Trial Outcomes & Findings for Study Investigating Safety, Tolerability, Pharmacokinetics (PK) and Antitumor Activities of Anti-PD-1 (Programmed Death-1) Monoclonal Antibody (NCT NCT04068519)

NCT ID: NCT04068519

Last Updated: 2024-10-26

Results Overview

Number of participants with adverse events (AEs) and serious adverse events (SAEs), as defined per NCI-CTCAE Version 4.03, including physical examination, electrocardiograms and laboratory assessments

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 300 participants
• Primary outcome timeframe: Up to approximately 23 months
• Results posted on: 2024-10-26

Participant Flow

A total of 300 participants were treated with at least 1 dose of tislelizumab. This was a single arm study with 3 parts: dose verification, pharmacokinetic (PK) sub-study, and indication expansion.

Participant milestones

Measure	Tislelizumab Tislelizumab 200 mg was administered intravenously (IV) once every 3 weeks (21 days per cycle) until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator.
Dose Verification STARTED	20
Dose Verification COMPLETED	4
Dose Verification NOT COMPLETED	16
Pharmacokinetic Sub-study STARTED	57
Pharmacokinetic Sub-study COMPLETED	16
Pharmacokinetic Sub-study NOT COMPLETED	41
Indication Expansion STARTED	223
Indication Expansion COMPLETED	54
Indication Expansion NOT COMPLETED	169

Reasons for withdrawal

Measure	Tislelizumab Tislelizumab 200 mg was administered intravenously (IV) once every 3 weeks (21 days per cycle) until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator.
Dose Verification Death	15
Dose Verification Withdrawal by Subject	1
Pharmacokinetic Sub-study Death	35
Pharmacokinetic Sub-study Withdrawal by Subject	1
Pharmacokinetic Sub-study Lost to Follow-up	4
Pharmacokinetic Sub-study Other not specified	1
Indication Expansion Death	152
Indication Expansion Withdrawal by Subject	10
Indication Expansion Lost to Follow-up	7

Baseline Characteristics

Study Investigating Safety, Tolerability, Pharmacokinetics (PK) and Antitumor Activities of Anti-PD-1 (Programmed Death-1) Monoclonal Antibody

Baseline characteristics by cohort

Measure	Tislelizumab n=300 Participants Tislelizumab 200 mg was administered intravenously (IV) once every 3 weeks (21 days per cycle) until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator.
Age, Continuous	55.5 Years STANDARD_DEVIATION 11.48 • n=5 Participants
Sex: Female, Male Female	93 Participants n=5 Participants
Sex: Female, Male Male	207 Participants n=5 Participants
Race/Ethnicity, Customized Chinese	300 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to approximately 23 months

Population: The Safety Analysis Set (SAS) included all participants who received ≥ 1 dose of tislelizumab

Number of participants with adverse events (AEs) and serious adverse events (SAEs), as defined per NCI-CTCAE Version 4.03, including physical examination, electrocardiograms and laboratory assessments

Outcome measures

Measure	Dose Verification n=20 Participants Tislelizumab 200 mg intravenously (IV) once every 3 weeks (21 days per cycle) until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator	PK Sub-study n=57 Participants Tislelizumab 200 mg intravenously (IV) on Day 1 of the first 28 days followed by once every 3 weeks (21 days per cycle) for subsequent cycles until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator
Dose Verification and PK Sub-study: Number Participants With Adverse Events At least one treatment-emergent adverse event (TEAE)	20 Participants	54 Participants
Dose Verification and PK Sub-study: Number Participants With Adverse Events TEAE Grade 3 of higher	9 Participants	21 Participants
Dose Verification and PK Sub-study: Number Participants With Adverse Events Serious adverse event	4 Participants	14 Participants

PRIMARY outcome

Timeframe: Up to approximately 23 months

Population: The Safety Analysis Set (SAS) included all participants who received ≥ 1 dose of tislelizumab

Recommended dose of tislelizumab for indication cohorts based on safety and tolerability

Outcome measures

Measure	Dose Verification n=20 Participants Tislelizumab 200 mg intravenously (IV) once every 3 weeks (21 days per cycle) until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator	PK Sub-study Tislelizumab 200 mg intravenously (IV) on Day 1 of the first 28 days followed by once every 3 weeks (21 days per cycle) for subsequent cycles until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator
Dose Verification: Recommended Dose of Tislelizumab	200 milligrams	—

PRIMARY outcome

Timeframe: Predose, end of infusion, 3 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22, and Day 29 predose

Population: The PK Analysis Set included participants in the SAS for whom at least 1 valid PK parameter could be derived for tislelizumab

Pharmacokinetics from products derived from two manufacturing scales at 500 liter and 2000 liter final manufacturing process (FMP) were evaluated

Outcome measures

Measure	Dose Verification n=56 Participants Tislelizumab 200 mg intravenously (IV) once every 3 weeks (21 days per cycle) until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator	PK Sub-study Tislelizumab 200 mg intravenously (IV) on Day 1 of the first 28 days followed by once every 3 weeks (21 days per cycle) for subsequent cycles until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator
PK Sub-study: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of Tislelizumab From Two Manufacturing Processes and Scales 500L-FMP	1113.9 µg/mL*day Interval 997.6 to 1244.0	—
PK Sub-study: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of Tislelizumab From Two Manufacturing Processes and Scales 2000L-FMP	1108 µg/mL*day Interval 985.2 to 1246.0	—

PRIMARY outcome

Timeframe: Predose, end of infusion, 3 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22, and Day 29 predose

Population: The PK Analysis Set included participants in the SAS for whom at least 1 valid PK parameter could be derived for tislelizumab

Pharmacokinetics from products derived from two manufacturing scales at 500 liter and 2000 liter final manufacturing process (FMP) were evaluated

Outcome measures

Measure	Dose Verification n=56 Participants Tislelizumab 200 mg intravenously (IV) once every 3 weeks (21 days per cycle) until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator	PK Sub-study Tislelizumab 200 mg intravenously (IV) on Day 1 of the first 28 days followed by once every 3 weeks (21 days per cycle) for subsequent cycles until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator
PK Sub-study: Area Under the Concentration-time Curve From Time 0 to 28 Days Postdose (AUC0-28d) of Tislelizumab From Two Manufacturing Processes and Scales 500L-FMP	810.2 µg/mL*day Interval 746.0 to 879.9	—
PK Sub-study: Area Under the Concentration-time Curve From Time 0 to 28 Days Postdose (AUC0-28d) of Tislelizumab From Two Manufacturing Processes and Scales 2000L-FMP	801.7 µg/mL*day Interval 740.8 to 867.5	—

PRIMARY outcome

Timeframe: Predose, end of infusion, 3 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22, and Day 29 predose

Population: PK Analysis Set included participants in the SAS for whom at least 1 valid PK parameter could be derived for tislelizumab

Pharmacokinetics from products derived from two manufacturing scales at 500 liter and 2000 liter FMP were evaluated

Outcome measures

Measure	Dose Verification n=56 Participants Tislelizumab 200 mg intravenously (IV) once every 3 weeks (21 days per cycle) until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator	PK Sub-study Tislelizumab 200 mg intravenously (IV) on Day 1 of the first 28 days followed by once every 3 weeks (21 days per cycle) for subsequent cycles until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator
PK Sub-study: Maximum Observed Concentration (Cmax) of Tislelizumab From Two Manufacturing Processes and Scales 500L-FMP	77.3 µg/mL Interval 73.6 to 81.2	—
PK Sub-study: Maximum Observed Concentration (Cmax) of Tislelizumab From Two Manufacturing Processes and Scales 2000L-FMP	75.7 µg/mL Interval 70.7 to 81.0	—

PRIMARY outcome

Timeframe: Up to approximately 3 years and 5 months

Population: The Safety Analysis Set (SAS) included all participants who received ≥ 1 dose of tislelizumab; one participant is included in both MSI-H/dMMR and GC indications.

Objective response rate (ORR) is defined as the percentage of participants who achieved objective tumor response (complete response or partial response) according to RECIST Version 1.1. Indication expansion includes participants from all parts in the following indications: non-small cell lung cancer (NSCLC), melanoma, esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), urothelial carcinoma (UC), nasopharyngeal carcinoma (NPC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors, and other tumor types.

Outcome measures

Measure	Dose Verification n=300 Participants Tislelizumab 200 mg intravenously (IV) once every 3 weeks (21 days per cycle) until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator	PK Sub-study Tislelizumab 200 mg intravenously (IV) on Day 1 of the first 28 days followed by once every 3 weeks (21 days per cycle) for subsequent cycles until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator
Indication Expansion: Objective Response Rate NSCLC	17.9 Percentage of participants Interval 8.9 to 30.4	—
Indication Expansion: Objective Response Rate Melanoma	17.6 Percentage of participants Interval 6.8 to 34.5	—
Indication Expansion: Objective Response Rate ESCC	7.7 Percentage of participants Interval 0.9 to 25.1	—
Indication Expansion: Objective Response Rate GC	16.7 Percentage of participants Interval 4.7 to 37.4	—
Indication Expansion: Objective Response Rate UC	18.2 Percentage of participants Interval 5.2 to 40.3	—
Indication Expansion: Objective Response Rate NPC	47.6 Percentage of participants Interval 25.7 to 70.2	—
Indication Expansion: Objective Response Rate RCC	9.5 Percentage of participants Interval 1.2 to 30.4	—
Indication Expansion: Objective Response Rate HCC	16.7 Percentage of participants Interval 3.6 to 41.4	—
Indication Expansion: Objective Response Rate MSI-H/dMMR	25.0 Percentage of participants Interval 7.3 to 52.4	—
Indication Expansion: Objective Response Rate Other	9.5 Percentage of participants Interval 3.6 to 19.6	—

SECONDARY outcome

Timeframe: Predose, end of infusion, 1.5 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22 predose in Cycle 1 and Cycle 5 (21 days per cycle)

Population: PK Analysis Set included participants in the SAS for whom at least 1 valid PK parameter could be derived for tislelizumab

Outcome measures

Measure	Dose Verification n=20 Participants Tislelizumab 200 mg intravenously (IV) once every 3 weeks (21 days per cycle) until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator	PK Sub-study Tislelizumab 200 mg intravenously (IV) on Day 1 of the first 28 days followed by once every 3 weeks (21 days per cycle) for subsequent cycles until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator
Dose Verification: Area Under the Concentration-time Curve From Time 0 to 21 Days Postdose (AUC0-tau) of Tislelizumab Cycle 1	600.1 µg/mL*day Standard Deviation 144.5	—
Dose Verification: Area Under the Concentration-time Curve From Time 0 to 21 Days Postdose (AUC0-tau) of Tislelizumab Cycle 5	1122 µg/mL*day Standard Deviation 352	—

SECONDARY outcome

Timeframe: Predose, end of infusion, 1.5 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22 predose in Cycle 1 and Cycle 5 (21 days per cycle)

Population: PK Analysis Set included participants in the SAS for whom at least 1 valid PK parameter could be derived for tislelizumab

Outcome measures

Measure	Dose Verification n=20 Participants Tislelizumab 200 mg intravenously (IV) once every 3 weeks (21 days per cycle) until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator	PK Sub-study Tislelizumab 200 mg intravenously (IV) on Day 1 of the first 28 days followed by once every 3 weeks (21 days per cycle) for subsequent cycles until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator
Dose Verification: Maximum Observed Concentration (Cmax) of Tislelizumab Cycle 1	67.8 µg/mL Standard Deviation 12.8	—
Dose Verification: Maximum Observed Concentration (Cmax) of Tislelizumab Cycle 5	131 µg/mL Standard Deviation 37.7	—

SECONDARY outcome

Timeframe: Predose, end of infusion, 1.5 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22 predose in Cycle 1 and Cycle 5 (21 days per cycle)

Population: PK Analysis Set included participants in the SAS for whom at least 1 valid PK parameter could be derived for tislelizumab

Outcome measures

Measure	Dose Verification n=15 Participants Tislelizumab 200 mg intravenously (IV) once every 3 weeks (21 days per cycle) until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator	PK Sub-study Tislelizumab 200 mg intravenously (IV) on Day 1 of the first 28 days followed by once every 3 weeks (21 days per cycle) for subsequent cycles until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator
Dose Verification: Predose Plasma Concentration of Tislelizumab During Multiple Dosing (Ctrough) Cycle 1	15.8 µg/mL Standard Deviation 4.73	—
Dose Verification: Predose Plasma Concentration of Tislelizumab During Multiple Dosing (Ctrough) Cycle 5	31.4 µg/mL Standard Deviation 9.55	—

SECONDARY outcome

Timeframe: Predose, end of infusion, 1.5 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22 predose in Cycle 1 and Cycle 5 (21 days per cycle)

Population: PK Analysis Set included participants in the SAS for whom at least 1 valid PK parameter could be derived for tislelizumab

Outcome measures

Measure	Dose Verification n=19 Participants Tislelizumab 200 mg intravenously (IV) once every 3 weeks (21 days per cycle) until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator	PK Sub-study Tislelizumab 200 mg intravenously (IV) on Day 1 of the first 28 days followed by once every 3 weeks (21 days per cycle) for subsequent cycles until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator
Dose Verification: Apparent Terminal Half-life of Tislelizumab (t1/2) Cycle 1	13.3 Days Standard Deviation 2.95	—
Dose Verification: Apparent Terminal Half-life of Tislelizumab (t1/2) Cycle 5	16.9 Days Standard Deviation 3.79	—

SECONDARY outcome

Timeframe: Predose, end of infusion, 1.5 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22 predose in Cycle 1 (21 days per cycle)

Population: PK Analysis Set included participants in the SAS for whom at least 1 valid PK parameter could be derived for tislelizumab

Outcome measures

Measure	Dose Verification n=20 Participants Tislelizumab 200 mg intravenously (IV) once every 3 weeks (21 days per cycle) until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator	PK Sub-study Tislelizumab 200 mg intravenously (IV) on Day 1 of the first 28 days followed by once every 3 weeks (21 days per cycle) for subsequent cycles until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator
Dose Verification: Clearance (Cl)	0.247 Liters/day Standard Deviation 0.0918	—

SECONDARY outcome

Timeframe: Up to approximately 3 years and 5 months

Population: The Safety Analysis Set (SAS) included all participants who received ≥ 1 dose of tislelizumab; one participant is included in both MSI-H/dMMR and GC indications.

Progression-free survival is defined as the time from the date of first study dose to disease progression or death, whichever comes first, as determined by Investigator per RECIST version 1.1. Indication expansion includes participants from all parts in the following indications: non-small cell lung cancer (NSCLC), melanoma, esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), urothelial carcinoma (UC), nasopharyngeal carcinoma (NPC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors, and other tumor types.

Outcome measures

Measure	Dose Verification n=300 Participants Tislelizumab 200 mg intravenously (IV) once every 3 weeks (21 days per cycle) until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator	PK Sub-study Tislelizumab 200 mg intravenously (IV) on Day 1 of the first 28 days followed by once every 3 weeks (21 days per cycle) for subsequent cycles until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator
Indication Expansion: Progression-free Survival (PFS) NSCLC	4.0 Months Interval 2.1 to 8.1	—
Indication Expansion: Progression-free Survival (PFS) Melanoma	2.2 Months Interval 2.0 to 6.1	—
Indication Expansion: Progression-free Survival (PFS) ESCC	2.1 Months Interval 2.0 to 4.2	—
Indication Expansion: Progression-free Survival (PFS) GC	2.1 Months Interval 1.9 to 4.0	—
Indication Expansion: Progression-free Survival (PFS) UC	2.1 Months Interval 2.0 to 4.3	—
Indication Expansion: Progression-free Survival (PFS) NPC	8.2 Months Interval 4.2 to 11.4	—
Indication Expansion: Progression-free Survival (PFS) RCC	4.1 Months Interval 2.1 to 10.4	—
Indication Expansion: Progression-free Survival (PFS) HCC	4.0 Months Interval 2.1 to 12.4	—
Indication Expansion: Progression-free Survival (PFS) MSI-H/dMMR	6.1 Months Interval 2.0 to 15.3	—
Indication Expansion: Progression-free Survival (PFS) Other	2.3 Months Interval 2.2 to 2.8	—

SECONDARY outcome

Timeframe: Up to approximately 3 years and 5 months

Population: The Safety Analysis Set (SAS) included all participants who received ≥ 1 dose of tislelizumab; one participant is included in both MSI-H/dMMR and GC indications.

Duration of response for responders with complete or partial response is defined as the time interval between the date of the earliest qualifying response and the date of progressive disease or death for any cause, whichever occurs earlier as determined by Investigator per RECIST version 1.1. Indication expansion includes participants from all parts in the following indications: non-small cell lung cancer (NSCLC), melanoma, esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), urothelial carcinoma (UC), nasopharyngeal carcinoma (NPC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors, and other tumor types.

Outcome measures

Measure	Dose Verification n=51 Participants Tislelizumab 200 mg intravenously (IV) once every 3 weeks (21 days per cycle) until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator	PK Sub-study Tislelizumab 200 mg intravenously (IV) on Day 1 of the first 28 days followed by once every 3 weeks (21 days per cycle) for subsequent cycles until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator
Indication Expansion: Duration of Response NSCLC	30.4 Months Interval 8.3 to 30.4	—
Indication Expansion: Duration of Response Melanoma	12.5 Months Interval 4.2 to Not estimable due to insufficient number of participants with events	—
Indication Expansion: Duration of Response ESCC	NA Months Interval 13.8 to Not estimable due to insufficient number of participants with events	—
Indication Expansion: Duration of Response GC	NA Months Interval 13.9 to Not estimable due to insufficient number of participants with events	—
Indication Expansion: Duration of Response UC	NA Months Interval 8.3 to Not estimable due to insufficient number of participants with events	—
Indication Expansion: Duration of Response NPC	8.8 Months Interval 3.9 to 14.8	—
Indication Expansion: Duration of Response RCC	NA Months Interval 4.4 to Not estimable due to insufficient number of participants with events	—
Indication Expansion: Duration of Response HCC	NA Months Interval 8.3 to Not estimable due to insufficient number of participants with events	—
Indication Expansion: Duration of Response MSI-H/dMMR	NA Months Interval 5.1 to Not estimable due to insufficient number of participants with events	—
Indication Expansion: Duration of Response Other	NA Months Interval 8.3 to Not estimable due to insufficient number of participants with events	—

SECONDARY outcome

Timeframe: Up to approximately 3 years and 5 months

Population: The Safety Analysis Set (SAS) included all participants who received ≥ 1 dose of tislelizumab; one participant is included in both MSI-H/dMMR and GC indications.

Clinical benefit rate is defined as the percentage of participants in specific tumor types reaching confirmed CR, PR and durable stable disease (SD; at ≥ 24 weeks) in accordance with RECIST version 1.1. Indication expansion includes participants from all parts in the following indications: non-small cell lung cancer (NSCLC), melanoma, esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), urothelial carcinoma (UC), nasopharyngeal carcinoma (NPC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors, and other tumor types.

Outcome measures

Measure	Dose Verification n=300 Participants Tislelizumab 200 mg intravenously (IV) once every 3 weeks (21 days per cycle) until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator	PK Sub-study Tislelizumab 200 mg intravenously (IV) on Day 1 of the first 28 days followed by once every 3 weeks (21 days per cycle) for subsequent cycles until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator
Indication Expansion: Clinical Benefit Rate NSCLC	33.9 Percentage of participants Interval 21.8 to 47.8	—
Indication Expansion: Clinical Benefit Rate Melanoma	32.4 Percentage of participants Interval 17.4 to 50.5	—
Indication Expansion: Clinical Benefit Rate ESCC	15.4 Percentage of participants Interval 4.4 to 34.9	—
Indication Expansion: Clinical Benefit Rate GC	25.0 Percentage of participants Interval 9.8 to 46.7	—
Indication Expansion: Clinical Benefit Rate UC	27.3 Percentage of participants Interval 10.7 to 50.2	—
Indication Expansion: Clinical Benefit Rate NPC	61.9 Percentage of participants Interval 38.4 to 81.9	—
Indication Expansion: Clinical Benefit Rate RCC	38.1 Percentage of participants Interval 18.1 to 61.6	—
Indication Expansion: Clinical Benefit Rate HCC	38.9 Percentage of participants Interval 17.3 to 64.3	—
Indication Expansion: Clinical Benefit Rate MSI-H/dMMR	50.0 Percentage of participants Interval 24.7 to 75.3	—
Indication Expansion: Clinical Benefit Rate Other	22.2 Percentage of participants Interval 12.7 to 34.5	—

SECONDARY outcome

Timeframe: Up to approximately 3 years and 5 months

Population: The Safety Analysis Set (SAS) included all participants who received ≥ 1 dose of tislelizumab; one participant is included in both MSI-H/dMMR and GC indications.

Overall survival is defined as the time from the date of the first study dose to death. Indication expansion includes participants from all parts in the following indications: non-small cell lung cancer (NSCLC), melanoma, esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), urothelial carcinoma (UC), nasopharyngeal carcinoma (NPC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors, and other tumor types.

Outcome measures

Measure	Dose Verification n=300 Participants Tislelizumab 200 mg intravenously (IV) once every 3 weeks (21 days per cycle) until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator	PK Sub-study Tislelizumab 200 mg intravenously (IV) on Day 1 of the first 28 days followed by once every 3 weeks (21 days per cycle) for subsequent cycles until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator
Indication Expansion: Overall Survival ESCC	4.8 Months Interval 3.6 to 8.5	—
Indication Expansion: Overall Survival NSCLC	22.1 Months Interval 10.1 to 33.5	—
Indication Expansion: Overall Survival Melanoma	11.8 Months Interval 7.0 to 24.2	—
Indication Expansion: Overall Survival GC	4.7 Months Interval 2.4 to 14.6	—
Indication Expansion: Overall Survival UC	4.3 Months Interval 2.1 to 22.9	—
Indication Expansion: Overall Survival NPC	25.0 Months Interval 11.7 to Not estimable due to insufficient number of participants with events	—
Indication Expansion: Overall Survival RCC	19.8 Months Interval 8.0 to 24.3	—
Indication Expansion: Overall Survival HCC	25.1 Months Interval 5.5 to Not estimable due to insufficient number of participants with events	—
Indication Expansion: Overall Survival MSI-H/dMMR	19.4 Months Interval 4.2 to Not estimable due to insufficient number of participants with events	—
Indication Expansion: Overall Survival Other	9.0 Months Interval 4.8 to 13.4	—

SECONDARY outcome

Timeframe: Up to approximately 3 years and 5 months

Population: The Safety Analysis Set (SAS) included all participants who received ≥ 1 dose of tislelizumab; one participant is included in both MSI-H/dMMR and GC indications.

Disease control rate is defined as the percentage of participants reaching CR, PR, and SD according to RECIST version 1.1. Indication expansion includes participants from all parts in the following indications: non-small cell lung cancer (NSCLC), melanoma, esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), urothelial carcinoma (UC), nasopharyngeal carcinoma (NPC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors, and other tumor types.

Outcome measures

Measure	Dose Verification n=300 Participants Tislelizumab 200 mg intravenously (IV) once every 3 weeks (21 days per cycle) until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator	PK Sub-study Tislelizumab 200 mg intravenously (IV) on Day 1 of the first 28 days followed by once every 3 weeks (21 days per cycle) for subsequent cycles until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator
Indication Expansion: Disease Control Rate NSCLC	55.4 Percentage of participants Interval 41.5 to 68.7	—
Indication Expansion: Disease Control Rate Melanoma	38.2 Percentage of participants Interval 22.2 to 56.4	—
Indication Expansion: Disease Control Rate ESCC	34.6 Percentage of participants Interval 17.2 to 55.7	—
Indication Expansion: Disease Control Rate GC	25.0 Percentage of participants Interval 9.8 to 46.7	—
Indication Expansion: Disease Control Rate UC	40.9 Percentage of participants Interval 20.7 to 63.6	—
Indication Expansion: Disease Control Rate NPC	81.0 Percentage of participants Interval 58.1 to 94.6	—
Indication Expansion: Disease Control Rate RCC	52.4 Percentage of participants Interval 29.8 to 74.3	—
Indication Expansion: Disease Control Rate HCC	55.6 Percentage of participants Interval 30.8 to 78.5	—
Indication Expansion: Disease Control Rate MSI-H/dMMR	50.0 Percentage of participants Interval 24.7 to 75.3	—
Indication Expansion: Disease Control Rate Other	31.7 Percentage of participants Interval 20.6 to 44.7	—

SECONDARY outcome

Timeframe: Up to approximately 23 months

Population: Evaluable participants had non-missing baseline ADA and at least 1 non-missing postbaseline ADA result.

Outcome measures

Measure	Dose Verification n=279 Participants Tislelizumab 200 mg intravenously (IV) once every 3 weeks (21 days per cycle) until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator	PK Sub-study Tislelizumab 200 mg intravenously (IV) on Day 1 of the first 28 days followed by once every 3 weeks (21 days per cycle) for subsequent cycles until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator
Number of Participants With Positive Anti-drug Antibody (ADA) Status to Tislelizumab Treatment-emergent	43 Participants	—
Number of Participants With Positive Anti-drug Antibody (ADA) Status to Tislelizumab Treatment-boosted	2 Participants	—
Number of Participants With Positive Anti-drug Antibody (ADA) Status to Tislelizumab Treatment-induced	41 Participants	—

Adverse Events

Tislelizumab

Serious events: 85 serious events

Other events: 277 other events

Deaths: 202 deaths

Serious adverse events

Measure	Tislelizumab n=300 participants at risk Tislelizumab 200 mg was administered intravenously (IV) once every 3 weeks (21 days per cycle) until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator. Safety analysis data are summarized for the overall population given that the same dose was applied, regardless of part assignment, as pre-specified in the clinical study report.
Blood and lymphatic system disorders Anaemia	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Cardiac disorders Atrial fibrillation	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Cardiac disorders Cardiopulmonary failure	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Cardiac disorders Immune-mediated myocarditis	0.67% 2/300 • Number of events 3 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Eye disorders Cataract	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Eye disorders Retinal detachment	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Gastrointestinal disorders Abdominal pain	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Gastrointestinal disorders Ascites	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Gastrointestinal disorders Diarrhoea	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Gastrointestinal disorders Dysphagia	0.67% 2/300 • Number of events 2 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Gastrointestinal disorders Gastric haemorrhage	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Gastrointestinal disorders Intestinal obstruction	1.3% 4/300 • Number of events 4 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Gastrointestinal disorders Large intestinal obstruction	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Gastrointestinal disorders Nausea	0.33% 1/300 • Number of events 2 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	2.0% 6/300 • Number of events 8 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Gastrointestinal disorders Vomiting	0.67% 2/300 • Number of events 4 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
General disorders Death	1.7% 5/300 • Number of events 5 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
General disorders Fatigue	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
General disorders General physical health deterioration	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
General disorders Multiple organ dysfunction syndrome	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
General disorders Non-cardiac chest pain	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
General disorders Pyrexia	1.0% 3/300 • Number of events 6 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Hepatobiliary disorders Cholecystitis acute	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Hepatobiliary disorders Immune-mediated hepatitis	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Immune system disorders Contrast media allergy	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Infections and infestations Abdominal infection	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Infections and infestations Epstein-Barr virus infection	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Infections and infestations Herpes zoster	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Infections and infestations Liver abscess	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Infections and infestations Lower respiratory tract infection bacterial	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Infections and infestations Osteomyelitis	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Infections and infestations Pneumonia	3.7% 11/300 • Number of events 13 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Infections and infestations Respiratory tract infection	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Infections and infestations Sinusitis	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Infections and infestations Upper respiratory tract infection	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Infections and infestations Urinary tract infection	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Injury, poisoning and procedural complications Anastomotic fistula	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Injury, poisoning and procedural complications Anastomotic leak	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Injury, poisoning and procedural complications Anastomotic stenosis	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Investigations Alanine aminotransferase increased	0.33% 1/300 • Number of events 2 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Investigations Aspartate aminotransferase increased	0.67% 2/300 • Number of events 4 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Investigations Blood magnesium decreased	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Metabolism and nutrition disorders Decreased appetite	0.67% 2/300 • Number of events 2 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Metabolism and nutrition disorders Hypercalcaemia	0.67% 2/300 • Number of events 3 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Metabolism and nutrition disorders Hyperglycaemia	0.67% 2/300 • Number of events 2 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Metabolism and nutrition disorders Hyperuricaemia	1.0% 3/300 • Number of events 3 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Metabolism and nutrition disorders Hypocalcaemia	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Metabolism and nutrition disorders Hypoglycaemia	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Musculoskeletal and connective tissue disorders Arthritis	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Musculoskeletal and connective tissue disorders Pain in extremity	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.67% 2/300 • Number of events 2 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Nervous system disorders Brain oedema	0.33% 1/300 • Number of events 2 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Nervous system disorders Cerebral artery embolism	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Nervous system disorders Cerebral haemorrhage	0.33% 1/300 • Number of events 2 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Nervous system disorders Dizziness	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Nervous system disorders Haemorrhage intracranial	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Nervous system disorders Headache	0.33% 1/300 • Number of events 2 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Nervous system disorders Lacunar infarction	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Nervous system disorders Paralysis	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Nervous system disorders Syncope	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.0% 3/300 • Number of events 3 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.67% 2/300 • Number of events 2 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Organising pneumonia	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.67% 2/300 • Number of events 2 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.67% 2/300 • Number of events 2 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.67% 2/300 • Number of events 2 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Skin and subcutaneous tissue disorders Drug eruption	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Vascular disorders Deep vein thrombosis	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Vascular disorders Hypotension	0.33% 1/300 • Number of events 1 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.

Other adverse events

Measure	Tislelizumab n=300 participants at risk Tislelizumab 200 mg was administered intravenously (IV) once every 3 weeks (21 days per cycle) until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator. Safety analysis data are summarized for the overall population given that the same dose was applied, regardless of part assignment, as pre-specified in the clinical study report.
Blood and lymphatic system disorders Anaemia	36.7% 110/300 • Number of events 227 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Blood and lymphatic system disorders Leukopenia	3.0% 9/300 • Number of events 22 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Endocrine disorders Hyperthyroidism	4.7% 14/300 • Number of events 15 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Endocrine disorders Hypothyroidism	15.0% 45/300 • Number of events 67 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Gastrointestinal disorders Abdominal pain	3.7% 11/300 • Number of events 14 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Gastrointestinal disorders Constipation	9.7% 29/300 • Number of events 37 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Gastrointestinal disorders Diarrhoea	7.0% 21/300 • Number of events 25 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Gastrointestinal disorders Dysphagia	3.0% 9/300 • Number of events 13 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Gastrointestinal disorders Nausea	6.3% 19/300 • Number of events 24 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Gastrointestinal disorders Vomiting	6.3% 19/300 • Number of events 23 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
General disorders Fatigue	6.7% 20/300 • Number of events 22 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
General disorders Malaise	8.7% 26/300 • Number of events 32 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
General disorders Non-cardiac chest pain	4.0% 12/300 • Number of events 13 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
General disorders Pyrexia	13.0% 39/300 • Number of events 63 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Infections and infestations Pneumonia	3.7% 11/300 • Number of events 21 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Infections and infestations Upper respiratory tract infection	8.7% 26/300 • Number of events 33 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Infections and infestations Urinary tract infection	3.7% 11/300 • Number of events 14 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Investigations Alanine aminotransferase increased	23.7% 71/300 • Number of events 129 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Investigations Aspartate aminotransferase increased	27.0% 81/300 • Number of events 138 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Investigations Bilirubin conjugated increased	12.3% 37/300 • Number of events 127 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Investigations Blood albumin decreased	3.0% 9/300 • Number of events 13 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Investigations Blood alkaline phosphatase increased	8.0% 24/300 • Number of events 40 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Investigations Blood bilirubin increased	17.3% 52/300 • Number of events 186 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Investigations Blood bilirubin unconjugated increased	7.0% 21/300 • Number of events 87 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Investigations Blood creatine phosphokinase increased	5.3% 16/300 • Number of events 38 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Investigations Blood creatinine increased	5.3% 16/300 • Number of events 37 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Investigations Blood glucose increased	4.3% 13/300 • Number of events 28 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Investigations Blood lactate dehydrogenase increased	7.3% 22/300 • Number of events 33 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Investigations Blood thyroid stimulating hormone increased	4.3% 13/300 • Number of events 14 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Investigations Blood triglycerides increased	4.3% 13/300 • Number of events 36 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Investigations Blood urea increased	4.0% 12/300 • Number of events 40 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Investigations Blood uric acid increased	4.7% 14/300 • Number of events 35 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Investigations Gamma-glutamyltransferase increased	15.7% 47/300 • Number of events 102 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Investigations Haemoglobin decreased	4.0% 12/300 • Number of events 20 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Investigations Neutrophil count decreased	7.3% 22/300 • Number of events 80 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Investigations Neutrophil count increased	4.7% 14/300 • Number of events 14 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Investigations Platelet count decreased	8.7% 26/300 • Number of events 74 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Investigations Protein urine present	5.7% 17/300 • Number of events 22 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Investigations Red blood cells urine positive	5.7% 17/300 • Number of events 34 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Investigations Weight decreased	16.7% 50/300 • Number of events 82 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Investigations Weight increased	11.0% 33/300 • Number of events 97 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Investigations White blood cell count decreased	12.0% 36/300 • Number of events 137 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Investigations White blood cells urine positive	6.3% 19/300 • Number of events 34 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Metabolism and nutrition disorders Decreased appetite	9.0% 27/300 • Number of events 29 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Metabolism and nutrition disorders Hyperglycaemia	5.7% 17/300 • Number of events 28 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Metabolism and nutrition disorders Hypertriglyceridaemia	4.0% 12/300 • Number of events 34 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Metabolism and nutrition disorders Hyperuricaemia	7.3% 22/300 • Number of events 55 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Metabolism and nutrition disorders Hypoalbuminaemia	11.3% 34/300 • Number of events 64 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Metabolism and nutrition disorders Hypokalaemia	7.0% 21/300 • Number of events 38 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Metabolism and nutrition disorders Hyponatraemia	7.0% 21/300 • Number of events 45 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Metabolism and nutrition disorders Hypophosphataemia	3.3% 10/300 • Number of events 16 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Musculoskeletal and connective tissue disorders Arthralgia	4.0% 12/300 • Number of events 15 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Musculoskeletal and connective tissue disorders Back pain	6.7% 20/300 • Number of events 23 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Musculoskeletal and connective tissue disorders Pain in extremity	3.0% 9/300 • Number of events 14 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Nervous system disorders Dizziness	3.7% 11/300 • Number of events 14 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Psychiatric disorders Insomnia	6.0% 18/300 • Number of events 18 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Renal and urinary disorders Proteinuria	17.3% 52/300 • Number of events 114 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Cough	12.0% 36/300 • Number of events 48 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Haemoptysis	4.0% 12/300 • Number of events 18 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Productive cough	5.3% 16/300 • Number of events 27 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Skin and subcutaneous tissue disorders Pruritus	7.3% 22/300 • Number of events 30 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Skin and subcutaneous tissue disorders Rash	8.3% 25/300 • Number of events 45 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.
Vascular disorders Hypertension	4.7% 14/300 • Number of events 43 • Up to 30 days after the last dose of study treatment; Up to approximately 3 years and 5 months All AEs will be recorded during the study (AE from the time of the first dose and SAEs from the time of signing of informed consent) and for up to 30 days after the last dose of study treatment or until the initiation of another anticancer therapy, whichever occurs first.

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