/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Nervous system disorders Haemorrhage Intracranial	0.00% 0/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	1.8% 1/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Nervous system disorders Encephalopathy	1.6% 1/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	0.00% 0/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Nervous system disorders Tumor Hemorrhage	0.00% 0/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	1.8% 1/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Musculoskeletal and connective tissue disorders Musculoskeletal Chest Pain	0.00% 0/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	1.8% 1/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Metabolism and nutrition disorders Tumor Lysis Syndrome	1.6% 1/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	0.00% 0/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Metabolism and nutrition disorders Hyponatremia	1.6% 1/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	0.00% 0/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Metabolism and nutrition disorders Failure To Thrive	0.00% 0/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	1.8% 1/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Metabolism and nutrition disorders Dehydration	1.6% 1/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	0.00% 0/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Investigations Aspartate Aminotransferase Increased	0.00% 0/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	1.8% 1/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Investigations Alanine Aminotransferase Increased	0.00% 0/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	1.8% 1/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Injury, poisoning and procedural complications Subdural Hematoma	1.6% 1/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	0.00% 0/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Injury, poisoning and procedural complications Rib Fracture	1.6% 1/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	0.00% 0/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Injury, poisoning and procedural complications Infusion Related Reaction	1.6% 1/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	0.00% 0/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Injury, poisoning and procedural complications Fall	0.00% 0/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	1.8% 1/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Injury, poisoning and procedural complications Clavicle Fracture	1.6% 1/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	0.00% 0/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Infections and infestations Urinary Tract Infection	1.6% 1/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	0.00% 0/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Infections and infestations Osteomyelitis	1.6% 1/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	0.00% 0/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Infections and infestations Meningitis Aseptic	1.6% 1/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	0.00% 0/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Infections and infestations Influenza	1.6% 1/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	0.00% 0/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Infections and infestations Bacteremia	1.6% 1/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	0.00% 0/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Hepatobiliary disorders Acute Hepatic Failure	0.00% 0/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	1.8% 1/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
General disorders Multi-Organ Failure	0.00% 0/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	1.8% 1/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
General disorders Chest Pain	1.6% 1/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	0.00% 0/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Gastrointestinal disorders Upper Gastrointestinal Hemorrhage	1.6% 1/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	0.00% 0/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Gastrointestinal disorders Proctalgia	1.6% 1/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	0.00% 0/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.

Other adverse events
Measure	TRC105 + Votrient n=63 participants at risk All patients that received at least one dose of TRC105 in combination with pazopanib	Votrient n=57 participants at risk All patients that received at least one dose of pazopanib alone.
General disorders Fatigue	66.7% 42/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	57.9% 33/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Gastrointestinal disorders Diarrhea	60.3% 38/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	54.4% 31/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Gastrointestinal disorders Nausea	54.0% 34/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	45.6% 26/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Vascular disorders Hypertension	38.1% 24/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	56.1% 32/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Nervous system disorders Headache	66.7% 42/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	24.6% 14/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Respiratory, thoracic and mediastinal disorders Epistaxis	69.8% 44/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	7.0% 4/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Metabolism and nutrition disorders Decreased Appetite	41.3% 26/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	33.3% 19/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Gastrointestinal disorders Vomiting	39.7% 25/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	22.8% 13/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Blood and lymphatic system disorders Anemia	52.4% 33/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	8.8% 5/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Investigations Weight Decreased	36.5% 23/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	17.5% 10/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Nervous system disorders Dysgeusia	23.8% 15/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	26.3% 15/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Investigations Aspartate Aminotransferase Increased	25.4% 16/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	24.6% 14/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Investigations Alanine Aminotransferase Increased	23.8% 15/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	21.1% 12/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Gastrointestinal disorders Abdominal Pain	22.2% 14/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	17.5% 10/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Respiratory, thoracic and mediastinal disorders Dyspnea	25.4% 16/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	10.5% 6/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Gastrointestinal disorders Constipation	20.6% 13/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	15.8% 9/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Gastrointestinal disorders Stomatitis	25.4% 16/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	8.8% 5/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Gastrointestinal disorders Gingival Bleeding	27.0% 17/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	3.5% 2/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Musculoskeletal and connective tissue disorders Back Pain	20.6% 13/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	10.5% 6/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
General disorders Edema Peripheral	20.6% 13/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	10.5% 6/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Metabolism and nutrition disorders Hypokalemia	22.2% 14/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	7.0% 4/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Skin and subcutaneous tissue disorders Palmar-Plantar Erythrodysaesthesia Syndrome	14.3% 9/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	15.8% 9/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Endocrine disorders Hypothyroidism	17.5% 11/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	8.8% 5/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Investigations Platelet Count Decreased	14.3% 9/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	12.3% 7/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
General disorders Pyrexia	17.5% 11/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	7.0% 4/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Investigations Lipase Increased	14.3% 9/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	10.5% 6/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Investigations Blood Bilirubin Increased	9.5% 6/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	15.8% 9/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Vascular disorders Hypotension	17.5% 11/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	5.3% 3/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
General disorders Chills	15.9% 10/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	7.0% 4/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Musculoskeletal and connective tissue disorders Myalgia	12.7% 8/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	10.5% 6/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Metabolism and nutrition disorders Dehydration	15.9% 10/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	5.3% 3/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Vascular disorders Flushing	17.5% 11/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	1.8% 1/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Musculoskeletal and connective tissue disorders Arthralgia	11.1% 7/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	8.8% 5/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Gastrointestinal disorders Dyspepsia	11.1% 7/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	8.8% 5/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Infections and infestations Urinary Tract Infection	14.3% 9/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	3.5% 2/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
General disorders Mucosal Inflammation	11.1% 7/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	7.0% 4/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Psychiatric disorders Anxiety	9.5% 6/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	8.8% 5/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Eye disorders Vision Blurred	9.5% 6/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	8.8% 5/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	7.9% 5/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	10.5% 6/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
Metabolism and nutrition disorders Hypoalbuminaemia	14.3% 9/63 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.	1.8% 1/57 • Adverse events were collected over the entire duration of the study (a period of 26 months). AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.