Phase 3
N=684
A Study of Tislelizumab Versus Sorafenib in Participants With Unresectable Hepatocellular Carcinoma (HCC)
Hepatocellular Carcinoma (HCC)
Bottom Line
View on ClinicalTrials.gov: NCT03412773 ↗Enrolled (actual)
684
Serious AEs
15.0%
Results posted
Oct 2025
Primary outcome: Primary: Safety Run-in Sub-study: Number of Participants With Treatment-emergent Adverse Events (TEAEs) — 8; 1 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Tislelizumab (Drug); Sorafenib (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- BeiGene
- Primary completion
- Jul 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Safety Run-in Sub-study: Number of Participants With Treatment-emergent Adverse Events (TEAEs) |
8; 1 | — |
| PRIMARY Safety Run-in Sub-study: Serum Concentration of Tislelizumab |
63.21; 53.04; 42.06; 32.61; 23.74; 27.17 | — |
| PRIMARY Main Study: Overall Survival (OS) |
15.9; 14.1 | 0.0398 sig |
| SECONDARY Overall Response Rate (ORR) as Assessed by Blinded Independent Review Committee (BIRC) |
14.3; 5.4 | 0.0003 sig |
| SECONDARY Overall Response Rate (ORR) as Assessed by the Investigator |
20; 15.5; 5.7 | <0.0001 sig |
| SECONDARY Progression Free Survival (PFS) as Assessed by BIRC |
2.1; 3.4 | 0.1364 |
| SECONDARY Progression Free Survival (PFS) Assessed by the Investigator |
2.1; 2.1; 4.0 | 0.2622 |
| SECONDARY Duration of Response (DOR) as Assessed by BIRC |
36.1; 11.0 | — |
| SECONDARY Duration of Response (DOR) Assessed by the Investigator |
NA; 25.2; 13.8 | — |
| SECONDARY Time to Progression (TTP) Assessed by BIRC |
2.2; 4.1 | 0.0859 |
| SECONDARY Time to Progression (TTP) as Assessed by the Investigator |
2.1; 4.1 | 0.1182 |
| SECONDARY Safety Run-in Sub-study: Overall Survival |
29.7 | — |
| SECONDARY Disease Control Rate (DCR) as Assessed by BIRC |
44.2; 50.3 | — |
| SECONDARY Disease Control Rate (DCR) as Assessed by the Investigator |
44.2; 52.4 | — |
| SECONDARY Clinical Benefit Rate (CBR) as Assessed by BIRC |
25.4; 24.4 | — |
| SECONDARY Clinical Benefit Rate (CBR) as Assessed by the Investigator |
25.7; 28.9 | — |
| SECONDARY 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; 3.9 | 0.0033 sig |
| SECONDARY Change From Baseline in the European EORTC QLQ HCC 18 Index Score at Cycle 6 |
2.2; 4.9 | 0.0096 sig |
| SECONDARY 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; -5.1 | 0.0037 sig |
| SECONDARY Change From Baseline in the EORTC QLQ-C30 Global Health Status/Quality of Life Score at Cycle 6 |
-0.9; -5.9 | 0.0022 sig |
| SECONDARY 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; -4.3 | — |
| SECONDARY Change From Baseline in the EQ-5D-5L VAS at Cycle 6 |
-0.2; -5.4 | — |
| SECONDARY Main Study: Number of Participants With Treatment-emergent Adverse Events |
325; 324; 104; 91 | — |
| SECONDARY Safety Run-in Sub-study: Number of Participants Who Developed Anti-tislelizumab Antibodies |
1; 0 | — |
Summary
This Phase 3 study was a global, multicenter trial that randomly assigned participants to either tislelizumab or sorafenib as a first-line treatment for adults with advanced liver cancer (hepatocellular carcinoma) that could not be surgically removed. Before enrolling Japanese participants in the main Phase 3 study, a preliminary assessment of safety and tolerability (the Safety Run-In Sub-study) was conducted in Japan.
Eligibility Criteria
Safety Run-In Sub-study Eligibility Criteria: The study included adult Japanese participants (≥ 20 years) with histologically confirmed hepatocellular carcinoma (HCC) at Barcelona Clinic Liver Cancer (BCLC) Stage C or B. Eligible participants had either received, were ineligible for, or declined standard treatment. Additional requirements were a Child-Pugh A classification within 7 days before enrollment, at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and an Eastern Cooperative Oncology Group (ECOG) Performance Status score of ≤ 1.
Main Study Key Inclusion Criteria:
- Histologically confirmed diagnosis of HCC
- Barcelona Clinic Liver Cancer (BCLC) Stage B or C disease not amenable to or progressing after loco-regional therapy and not amenable to a curative treatment approach
- No prior systemic therapy for HCC (with the exception of HCC participants enrolled in the safety run-in substudy [Japan only])
- Measurable disease
- Child-Pugh score A
- Easter Cooperative Oncology Group (ECOG) Performance Status ≤ 1
- Adequate organ function
Main Study Key Exclusion Criteria:
- Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC histology
- Tumor thrombus involving main trunk of portal vein or inferior vena cava
- Loco-regional therapy to the liver within 28 days before randomization
- Clinical evidence of portal hypertension with bleeding esophageal or gastric varices at Screening, or within 6 months before randomization
- Bleeding or thrombotic disorder or any prescribed anticoagulant requiring therapeutic international normalized ratio monitoring (eg, warfarin or similar agents) at Screening, or within 6 months before randomization/enrollment
- Presence at Screening of active immune deficiency or autoimmune disease and/or prior history of any immune deficiency or autoimmune disease that may relapse
- Participant with any condition requiring systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication within 14 days before randomization
- History of interstitial lung disease or non-infectious pneumonitis, unless induced by radiation therapy
- QT interval corrected for heart rate (QTc) (corrected by Fridericia's method) > 450 msec at Screening
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Data sourced from ClinicalTrials.gov (NCT03412773). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.