Trial Outcomes & Findings for A Study of Tislelizumab Versus Sorafenib in Participants With Unresectable Hepatocellular Carcinoma (HCC) (NCT NCT03412773)

Last Updated: 2025-10-14

Results Overview

An adverse event (AE) is any unfavorable or unintended sign (e.g., abnormal lab result), symptom, or disease temporally associated with study drug use, regardless of causality. A serious adverse event (SAE) is defined as any adverse event that: * Resulted in death * Was life-threatening * Required or prolonged hospitalization * Caused disability/incapacity * Lead to a congenital anomaly/birth defect * Was deemed medically significant by the investigator (e.g., required intervention to prevent severe outcomes).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

684 participants

Primary outcome timeframe

From the first dose to 30 days after the last dose, new anticancer therapy, or the analysis cutoff of December 14th, 2023 (a maximum of 64 months)

Results posted on

2025-10-14

Participant Flow

The main study enrolled participants across centers in Asia, Europe, and the U.S. The first participant consented on December 18, 2017, and the study concluded on December 14, 2023. In Japan, a safety run-in sub-study was conducted to evaluate tislelizumab's safety and tolerability in Japanese patients with hepatocellular carcinoma (HCC). Sub-study participants were not assessed for the same primary and secondary endpoints specified for the main study.

The main study had 4 phases: Screening, Treatment, Safety Follow-up (up to 30 days post-treatment or 90 days post-tislelizumab for immune events); and Survival Follow-up (duration varied). Randomization in the main study was stratified by macrovascular invasion (present vs absent), extrahepatic spread (present vs absent), etiology (hepatitis C virus vs other), Eastern Cooperative Oncology Group Performance Status (0 vs 1) and geography (Asia \[excluding Japan\] vs Japan vs Rest of World).

Participant milestones

Participant milestones
Measure	Arm A: Tislelizumab Participants received 200 mg of intravenous tislelizumab every 3 weeks until intolerable toxicity, withdrawal of consent, or the investigator determined no further benefit from the therapy.	Safety Run-In Sub-study Japanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability.	Arm B: Sorafenib Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.
Overall Study STARTED	342	10	332
Overall Study Treated	338	10	324
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	342	10	332

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A: Tislelizumab Participants received 200 mg of intravenous tislelizumab every 3 weeks until intolerable toxicity, withdrawal of consent, or the investigator determined no further benefit from the therapy.	Safety Run-In Sub-study Japanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability.	Arm B: Sorafenib Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.
Overall Study Lost to Follow-up	7	0	6
Overall Study Withdrawal by Subject	15	0	19
Overall Study Study Closed By Sponsor	46	3	33
Overall Study Transfer to Long Term Extension (BGB-A317-290-LTE1) or Post Trial Supply (PTS)	15	0	0
Overall Study Death	259	7	273
Overall Study Physician Decision	0	0	1

Baseline Characteristics

A Study of Tislelizumab Versus Sorafenib in Participants With Unresectable Hepatocellular Carcinoma (HCC)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Safety Run-In Sub-study n=10 Participants Japanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability.	Arm A: Tislelizumab n=342 Participants Participants received 200 mg of intravenous tislelizumab every 3 weeks until intolerable toxicity, withdrawal of consent, or the investigator determined no further benefit from the therapy.	Arm B: Sorafenib n=332 Participants Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.	Total n=684 Participants Total of all reporting groups
Age, Continuous	71.70 years STANDARD_DEVIATION 8.247 • n=5 Participants	60.45 years STANDARD_DEVIATION 12.528 • n=7 Participants	59.51 years STANDARD_DEVIATION 12.737 • n=5 Participants	60.15 years STANDARD_DEVIATION 12.652 • n=4 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	53 Participants n=7 Participants	51 Participants n=5 Participants	107 Participants n=4 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	289 Participants n=7 Participants	281 Participants n=5 Participants	577 Participants n=4 Participants
Race/Ethnicity, Customized Asian	10 Participants n=5 Participants	255 Participants n=7 Participants	250 Participants n=5 Participants	515 Participants n=4 Participants
Race/Ethnicity, Customized White	0 Participants n=5 Participants	71 Participants n=7 Participants	73 Participants n=5 Participants	144 Participants n=4 Participants
Race/Ethnicity, Customized Not Reported	0 Participants n=5 Participants	9 Participants n=7 Participants	6 Participants n=5 Participants	15 Participants n=4 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 (Fully active)	9 Participants n=5 Participants	182 Participants n=7 Participants	180 Participants n=5 Participants	371 Participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1 (Restricted but ambulatory)	1 Participants n=5 Participants	160 Participants n=7 Participants	152 Participants n=5 Participants	313 Participants n=4 Participants
Macrovascular Invasion Present	0 Participants n=5 Participants	51 Participants n=7 Participants	48 Participants n=5 Participants	99 Participants n=4 Participants
Macrovascular Invasion Absent	10 Participants n=5 Participants	291 Participants n=7 Participants	284 Participants n=5 Participants	585 Participants n=4 Participants
Extrahepatic Spread Present	4 Participants n=5 Participants	219 Participants n=7 Participants	198 Participants n=5 Participants	421 Participants n=4 Participants
Extrahepatic Spread Absent	6 Participants n=5 Participants	123 Participants n=7 Participants	134 Participants n=5 Participants	263 Participants n=4 Participants
Geographic Region Asia (excluding Japan)	0 participants n=5 Participants	215 participants n=7 Participants	210 participants n=5 Participants	425 participants n=4 Participants
Geographic Region Japan	10 participants n=5 Participants	38 participants n=7 Participants	39 participants n=5 Participants	87 participants n=4 Participants
Geographic Region European Union (EU)/United States (US)	0 participants n=5 Participants	89 participants n=7 Participants	83 participants n=5 Participants	172 participants n=4 Participants
Etiology Hepatitis C Virus	4 Participants n=5 Participants	46 Participants n=7 Participants	39 Participants n=5 Participants	89 Participants n=4 Participants
Etiology Other	6 Participants n=5 Participants	296 Participants n=7 Participants	293 Participants n=5 Participants	595 Participants n=4 Participants

PRIMARY outcome

Timeframe: From the first dose to 30 days after the last dose, new anticancer therapy, or the analysis cutoff of December 14th, 2023 (a maximum of 64 months)

Population: The Sub-study Safety Analysis Set includes all participants in the safety run-in sub-study who received at least one dose of any study drug.

Outcome measures

Outcome measures
Measure	Safety Run-In Sub-study n=10 Participants Japanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability.	Arm B: Sorafenib Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.	Arm B: Sorafenib Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.
Safety Run-in Sub-study: Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAEs	8 Participants	—	—
Safety Run-in Sub-study: Number of Participants With Treatment-emergent Adverse Events (TEAEs) SAEs	1 Participants	—	—

PRIMARY outcome

Timeframe: Cycle 1 and Cycle 5 at end of infusion, 24 hand 72 hours post-dose, and 8 days and 15 days post-dose (each cycle was 3 weeks).

Population: The Sub-study Pharmacokinetic (PK) Analysis Set includes all participants in the safety run-in sub-study who received at least 1 dose of tislelizumab per the protocol, for whom any post-dose PK data were available at each time point.

Serum concentration of tislelizumab was a pre-specified primary endpoint for the sub-study only.

Outcome measures

Outcome measures
Measure	Safety Run-In Sub-study n=10 Participants Japanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability.	Arm B: Sorafenib Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.	Arm B: Sorafenib Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.
Safety Run-in Sub-study: Serum Concentration of Tislelizumab Cycle 1 End of Infusion	63.21 µg/mL Geometric Coefficient of Variation 22.304	—	—
Safety Run-in Sub-study: Serum Concentration of Tislelizumab Cycle 1: 24 Hours Post Dose	53.04 µg/mL Geometric Coefficient of Variation 20.901	—	—
Safety Run-in Sub-study: Serum Concentration of Tislelizumab Cycle 1: 72 Hours Post Dose	42.06 µg/mL Geometric Coefficient of Variation 23.649	—	—
Safety Run-in Sub-study: Serum Concentration of Tislelizumab Cycle 1: 8 Days Post Dose	32.61 µg/mL Geometric Coefficient of Variation 16.920	—	—
Safety Run-in Sub-study: Serum Concentration of Tislelizumab Cycle 1: 15 Days Post Dose	23.74 µg/mL Geometric Coefficient of Variation 18.328	—	—
Safety Run-in Sub-study: Serum Concentration of Tislelizumab Cycle 5 Day 1: Predose	27.17 µg/mL Geometric Coefficient of Variation 34.436	—	—
Safety Run-in Sub-study: Serum Concentration of Tislelizumab Cycle 5 Day 1: End of Infusion	87.54 µg/mL Geometric Coefficient of Variation 27.508	—	—
Safety Run-in Sub-study: Serum Concentration of Tislelizumab Cycle 5: 24 Hours Post Dose	80.54 µg/mL Geometric Coefficient of Variation 27.006	—	—
Safety Run-in Sub-study: Serum Concentration of Tislelizumab Cycle 5: 72 Hours Post Dose	64.80 µg/mL Geometric Coefficient of Variation 23.837	—	—
Safety Run-in Sub-study: Serum Concentration of Tislelizumab Cycle 5: 8 Days Post Dose	52.65 µg/mL Geometric Coefficient of Variation 26.759	—	—
Safety Run-in Sub-study: Serum Concentration of Tislelizumab Cycle 5: 15 Days Post Dose	37.57 µg/mL Geometric Coefficient of Variation 24.982	—	—

PRIMARY outcome

Timeframe: Through the primary analysis data cut-off date of July 11th, 2022 (up to approximately 55 months)

Population: The Intent-To-Treat (ITT) analysis set included all randomized participants in the main study.

Defined as the time from the date of randomization to the date of death due to any cause. Median OS was estimated using Kaplan-Meier methodology. Overall survival was a pre-specified primary endpoint for the main study only.

Outcome measures

Outcome measures
Measure	Safety Run-In Sub-study n=342 Participants Japanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability.	Arm B: Sorafenib n=332 Participants Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.	Arm B: Sorafenib Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.
Main Study: Overall Survival (OS)	15.9 Months Interval 13.2 to 19.7	14.1 Months Interval 12.6 to 17.4	—

SECONDARY outcome

Timeframe: Through the primary analysis data cut-off date of July 11th, 2022 (up to approximately 55 months)

Population: ITT Analysis Set

Defined as the percentage of participants who had partial response or complete response as determined by Blinded Independent Review Committee (BIRC) per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in all randomized participants with measurable disease at baseline. ORR was not assessed by the BIRC for participants in the sub-study, and this was not a pre-specified sub-study endpoint.

Outcome measures

Outcome measures
Measure	Safety Run-In Sub-study n=342 Participants Japanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability.	Arm B: Sorafenib n=332 Participants Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.	Arm B: Sorafenib Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.
Overall Response Rate (ORR) as Assessed by Blinded Independent Review Committee (BIRC)	14.3 percentage of participants Interval 10.8 to 18.5	5.4 percentage of participants Interval 3.2 to 8.4	—

SECONDARY outcome

Timeframe: Through the study completion data cut-off date of December 14th, 2023 (up to approximately 65 months)

Population: Sub-study Safety Analysis Set; Main study ITT Analysis Set

Defined as the percentage of participants who had partial response or complete response as determined by the investigator per RECIST v1.1 in all randomized participants with measurable disease at baseline.

Outcome measures

Outcome measures
Measure	Safety Run-In Sub-study n=10 Participants Japanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability.	Arm B: Sorafenib n=342 Participants Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.	Arm B: Sorafenib n=332 Participants Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.
Overall Response Rate (ORR) as Assessed by the Investigator	20 percentage of participants Interval 2.5 to 55.6	15.5 percentage of participants Interval 11.8 to 19.8	5.7 percentage of participants Interval 3.5 to 8.8

SECONDARY outcome

Timeframe: Through the primary analysis data cut-off date of July 11th, 2022 (up to approximately 55 months)

Population: ITT Analysis Set

Defined as the time from randomization to the first objectively documented disease progression, or death from any cause, whichever occurred first, as assessed by the BIRC per RECIST v1.1. Kaplan-Meier methodology was used to estimate the median PFS. PFS was not assessed by the BIRC for participants in the sub-study, and this was not a pre-specified sub-study endpoint.

Outcome measures

Outcome measures
Measure	Safety Run-In Sub-study n=342 Participants Japanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability.	Arm B: Sorafenib n=332 Participants Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.	Arm B: Sorafenib Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.
Progression Free Survival (PFS) as Assessed by BIRC	2.1 months Interval 2.1 to 3.5	3.4 months Interval 2.2 to 4.1	—

SECONDARY outcome

Timeframe: Through the study completion data cut-off date of December 14th, 2023 (up to approximately 65 months)

Population: Sub-study Safety Analysis Set; Main study ITT Analysis Set

Defined as the time from randomization to the first objectively documented disease progression, or death from any cause, whichever occurred first, as assessed by the investigator per RECIST v1.1. Kaplan-Meier methodology was used to estimate the median PFS.

Outcome measures

Outcome measures
Measure	Safety Run-In Sub-study n=10 Participants Japanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability.	Arm B: Sorafenib n=342 Participants Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.	Arm B: Sorafenib n=332 Participants Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.
Progression Free Survival (PFS) Assessed by the Investigator	2.1 Months Interval 1.9 to 16.0	2.1 Months Interval 2.1 to 2.3	4.0 Months Interval 2.7 to 4.1

SECONDARY outcome

Timeframe: Through the primary analysis data cut-off date of July 11th, 2022 (up to approximately 55 months)

Population: ITT Analysis Set. Only participants with best overall response of complete response or partial response confirmed per RECIST v1.1 were included in the analysis, and percentages were based on the number of responders.

Defined as the time from the first occurrence of a documented objective response until the first documentation of progression or death from any cause, whichever occurred first, as determined by the BIRC per RECIST v1.1. Median DOR was estimated using Kaplan-Meier methodology. DOR was not assessed by the BIRC for participants in the sub-study, and this was not a pre-specified sub-study endpoint.

Outcome measures

Outcome measures
Measure	Safety Run-In Sub-study n=49 Participants Japanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability.	Arm B: Sorafenib n=18 Participants Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.	Arm B: Sorafenib Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.
Duration of Response (DOR) as Assessed by BIRC	36.1 months Interval 16.8 to Not estimable due to insufficient number of participants with events	11.0 months Interval 6.2 to 14.7	—

SECONDARY outcome

Timeframe: Through the study completion data cut-off date of December 14th, 2023 (up to approximately 65 months)

Population: Sub-study Safety Analysis Set; Main study ITT Analysis Set; Only participants with best overall response of complete response or partial response per investigator assessment were included in the analysis.

Defined as the time from the first occurrence of a documented objective response until the first documentation of progression or death from any cause, whichever occurred first, as assessed by the investigator per RECIST v1.1. Median DOR was estimated using Kaplan-Meier methodology.

Outcome measures

Outcome measures
Measure	Safety Run-In Sub-study n=2 Participants Japanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability.	Arm B: Sorafenib n=53 Participants Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.	Arm B: Sorafenib n=19 Participants Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.
Duration of Response (DOR) Assessed by the Investigator	NA Months Not estimable due to insufficient number of participants with events	25.2 Months Interval 18.1 to 46.8	13.8 Months Interval 6.2 to 20.3

SECONDARY outcome

Timeframe: Through the primary analysis data cut-off date of July 11th, 2022 (up to approximately 55 months)

Population: ITT Analysis Set

Defined as the time from the date of randomization to the date of the first objectively documented tumor progression as assessed by the BIRC per RECIST v1.1. Median TTP was estimated using Kaplan-Meier methodology. TTP was not assessed by the BIRC for participants in the sub-study, and this was not a pre-specified sub-study endpoint.

Outcome measures

Outcome measures
Measure	Safety Run-In Sub-study n=342 Participants Japanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability.	Arm B: Sorafenib n=332 Participants Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.	Arm B: Sorafenib Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.
Time to Progression (TTP) Assessed by BIRC	2.2 Months Interval 2.1 to 3.6	4.1 Months Interval 2.2 to 4.1	—

SECONDARY outcome

Timeframe: Through the study completion data cut-off date of December 14th, 2023 (up to approximately 65 months)

Population: ITT Analysis Set

Defined as the time from the date of randomization to the date of the first objectively documented tumor progression as assessed by the investigator per RECIST v1.1. Median TTP was estimated using Kaplan-Meier methodology. TTP was not a pre-specified sub-study endpoint.

Outcome measures

Outcome measures
Measure	Safety Run-In Sub-study n=342 Participants Japanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability.	Arm B: Sorafenib n=332 Participants Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.	Arm B: Sorafenib Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.
Time to Progression (TTP) as Assessed by the Investigator	2.1 months Interval 2.1 to 3.3	4.1 months Interval 3.4 to 4.2	—

SECONDARY outcome

Timeframe: Up a to 64 months

Population: Sub-study Safety Analysis Set

Defined as the time from the date of randomization to the date of death due to any cause. Median OS was estimated using Kaplan-Meier methodology.

Outcome measures

Outcome measures
Measure	Safety Run-In Sub-study n=10 Participants Japanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability.	Arm B: Sorafenib Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.	Arm B: Sorafenib Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.
Safety Run-in Sub-study: Overall Survival	29.7 months Interval 3.0 to Not estimable due to insufficient number of participants with events	—	—

SECONDARY outcome

Timeframe: Through the primary analysis data cut-off date of July 11th, 2022 (up to approximately 55 months)

Population: ITT Analysis Set

Defined as the percentage of participants whose best overall response (BOR) was complete response, partial response, or stable disease as assessed by the BIRC per RECIST v1.1. DCR was not a pre-specified endpoint for participants in the sub-study.

Outcome measures

Outcome measures
Measure	Safety Run-In Sub-study n=342 Participants Japanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability.	Arm B: Sorafenib n=332 Participants Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.	Arm B: Sorafenib Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.
Disease Control Rate (DCR) as Assessed by BIRC	44.2 percentage of participants	50.3 percentage of participants	—

SECONDARY outcome

Timeframe: Through the study completion data cut-off date of December 14th, 2023 (up to approximately 65 months)

Population: ITT Analysis Set

Defined as the percentage of participants whose best overall response (BOR) was complete response, partial response, or stable disease as assessed by the investigator per RECIST v1.1. DCR was not a pre-specified endpoint for participants in the sub-study.

Outcome measures

Outcome measures
Measure	Safety Run-In Sub-study n=342 Participants Japanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability.	Arm B: Sorafenib n=332 Participants Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.	Arm B: Sorafenib Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.
Disease Control Rate (DCR) as Assessed by the Investigator	44.2 percentage of participants	52.4 percentage of participants	—

SECONDARY outcome

Timeframe: Through the primary analysis data cut-off date of July 11th, 2022 (up to approximately 55 months)

Population: ITT Analysis Set

Defined as the percentage of participants whose best overall response (BOR) was complete response, partial response, or stable disease greater than or equal to 24 weeks in duration, as assessed by the BIRC per RECIST v1.1. CBR was not a pre-specified endpoint for participants in the sub-study.

Outcome measures

Outcome measures
Measure	Safety Run-In Sub-study n=342 Participants Japanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability.	Arm B: Sorafenib n=332 Participants Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.	Arm B: Sorafenib Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.
Clinical Benefit Rate (CBR) as Assessed by BIRC	25.4 percentage of participants	24.4 percentage of participants	—

SECONDARY outcome

Timeframe: Through the study completion data cut-off date of December 14th, 2023 (up to approximately 65 months)

Population: ITT Analysis Set

Defined as the percentage of participants whose best overall response (BOR) is complete response, partial response, or stable disease greater than or equal to 24 weeks in duration, as assessed by the investigator per RECIST v1.1. CBR was not a pre-specified endpoint for participants in the sub-study.

Outcome measures

Outcome measures
Measure	Safety Run-In Sub-study n=342 Participants Japanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability.	Arm B: Sorafenib n=332 Participants Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.	Arm B: Sorafenib Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.
Clinical Benefit Rate (CBR) as Assessed by the Investigator	25.7 percentage of participants	28.9 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline to Cycle 4 (each cycle was 21 days)

Population: ITT Analysis Set. Only participants with data at both Baseline and Cycle 4 are included

The EORTC QLQ-HCC18 is a questionnaire specifically designed to assess health-related quality of life in participants with hepatocellular carcinoma. It includes six symptom scales measuring Fatigue (3 items), Jaundice (2 items), Body Image (2 items), Nutrition (5 items), Pain (2 items), Fever (2 items) and two single items measuring Sex Life and Abdominal Swelling. Participants respond on a scale from 1 = "Not at all" to 4 = "Very Much. Raw scores are transformed into a 0 to 100 scale using linear transformation. The HCC18 Index score is calculated from each of the 6 symptom scales and the 2 single items, and ranges from 0 to 100. Higher scores indicate greater symptom burden or worse quality of life. The EORTC QLQ-HCC18 was not assessed for participants in the sub-study.

Outcome measures

Outcome measures
Measure	Safety Run-In Sub-study n=220 Participants Japanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability.	Arm B: Sorafenib n=176 Participants Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.	Arm B: Sorafenib Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.
Change From Baseline in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Hepatocellular Carcinoma 18 Questions (EORTC QLQ HCC 18) Index Score at Cycle 4	1.6 score on a scale Interval 0.4 to 2.9	3.9 score on a scale Interval 2.6 to 5.2	—

SECONDARY outcome

Timeframe: Baseline to Cycle 6 (Each cycle was 21 days)

Population: ITT Analysis Set. Only participants with data at both baseline and Cycle 6 are included

The EORTC QLQ-HCC18 is a questionnaire specifically designed to assess health-related quality of life in participants with hepatocellular carcinoma. It includes six symptom scales measuring Fatigue (3 items), Jaundice (2 items), Body Image (2 items), Nutrition (5 items), Pain (2 items), Fever (2 items) and two single items measuring Sex Life and Abdominal Swelling. Participants respond on a scale from 1 = "Not at all" to 4 = "Very Much. Raw scores are transformed into a 0 to 100 scale using linear transformation. The HCC18 Index score is calculated from each of the 6 symptom scales and the 2 single items, and ranges from 0 to 100. Higher scores indicate greater symptom burden or worse quality of life. The HEORTC QLQ-HCC18 was not assessed in participants in the sub-study.

Outcome measures

Outcome measures
Measure	Safety Run-In Sub-study n=166 Participants Japanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability.	Arm B: Sorafenib n=138 Participants Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.	Arm B: Sorafenib Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.
Change From Baseline in the European EORTC QLQ HCC 18 Index Score at Cycle 6	2.2 score on a scale Interval 0.6 to 3.7	4.9 score on a scale Interval 3.2 to 6.5	—

SECONDARY outcome

Timeframe: Baseline to Cycle 4 (each cycle was 21 days)

Population: ITT Analysis Set. Only participants with data at both Baseline and Cycle 4 are included.

The EORTC QLQ-C30 v3.0 is a questionnaire that assesses quality of life of participants with cancer. It includes global health status and quality of life questions related to overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. A higher score indicates better health outcomes. The EORTC QLQ-C30 was not assessed in participants in the sub-study.

Outcome measures

Outcome measures
Measure	Safety Run-In Sub-study n=220 Participants Japanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability.	Arm B: Sorafenib n=176 Participants Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.	Arm B: Sorafenib Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.
Change From Baseline in the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life Score at Cycle 4	-0.7 score on a scale Interval -3.0 to 1.6	-5.1 score on a scale Interval -7.6 to -2.6	—

SECONDARY outcome

Timeframe: Baseline to Cycle 6 (each cycle was 21 days)

Population: ITT Analysis Set. Only participants with data at both Baseline and Cycle 6 are included.

Outcome measures

Outcome measures
Measure	Safety Run-In Sub-study n=165 Participants Japanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability.	Arm B: Sorafenib n=137 Participants Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.	Arm B: Sorafenib Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.
Change From Baseline in the EORTC QLQ-C30 Global Health Status/Quality of Life Score at Cycle 6	-0.9 score on a scale Interval -3.4 to 1.6	-5.9 score on a scale Interval -8.6 to -3.2	—

SECONDARY outcome

Timeframe: Baseline to Cycle 4 (each cycle was 21 days)

Population: ITT Analysis Set. Only participants with data at both Baseline and Cycle 4 are included in the analysis.

The EQ-5D-5L comprises a descriptive module and a Visual Analogue scale (VAS). The EQ-5D-5L VAS measures respondent's self-rated health status on a 0 to 100 scale, with 100 = 'the best health you can imagine' and 0 = 'the worst health you can imagine'. Higher scores on VAS indicate higher health status. The EQ-5D-5L VAS was not assessed in participants in the sub-study.

Outcome measures

Outcome measures
Measure	Safety Run-In Sub-study n=213 Participants Japanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability.	Arm B: Sorafenib n=170 Participants Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.	Arm B: Sorafenib Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.
Change From Baseline in the European Quality of Life 5 Dimensions, 5-level (EQ-5D-5L) Visual Analogue Scale (VAS) at Cycle 4	-0.4 score on a scale Standard Deviation 14.52	-4.3 score on a scale Standard Deviation 12.92	—

SECONDARY outcome

Timeframe: Baseline to Cycle 6 (each cycle was 21 days)

Population: ITT Analysis Set. Only participants with data at both Baseline and Cycle 6 are included in the analysis.

The EQ-5D-5L comprises a descriptive module and a visual analogue scale (VAS). The EQ-5D-5L VAS measures respondent's self-rated health status on a 0 to 100 scale, with 100 = 'the best health you can imagine' and 0 = 'the worst health you can imagine'. Higher scores on VAS indicate higher health status. The EQ-5D-5L VAS was not assessed in participants in the sub-study.

Outcome measures

Outcome measures
Measure	Safety Run-In Sub-study n=161 Participants Japanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability.	Arm B: Sorafenib n=132 Participants Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.	Arm B: Sorafenib Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.
Change From Baseline in the EQ-5D-5L VAS at Cycle 6	-0.2 score on a scale Standard Deviation 17.03	-5.4 score on a scale Standard Deviation 13.09	—

SECONDARY outcome

Timeframe: From the first dose to 30 days after the last dose, new anticancer therapy, or the study completion analysis cutoff on December 14th, 2023 (a maximum of 61 months for participants in Arm A and 63 months for participants in Arm B).

Population: The Safety Analysis Set includes all randomized participants who received at least one dose of any study drug.

Outcome measures

Outcome measures
Measure	Safety Run-In Sub-study n=338 Participants Japanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability.	Arm B: Sorafenib n=324 Participants Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.	Arm B: Sorafenib Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.
Main Study: Number of Participants With Treatment-emergent Adverse Events TEAEs	325 Participants	324 Participants	—
Main Study: Number of Participants With Treatment-emergent Adverse Events SAEs	104 Participants	91 Participants	—

SECONDARY outcome

Timeframe: From the first dose to 30 days after the last dose, new anticancer therapy, or the analysis cutoff of December 14th, 2023 (a maximum of 64 months)

Population: The Sub-study Antidrug antibody (ADA) Analysis Set includes all participants enrolled in the sub-study who received at least one dose of tislelizumab for whom both baseline ADA and at least one postbaseline ADA results were available.

Treatment-emergent anti-drug antibodies (ADA): participants who were ADA negative at baseline and ADA positive post-baseline. Treatment-boosted ADA: participants who were ADA positive at baseline that was boosted to a 4-fold or higher-level following drug administration. ADA assessments were not performed for participants enrolled in the main study.

Outcome measures

Outcome measures
Measure	Safety Run-In Sub-study n=10 Participants Japanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability.	Arm B: Sorafenib Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.	Arm B: Sorafenib Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.
Safety Run-in Sub-study: Number of Participants Who Developed Anti-tislelizumab Antibodies Treatment-Emergent ADA	1 Participants	—	—
Safety Run-in Sub-study: Number of Participants Who Developed Anti-tislelizumab Antibodies Treatment-Boosted ADA	0 Participants	—	—

Adverse Events

Safety Run-In Sub-study

Serious events: 1 serious events

Other events: 8 other events

Deaths: 7 deaths

Arm A: Tislelizumab

Serious events: 104 serious events

Other events: 313 other events

Deaths: 258 deaths

Arm B: Sorafenib

Serious events: 91 serious events

Other events: 318 other events

Deaths: 273 deaths

Screening Period: All Enrolled Participants

Serious events: 7 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

BeiGene

Phone: 1-877-828-5568

Email: [email protected]

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