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NCT Number: NCT03412773

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

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.

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Key information

Conditions

Hepatocellular Carcinoma (HCC) Adenocarcinoma Carcinoma Carcinoma, Hepatocellular Digestive System Diseases Digestive System Neoplasms Liver Diseases Liver Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Tislelizumab

Drug

Tislelizumab 200 mg intravenously (IV) once every three weeks (Q3W)

Other names: BGB-A317

Sorafenib

Drug

Sorafenib 400 mg orally (PO) twice daily (BID)

Other names: Nexavar, BAY43-9006

Primary outcomes

  1. Safety Run-in Sub-study: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

    Time frame: 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)

    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).

  2. Safety Run-in Sub-study: Serum Concentration of Tislelizumab

    Time frame: 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).

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

  3. Main Study: Overall Survival (OS)

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

    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.

Secondary outcomes

  1. Overall Response Rate (ORR) as Assessed by Blinded Independent Review Committee (BIRC)

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

    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.

  2. Overall Response Rate (ORR) as Assessed by the Investigator

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

    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.

  3. Progression Free Survival (PFS) as Assessed by BIRC

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

    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.

  4. Progression Free Survival (PFS) Assessed by the Investigator

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

    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.

  5. Duration of Response (DOR) as Assessed by BIRC

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

    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.

  6. Duration of Response (DOR) Assessed by the Investigator

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

    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.

  7. Time to Progression (TTP) Assessed by BIRC

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

    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.

  8. Time to Progression (TTP) as Assessed by the Investigator

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

    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.

  9. Safety Run-in Sub-study: Overall Survival

    Time frame: Up a to 64 months

    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.

  10. Disease Control Rate (DCR) as Assessed by BIRC

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

    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.

  11. Disease Control Rate (DCR) as Assessed by the Investigator

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

    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.

  12. Clinical Benefit Rate (CBR) as Assessed by BIRC

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

    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.

  13. Clinical Benefit Rate (CBR) as Assessed by the Investigator

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

    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.

  14. 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

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

    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.

  15. Change From Baseline in the European EORTC QLQ HCC 18 Index Score at Cycle 6

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

    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.

  16. 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

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

    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.

  17. Change From Baseline in the EORTC QLQ-C30 Global Health Status/Quality of Life Score at Cycle 6

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

    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.

  18. Change From Baseline in the European Quality of Life 5 Dimensions, 5-level (EQ-5D-5L) Visual Analogue Scale (VAS) at Cycle 4

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

    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.

  19. Change From Baseline in the EQ-5D-5L VAS at Cycle 6

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

    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.

  20. Main Study: Number of Participants With Treatment-emergent Adverse Events

    Time frame: 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).

    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).

  21. Safety Run-in Sub-study: Number of Participants Who Developed Anti-tislelizumab Antibodies

    Time frame: 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)

    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.

Sponsors and collaborators

Lead sponsor

BeiGene

Industry

Registry information

Official study title

A Randomized, Open-label, Multicenter Phase 3 Study to Compare the Efficacy and Safety of BGB-A317 Versus Sorafenib as First-Line Treatment in Patients With Unresectable Hepatocellular Carcinoma

Important dates

Study start
2017
Primary completion
2022
Study completion
2023
First posted
Jan 26, 2018
Registry last updated
Oct 14, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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