Clinical Trials List
Protocol NumberBGB-A317-301
NCT Number(ClinicalTrials.gov Identfier)NCT03412773
Completed
2017-11-01 - 2021-05-20
Phase III
Terminated9
ICD-10C22
Malignant neoplasm of liver and intrahepatic bile ducts
ICD-10C22.0
Liver cell carcinoma
A Randomized, Open-label, Multi-center Phase 3 study to Compare the efficacy and Safety of BGB-A317 versus Sorafenib as First-Line Treatment in patients with Unresectable Hepatocellular Carcinoma
-
Trial Applicant
PAREXEL INTERNATIONAL CO., LTD.
-
Sponsor
BeiGene, Ltd. c/o BeiGene USA, Inc.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Ming-Huang Chen Division of Hematology & Oncology
- Rheun-Chuan Lee Division of Radiology
- Yi-Ping Hung Division of Hematology & Oncology
- Chung-Pin Li Digestive System Department
- San-Chi Chen Division of Hematology & Oncology
- Yi-Hsiang Huang Digestive System Department
The Actual Total Number of Participants Enrolled
2 Stop recruiting
Audit
None
Co-Principal Investigator
- 洪肇宏 Division of Radiation Therapy
- 郭垣宏 Division of Radiation Therapy
- 陳彥仰 Division of Radiation Therapy
- 紀廣明 Division of Radiation Therapy
- 顏毅豪 Division of Radiation Therapy
- 許獻文 Division of Radiation Therapy
- 盧勝男 Division of Radiation Therapy
- 陳建宏 Division of Radiation Therapy
- 饒坤銘 Division of Radiation Therapy
- 張國欽 Division of Radiation Therapy
- 蔡明釗 Division of Radiation Therapy
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 許家豪 外科及內科部
- Po-Heng Chuang 外科及內科部
- Hsueh-Chou Lai 外科及內科部
- 楊宏仁 外科及內科部
- Li-Yuan Bai 外科及內科部
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 吳宜穎 Division of Hematology & Oncology
- 陳登偉 Division of Hematology & Oncology
- 陳宇欽 Division of Hematology & Oncology
- 黃子權 Division of Hematology & Oncology
- 樊修龍 Division of Hematology & Oncology
- 張平穎 Division of Hematology & Oncology
- 葉人華 Division of Hematology & Oncology
- 謝財源 Division of Hematology & Oncology
- 戴明燊 Division of Hematology & Oncology
- 陳佳宏 Division of Hematology & Oncology
- 施宇隆 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
Audit
None
Principal Investigator
Linkou Chang Gung Medical Foundation
Taiwan National PI
Ming-Mo Hou
Co-Principal Investigator
- Tsai-Sheng Yang Division of General Surgery
- Wei-Chen Lee Division of General Surgery
- Ming-Chin Yu Division of General Surgery
- Shi-Ming Lin Division of General Surgery
- Kun-Ming Chan Division of General Surgery
- 呂嘉偉 Division of General Surgery
- Ming-Mo Hou Division of General Surgery
- Chien-Hao Huang Division of General Surgery
- 黃振洋 Division of General Surgery
- Chen-Chun Lin Division of General Surgery
- Chia-Hsun Hsieh Division of General Surgery
- 潘廣澤 Division of General Surgery
The Actual Total Number of Participants Enrolled
1 Stop recruiting
Audit
None
Co-Principal Investigator
Audit
None
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 邱彥程 Division of General Internal Medicine
- Liu Yi-Sheng Division of General Internal Medicine
- Chiu Hung Chiu Division of General Internal Medicine
- Yih-Jyh Lin Division of General Internal Medicine
- 吳毅晉 Division of General Internal Medicine
- Nai-Jung Chiang Division of General Internal Medicine
- Pin-Nan Cheng Division of General Internal Medicine
- 簡世杰 Division of General Internal Medicine
- 姜乃榕 Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Condition/Disease
unresectable HCC
Objectives
To compare overall survival (OS) between BGB-A317 and sorafenib as first-line treatment in patients with unresectable hepatocellular carcinoma(HCC)
Test Drug
Tislelizumab
Active Ingredient
BGB-A317
Dosage Form
solution for injection
Dosage
10 mg/mL/vial
Endpoints
Primary:
• OS
Secondary:
• ORR by BIRC
• PFS by BIRC
• DOR by BIRC
• TTP by BIRC
• HRQoL
• Tumor assessments (ORR, PFS, DOR, and TTP) assessed by Investigator per RECIST v1.1
• DCR by BIRC and Investigator
• CBR by BIRC and Investigator
• Safety assessment (eg, new adverse events [AEs], AEs present at baseline that worsen in severity during the study, and clinical laboratory abnormalities)
Exploratory:
• PD-L1 expression and other potential predictive biomarkers
• Summary of serum concentrations of BGB-A317
• Assessments of immunogenicity of BGB-A317 by determining the incidence of antidrug antibodies (ADAs)
• OS
Secondary:
• ORR by BIRC
• PFS by BIRC
• DOR by BIRC
• TTP by BIRC
• HRQoL
• Tumor assessments (ORR, PFS, DOR, and TTP) assessed by Investigator per RECIST v1.1
• DCR by BIRC and Investigator
• CBR by BIRC and Investigator
• Safety assessment (eg, new adverse events [AEs], AEs present at baseline that worsen in severity during the study, and clinical laboratory abnormalities)
Exploratory:
• PD-L1 expression and other potential predictive biomarkers
• Summary of serum concentrations of BGB-A317
• Assessments of immunogenicity of BGB-A317 by determining the incidence of antidrug antibodies (ADAs)
Inclution Criteria
1. Main inclusion criteria:
To be eligible to participate in this study, a patient must meet all of the following criteria:
1. Is male or female, aged ≥ 20 years on the day the patient voluntarily agrees to participate in
the study
2. Has a histologically confirmed diagnosis of HCC
3. Has either BCLC Stage C disease, or BCLC Stage B disease that is not amenable to or has
progressed after loco-regional therapy, and is not amenable to a curative treatment
approach
4. Has received no prior systemic therapy for HCC
NOTE: Patients who have received prior local therapy (eg,TACE) are not excluded.
5. Has ≥ 1 measurable lesion as defined per RECIST v1.1, provided that:
The target lesion(s) selected have not been previously treated with local therapy OR
The target lesion(s) selected that are within the field of prior local therapy have
subsequently progressed as defined by RECIST v1.1
6. Has Child-Pugh A classification for liver function assessed within 7 days of randomization
7. Has ECOG PS score ≤ 1
8. Has adequate organ function, as demonstrated by meeting all of the following clinical
laboratory assessment criteria at Screening:
Absolute neutrophil count ≥ 1.5 × 10
9
/L, platelets ≥ 75 × 10
9
/L, and hemoglobin ≥ 85
g/L
NOTE: Patients must not have required a transfusion of blood products and/or
hematopoietic growth factors within the 14 days before sample collection.
estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m2
by Chronic Kidney
Disease Epidemiology Collaboration equation
Serum albumin ≥ 29 g/L
Serum total bilirubin ≤ 51.3 µmol/L (3 mg/dl)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both ≤ 5 ×
ULN
9. If patient has HBV or HCV infection, meets the following criteria as applicable to the
infection type:
For patients with inactive/asymptomatic carrier, chronic, or active HBV:
Has HBV deoxyribonucleic acid (DNA) < 500 IU/mL (or 2500 copies/mL) at
Screening
NOTE: Patients with detectable hepatitis B surface antigen (HBsAg) or detectable
HBV DNA should be managed per treatment guidelines. Patientsreceiving antivirals at Screening should have been treated for > 2 weeks prior to randomization and
should continue treatment on study.
For patients with HCV:
Infection is evidenced by detectable HCV ribonucleic acid (RNA)
10.If a female of childbearing potential (i.e., physiologically capable of becoming pregnant),
agrees to practice highly effective methods of birth control for the duration of the study
and (for patients in Arm A) for > 120 days after the last dose of BGB-A317 OR (for
patients in Arm B) > 30 days after the last dose of sorafenib, and have a negative urine or
serum pregnancy test within 7 days of the first study drug administration.
11.If a non-sterile male, agrees to practice highly effective methods of birth control for
theduration of the study and (for patients in Arm A) for > 120 days after the last dose of
BGB- A317 OR (for patients in Arm B) > 14 days after the last dose of sorafenib
To be eligible to participate in this study, a patient must meet all of the following criteria:
1. Is male or female, aged ≥ 20 years on the day the patient voluntarily agrees to participate in
the study
2. Has a histologically confirmed diagnosis of HCC
3. Has either BCLC Stage C disease, or BCLC Stage B disease that is not amenable to or has
progressed after loco-regional therapy, and is not amenable to a curative treatment
approach
4. Has received no prior systemic therapy for HCC
NOTE: Patients who have received prior local therapy (eg,TACE) are not excluded.
5. Has ≥ 1 measurable lesion as defined per RECIST v1.1, provided that:
The target lesion(s) selected have not been previously treated with local therapy OR
The target lesion(s) selected that are within the field of prior local therapy have
subsequently progressed as defined by RECIST v1.1
6. Has Child-Pugh A classification for liver function assessed within 7 days of randomization
7. Has ECOG PS score ≤ 1
8. Has adequate organ function, as demonstrated by meeting all of the following clinical
laboratory assessment criteria at Screening:
Absolute neutrophil count ≥ 1.5 × 10
9
/L, platelets ≥ 75 × 10
9
/L, and hemoglobin ≥ 85
g/L
NOTE: Patients must not have required a transfusion of blood products and/or
hematopoietic growth factors within the 14 days before sample collection.
estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m2
by Chronic Kidney
Disease Epidemiology Collaboration equation
Serum albumin ≥ 29 g/L
Serum total bilirubin ≤ 51.3 µmol/L (3 mg/dl)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both ≤ 5 ×
ULN
9. If patient has HBV or HCV infection, meets the following criteria as applicable to the
infection type:
For patients with inactive/asymptomatic carrier, chronic, or active HBV:
Has HBV deoxyribonucleic acid (DNA) < 500 IU/mL (or 2500 copies/mL) at
Screening
NOTE: Patients with detectable hepatitis B surface antigen (HBsAg) or detectable
HBV DNA should be managed per treatment guidelines. Patientsreceiving antivirals at Screening should have been treated for > 2 weeks prior to randomization and
should continue treatment on study.
For patients with HCV:
Infection is evidenced by detectable HCV ribonucleic acid (RNA)
10.If a female of childbearing potential (i.e., physiologically capable of becoming pregnant),
agrees to practice highly effective methods of birth control for the duration of the study
and (for patients in Arm A) for > 120 days after the last dose of BGB-A317 OR (for
patients in Arm B) > 30 days after the last dose of sorafenib, and have a negative urine or
serum pregnancy test within 7 days of the first study drug administration.
11.If a non-sterile male, agrees to practice highly effective methods of birth control for
theduration of the study and (for patients in Arm A) for > 120 days after the last dose of
BGB- A317 OR (for patients in Arm B) > 14 days after the last dose of sorafenib
Exclusion Criteria
To be eligible to participate in this study, a patient cannot meet any of the following exclusioncriteria:
1. Has known fibrolamellar HCC,sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
histology
2. Has tumor thrombus involving main trunk of portal vein or inferior vena cava
3. Has received within 28 days before randomization loco-regional therapy to the liver (i.e.,
TACE, transcatheter embolization, hepatic arterial infusion, radiation, radioembolization,
or ablation)
4. Has received within 28 days before randomization any prior immunotherapy (e.g.,
interleukin, interferon, thymoxin, et cetera) or within 14 days any Chinese herbal medicine
or patent medicine used to control cancer
5. Has at Screening and/or has any prior history of ≥ Grade 2 hepatic encephalopathy
6. Has at Screening pericardial effusion, uncontrollable pleural effusion, or clinically
significant ascites defined as meeting either of (a) detectable ascites on Screening physical
examination OR (b) has at Screening, ascites requiring paracentesis
7. Has, a history of severe hypersensitivity reaction to other monoclonal antibodies
8. Has, at Screening, or has had within 6 months before randomization any clinical evidence
of portal hypertension with bleeding esophageal or gastric varices
9. Patients with toxicities which have not recovered to baseline or stabilized as a result of
prior anticancer therapy, except alopecia
10. Has, at Screening, or has had within 6 months before randomization, any bleeding or
thrombotic disorder or any prescribed anticoagulant requiring therapeutic International
Normalized Ratio monitoring (e.g., warfarin or similar agents)
11. Has, at Screening, or has had within the 2 years before randomization, any active
malignancy, with the exception of the HCC under investigation in this trial and any locally
recurring cancer that has been treated curatively (e.g., resected basal or squamous cell skin
cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast)
12.Has, at Screening, any known central nervous system metastasis and/or leptomeningeal
disease
13. Has, at Screening any active immune deficiency or autoimmune disease and/or has a
history of any immune deficiency or autoimmune disease that may relapse
NOTE: Patients with the following diseases are not excluded:
Type 1 diabetes
Hypothyroidism (provided it is managed with hormone replacement therapy only)
Controlled celiac disease
Skin diseases not requiring systemic treatment (e.g., vitiligo, psoriasis, alopecia)
Any other disease that is not expected to recur in the absence of external triggering
factors
14. Has any condition that has required systemic treatment with either corticosteroids (> 10 mg
daily of prednisone or equivalent) or other immunosuppressive medication within 14 days
before randomization
NOTE: Patients who are currently or have previously been on any of the following
steroid regimens are not excluded:
Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent) in the
absence of active autoimmune disease
Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with minimal
systemic absorption
Short course of corticosteroid prescribed prophylactically (e.g., for contrast dye
allergy) or for the treatment of a non-autoimmune condition (e.g., delayed-type
hypersensitivity reaction caused by contact allergen)
15. Has any history of interstitial lung disease or non-infectious pneumonitis, unless induced
by radiation therapy
16. Has, at Screening, any severe chronic or active infection (excluding viral hepatitis)
requiring systemic antibacterial, antifungal, or antiviral therapy (e.g., tuberculosis)
17. Has Screening ECGs with QT interval corrected for heart rate (QTc) (corrected by
Fridericia’s method) > 450 msec
NOTE: If any patient has QTc > 450 msec on initial ECG, a follow-up ECG will be
performed to confirm result
18. Has any of the following cardiovascular risk factors:
Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily
living (ADL), within 28 days before randomization
Symptomatic pulmonary embolism within 28 days before randomization
Any history of acute myocardial infarction within 6 months before randomization
Any history of heart failure meeting New York Heart Association Classification III or
IV within 6 months before randomization
Any event of ventricular arrhythmia > Grade 2 in severity within 6 months before
randomization
Any history of cerebrovascular accident or transient ischemic attack within 6 months
before randomization
19. Has a known history of human immunodeficiency virus
20. Has any underlying medical condition that, in the Investigator’s opinion, will make the administration of study treatment hazardous or potentially obscure the interpretation of
AEs/toxicities
21. Has undergone prior allogeneic stem cell transplantation or organ transplantation
22. Has been administered a live vaccine within 4 weeks before randomization
NOTE: Seasonal vaccines for influenza are generally inactivated vaccines and are
allowed. Intranasal vaccines are live vaccines, and are not allowed.
23. Has undergone any major surgical procedure within 28 days before randomization
24. Has any contraindication for sorafenib treatment (e.g., severe hypersensitivity to sorafenib
or any other component of NEXAVAR)
25. Female patients who are nursing
1. Has known fibrolamellar HCC,sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
histology
2. Has tumor thrombus involving main trunk of portal vein or inferior vena cava
3. Has received within 28 days before randomization loco-regional therapy to the liver (i.e.,
TACE, transcatheter embolization, hepatic arterial infusion, radiation, radioembolization,
or ablation)
4. Has received within 28 days before randomization any prior immunotherapy (e.g.,
interleukin, interferon, thymoxin, et cetera) or within 14 days any Chinese herbal medicine
or patent medicine used to control cancer
5. Has at Screening and/or has any prior history of ≥ Grade 2 hepatic encephalopathy
6. Has at Screening pericardial effusion, uncontrollable pleural effusion, or clinically
significant ascites defined as meeting either of (a) detectable ascites on Screening physical
examination OR (b) has at Screening, ascites requiring paracentesis
7. Has, a history of severe hypersensitivity reaction to other monoclonal antibodies
8. Has, at Screening, or has had within 6 months before randomization any clinical evidence
of portal hypertension with bleeding esophageal or gastric varices
9. Patients with toxicities which have not recovered to baseline or stabilized as a result of
prior anticancer therapy, except alopecia
10. Has, at Screening, or has had within 6 months before randomization, any bleeding or
thrombotic disorder or any prescribed anticoagulant requiring therapeutic International
Normalized Ratio monitoring (e.g., warfarin or similar agents)
11. Has, at Screening, or has had within the 2 years before randomization, any active
malignancy, with the exception of the HCC under investigation in this trial and any locally
recurring cancer that has been treated curatively (e.g., resected basal or squamous cell skin
cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast)
12.Has, at Screening, any known central nervous system metastasis and/or leptomeningeal
disease
13. Has, at Screening any active immune deficiency or autoimmune disease and/or has a
history of any immune deficiency or autoimmune disease that may relapse
NOTE: Patients with the following diseases are not excluded:
Type 1 diabetes
Hypothyroidism (provided it is managed with hormone replacement therapy only)
Controlled celiac disease
Skin diseases not requiring systemic treatment (e.g., vitiligo, psoriasis, alopecia)
Any other disease that is not expected to recur in the absence of external triggering
factors
14. Has any condition that has required systemic treatment with either corticosteroids (> 10 mg
daily of prednisone or equivalent) or other immunosuppressive medication within 14 days
before randomization
NOTE: Patients who are currently or have previously been on any of the following
steroid regimens are not excluded:
Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent) in the
absence of active autoimmune disease
Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with minimal
systemic absorption
Short course of corticosteroid prescribed prophylactically (e.g., for contrast dye
allergy) or for the treatment of a non-autoimmune condition (e.g., delayed-type
hypersensitivity reaction caused by contact allergen)
15. Has any history of interstitial lung disease or non-infectious pneumonitis, unless induced
by radiation therapy
16. Has, at Screening, any severe chronic or active infection (excluding viral hepatitis)
requiring systemic antibacterial, antifungal, or antiviral therapy (e.g., tuberculosis)
17. Has Screening ECGs with QT interval corrected for heart rate (QTc) (corrected by
Fridericia’s method) > 450 msec
NOTE: If any patient has QTc > 450 msec on initial ECG, a follow-up ECG will be
performed to confirm result
18. Has any of the following cardiovascular risk factors:
Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily
living (ADL), within 28 days before randomization
Symptomatic pulmonary embolism within 28 days before randomization
Any history of acute myocardial infarction within 6 months before randomization
Any history of heart failure meeting New York Heart Association Classification III or
IV within 6 months before randomization
Any event of ventricular arrhythmia > Grade 2 in severity within 6 months before
randomization
Any history of cerebrovascular accident or transient ischemic attack within 6 months
before randomization
19. Has a known history of human immunodeficiency virus
20. Has any underlying medical condition that, in the Investigator’s opinion, will make the administration of study treatment hazardous or potentially obscure the interpretation of
AEs/toxicities
21. Has undergone prior allogeneic stem cell transplantation or organ transplantation
22. Has been administered a live vaccine within 4 weeks before randomization
NOTE: Seasonal vaccines for influenza are generally inactivated vaccines and are
allowed. Intranasal vaccines are live vaccines, and are not allowed.
23. Has undergone any major surgical procedure within 28 days before randomization
24. Has any contraindication for sorafenib treatment (e.g., severe hypersensitivity to sorafenib
or any other component of NEXAVAR)
25. Female patients who are nursing
The Estimated Number of Participants
-
Taiwan
14 participants
-
Global
674 participants
