Clinical Trials List
Protocol NumberBGB-A317-208
NCT Number(ClinicalTrials.gov Identfier)NCT03419897
2018-03-01 - 2021-01-04
Phase II
Recruiting5
Terminated1
ICD-10C22.0
Liver cell carcinoma
ICD-10C22
Malignant neoplasm of liver and intrahepatic bile ducts
RATIONALE-208: A Phase 2, Open-label, Multicenter Study to Investigate the Efficacy, Safety, and Pharmacokinetics of the Anti-PD-1 Monoclonal Antibody BGB-A317 in Patients With Previously Treated Hepatocellular Unresectable Carcinoma
-
Trial Applicant
IQVIA RDS Taiwan Ltd.
-
Sponsor
BeiGene, Ltd. c/o BeiGene USA, Inc.
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Shang-Yin Wu Division of General Internal Medicine
- 劉奕廷 Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Co-Principal Investigator
- Yi-Ping Hung Division of Hematology & Oncology
- Chung-Pin Li Division of General Internal Medicine
- Yi-Hsiang Huang Division of General Internal Medicine
- Ming-Huang Chen Division of Hematology & Oncology
- Rheun-Chuan Lee Division of Radiology
- San-Chi Chen Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
2 Terminated
Audit
None
Co-Principal Investigator
- 陳彥仰 Division of General Internal Medicine
- 劉建廷 Division of General Internal Medicine
- Tai-Jan Chiu Division of General Internal Medicine
- 陳彥豪 Division of General Internal Medicine
- Yu-Li Su Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Tsai-Sheng Yang Division of General Internal Medicine
- Kun-Ming Chan Division of General Surgery
- Chia-Hsun Hsieh Division of General Internal Medicine
- 呂嘉偉 Division of Radiology
- Chen-Chun Lin Division of General Internal Medicine
- Ming-Chin Yu Division of General Surgery
- Shi-Ming Lin Division of General Internal Medicine
- Chien-Hao Huang Division of General Internal Medicine
- 潘廣澤 Division of Radiology
The Actual Total Number of Participants Enrolled
4 Recruiting
Audit
CRO
Co-Principal Investigator
- Ann-Lii Cheng Division of Hematology & Oncology
- YU-YUN SHAO Division of Hematology & Oncology
- Chih-Hung Hsu Division of Hematology & Oncology
- 呂理駿 Division of Hematology & Oncology
- Ying-Chun Shen Division of Hematology & Oncology
- Ming-Chih Ho Division of General Surgery
- 林宗哲 Division of Hematology & Oncology
- Chien-Hung Chen Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Condition/Disease
Previously Treated Unresectable Hepatocellular Carcinoma
Objectives
Primary Objective
The primary objective of the study is to evaluate the efficacy of BGB-A317 through Independent Review
Committee (IRC) assessed ORR by Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1
in previously treated, unresectable HCC.
Secondary Objectives
The secondary objectives of the study are as follows:
To assess the efficacy of BGB-A317 through duration of response (DOR), progression-free survival
(PFS), disease control rate (DCR) and clinical benefit rate (CBR) assessed by IRC and OS
To assess efficacy of BGB-A317 through ORR, DOR, PFS, DCR, and CBR assessed by the
investigators
To assess the safety and tolerability of BGB-A317 in patients with previously treated unresectable
HCC
To assess the health-related quality of life (HRQoL) of BGB-A317 in patients with previously
treated unresectable HCC
Exploratory Objectives
The exploratory objectives of the study are:
To assess potential predictive biomarkers
To characterize the PK of BGB-A317
To assess host immunogenicity to BGB-A317
Test Drug
BGB-A317
Active Ingredient
BGB-A317
Dosage Form
injection
Dosage
100 mg
Endpoints
Primary Endpoint
The primary endpoint is ORR (CR + PR) based on RECIST v 1.1 in patients with previously treated
unresectable HCC as evaluated by an IRC.
Secondary Endpoints
DOR, PFS, DCR and CBR assessed by IRC, and OS
ORR, DOR. PFS, DCR and CBR assessed by investigators
Safety and tolerability assessment of AEs, SAEs, physical examination, vital signs, ECG, and
laboratory measurements
HRQoL measured using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Hepatocellular Carcinoma 18 Questions (EORTC QLQ HCC18) index score,
European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30
(EORTC QLQ-C30) index-score, and 5-level version of the European Quality of Life 5-Dimensional
Questionnaire (EQ-5D-5L)
Exploratory Endpoints
A predictive biomarker (for example, PD-L1 expression and gene expression profiling in tumor
tissue)
Pharmacokinetics: summary of plasma concentrations of BGB-A317
Immunogenicity: assessments of immunogenicity of BGB-A317 to determine the incidence of
anti-drug antibodies (ADAs)
The primary endpoint is ORR (CR + PR) based on RECIST v 1.1 in patients with previously treated
unresectable HCC as evaluated by an IRC.
Secondary Endpoints
DOR, PFS, DCR and CBR assessed by IRC, and OS
ORR, DOR. PFS, DCR and CBR assessed by investigators
Safety and tolerability assessment of AEs, SAEs, physical examination, vital signs, ECG, and
laboratory measurements
HRQoL measured using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Hepatocellular Carcinoma 18 Questions (EORTC QLQ HCC18) index score,
European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30
(EORTC QLQ-C30) index-score, and 5-level version of the European Quality of Life 5-Dimensional
Questionnaire (EQ-5D-5L)
Exploratory Endpoints
A predictive biomarker (for example, PD-L1 expression and gene expression profiling in tumor
tissue)
Pharmacokinetics: summary of plasma concentrations of BGB-A317
Immunogenicity: assessments of immunogenicity of BGB-A317 to determine the incidence of
anti-drug antibodies (ADAs)
Inclution Criteria
Inclusion Criteria
Each patient eligible to participate in this study must meet all of the following criteria:
1. Able to provide written informed consent and can understand and comply with the requirements of the
study
2. Age ≥ 18 years on the day of signing the informed consent form
3. Patients must meet the following criteria:
a. Histologically confirmed HCC
b. Patients with BCLC stage C, BCLC stage B not amenable to locoregional therapy or relapsed
after locoregional therapy, and not amenable to a curative treatment approach
c. Child-Pugh A (Appendix 2)
d. Has received at least 1 line of systemic therapy for unresectable HCC (must have progressed
on or is intolerant to, in the first-line setting, either sorafenib, chemotherapy, or an
experimental therapy that has demonstrated efficacy in a Phase 3 study [eg, lenvatinib]; see
Appendix 10 for additional guidance)
4. Has at least 1 measurable lesion as defined per RECIST v1.1
5. Has ECOG PS ≤ 1
6. If patient has HBV, 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. Patients receiving antivirals at Screening should
have been treated for > 2 weeks prior to enrollment and should continue treatment on study.
7. Has adequate organ function as indicated by the following laboratory values:
a. Absolute neutrophil count (ANC) ≥ 1500/mcl, platelets ≥ 60000/mcl, hemoglobin ≥ 85 g/L or
5.6 mmol/L; Note: Patients must not have required a transfusion of blood product or growth
factor support within the 14 days before sample collection
b. Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min by Chronic Kidney Disease
Epidemiology Collaboration equation (Appendix 9)
c. Serum total bilirubin ≤ 34.2 μmol/L (2 mg/dL)
d. International normalized ratio (INR) or prothrombin time (PT) ≤ 1.7 × upper limit of normal (ULN)
e. Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN
f. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × ULN
g. Serum albumin ≥29 g/L
8. Females of childbearing potential must be willing to use a highly effective method of birth control for
the duration of the study, and for at least 120 days after the last dose of BGB-A317, and have a
negative urine or serum pregnancy test within 7 days of the first study drug administration
9. Non-sterile males must be willing to use a highly effective method of birth control for the duration of
the study and for at least 120 days after the last dose of BGB-A317
10. Must be willing to abstain from alcohol consumption while receiving BGB-A317
Each patient eligible to participate in this study must meet all of the following criteria:
1. Able to provide written informed consent and can understand and comply with the requirements of the
study
2. Age ≥ 18 years on the day of signing the informed consent form
3. Patients must meet the following criteria:
a. Histologically confirmed HCC
b. Patients with BCLC stage C, BCLC stage B not amenable to locoregional therapy or relapsed
after locoregional therapy, and not amenable to a curative treatment approach
c. Child-Pugh A (Appendix 2)
d. Has received at least 1 line of systemic therapy for unresectable HCC (must have progressed
on or is intolerant to, in the first-line setting, either sorafenib, chemotherapy, or an
experimental therapy that has demonstrated efficacy in a Phase 3 study [eg, lenvatinib]; see
Appendix 10 for additional guidance)
4. Has at least 1 measurable lesion as defined per RECIST v1.1
5. Has ECOG PS ≤ 1
6. If patient has HBV, 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. Patients receiving antivirals at Screening should
have been treated for > 2 weeks prior to enrollment and should continue treatment on study.
7. Has adequate organ function as indicated by the following laboratory values:
a. Absolute neutrophil count (ANC) ≥ 1500/mcl, platelets ≥ 60000/mcl, hemoglobin ≥ 85 g/L or
5.6 mmol/L; Note: Patients must not have required a transfusion of blood product or growth
factor support within the 14 days before sample collection
b. Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min by Chronic Kidney Disease
Epidemiology Collaboration equation (Appendix 9)
c. Serum total bilirubin ≤ 34.2 μmol/L (2 mg/dL)
d. International normalized ratio (INR) or prothrombin time (PT) ≤ 1.7 × upper limit of normal (ULN)
e. Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN
f. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × ULN
g. Serum albumin ≥29 g/L
8. Females of childbearing potential must be willing to use a highly effective method of birth control for
the duration of the study, and for at least 120 days after the last dose of BGB-A317, and have a
negative urine or serum pregnancy test within 7 days of the first study drug administration
9. Non-sterile males must be willing to use a highly effective method of birth control for the duration of
the study and for at least 120 days after the last dose of BGB-A317
10. Must be willing to abstain from alcohol consumption while receiving BGB-A317
Exclusion Criteria
Exclusion Criteria
Patients who meet any of the following criteria must be excluded from this study:
1. Has known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
2. Prior therapies targeting PD-1 or PD-L1
3. Has known brain or leptomeningeal metastasis
4. Has received within 4 weeks before enrollment locoregional therapy to the liver (ie, transarterial
chemoembolization, transcatheter embolization, hepatic arterial infusion, radiation, radioembolization,
or ablation)
5. Has received:
a. Within 28 days or 5 half-lives (whichever is shorter) of the first study drug administration:
any chemotherapy, immunotherapy (eg, interleukin, interferon, thymoxin) or any
investigational therapies
b. Within 14 days of the first study drug administration: sorafenib, regorafenib, or any Chinese
herbal medicine or Chinese patent medicines used to control cancer
6. Has tumor thrombus involving main trunk of portal vein or inferior vena cava
7. Has at screening and/or has any prior history of ≥ Grade 2 hepatic encephalopathy (Appendix 2)
8. 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
9. Active autoimmune diseases or history of autoimmune diseases that may relapse.
Note: Patients with the following diseases are not excluded and may proceed to further screening:
a. Type I diabetes
b. Hypothyroidism (provided it is managed with hormone replacement therapy only)
c. Controlled celiac disease
d. Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis, alopecia)
e. Any other disease that is not expected to recur in the absence of external triggering factors
10. Has any condition that required systemic treatment with either corticosteroids (> 10 mg daily of
prednisone or equivalent) or other immunosuppressive medication within 14 days before study drug
administration
Note: Patients who are currently or have previously been on any of the following steroid regimens are
not excluded:
a. Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent)
b. Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with minimal
systemic absorption
c. Short course (≤ 7 days) of corticosteroid prescribed prophylactically (eg, for contrast dye
allergy) or for the treatment of a non-autoimmune condition (eg, delayed-type
hypersensitivity reaction caused by contact allergen)
11. With history of interstitial lung disease, non-infectious pneumonitis or uncontrolled systemic diseases,
including diabetes, hypertension, pulmonary fibrosis, acute lung diseases, etc.
12. Has a known history of HIV infection
13. Has undergone prior allogeneic stem cell transplantation or organ transplantation
14. Has any of the following cardiovascular risk factors:
a. Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living,
within 28 days before the first study drug administration
b. Symptomatic pulmonary embolism within 28 days before the first study drug administration
c. Any history of acute myocardial infarction within 6 months before the first study drug
administration
d. Any history of heart failure meeting New York Heart Association (NYHA) Classification III
or IV (Appendix 6) within 6 months before the first study drug administration
e. Any event of ventricular arrhythmia ≥ Grade 2 in severity within 6 months before
administration of study drug(s)
f. Any history of cerebrovascular accident within 6 months before the first study drug
administration
15. Has a history of severe hypersensitivity reactions to other monoclonal antibodies
16. Patients with toxicities (as a result of prior anticancer therapy) which have not recovered to baseline
or stabilized, except for AEs not considered a likely safety risk (eg, alopecia, neuropathy and specific
laboratory abnormalities)
17. Has been administered a live vaccine within 28 days prior to study drug administration
Note: Seasonal vaccines for influenza are generally inactivated vaccines and are allowed. Intranasal
vaccines are live vaccines, and are not allowed.
18. Underlying medical conditions or drug abuse or dependence that, in the investigator’s opinion, will be
unfavorable for the administration of study drug or affect the explanation of drug toxicity or adverse events (AEs); or insufficient compliance during the study according to investigator’s judgement. (
19. Concurrent participation in another therapeutic clinical trial or enrollment in a prior BeiGene trial for
the treatment of HCC
20. Prior malignancy active within the previous 2 years except for tumor for which a subject is enrolled in
the study, and locally curable cancers that have been apparently cured, such as basal or squamous cell
skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast
Patients who meet any of the following criteria must be excluded from this study:
1. Has known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
2. Prior therapies targeting PD-1 or PD-L1
3. Has known brain or leptomeningeal metastasis
4. Has received within 4 weeks before enrollment locoregional therapy to the liver (ie, transarterial
chemoembolization, transcatheter embolization, hepatic arterial infusion, radiation, radioembolization,
or ablation)
5. Has received:
a. Within 28 days or 5 half-lives (whichever is shorter) of the first study drug administration:
any chemotherapy, immunotherapy (eg, interleukin, interferon, thymoxin) or any
investigational therapies
b. Within 14 days of the first study drug administration: sorafenib, regorafenib, or any Chinese
herbal medicine or Chinese patent medicines used to control cancer
6. Has tumor thrombus involving main trunk of portal vein or inferior vena cava
7. Has at screening and/or has any prior history of ≥ Grade 2 hepatic encephalopathy (Appendix 2)
8. 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
9. Active autoimmune diseases or history of autoimmune diseases that may relapse.
Note: Patients with the following diseases are not excluded and may proceed to further screening:
a. Type I diabetes
b. Hypothyroidism (provided it is managed with hormone replacement therapy only)
c. Controlled celiac disease
d. Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis, alopecia)
e. Any other disease that is not expected to recur in the absence of external triggering factors
10. Has any condition that required systemic treatment with either corticosteroids (> 10 mg daily of
prednisone or equivalent) or other immunosuppressive medication within 14 days before study drug
administration
Note: Patients who are currently or have previously been on any of the following steroid regimens are
not excluded:
a. Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent)
b. Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with minimal
systemic absorption
c. Short course (≤ 7 days) of corticosteroid prescribed prophylactically (eg, for contrast dye
allergy) or for the treatment of a non-autoimmune condition (eg, delayed-type
hypersensitivity reaction caused by contact allergen)
11. With history of interstitial lung disease, non-infectious pneumonitis or uncontrolled systemic diseases,
including diabetes, hypertension, pulmonary fibrosis, acute lung diseases, etc.
12. Has a known history of HIV infection
13. Has undergone prior allogeneic stem cell transplantation or organ transplantation
14. Has any of the following cardiovascular risk factors:
a. Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living,
within 28 days before the first study drug administration
b. Symptomatic pulmonary embolism within 28 days before the first study drug administration
c. Any history of acute myocardial infarction within 6 months before the first study drug
administration
d. Any history of heart failure meeting New York Heart Association (NYHA) Classification III
or IV (Appendix 6) within 6 months before the first study drug administration
e. Any event of ventricular arrhythmia ≥ Grade 2 in severity within 6 months before
administration of study drug(s)
f. Any history of cerebrovascular accident within 6 months before the first study drug
administration
15. Has a history of severe hypersensitivity reactions to other monoclonal antibodies
16. Patients with toxicities (as a result of prior anticancer therapy) which have not recovered to baseline
or stabilized, except for AEs not considered a likely safety risk (eg, alopecia, neuropathy and specific
laboratory abnormalities)
17. Has been administered a live vaccine within 28 days prior to study drug administration
Note: Seasonal vaccines for influenza are generally inactivated vaccines and are allowed. Intranasal
vaccines are live vaccines, and are not allowed.
18. Underlying medical conditions or drug abuse or dependence that, in the investigator’s opinion, will be
unfavorable for the administration of study drug or affect the explanation of drug toxicity or adverse events (AEs); or insufficient compliance during the study according to investigator’s judgement. (
19. Concurrent participation in another therapeutic clinical trial or enrollment in a prior BeiGene trial for
the treatment of HCC
20. Prior malignancy active within the previous 2 years except for tumor for which a subject is enrolled in
the study, and locally curable cancers that have been apparently cured, such as basal or squamous cell
skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast
The Estimated Number of Participants
-
Taiwan
120 participants
-
Global
228 participants
