Trial Outcomes & Findings for A Phase 1B Dose-escalation and Phase 2a Study of Carotuximab (TRC105) in Combination With Pazopanib in Patients With Advanced Soft Tissue Sarcoma (NCT NCT01975519)

NCT ID: NCT01975519

Last Updated: 2020-05-20

Results Overview

For DLT evaluation, severity (grade) was classified according to common terminology criteria for adverse events version 4.0 (CTCAE v4.0). DLTs were defined as grade 4 neutropenia persisting for ≥ 5 days, febrile neutropenia (grade 4 neutropenia with fever \> 38.5 ºC both sustained over a 24 hour period), neutropenic infection (grade ≥ 3 neutropenia with grade ≥ 3 infection), anemia ≥ grade 4, grade \> 4 thrombocytopenia or grade ≥ 3 thrombocytopenia and grade ≥ 3 hemorrhage, or grade 3 or 4 nonhematologic toxicity with the following exceptions: nausea, vomiting, or diarrhea for \<48 hours, asymptomatic electrolyte abnormalities that are corrected to grade 1 or better in \< 72 hours, or headache lasting less than 48 hours.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 111 participants
• Primary outcome timeframe: 56 days
• Results posted on: 2020-05-20

Participant Flow

Participant milestones

Measure	8 mg/kg TRC105 + Pazopanib 8 mg/kg of TRC105 in combination with standard dose pazopanib in patients with advanced soft tissue sarcoma.	10 mg/kg TRC105 + Pazopanib 10 mg/kg of TRC105 in combination with standard dose pazopanib in patients with advanced soft tissue sarcoma.
Overall Study STARTED	3	108
Overall Study Phase 1b	3	23
Overall Study Phase 2a Soft Tissue Sarcoma	0	63
Overall Study Phase 2a Angiosarcoma Cohort	0	22
Overall Study COMPLETED	3	108
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Phase 1B Dose-escalation and Phase 2a Study of Carotuximab (TRC105) in Combination With Pazopanib in Patients With Advanced Soft Tissue Sarcoma

Baseline characteristics by cohort

Measure	8 mg/kg TRC105 + Pazopanib n=3 Participants 8 mg/kg of TRC105 in combination with standard dose pazopanib in patients with advanced soft tissue sarcoma.	10 mg/kg TRC105 + Pazopanib n=108 Participants 10 mg/kg of TRC105 in combination with standard dose pazopanib in patients with advanced soft tissue sarcoma.	Total n=111 Participants Total of all reporting groups
Age, Continuous	55 years n=5 Participants	58 years n=7 Participants	58 years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	59 Participants n=7 Participants	60 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	49 Participants n=7 Participants	51 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	8 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	2 Participants n=5 Participants	89 Participants n=7 Participants	91 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	0 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment United States	3 participants n=5 Participants	108 participants n=7 Participants	111 participants n=5 Participants
ECOG Performance Status ECOG Grade 0	2 Participants n=5 Participants	31 Participants n=7 Participants	33 Participants n=5 Participants
ECOG Performance Status ECOG Grade 1	1 Participants n=5 Participants	77 Participants n=7 Participants	78 Participants n=5 Participants
ECOG Performance Status ECOG Grade 2	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
ECOG Performance Status ECOG Grade 3	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
ECOG Performance Status ECOG Grade 4	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
ECOG Performance Status ECOG Grade 5	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 56 days

Population: All phase 1b patients who received at least a portion of a dose of TRC105

For DLT evaluation, severity (grade) was classified according to common terminology criteria for adverse events version 4.0 (CTCAE v4.0). DLTs were defined as grade 4 neutropenia persisting for ≥ 5 days, febrile neutropenia (grade 4 neutropenia with fever > 38.5 ºC both sustained over a 24 hour period), neutropenic infection (grade ≥ 3 neutropenia with grade ≥ 3 infection), anemia ≥ grade 4, grade > 4 thrombocytopenia or grade ≥ 3 thrombocytopenia and grade ≥ 3 hemorrhage, or grade 3 or 4 nonhematologic toxicity with the following exceptions: nausea, vomiting, or diarrhea for <48 hours, asymptomatic electrolyte abnormalities that are corrected to grade 1 or better in < 72 hours, or headache lasting less than 48 hours.

Outcome measures

Measure	TRC105 Plus Pazopanib n=26 Participants All patients in Phase 1b portion of study who received TRC105 + Pazopanib TRC105: IV (8 mg/kg or 10 mg/kg). Pazopanib: oral (800 mg)	10 mg/kg TRC105 + Pazopanib All patients who received 10 mg/kg TRC105 + Pazopanib
Number of Participants With Dose Limiting Toxicity (DLT) Patients with DLT at 8 mg/kg	0 Participants	—
Number of Participants With Dose Limiting Toxicity (DLT) Patients without DLT at 8 mg/kg	3 Participants	—
Number of Participants With Dose Limiting Toxicity (DLT) Patients with DLT at 10 mg/kg	1 Participants	—
Number of Participants With Dose Limiting Toxicity (DLT) Patients without DLT at 10 mg/kg	22 Participants	—

PRIMARY outcome

Timeframe: from screening to either disease progression or death

Population: All patients with scans completed at baseline and at least 1 time point on study.

Number of patients with progression free survival, as defined as time from screening to either first disease progression or death from any cause per RECIST version 1.1

Outcome measures

Measure	TRC105 Plus Pazopanib n=3 Participants All patients in Phase 1b portion of study who received TRC105 + Pazopanib TRC105: IV (8 mg/kg or 10 mg/kg). Pazopanib: oral (800 mg)	10 mg/kg TRC105 + Pazopanib n=90 Participants All patients who received 10 mg/kg TRC105 + Pazopanib
Progression Free Survival of Patients With Advanced Soft Tissue Sarcoma (Phase 1 and 2)	5.06 months Interval 4.96 to Not enough events to estimate an upper confidence level	3.45 months Interval 2.56 to 3.85

PRIMARY outcome

Timeframe: 1.5 years

The best response according to RECIST 1.1 for each patient in the phase 2 angiosarcoma cohort with measurable disease and who received at least one dose of study drug will be listed by cohort and tumor type

Outcome measures

Measure	TRC105 Plus Pazopanib n=5 Participants All patients in Phase 1b portion of study who received TRC105 + Pazopanib TRC105: IV (8 mg/kg or 10 mg/kg). Pazopanib: oral (800 mg)	10 mg/kg TRC105 + Pazopanib All patients who received 10 mg/kg TRC105 + Pazopanib
Objective Response Rate in a Cohort of Patients With Angiosarcoma Complete Response (CR)	2 Participants	—
Objective Response Rate in a Cohort of Patients With Angiosarcoma Partial Response (PR)	0 Participants	—
Objective Response Rate in a Cohort of Patients With Angiosarcoma Stable Disease (SD)	3 Participants	—
Objective Response Rate in a Cohort of Patients With Angiosarcoma Progressive Disease (PD)	0 Participants	—
Objective Response Rate in a Cohort of Patients With Angiosarcoma Not Evaluable	0 Participants	—

SECONDARY outcome

Timeframe: 4, 6, 8, and 10 weeks

Population: All patients who received at least a portion of a dose of TRC105 with PK samples collected at baseline and at least 1 time point on study

Trough serum TRC105 concentrations will be measured using validated ELISA methods.

Outcome measures

Measure	TRC105 Plus Pazopanib n=6 Participants All patients in Phase 1b portion of study who received TRC105 + Pazopanib TRC105: IV (8 mg/kg or 10 mg/kg). Pazopanib: oral (800 mg)	10 mg/kg TRC105 + Pazopanib All patients who received 10 mg/kg TRC105 + Pazopanib
Trough Concentrations of TRC105 (Phase 2) Cycle 2 Day 1 (4 weeks) trough PK concentrations	124 ug/mL Interval 80.0 to 174.0	—
Trough Concentrations of TRC105 (Phase 2) Cycle 2 Day 15 (6 weeks) trough PK concentrations	86 ug/mL Interval 62.0 to 144.0	—
Trough Concentrations of TRC105 (Phase 2) Cycle 3 Day 1 (8 weeks) trough PK concentrations	91 ug/mL Interval 73.0 to 121.0	—
Trough Concentrations of TRC105 (Phase 2) Cycle 3 Day 15 (10 weeks) trough PK concentrations	80 ug/mL Interval 63.0 to 100.0	—

SECONDARY outcome

Timeframe: 32 months

Population: All patients who received at least a portion of a dose of TRC105 with immunogenicity samples collected at baseline and at least 1 time point on study

Anti-product antibody concentrations will be measured using validated ELISA methods. Anti-product antibody concentrations will be evaluated in the context of pharmacokinetic parameters and AE profiles.

Outcome measures

Measure	TRC105 Plus Pazopanib n=3 Participants All patients in Phase 1b portion of study who received TRC105 + Pazopanib TRC105: IV (8 mg/kg or 10 mg/kg). Pazopanib: oral (800 mg)	10 mg/kg TRC105 + Pazopanib n=79 Participants All patients who received 10 mg/kg TRC105 + Pazopanib
Number of Patients With and Without Development of Immunogenicity Antibodies (Phase 1 and 2) Pt with treatment emergent ADA	1 Participants	12 Participants
Number of Patients With and Without Development of Immunogenicity Antibodies (Phase 1 and 2) Pt without treatment emergent ADA	2 Participants	67 Participants

SECONDARY outcome

Timeframe: 12 months

Population: All patients who received TRC105. Endoglin expression levels determined through archival tumor samples, which were drawn before dosing. Therefore dose levels combined.

Expression will be determined by immunohistochemistry for each patient who received at least one dose of TRC105

Outcome measures

Measure	TRC105 Plus Pazopanib n=66 Participants All patients in Phase 1b portion of study who received TRC105 + Pazopanib TRC105: IV (8 mg/kg or 10 mg/kg). Pazopanib: oral (800 mg)	10 mg/kg TRC105 + Pazopanib All patients who received 10 mg/kg TRC105 + Pazopanib
Number of Patients With and Without Expression of Endoglin on Sarcoma Tissue (Phase 1 and 2) Tumor endoglin expression positive	15 Participants	—
Number of Patients With and Without Expression of Endoglin on Sarcoma Tissue (Phase 1 and 2) Tumor endoglin expression negative	51 Participants	—

SECONDARY outcome

Timeframe: 12 months

The best response (CR, PR, SD or PD according to RECIST 1.1) for each patient (phase 1 and phase 2) with measurable disease who received at least one dose of TRC105 study drug

Outcome measures

Measure	TRC105 Plus Pazopanib n=3 Participants All patients in Phase 1b portion of study who received TRC105 + Pazopanib TRC105: IV (8 mg/kg or 10 mg/kg). Pazopanib: oral (800 mg)	10 mg/kg TRC105 + Pazopanib n=78 Participants All patients who received 10 mg/kg TRC105 + Pazopanib
Objective Response Rate in Patients With Advanced Soft Tissue Sarcoma by RECIST 1.1 Complete Response (CR)	0 Participants	3 Participants
Objective Response Rate in Patients With Advanced Soft Tissue Sarcoma by RECIST 1.1 Partial Response (PR)	0 Participants	1 Participants
Objective Response Rate in Patients With Advanced Soft Tissue Sarcoma by RECIST 1.1 Stable Disease (SD)	3 Participants	43 Participants
Objective Response Rate in Patients With Advanced Soft Tissue Sarcoma by RECIST 1.1 Progressive Disease (PD)	0 Participants	27 Participants
Objective Response Rate in Patients With Advanced Soft Tissue Sarcoma by RECIST 1.1 Not Evaluable	0 Participants	4 Participants

SECONDARY outcome

Timeframe: 26 months

Time from screening to either first disease progression or death from any cause per RECIST version 1.1

Outcome measures

Measure	TRC105 Plus Pazopanib n=9 Participants All patients in Phase 1b portion of study who received TRC105 + Pazopanib TRC105: IV (8 mg/kg or 10 mg/kg). Pazopanib: oral (800 mg)	10 mg/kg TRC105 + Pazopanib All patients who received 10 mg/kg TRC105 + Pazopanib
Progression Free Survival in a Cohort of Patients With Angiosarcoma (Phase 2)	5.59 months Interval 2.1 to 15.78	—

Adverse Events

8 mg/kg TRC105 + Pazopanib

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

10 mg/kg TRC105 + Pazopanib

Serious events: 9 serious events

Other events: 106 other events

Deaths: 9 deaths

Serious adverse events

Measure	8 mg/kg TRC105 + Pazopanib n=3 participants at risk 8 mg/kg of TRC105 in combination with standard dose pazopanib in patients with advanced soft tissue sarcoma.	10 mg/kg TRC105 + Pazopanib n=106 participants at risk 10 mg/kg of TRC105 in combination with standard dose pazopanib in patients with advanced soft tissue sarcoma.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	2.8% 3/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Respiratory, thoracic and mediastinal disorders Pulmonary Venous Thrombosis	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	0.94% 1/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Respiratory, thoracic and mediastinal disorders Pulmonary Hemorrhage	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	0.94% 1/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	0.94% 1/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Respiratory, thoracic and mediastinal disorders Acute Respiratory Distress Syndrome	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	0.94% 1/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Nervous system disorders Transient Ischemic Attack	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	0.94% 1/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	0.94% 1/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Metabolism and nutrition disorders Decreased Appetite	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	0.94% 1/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Gastrointestinal disorders Colitis	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	0.94% 1/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.

Other adverse events

Measure	8 mg/kg TRC105 + Pazopanib n=3 participants at risk 8 mg/kg of TRC105 in combination with standard dose pazopanib in patients with advanced soft tissue sarcoma.	10 mg/kg TRC105 + Pazopanib n=106 participants at risk 10 mg/kg of TRC105 in combination with standard dose pazopanib in patients with advanced soft tissue sarcoma.
General disorders Fatigue	66.7% 2/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	75.5% 80/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Nervous system disorders Headache	66.7% 2/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	70.8% 75/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Respiratory, thoracic and mediastinal disorders Epistaxis	100.0% 3/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	68.9% 73/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Gastrointestinal disorders Nausea	66.7% 2/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	62.3% 66/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Gastrointestinal disorders Diarrhea	100.0% 3/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	60.4% 64/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Gastrointestinal disorders Vomiting	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	49.1% 52/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Metabolism and nutrition disorders Decreased Appetite	66.7% 2/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	44.3% 47/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Vascular disorders Hypertension	66.7% 2/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	43.4% 46/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Blood and lymphatic system disorders Anemia	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	42.5% 45/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Gastrointestinal disorders Gingival Bleeding	66.7% 2/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	37.7% 40/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Respiratory, thoracic and mediastinal disorders Dyspnea	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	34.9% 37/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Nervous system disorders Dysgeusia	66.7% 2/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	29.2% 31/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
General disorders Pyrexia	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	29.2% 31/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Gastrointestinal disorders Stomatitis	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	23.6% 25/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
General disorders Edema Peripheral	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	23.6% 25/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Respiratory, thoracic and mediastinal disorders Cough	66.7% 2/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	20.8% 22/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Psychiatric disorders Insomnia	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	20.8% 22/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Injury, poisoning and procedural complications Back Pain	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	21.7% 23/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Injury, poisoning and procedural complications Infusion Related Reaction	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	21.7% 23/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Vascular disorders Flushing	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	20.8% 22/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Gastrointestinal disorders Constipation	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	20.8% 22/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Investigations Weight Decreased	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	19.8% 21/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Infections and infestations Urinary Tract Infection	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	19.8% 21/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Infections and infestations Palmar-Plantar Erythrodysaesthesia Syndrome	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	18.9% 20/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Nervous system disorders Dizziness	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	17.9% 19/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Gastrointestinal disorders Abdominal Pain	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	17.9% 19/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Musculoskeletal and connective tissue disorders Pain in Extremity	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	17.0% 18/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Skin and subcutaneous tissue disorders Rash	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	16.0% 17/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Psychiatric disorders Anxiety	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	16.0% 17/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Gastrointestinal disorders Oral Pain	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	15.1% 16/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	15.1% 16/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Musculoskeletal and connective tissue disorders Arthralgia	66.7% 2/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	13.2% 14/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Skin and subcutaneous tissue disorders Skin Hypopigmentation	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	13.2% 14/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Skin and subcutaneous tissue disorders Hair Color Changes	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	14.2% 15/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	14.2% 15/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Investigations Blood Thyroid Stimulating Hormone Increased	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	13.2% 14/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
General disorders Asthenia	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	14.2% 15/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Vascular disorders Hypotension	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	13.2% 14/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Skin and subcutaneous tissue disorders Telangiectasia	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	13.2% 14/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	12.3% 13/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
General disorders Chills	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	13.2% 14/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Gastrointestinal disorders Gingival Pain	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	12.3% 13/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	12.3% 13/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Nervous system disorders Migraine	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	12.3% 13/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Gastrointestinal disorders Abdominal Discomfort	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	12.3% 13/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Respiratory, thoracic and mediastinal disorders Nasal Congestion	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	11.3% 12/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Respiratory, thoracic and mediastinal disorders Dysphonia	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	10.4% 11/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Gastrointestinal disorders Dyspepsia	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	11.3% 12/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	10.4% 11/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Musculoskeletal and connective tissue disorders Myalgia	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	9.4% 10/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	10.4% 11/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Investigations Aspartate Aminotransferase	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	10.4% 11/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
General disorders Influenza-like Illness	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	10.4% 11/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
General disorders Glossodynia	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	10.4% 11/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Gastrointestinal disorders Dry Mouth	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	9.4% 10/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	9.4% 10/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Investigations Alanine Aminotransferase	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	9.4% 10/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Gastrointestinal disorders Oral Mucosal Exfoliation	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	8.5% 9/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Endocrine disorders Hypothyroidism	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	9.4% 10/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	9.4% 10/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Renal and urinary disorders Acute Kidney Injury	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	8.5% 9/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	8.5% 9/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Metabolism and nutrition disorders Hypomagnesemia	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	7.5% 8/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Investigations Blood Bilirubin Increased	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	7.5% 8/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Gastrointestinal disorders Mouth Hemorrhage	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	8.5% 9/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Gastrointestinal disorders Flatulence	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	8.5% 9/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Skin and subcutaneous tissue disorders Dry Skin	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	7.5% 8/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Psychiatric disorders Depression	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	7.5% 8/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Musculoskeletal and connective tissue disorders Musculoskeletal Chest Pain	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	7.5% 8/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Metabolism and nutrition disorders Hypocalcemia	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	6.6% 7/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
General disorders Mucosal Inflammation	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	7.5% 8/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
General disorders Malaise	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	7.5% 8/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
General disorders Chest Pain	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	6.6% 7/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Blood and lymphatic system disorders Neutropenia	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	7.5% 8/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	6.6% 7/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	6.6% 7/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Nervous system disorders Neuropathy Peripheral	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	6.6% 7/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Musculoskeletal and connective tissue disorders Muscle Spasms	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	6.6% 7/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Investigations Lipase Increased	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	6.6% 7/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Gastrointestinal disorders Toothache	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	6.6% 7/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Gastrointestinal disorders Gastroesophageal Reflux	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	6.6% 7/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Gastrointestinal disorders Dysphagia	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	5.7% 6/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Gastrointestinal disorders Abdominal Upper Pain	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	6.6% 7/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Skin and subcutaneous tissue disorders Rash Maculo-Papular	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	5.7% 6/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Skin and subcutaneous tissue disorders Dermatitis Acneiform	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	5.7% 6/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Metabolism and nutrition disorders Hyperglycemia	66.7% 2/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	3.8% 4/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Infections and infestations Upper Respiratory Infection	66.7% 2/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	3.8% 4/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Infections and infestations Bronchitis	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	5.7% 6/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
General disorders Disease Progression	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	5.7% 6/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Gastrointestinal disorders Oral Dysaesthesia	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	5.7% 6/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Eye disorders Vitreous Floaters	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	5.7% 6/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Cardiac disorders Bradycardia	0.00% 0/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	5.7% 6/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Respiratory, thoracic and mediastinal disorders Hemoptysis	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	3.8% 4/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Infections and infestations Sinusitis	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	3.8% 4/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Respiratory, thoracic and mediastinal disorders Respiratory Tract Congestion	66.7% 2/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	0.00% 0/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Skin and subcutaneous tissue disorders Vitiligo	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	0.94% 1/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Skin and subcutaneous tissue disorders Skin Ulcer	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	0.94% 1/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Skin and subcutaneous tissue disorders Skin Atrophy	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	0.94% 1/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Respiratory, thoracic and mediastinal disorders Dyspnea Exertional	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	2.8% 3/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Renal and urinary disorders Urinary Hesitation	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	0.00% 0/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Nervous system disorders Hypoaesthesia	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	2.8% 3/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Investigations Blood Calcium Decreased	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	2.8% 3/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Injury, poisoning and procedural complications Tooth Fracture	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	0.94% 1/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Gastrointestinal disorders Loose Tooth	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	0.94% 1/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Eye disorders Visual Impairment	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	2.8% 3/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.
Cardiac disorders Palpitations	33.3% 1/3 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.	1.9% 2/106 • Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 34 months.

Additional Information

Charles Theuer, Medical Monitor

TRACON Pharmaceuticals Inc

Phone: 8585500780

Email: ctheuer@traconpharma.com

Results disclosure agreements

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