Clinical Trials List
Protocol NumberBGB-A317-302
NCT Number(ClinicalTrials.gov Identfier)NCT03430843
Completed
2018-07-03 - 2020-08-31
Phase III
Terminated7
ICD-10C15
Malignant neoplasm of esophagus
A Randomized, Controlled, Open-label, Global Phase 3 Study Comparing the Efficacy of the Anti-PD-1 Antibody Tislelizumab (BGB-A317) Versus Chemotherapy as Second Line Treatment in Patients With Advanced Unresectable/Metastatic Esophageal Squamous Cell Carcinoma
-
Trial Applicant
PAREXEL INTERNATIONAL CO., LTD.
-
Sponsor
BeiGene, Ltd.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- 陳昭勳 Division of Hematology & Oncology
- 蕭聖諺 Division of Hematology & Oncology
- 郭雨萱 Division of Hematology & Oncology
- 黃文聰 Division of Hematology & Oncology
- 陳彥勳 Division of Hematology & Oncology
- 吳鴻昌 Division of Hematology & Oncology
- Shang-Wen Chen Division of Hematology & Oncology
- 馮盈勳 Division of Hematology & Oncology
- 曹朝榮 Division of Hematology & Oncology
- 林正耀 Division of Hematology & Oncology
- 黃健泰 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 黃泰霖 Division of Hematology & Oncology
- 劉建廷 Division of Hematology & Oncology
- 陳彥豪 Division of Hematology & Oncology
- 湯禹舜 Division of Hematology & Oncology
- Tai-Jan Chiu Division of Hematology & Oncology
- 吳佳哲 Division of Hematology & Oncology
- Yu-Li Su Division of Hematology & Oncology
- 林偉哲 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
- Chueh-Chuan Yen Division of Hematology & Oncology
- Sheng-Yu Chen Division of Hematology & Oncology
- Yi-Ping Hung Division of Hematology & Oncology
- 陳盛裕 Division of Hematology & Oncology
- Chung-Pin Li Division of Hematology & Oncology
- Ming-Huang Chen Division of Hematology & Oncology
- Rheun-Chuan Lee Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
6 Stop recruiting
Audit
None
Co-Principal Investigator
- Chang-Fang Chiu Division of Hematology & Oncology
- Chi-Ching Chen Division of Hematology & Oncology
- Ming-Yu Lien Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Kun-Huei Yeh Division of Hematology & Oncology
- JHE-CYUAN GUO Division of Hematology & Oncology
- Ann-Lii Cheng Division of Hematology & Oncology
- Wei-Wu Chen Division of Hematology & Oncology
- Chia-Chi Lin Division of Hematology & Oncology
- TA-CHEN HUANG Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Condition/Disease
Esophageal Squamous Cell Carcinoma
Objectives
Primary:
• To compare the overall survival (OS) following treatment with BGB-A317 vs. investigator chosen chemotherapy (ICC) when given as second line treatment in patients with advanced unresectable/metastatic Esophageal Squamous Cell Carcinoma (ESCC)
Test Drug
BGB-A317
Active Ingredient
BGB-A317(Tislelizumab)
Dosage Form
concentrate for solution for infusion
Dosage
10 mg/mL
Endpoints
Primary:
• OS - defined as the time from the date of randomization until the date of death due to
any cause
• OS - defined as the time from the date of randomization until the date of death due to
any cause
Inclution Criteria
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 ≥ 18 years on the day the patient voluntarily agrees to
participate in the study (or acceptable age according to local regulations, whichever is
older)
2. Voluntarily signed informed consent form for the study
3. Pathologically (histologically or cytologically) confirmed diagnosis of esophageal
squamous cell carcinoma (ESCC)
4. Tumor progression during or after first-line treatment for advanced unresectable /
metastatic ESCC
NOTE: Patients with disease progression that occurs during treatment or within 6
months of cessation of neoadjuvant/adjuvant treatment (chemotherapy or
chemoradiotherapy) are eligible provided all other criteria are met
5. At least one measurable/evaluable lesion by RECIST v1.1 as determined by local site
investigator/radiology assessment within 28 days prior to randomization
NOTE: Lesions that have been previously irradiated may be considered evaluable
provided there is evidence of disease progression following the completion of
radiation therapy.
6. Eastern Cooperative Oncology Group (ECOG) performance status (Appendix 3) of 0
or 1 prior to randomization
7. Laboratory data meeting the criteria below within 14 days prior to randomization.
Laboratory data will not be valid if the patient has received growth factors or blood
transfusion for prophylactic use within 7 days before the laboratory testing:
• Absolute neutrophil count (ANC) ≥1500 cells/mm3
• Platelet count ≥ 100,000 cells/mm3
• Hemoglobin ≥9 g/dL or ≥5.6 mmol/L
Serum creatinine ≤1.5× upper limit of normal (ULN) or creatinine clearance
≥50 mL/min for patient with creatinine levels > 1.5× institutional ULN
• Serum total bilirubin ≤1.5×ULN (or <3×ULN in patients with Gilbert’s
syndrome)
• Prothrombin time/International normalized ratio (INR) ≤1.5×ULN unless the
patient is receiving anti-coagulant therapy
• Aspartate transaminase (AST) and alanine aminotransferase (ALT)
≤2.5×ULN (or ≤5.0×ULN in patients with liver metastases)
8. 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. Patients
receiving 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)
9. Females of childbearing potential must have a negative serum pregnancy test within 7
days of randomization and must be willing to have additional pregnancy tests during
the study. Females of childbearing potential must be willing to practice highly
effective methods of birth control for the duration of the study, and for at least 120
days after the last dose of BGB-A317 and 180 days after the last dose of ICC
10. Non-sterile males must practice 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
180 days after the last dose of ICC
To be eligible to participate in this study, a patient must meet all of the following criteria:
1. Is male or female, aged ≥ 18 years on the day the patient voluntarily agrees to
participate in the study (or acceptable age according to local regulations, whichever is
older)
2. Voluntarily signed informed consent form for the study
3. Pathologically (histologically or cytologically) confirmed diagnosis of esophageal
squamous cell carcinoma (ESCC)
4. Tumor progression during or after first-line treatment for advanced unresectable /
metastatic ESCC
NOTE: Patients with disease progression that occurs during treatment or within 6
months of cessation of neoadjuvant/adjuvant treatment (chemotherapy or
chemoradiotherapy) are eligible provided all other criteria are met
5. At least one measurable/evaluable lesion by RECIST v1.1 as determined by local site
investigator/radiology assessment within 28 days prior to randomization
NOTE: Lesions that have been previously irradiated may be considered evaluable
provided there is evidence of disease progression following the completion of
radiation therapy.
6. Eastern Cooperative Oncology Group (ECOG) performance status (Appendix 3) of 0
or 1 prior to randomization
7. Laboratory data meeting the criteria below within 14 days prior to randomization.
Laboratory data will not be valid if the patient has received growth factors or blood
transfusion for prophylactic use within 7 days before the laboratory testing:
• Absolute neutrophil count (ANC) ≥1500 cells/mm3
• Platelet count ≥ 100,000 cells/mm3
• Hemoglobin ≥9 g/dL or ≥5.6 mmol/L
Serum creatinine ≤1.5× upper limit of normal (ULN) or creatinine clearance
≥50 mL/min for patient with creatinine levels > 1.5× institutional ULN
• Serum total bilirubin ≤1.5×ULN (or <3×ULN in patients with Gilbert’s
syndrome)
• Prothrombin time/International normalized ratio (INR) ≤1.5×ULN unless the
patient is receiving anti-coagulant therapy
• Aspartate transaminase (AST) and alanine aminotransferase (ALT)
≤2.5×ULN (or ≤5.0×ULN in patients with liver metastases)
8. 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. Patients
receiving 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)
9. Females of childbearing potential must have a negative serum pregnancy test within 7
days of randomization and must be willing to have additional pregnancy tests during
the study. Females of childbearing potential must be willing to practice highly
effective methods of birth control for the duration of the study, and for at least 120
days after the last dose of BGB-A317 and 180 days after the last dose of ICC
10. Non-sterile males must practice 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
180 days after the last dose of ICC
Exclusion Criteria
Exclusion Criteria
To be eligible to participate in this study, a patient cannot meet any of the following exclusion
criteria:
1. Eligible for treatment with any of the treatments of protocol-specified chemotherapy
2. Receipt of 2 or more prior systemic treatments for advanced/metastatic unresectable
ESCC
3. Palliative radiation treatment for ESCC within 14 days of study treatment initiation
(C1D1)
4. History of gastrointestinal perforation and /or fistula or aorto-esophageal fistula
within 6 months prior to randomization
5. Apparent tumor invasion into organs located adjacent to the esophageal disease site
(eg, aorta or respiratory tract) at an increased risk of fistula in the study treatment
assessed by investigator
6. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent
drainage (recurrence within 2 weeks of intervention)
7. Current or past history of severe hypersensitivity reactions to other humanized
monoclonal antibodies
8. Received prior therapies targeting PD-1 or PD-L1
9. 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)
10. Prior malignancy active within the previous 2 years (exceptions include the tumor
under investigation in this trial and surgically excised non-melanoma skin cancer,
adequately treated carcinoma in situ of the cervix, localized prostate cancer treated
with curative intent, adequately treated low-stage bladder cancer, ductal carcinoma in
situ treated surgically with curative intent, or a malignancy diagnosed >2 years ago,
with no current evidence of disease and no therapy ≤2 years prior to randomization)
11. Active brain or leptomeningeal metastasis. Patients with equivocal findings or with
confirmed brain metastases are eligible for enrollment provided that they are
asymptomatic and radiologically stable without the need for corticosteroid treatment
for at least 4 weeks prior to randomization
12. Has active autoimmune disease or history of autoimmune diseases at high risk for
relapse
NOTE: Patients with following diseases may be enrolled if they meet all other
eligibility criteria: controlled type I diabetes, hypothyroidism managed with
hormone replacement therapy only, controlled celiac disease, skin diseases not
requiring systemic treatment (such as vitiligo, psoriasis or alopecia), or diseases
not expected to recur in the absence of external triggering factors.
13. Has a condition requiring systemic treatment with either corticosteroids (> 10 mg
daily prednisone or equivalents) or other immunosuppressive medications within 14
days prior to randomization
• Adrenal replacement steroid dose ≤ 10 mg daily prednisone equivalents are
permitted in the absence of active autoimmune disease
• Patients are permitted to use topical, ocular, intra-articular, intranasal, and
inhalational corticosteroids (with minimal systemic absorption).
• A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or
for treatment of non-autoimmune conditions (e.g., delayed-type
hypersensitivity reaction caused by contact allergen) is permitted.
14. Undergone surgery requiring general anesthesia or epidural anesthesia within 28 days
prior to randomization
15. Undergone surgery involving local or topical anesthesia within 14 days prior to
randomization or central venous access device placement within 3 days prior to
randomization
16. Received any radiopharmaceuticals - (except for examination or diagnostic use of
radiopharmaceuticals) within 42 days prior to randomization.
17. Has received:
a. Within 28 days or 5 half-lives (whichever is shorter) of the first study drug
administration: any chemotherapy, any immunotherapy (eg, interleukin,
interferon, thymoxin) or any investigational therapies
b. Within 14 days of the first study drug administration: any Chinese herbal
medicine or Chinese patent medicines used to control cancer or boost immunity
18. Any serious or unstable pre-existing medical conditions (aside from malignancy
exceptions specified above), psychiatric disorders, or other conditions that could
interfere with the subject’s safety, obtaining informed consent, or compliance with
study procedures
19. Receipt of a live vaccine within 4 weeks prior to Cycle1 Day 1
NOTE: seasonal vaccines for influenza are generally inactivated vaccines and are
allowed. Intranasal vaccines are live viruses and are not allowed.
20. Known history of, or any evidence of interstitial lung disease, non-infectious
pneumonitis, pulmonary fibrosis diagnosed based on imaging or clinical findings, or
uncontrolled systemic diseases, including diabetes, hypertension, acute lung diseases,
etc
NOTE: Patients with radiation pneumonitis may be randomized if the radiation
pneumonitis has been confirmed as stable (beyond acute phase) without any
concerns about recurrence. Patients with severe but stable radiation-induced
pneumonitis may be required to undergo routine pulmonary function studies
21. Has a severe chronic or active infection requiring systemic antibacterial, antifungal or
antiviral therapy, including tuberculosis infection, etc
22. Known history of Human Immunodeficiency Virus (HIV)
23. Has any of the following cardiovascular risk factors:
• Ongoing cardiac chest pain, defined as moderate pain that limits instrumental
activities of daily living
• 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 (Appendix 6) 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
24. Severe malnutrition despite enteral or parenteral nutritional supplementation
25. Known, active alcohol or drug abuse or dependence
26. Pregnant or breastfeeding woman.
To be eligible to participate in this study, a patient cannot meet any of the following exclusion
criteria:
1. Eligible for treatment with any of the treatments of protocol-specified chemotherapy
2. Receipt of 2 or more prior systemic treatments for advanced/metastatic unresectable
ESCC
3. Palliative radiation treatment for ESCC within 14 days of study treatment initiation
(C1D1)
4. History of gastrointestinal perforation and /or fistula or aorto-esophageal fistula
within 6 months prior to randomization
5. Apparent tumor invasion into organs located adjacent to the esophageal disease site
(eg, aorta or respiratory tract) at an increased risk of fistula in the study treatment
assessed by investigator
6. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent
drainage (recurrence within 2 weeks of intervention)
7. Current or past history of severe hypersensitivity reactions to other humanized
monoclonal antibodies
8. Received prior therapies targeting PD-1 or PD-L1
9. 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)
10. Prior malignancy active within the previous 2 years (exceptions include the tumor
under investigation in this trial and surgically excised non-melanoma skin cancer,
adequately treated carcinoma in situ of the cervix, localized prostate cancer treated
with curative intent, adequately treated low-stage bladder cancer, ductal carcinoma in
situ treated surgically with curative intent, or a malignancy diagnosed >2 years ago,
with no current evidence of disease and no therapy ≤2 years prior to randomization)
11. Active brain or leptomeningeal metastasis. Patients with equivocal findings or with
confirmed brain metastases are eligible for enrollment provided that they are
asymptomatic and radiologically stable without the need for corticosteroid treatment
for at least 4 weeks prior to randomization
12. Has active autoimmune disease or history of autoimmune diseases at high risk for
relapse
NOTE: Patients with following diseases may be enrolled if they meet all other
eligibility criteria: controlled type I diabetes, hypothyroidism managed with
hormone replacement therapy only, controlled celiac disease, skin diseases not
requiring systemic treatment (such as vitiligo, psoriasis or alopecia), or diseases
not expected to recur in the absence of external triggering factors.
13. Has a condition requiring systemic treatment with either corticosteroids (> 10 mg
daily prednisone or equivalents) or other immunosuppressive medications within 14
days prior to randomization
• Adrenal replacement steroid dose ≤ 10 mg daily prednisone equivalents are
permitted in the absence of active autoimmune disease
• Patients are permitted to use topical, ocular, intra-articular, intranasal, and
inhalational corticosteroids (with minimal systemic absorption).
• A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or
for treatment of non-autoimmune conditions (e.g., delayed-type
hypersensitivity reaction caused by contact allergen) is permitted.
14. Undergone surgery requiring general anesthesia or epidural anesthesia within 28 days
prior to randomization
15. Undergone surgery involving local or topical anesthesia within 14 days prior to
randomization or central venous access device placement within 3 days prior to
randomization
16. Received any radiopharmaceuticals - (except for examination or diagnostic use of
radiopharmaceuticals) within 42 days prior to randomization.
17. Has received:
a. Within 28 days or 5 half-lives (whichever is shorter) of the first study drug
administration: any chemotherapy, any immunotherapy (eg, interleukin,
interferon, thymoxin) or any investigational therapies
b. Within 14 days of the first study drug administration: any Chinese herbal
medicine or Chinese patent medicines used to control cancer or boost immunity
18. Any serious or unstable pre-existing medical conditions (aside from malignancy
exceptions specified above), psychiatric disorders, or other conditions that could
interfere with the subject’s safety, obtaining informed consent, or compliance with
study procedures
19. Receipt of a live vaccine within 4 weeks prior to Cycle1 Day 1
NOTE: seasonal vaccines for influenza are generally inactivated vaccines and are
allowed. Intranasal vaccines are live viruses and are not allowed.
20. Known history of, or any evidence of interstitial lung disease, non-infectious
pneumonitis, pulmonary fibrosis diagnosed based on imaging or clinical findings, or
uncontrolled systemic diseases, including diabetes, hypertension, acute lung diseases,
etc
NOTE: Patients with radiation pneumonitis may be randomized if the radiation
pneumonitis has been confirmed as stable (beyond acute phase) without any
concerns about recurrence. Patients with severe but stable radiation-induced
pneumonitis may be required to undergo routine pulmonary function studies
21. Has a severe chronic or active infection requiring systemic antibacterial, antifungal or
antiviral therapy, including tuberculosis infection, etc
22. Known history of Human Immunodeficiency Virus (HIV)
23. Has any of the following cardiovascular risk factors:
• Ongoing cardiac chest pain, defined as moderate pain that limits instrumental
activities of daily living
• 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 (Appendix 6) 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
24. Severe malnutrition despite enteral or parenteral nutritional supplementation
25. Known, active alcohol or drug abuse or dependence
26. Pregnant or breastfeeding woman.
The Estimated Number of Participants
-
Taiwan
28 participants
-
Global
512 participants
