Trial Outcomes & Findings for A Phase 1b Study to Assess Sitravatinib in Combination With Tislelizumab in Participants With Advanced Solid Tumors (NCT NCT03666143)

NCT ID: NCT03666143

Last Updated: 2024-11-04

Results Overview

Number of participants with treatment-emergent AEs (TEAEs) and serious adverse events (SAEs), which includes laboratory tests, physical exams, electrocardiogram results and vital signs; TEAE was defined as an adverse event that had an onset date or a worsening in severity from baseline (pretreatment) on or after the first dose of study drug(s) up to 30 days following last dose of study drug(s) or initiation of a new anticancer therapy, whichever occurs first.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 216 participants
• Primary outcome timeframe: Up to approximately 4 years and 2 months
• Results posted on: 2024-11-04

Participant Flow

This study enrolled participants across study centers in Australia and China.

Participant milestones

Measure	Sitravatinib + Tislelizumab Sitravatinib 120 mg was administered orally once daily in combination with tislelizumab 200 mg intravenously (IV) once every 3 weeks
Overall Study STARTED	216
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	216

Reasons for withdrawal

Measure	Sitravatinib + Tislelizumab Sitravatinib 120 mg was administered orally once daily in combination with tislelizumab 200 mg intravenously (IV) once every 3 weeks
Overall Study Death	158
Overall Study Sponsor Decision	31
Overall Study Withdrawal by Subject	11
Overall Study Lost to Follow-up	5
Overall Study Physician Decision	1
Overall Study Rolled into extension study	9
Overall Study Progressive Disease	1

Baseline Characteristics

A Phase 1b Study to Assess Sitravatinib in Combination With Tislelizumab in Participants With Advanced Solid Tumors

Baseline characteristics by cohort

Measure	Sitravatinib + Tislelizumab n=216 Participants Sitravatinib 120 mg was administered orally once daily in combination with tislelizumab 200 mg IV once every 3 weeks
Age, Continuous	60.2 Years STANDARD_DEVIATION 11.03 • n=93 Participants
Sex: Female, Male Female	103 Participants n=93 Participants
Sex: Female, Male Male	113 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	213 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	143 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=93 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants
Race (NIH/OMB) White	70 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants

PRIMARY outcome

Timeframe: Up to approximately 4 years and 2 months

Population: The Safety Analysis Set is defined as all participants who received at least 1 dose of any study drug (any component of the combination therapy)

Number of participants with treatment-emergent AEs (TEAEs) and serious adverse events (SAEs), which includes laboratory tests, physical exams, electrocardiogram results and vital signs; TEAE was defined as an adverse event that had an onset date or a worsening in severity from baseline (pretreatment) on or after the first dose of study drug(s) up to 30 days following last dose of study drug(s) or initiation of a new anticancer therapy, whichever occurs first.

Outcome measures

Measure	Sitravatinib + Tislelizumab n=216 Participants Sitravatinib 120 mg was administered orally once daily in combination with tislelizumab 200 mg IV once every 3 weeks
Number of Participants With Adverse Events (AEs) At least 1 TEAE	216 Participants
Number of Participants With Adverse Events (AEs) At least 1 SAE	120 Participants

SECONDARY outcome

Timeframe: Up to approximately 4 years and 2 months

Population: The Efficacy Evaluable Analysis Set consists of all treated participants in the Safety Analysis Set with measurable baseline assessment per RECIST 1.1 who had at least one evaluable post-baseline tumor assessment unless treatment was discontinued due to clinical disease progression or early death (within 13 weeks of the first dose date)

ORR is defined as the percentage of participants with confirmed complete response (CR) or partial response (PR) as determined by the investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Efficacy was evaluated by cohort, as pre-specified in the statistical analysis plan.

Outcome measures

Measure	Sitravatinib + Tislelizumab n=199 Participants Sitravatinib 120 mg was administered orally once daily in combination with tislelizumab 200 mg IV once every 3 weeks
Objective Response Rate (ORR) Cohort A: NSCLC	4.3 Percentage of participants Interval 0.1 to 21.9
Objective Response Rate (ORR) Cohort B: NSCLC	23.8 Percentage of participants Interval 8.2 to 47.2
Objective Response Rate (ORR) Cohort C: RCC	66.7 Percentage of participants Interval 9.4 to 99.2
Objective Response Rate (ORR) Cohort D: RCC	0.0 Percentage of participants Interval 0.0 to 70.8
Objective Response Rate (ORR) Cohort E: OC	28.8 Percentage of participants Interval 17.8 to 42.1
Objective Response Rate (ORR) Cohort F: NSCLC	18.2 Percentage of participants Interval 5.2 to 40.3
Objective Response Rate (ORR) Cohort G: Melanoma	36.0 Percentage of participants Interval 18.0 to 57.5
Objective Response Rate (ORR) Cohort H: NSCLC	60.0 Percentage of participants Interval 36.1 to 80.9
Objective Response Rate (ORR) Cohort I: NSCLC	30.4 Percentage of participants Interval 13.2 to 52.9

SECONDARY outcome

Timeframe: Up to approximately 4 years and 2 months

Population: The Efficacy Evaluable Analysis Set consists of all treated participants in the Safety Analysis Set with measurable baseline assessment per RECIST 1.1 who had at least one evaluable post-baseline tumor assessment unless treatment was discontinued due to clinical disease progression or early death (within 13 weeks of the first dose date)

DOR is defined as the time from the first determination of an objective response until the first documentation of progressive disease, whichever comes first, as assessed by the investigator using RECIST v1.1. Results are reported for cohorts with responders, defined as CR or PR. Efficacy was evaluated by cohort, as pre-specified in the statistical analysis plan.

Outcome measures

Measure	Sitravatinib + Tislelizumab n=57 Participants Sitravatinib 120 mg was administered orally once daily in combination with tislelizumab 200 mg IV once every 3 weeks
Duration of Response (DOR) Cohort A: NSCLC	3.1 Months NA = Data not estimable due to low number of participants with events
Duration of Response (DOR) Cohort B: NSCLC	17.9 Months Interval 2.9 to NA = Data not estimable due to low number of participants with events
Duration of Response (DOR) Cohort C: RCC	11.4 Months Interval 9.7 to NA = Data not estimable due to low number of participants with events
Duration of Response (DOR) Cohort E: OC	5.6 Months Interval 2.8 to 12.5
Duration of Response (DOR) Cohort F: NSCLC	6.9 Months Interval 3.4 to NA = Data not estimable due to low number of participants with events
Duration of Response (DOR) Cohort G: Melanoma	19.1 Months Interval 2.8 to NA = Data not estimable due to low number of participants with events
Duration of Response (DOR) Cohort H: NSCLC	9.7 Months Interval 5.6 to 15.9
Duration of Response (DOR) Cohort I: NSCLC	8.1 Months Interval 5.5 to NA = Data not estimable due to low number of participants with events

SECONDARY outcome

Timeframe: Up to approximately 4 years and 2 months

Population: The Efficacy Evaluable Analysis Set consists of all treated participants in the Safety Analysis Set with measurable baseline assessment per RECIST 1.1 who had at least one evaluable post-baseline tumor assessment unless treatment was discontinued due to clinical disease progression or early death (within 13 weeks of the first dose date)

DCR is defined as the percentage of participants with best overall response as CR, PR, or stable disease (SD) as assessed by the investigator using RECIST v1.1. Efficacy was evaluated by cohort, as pre-specified in the statistical analysis plan.

Outcome measures

Measure	Sitravatinib + Tislelizumab n=199 Participants Sitravatinib 120 mg was administered orally once daily in combination with tislelizumab 200 mg IV once every 3 weeks
Disease Control Rate (DCR) Cohort A: NSCLC	78.3 Percentage of participants Interval 56.3 to 92.5
Disease Control Rate (DCR) Cohort B: NSCLC	85.7 Percentage of participants Interval 63.7 to 97.0
Disease Control Rate (DCR) Cohort C: RCC	100.0 Percentage of participants Interval 29.2 to 100.0
Disease Control Rate (DCR) Cohort D: RCC	100.0 Percentage of participants Interval 29.2 to 100.0
Disease Control Rate (DCR) Cohort E: OC	79.7 Percentage of participants Interval 67.2 to 89.0
Disease Control Rate (DCR) Cohort F: NSCLC	90.9 Percentage of participants Interval 70.8 to 98.9
Disease Control Rate (DCR) Cohort G: Melanoma	88.0 Percentage of participants Interval 68.8 to 97.5
Disease Control Rate (DCR) Cohort H: NSCLC	85.0 Percentage of participants Interval 62.1 to 96.8
Disease Control Rate (DCR) Cohort I: NSCLC	78.3 Percentage of participants Interval 56.3 to 92.5

SECONDARY outcome

Timeframe: Up to approximately 4 years and 2 months

Population: The Safety Analysis Set for this endpoint is defined as all participants who received at least 1 dose of any study drug (any component of the combination therapy) and who met tumor type criteria per latest protocol amendment

PFS is defined as the time from the date of first dose to the date of first documentation of progressive disease or death, whichever comes first, as assessed by the investigator using RECIST v1.1. Efficacy was evaluated by cohort, as pre-specified in the statistical analysis plan.

Outcome measures

Measure	Sitravatinib + Tislelizumab n=209 Participants Sitravatinib 120 mg was administered orally once daily in combination with tislelizumab 200 mg IV once every 3 weeks
Progression-free Survival (PFS) Cohort A: NSCLC	4.2 Months Interval 2.7 to 5.8
Progression-free Survival (PFS) Cohort B: NSCLC	7.0 Months Interval 2.7 to 11.2
Progression-free Survival (PFS) Cohort C: RCC	15.9 Months Interval 11.1 to NA = Data not estimable due to low number of participants with events
Progression-free Survival (PFS) Cohort D: RCC	2.7 Months Interval 2.6 to NA = Data not estimable due to low number of participants with events
Progression-free Survival (PFS) Cohort E: OC	4.1 Months Interval 3.5 to 5.1
Progression-free Survival (PFS) Cohort F: NSCLC	5.3 Months Interval 4.1 to 8.2
Progression-free Survival (PFS) Cohort G: Melanoma	6.7 Months Interval 4.1 to 29.7
Progression-free Survival (PFS) Cohort H: NSCLC	10.9 Months Interval 5.1 to 15.3
Progression-free Survival (PFS) Cohort I: NSCLC	5.4 Months Interval 2.8 to 9.5

SECONDARY outcome

Timeframe: Predose and up to 24 hours post dose on Cycle 1 Day 1 (C1D1) and Cycle 1 Day 21 (C1D21); 21 days per cycle

Population: The Sitravatinib Pharmacokinetic (PK) Analysis Set includes all participants who contributed at least 1 quantifiable PK sample for sitravatinib

Outcome measures

Measure	Sitravatinib + Tislelizumab n=42 Participants Sitravatinib 120 mg was administered orally once daily in combination with tislelizumab 200 mg IV once every 3 weeks
Maximum Plasma Concentration (Cmax) for Sitravatinib C1D1	49.49 nanograms/milliliter (ng/mL) Geometric Coefficient of Variation 82.688
Maximum Plasma Concentration (Cmax) for Sitravatinib C1D21	98.36 nanograms/milliliter (ng/mL) Geometric Coefficient of Variation 68.908

SECONDARY outcome

Timeframe: Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle

Population: The Sitravatinib PK Analysis Set includes all participants who contributed at least 1 quantifiable PK sample for sitravatinib

Outcome measures

Measure	Sitravatinib + Tislelizumab n=42 Participants Sitravatinib 120 mg was administered orally once daily in combination with tislelizumab 200 mg IV once every 3 weeks
Time to Maximum Plasma Concentration (Tmax) for Sitravatinib C1D1	6.09 Hours (h) Interval 2.0 to 24.8
Time to Maximum Plasma Concentration (Tmax) for Sitravatinib C1D21	6.08 Hours (h) Interval 0.0 to 23.2

SECONDARY outcome

Timeframe: Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle

Population: The Sitravatinib PK Analysis Set includes all participants who contributed at least 1 quantifiable PK sample for sitravatinib

Outcome measures

Measure	Sitravatinib + Tislelizumab n=42 Participants Sitravatinib 120 mg was administered orally once daily in combination with tislelizumab 200 mg IV once every 3 weeks
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Time Point (AUC(0-t)) for Sitravatinib C1D21	1539.96 h*ng/mL Geometric Coefficient of Variation 83.010
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Time Point (AUC(0-t)) for Sitravatinib C1D1	414.01 h*ng/mL Geometric Coefficient of Variation 115.833

SECONDARY outcome

Timeframe: Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle

Population: The Sitravatinib PK Analysis Set includes all participants who contributed at least 1 quantifiable PK sample for sitravatinib

Outcome measures

Measure	Sitravatinib + Tislelizumab n=14 Participants Sitravatinib 120 mg was administered orally once daily in combination with tislelizumab 200 mg IV once every 3 weeks
Clearance After Oral Administration (CL/F) for Sitravatinib C1D1	72.89 Liters/hour Geometric Coefficient of Variation 148.368
Clearance After Oral Administration (CL/F) for Sitravatinib C1D21	58.30 Liters/hour Geometric Coefficient of Variation 58.470

SECONDARY outcome

Timeframe: Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle

Population: The Sitravatinib PK Analysis Set includes all participants who contributed at least 1 quantifiable PK sample for sitravatinib

Outcome measures

Measure	Sitravatinib + Tislelizumab n=14 Participants Sitravatinib 120 mg was administered orally once daily in combination with tislelizumab 200 mg IV once every 3 weeks
Area Under the Plasma Concentration-time Curve During the Dosing Interval (AUC(0-tau)) for Sitravatinib C1D1	1050.57 h*ng/mL Geometric Coefficient of Variation 75.432
Area Under the Plasma Concentration-time Curve During the Dosing Interval (AUC(0-tau)) for Sitravatinib C1D21	2058.23 h*ng/mL Geometric Coefficient of Variation 58.470

SECONDARY outcome

Timeframe: Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle

Population: The Sitravatinib PK Analysis Set includes all participants who contributed at least 1 quantifiable PK sample for sitravatinib

Presented as geometric mean ratio and confidence interval, transformed from the difference of least square means and confidence interval of the least square differences in the logarithmic scale by exponentiation

Outcome measures

Measure	Sitravatinib + Tislelizumab n=7 Participants Sitravatinib 120 mg was administered orally once daily in combination with tislelizumab 200 mg IV once every 3 weeks
Observed Accumulation Ratio (Ro) for AUC0-tau for Sitravatinib	1.83 Ratio Interval 1.18 to 2.82

SECONDARY outcome

Timeframe: Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle

Population: The Sitravatinib PK Analysis Set includes all participants who contributed at least 1 quantifiable PK sample for sitravatinib

Presented as geometric mean ratio and confidence interval, transformed from the difference of least square means and confidence interval of the least square differences in the logarithmic scale by exponentiation

Outcome measures

Measure	Sitravatinib + Tislelizumab n=27 Participants Sitravatinib 120 mg was administered orally once daily in combination with tislelizumab 200 mg IV once every 3 weeks
Observed Accumulation Ratio (Ro) for Cmax for Sitravatinib	2.23 Ratio Interval 1.69 to 2.95

Adverse Events

Sitravatinib + Tislelizumab

Serious events: 120 serious events

Other events: 213 other events

Deaths: 158 deaths

Serious adverse events

Measure	Sitravatinib + Tislelizumab n=216 participants at risk Sitravatinib 120 mg was administered orally once daily in combination with tislelizumab 200 mg intravenously (IV) once every 3 weeks
Blood and lymphatic system disorders Anaemia	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Cardiac disorders Acute coronary syndrome	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Cardiac disorders Acute myocardial infarction	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Cardiac disorders Arteriosclerosis coronary artery	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Cardiac disorders Atrial fibrillation	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Cardiac disorders Bradycardia	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Cardiac disorders Cardiac failure	0.93% 2/216 • Number of events 2 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Cardiac disorders Immune-mediated myocarditis	0.93% 2/216 • Number of events 2 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Cardiac disorders Myocarditis	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Cardiac disorders Pericardial effusion	0.93% 2/216 • Number of events 2 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Cardiac disorders Ventricular extrasystoles	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Endocrine disorders Adrenal insufficiency	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Endocrine disorders Adrenocortical insufficiency acute	0.93% 2/216 • Number of events 2 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Endocrine disorders Hyperthyroidism	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Endocrine disorders Hypophysitis	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Endocrine disorders Immune-mediated hyperthyroidism	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Abdominal distension	1.4% 3/216 • Number of events 3 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Abdominal pain	3.7% 8/216 • Number of events 8 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Abdominal pain upper	0.93% 2/216 • Number of events 2 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Ascites	1.9% 4/216 • Number of events 6 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Colitis	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Constipation	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Diarrhoea	5.1% 11/216 • Number of events 12 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Diarrhoea haemorrhagic	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Gastric ulcer	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Gastritis	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Gastrointestinal necrosis	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Haematochezia	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Immune-mediated enterocolitis	0.93% 2/216 • Number of events 2 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Intestinal obstruction	1.9% 4/216 • Number of events 8 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Large intestinal obstruction	0.93% 2/216 • Number of events 2 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Malignant gastrointestinal obstruction	0.93% 2/216 • Number of events 2 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Nausea	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Pancreatitis	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Small intestinal obstruction	2.8% 6/216 • Number of events 12 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Terminal ileitis	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Vomiting	3.2% 7/216 • Number of events 7 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
General disorders Death	4.2% 9/216 • Number of events 9 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
General disorders Device related thrombosis	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
General disorders Fatigue	1.9% 4/216 • Number of events 4 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
General disorders Multiple organ dysfunction syndrome	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
General disorders Non-cardiac chest pain	0.93% 2/216 • Number of events 2 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
General disorders Pain	1.4% 3/216 • Number of events 3 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
General disorders Pyrexia	3.7% 8/216 • Number of events 8 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Hepatobiliary disorders Cholecystitis	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Hepatobiliary disorders Cholelithiasis	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Hepatobiliary disorders Hepatic failure	0.93% 2/216 • Number of events 2 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Hepatobiliary disorders Hepatic function abnormal	1.9% 4/216 • Number of events 4 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Hepatobiliary disorders Hepatic pain	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Hepatobiliary disorders Hypertransaminasaemia	0.93% 2/216 • Number of events 2 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Hepatobiliary disorders Immune-mediated hepatitis	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Immune system disorders Anaphylactic reaction	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Infections and infestations Abdominal wall abscess	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Infections and infestations Anal abscess	1.4% 3/216 • Number of events 3 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Infections and infestations Appendicitis perforated	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Infections and infestations Bacteraemia	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Infections and infestations Furuncle	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Infections and infestations Gastroenteritis	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Infections and infestations Gastroenteritis viral	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Infections and infestations Influenza	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Infections and infestations Lower respiratory tract infection	0.93% 2/216 • Number of events 3 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Infections and infestations Pneumonia	4.6% 10/216 • Number of events 11 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Infections and infestations Pneumonia aspiration	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Infections and infestations Rhinitis	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Infections and infestations Tooth abscess	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Infections and infestations Urinary tract infection	1.9% 4/216 • Number of events 4 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Infections and infestations Urosepsis	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Infections and infestations Viral infection	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Injury, poisoning and procedural complications Incarcerated parastomal hernia	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Alanine aminotransferase increased	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Aspartate aminotransferase increased	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Blood creatine phosphokinase MB increased	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Blood creatine phosphokinase increased	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Blood creatinine increased	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Blood pressure increased	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Electrocardiogram QT prolonged	0.93% 2/216 • Number of events 2 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Transaminases increased	1.4% 3/216 • Number of events 3 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Troponin I increased	0.93% 2/216 • Number of events 2 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Troponin increased	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Metabolism and nutrition disorders Decreased appetite	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Metabolism and nutrition disorders Electrolyte imbalance	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Metabolism and nutrition disorders Hyperglycaemia	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Metabolism and nutrition disorders Hypokalaemia	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Metabolism and nutrition disorders Hyponatraemia	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Musculoskeletal and connective tissue disorders Back pain	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Musculoskeletal and connective tissue disorders Bursitis	0.46% 1/216 • Number of events 2 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Musculoskeletal and connective tissue disorders Muscular weakness	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Musculoskeletal and connective tissue disorders Myalgia	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Musculoskeletal and connective tissue disorders Spinal pain	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour invasion	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Nervous system disorders Brain oedema	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Nervous system disorders Cerebral infarction	0.93% 2/216 • Number of events 2 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Nervous system disorders Dizziness postural	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Nervous system disorders Embolic stroke	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Nervous system disorders Headache	0.93% 2/216 • Number of events 2 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Nervous system disorders Ischaemic stroke	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Nervous system disorders Lethargy	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Nervous system disorders Syncope	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Nervous system disorders Transient ischaemic attack	0.93% 2/216 • Number of events 2 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Product Issues Device occlusion	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Renal and urinary disorders Ureteric obstruction	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Reproductive system and breast disorders Female genital tract fistula	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Reproductive system and breast disorders Vaginal haemorrhage	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.3% 5/216 • Number of events 7 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.93% 2/216 • Number of events 3 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Respiratory, thoracic and mediastinal disorders Immune-mediated lung disease	1.4% 3/216 • Number of events 3 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Respiratory, thoracic and mediastinal disorders Lung consolidation	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.4% 3/216 • Number of events 4 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.93% 2/216 • Number of events 2 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Respiratory, thoracic and mediastinal disorders Pulmonary infarction	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.93% 2/216 • Number of events 2 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Skin and subcutaneous tissue disorders Rash	0.93% 2/216 • Number of events 2 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Vascular disorders Aortic dissection	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Vascular disorders Deep vein thrombosis	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Vascular disorders Hypertension	1.4% 3/216 • Number of events 3 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Vascular disorders Jugular vein thrombosis	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Vascular disorders Peripheral ischaemia	0.46% 1/216 • Number of events 1 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.

Other adverse events

Measure	Sitravatinib + Tislelizumab n=216 participants at risk Sitravatinib 120 mg was administered orally once daily in combination with tislelizumab 200 mg intravenously (IV) once every 3 weeks
Blood and lymphatic system disorders Anaemia	18.1% 39/216 • Number of events 56 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Cardiac disorders Sinus bradycardia	3.2% 7/216 • Number of events 7 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Cardiac disorders Sinus tachycardia	3.7% 8/216 • Number of events 12 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Cardiac disorders Ventricular extrasystoles	3.2% 7/216 • Number of events 10 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Endocrine disorders Hyperthyroidism	6.9% 15/216 • Number of events 17 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Endocrine disorders Hypothyroidism	32.9% 71/216 • Number of events 78 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Abdominal distension	4.2% 9/216 • Number of events 9 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Abdominal pain	13.9% 30/216 • Number of events 39 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Abdominal pain upper	11.6% 25/216 • Number of events 28 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Constipation	21.3% 46/216 • Number of events 52 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Diarrhoea	52.8% 114/216 • Number of events 224 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Dry mouth	6.5% 14/216 • Number of events 14 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Gastrooesophageal reflux disease	6.9% 15/216 • Number of events 16 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Mouth ulceration	8.8% 19/216 • Number of events 22 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Nausea	31.0% 67/216 • Number of events 86 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Stomatitis	11.1% 24/216 • Number of events 28 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Toothache	4.6% 10/216 • Number of events 11 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Gastrointestinal disorders Vomiting	26.4% 57/216 • Number of events 97 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
General disorders Asthenia	3.7% 8/216 • Number of events 9 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
General disorders Fatigue	20.8% 45/216 • Number of events 52 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
General disorders Influenza like illness	4.6% 10/216 • Number of events 10 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
General disorders Malaise	7.4% 16/216 • Number of events 17 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
General disorders Non-cardiac chest pain	3.2% 7/216 • Number of events 7 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
General disorders Oedema peripheral	5.6% 12/216 • Number of events 12 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
General disorders Pyrexia	11.6% 25/216 • Number of events 39 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Hepatobiliary disorders Hepatic function abnormal	3.7% 8/216 • Number of events 17 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Infections and infestations Pneumonia	4.2% 9/216 • Number of events 9 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Infections and infestations Upper respiratory tract infection	3.7% 8/216 • Number of events 9 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Infections and infestations Urinary tract infection	9.7% 21/216 • Number of events 27 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Alanine aminotransferase increased	46.8% 101/216 • Number of events 198 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Aspartate aminotransferase increased	44.9% 97/216 • Number of events 181 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Bilirubin conjugated increased	10.2% 22/216 • Number of events 35 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Blood alkaline phosphatase increased	8.8% 19/216 • Number of events 27 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Blood bilirubin increased	9.7% 21/216 • Number of events 38 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Blood cholesterol increased	11.1% 24/216 • Number of events 51 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Blood creatine phosphokinase MB increased	12.0% 26/216 • Number of events 42 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Blood creatine phosphokinase increased	19.9% 43/216 • Number of events 95 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Blood creatinine increased	6.0% 13/216 • Number of events 20 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Blood lactate dehydrogenase increased	15.3% 33/216 • Number of events 55 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Blood potassium decreased	3.2% 7/216 • Number of events 23 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Blood pressure increased	6.9% 15/216 • Number of events 22 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Blood thyroid stimulating hormone increased	12.0% 26/216 • Number of events 33 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Electrocardiogram QT prolonged	6.5% 14/216 • Number of events 14 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Electrocardiogram T wave abnormal	6.0% 13/216 • Number of events 40 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Gamma-glutamyltransferase increased	13.0% 28/216 • Number of events 51 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Neutrophil count decreased	5.1% 11/216 • Number of events 16 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Neutrophil count increased	3.2% 7/216 • Number of events 13 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Platelet count decreased	10.6% 23/216 • Number of events 44 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Urobilinogen urine increased	4.2% 9/216 • Number of events 14 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Weight decreased	38.0% 82/216 • Number of events 98 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations Weight increased	3.2% 7/216 • Number of events 8 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations White blood cell count decreased	6.5% 14/216 • Number of events 23 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations White blood cell count increased	3.2% 7/216 • Number of events 14 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Investigations White blood cells urine positive	5.1% 11/216 • Number of events 32 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Metabolism and nutrition disorders Decreased appetite	32.9% 71/216 • Number of events 77 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Metabolism and nutrition disorders Hyperglycaemia	9.7% 21/216 • Number of events 40 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Metabolism and nutrition disorders Hypertriglyceridaemia	8.8% 19/216 • Number of events 47 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Metabolism and nutrition disorders Hyperuricaemia	7.4% 16/216 • Number of events 34 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Metabolism and nutrition disorders Hypoalbuminaemia	21.8% 47/216 • Number of events 63 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Metabolism and nutrition disorders Hypocalcaemia	12.0% 26/216 • Number of events 47 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Metabolism and nutrition disorders Hypochloraemia	3.2% 7/216 • Number of events 15 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Metabolism and nutrition disorders Hypokalaemia	13.9% 30/216 • Number of events 75 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Metabolism and nutrition disorders Hypomagnesaemia	8.3% 18/216 • Number of events 23 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Metabolism and nutrition disorders Hyponatraemia	13.4% 29/216 • Number of events 43 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Metabolism and nutrition disorders Hypophosphataemia	6.5% 14/216 • Number of events 22 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Musculoskeletal and connective tissue disorders Arthralgia	11.1% 24/216 • Number of events 27 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Musculoskeletal and connective tissue disorders Back pain	11.1% 24/216 • Number of events 26 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Musculoskeletal and connective tissue disorders Muscle spasms	3.7% 8/216 • Number of events 12 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	3.2% 7/216 • Number of events 7 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Musculoskeletal and connective tissue disorders Myalgia	3.2% 7/216 • Number of events 8 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Musculoskeletal and connective tissue disorders Pain in extremity	5.1% 11/216 • Number of events 12 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Nervous system disorders Dizziness	8.3% 18/216 • Number of events 19 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Nervous system disorders Headache	12.0% 26/216 • Number of events 32 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Nervous system disorders Hypoaesthesia	3.2% 7/216 • Number of events 7 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Nervous system disorders Lethargy	3.7% 8/216 • Number of events 8 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Psychiatric disorders Insomnia	6.5% 14/216 • Number of events 14 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Renal and urinary disorders Proteinuria	19.0% 41/216 • Number of events 76 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Respiratory, thoracic and mediastinal disorders Cough	12.0% 26/216 • Number of events 30 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Respiratory, thoracic and mediastinal disorders Dysphonia	16.2% 35/216 • Number of events 36 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.0% 13/216 • Number of events 13 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Respiratory, thoracic and mediastinal disorders Epistaxis	4.2% 9/216 • Number of events 9 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Respiratory, thoracic and mediastinal disorders Haemoptysis	5.6% 12/216 • Number of events 22 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	6.9% 15/216 • Number of events 15 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Respiratory, thoracic and mediastinal disorders Productive cough	4.2% 9/216 • Number of events 9 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	29.2% 63/216 • Number of events 83 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Skin and subcutaneous tissue disorders Pruritus	4.2% 9/216 • Number of events 12 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Skin and subcutaneous tissue disorders Rash	17.6% 38/216 • Number of events 49 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.
Vascular disorders Hypertension	37.5% 81/216 • Number of events 97 • From the first dose up to 30 days after the last dose of study drug; Up to approximately 4 years and 2 months An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.

Additional Information

Study Director

BeiGene

Phone: 1-877-828-5568

Email: clinicaltrials@beigene.com

Results disclosure agreements

• Principal investigator is a sponsor employee BeiGene has 18 months from the end of the study at all sites to publish overall study results. After the 1st multi-site publication or the expiration of publication period, Investigators are free to publish/present the results of the study. Investigators must submit all draft publications/presentations to us for review 60 days prior to the planned publication/presentation date. BeiGene may request deletion of its confidential information \& may request a further delay to protect its IP rights.
• Publication restrictions are in place

Restriction type: OTHER