Clinical Trials List
Protocol NumberBGB-A317-305
NCT Number(ClinicalTrials.gov Identfier)NCT03777657
2019-01-01 - 2024-05-17
Phase III
Recruiting3
ICD-10C16
Malignant neoplasm of stomach
A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Clinical Study Comparing the Efficacy and Safety of Tislelizumab (BGB-A317) plus Platinum and Fluoropyrimidine Versus Placebo plus Platinum and Fluoropyrimidine as First-Line Treatment in Patients with Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
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Trial Applicant
-
Sponsor
BeiGene Ltd
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Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
2 Recruiting
Audit
None
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Shang-Yin Wu 無
- Yan-Shen Shan 無
- 趙盈瑞 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Co-Principal Investigator
- 陳巧雲 未分科
- Sheau-Fang Yang 未分科
- I-CHEN WU 無
- 徐旭亮 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
Objectives
To compare overall survival of tislelizumab plus chemotherapy versus placebo plus chemotherapy in the programmed cell death protein ligand-1 positive and intent-totreat analysis sets
Test Drug
Tislelizumab
Active Ingredient
BGB-A317
Dosage Form
IV Injection
Dosage
100
Endpoints
Overall survival – defined as the time from the date of randomization to the date of death due to any cause
Inclution 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. Adult patients (≥ 18 years of age or acceptable age according to local regulations, whichever is older) at the time of voluntarily signing informed consent
3. Locally advanced unresectable or metastatic GC or GEJ carcinoma and have histologically confirmed adenocarcinoma
4. At least 1 measurable or non-measurable lesion per RECIST v1.1 as determined by investigator assessment.
5. No previous systemic therapy for locally advanced unresectable or metastatic gastric/GEJ cancer. NOTE: Patients may have received prior neoadjuvant or adjuvant therapy as long as it was completed and have no recurrence or disease progression for at least 6 months.
6. Patients must be able to provide tumor tissues (FFPE blocks or approximately 15 [≥ 7 if MSI/MMR and HER2 results are available] freshly cut unstained FFPE slides) with an associated pathological report. A fresh biopsy sample is highly preferred if feasible in clinic. If no archival samples are available, a fresh tumor biopsy at baseline is mandatorily required and slides requirement is the same with that in archival tumor tissues. PD-L1 expression will be assessed centrally, and patients who have evaluable PD-L1 results are eligible.
7. ECOG PS ≤ 1 within 7 days prior to randomization
8. Adequate organ function as indicated by the following laboratory values ≤ 7 days prior to randomization:
a. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, hemoglobin
≥ 90 g/L. NOTE: Patients must not have required a blood transfusion or growth factor support ≤ 14 days before sample collection
b. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or estimated Glomerular Filtration Rate ≥ 60 mL/min/1.73 m2. (Appendix 8)
c. Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
d. Serum total bilirubin ≤ 1.5 x ULN (total bilirubin must be < 3 x ULN for patients with Gilberts syndrome)
e. International normalized ratio (INR) or prothrombin time (PT) (or prothrombin time ratio) ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy and PT values are within the intended therapeutic range of the anticoagulant
f. Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN
g. Albumin ≥ 3.0 g/dL or 30 g/liter
9. Patients with inactive/asymptomatic carrier, chronic, or active HBV infection must meet the following criteria: HBV deoxyribonucleic acid (DNA) < 500 IU/mL (or 2500 copies/mL) at screening. Patients with cured hepatitis C virus (HCV) infection at
screening can be enrolled.
Eligible
HBV
HB sAg (-)
HB sAg (+) and
HBV DNA < 500 IU/mL (or 2500 copies/mL)
HCV
HCV Ab (-)
HCV Ab (+) and HCV RNA (-)
10. Females of childbearing potential must have a negative urine or serum pregnancy test within 7 days of randomization and must be willing to use a highly effective method of birth control (Appendix 9) for the duration of the study, and ≥ 120 days after the last dose of tislelizumab or placebo and 180 days after the last dose of chemotherapy.
11. Non-sterile males must be willing to use a highly effective method of birth control (Appendix 9) for the duration of the study and for ≥ 120 days after the last dose of tislelizumab or placebo and 180 days after the last dose of chemotherapy.
1. Able to provide written informed consent and can understand and comply with the requirements of the study
2. Adult patients (≥ 18 years of age or acceptable age according to local regulations, whichever is older) at the time of voluntarily signing informed consent
3. Locally advanced unresectable or metastatic GC or GEJ carcinoma and have histologically confirmed adenocarcinoma
4. At least 1 measurable or non-measurable lesion per RECIST v1.1 as determined by investigator assessment.
5. No previous systemic therapy for locally advanced unresectable or metastatic gastric/GEJ cancer. NOTE: Patients may have received prior neoadjuvant or adjuvant therapy as long as it was completed and have no recurrence or disease progression for at least 6 months.
6. Patients must be able to provide tumor tissues (FFPE blocks or approximately 15 [≥ 7 if MSI/MMR and HER2 results are available] freshly cut unstained FFPE slides) with an associated pathological report. A fresh biopsy sample is highly preferred if feasible in clinic. If no archival samples are available, a fresh tumor biopsy at baseline is mandatorily required and slides requirement is the same with that in archival tumor tissues. PD-L1 expression will be assessed centrally, and patients who have evaluable PD-L1 results are eligible.
7. ECOG PS ≤ 1 within 7 days prior to randomization
8. Adequate organ function as indicated by the following laboratory values ≤ 7 days prior to randomization:
a. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, hemoglobin
≥ 90 g/L. NOTE: Patients must not have required a blood transfusion or growth factor support ≤ 14 days before sample collection
b. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or estimated Glomerular Filtration Rate ≥ 60 mL/min/1.73 m2. (Appendix 8)
c. Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
d. Serum total bilirubin ≤ 1.5 x ULN (total bilirubin must be < 3 x ULN for patients with Gilberts syndrome)
e. International normalized ratio (INR) or prothrombin time (PT) (or prothrombin time ratio) ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy and PT values are within the intended therapeutic range of the anticoagulant
f. Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN
g. Albumin ≥ 3.0 g/dL or 30 g/liter
9. Patients with inactive/asymptomatic carrier, chronic, or active HBV infection must meet the following criteria: HBV deoxyribonucleic acid (DNA) < 500 IU/mL (or 2500 copies/mL) at screening. Patients with cured hepatitis C virus (HCV) infection at
screening can be enrolled.
Eligible
HBV
HB sAg (-)
HB sAg (+) and
HBV DNA < 500 IU/mL (or 2500 copies/mL)
HCV
HCV Ab (-)
HCV Ab (+) and HCV RNA (-)
10. Females of childbearing potential must have a negative urine or serum pregnancy test within 7 days of randomization and must be willing to use a highly effective method of birth control (Appendix 9) for the duration of the study, and ≥ 120 days after the last dose of tislelizumab or placebo and 180 days after the last dose of chemotherapy.
11. Non-sterile males must be willing to use a highly effective method of birth control (Appendix 9) for the duration of the study and for ≥ 120 days after the last dose of tislelizumab or placebo and 180 days after the last dose of chemotherapy.
Exclusion Criteria
Patients who meet any of the following criteria must be excluded from this study:
1. Patient has squamous cell or undifferentiated or other histological type GC
2. Active leptomeningeal disease or uncontrolled brain 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 ≥ 4 weeks before randomization.
3. Active autoimmune diseases or history of autoimmune diseases that may relapse (Appendix 5).
NOTE: Patients with the following diseases are not excluded and may proceed to further screening:
a. Controlled 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
4. Any active malignancy ≤ 2 years before randomization, with the exception of the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast).
5. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage (at least once a week) and/or diuretics within 7 days prior to randomization (the cytological confirmation of any effusion is permitted).
6. Have clinically significant bleeding (CTCAE ≥ Grade 2) from the gastrointestinal (GI) tract within 1 month prior to randomization
7. Have a history of ≥ Grade 2 (CTCAE) GI perforation and/or fistulae (including prior gastric fistula operation) within 6 months prior to randomization
8. Have a clinically significant bowel obstruction (CTCAE ≥ Grade 2)
9. Diagnosed with gastric or GEJ adenocarcinoma with positive HER2
10. Any condition that requires systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before randomization
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 antiemetic therapy for specific chemotherapy) 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.
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
12. With severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection, etc.
13. A known history of HIV infection
14. Any of the following cardiovascular risk factors:
a. Cardiac chest pain, defined as moderate pain that limits instrumental activities of
daily living, ≤ 28 days before randomization
b. Symptomatic pulmonary embolism ≤ 28 days before randomization
c. Any history of acute myocardial infarction ≤ 6 months before randomization
d. Any history of heart failure meeting New York Heart Association Classification III or
IV (Appendix 6) ≤ 6 months before randomization
e. Any event of ventricular arrhythmia ≥ Grade 2 in severity ≤ 6 months before
randomization
BGB-A317-305 BeiGene
Protocol Amendment 2.0 03 April 2020
CONFIDENTIAL Page 59
f. Any history of cerebrovascular accident ≤ 6 months before randomization
15. Patients with weight loss ≥ 20% within 2 months prior to randomization and/or CTCAE
≥ Grade 2 anorexia within 7 days prior to randomization
16. Within 28 days or 5 half-lives (whichever is shorter but at least 14 days) prior to
randomization: any immunotherapy (eg, interleukin, interferon, thymoxin, etc) or any
investigational therapies; Within 28 days prior to randomization for investigational
devices.
17. Within 14 days prior to randomization: any Chinese herbal medicine or Chinese patent
medicines used to control cancer or boost immunity
18. Palliative radiation treatment within 14 days prior to randomization
19. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 or any other antibody or drug
specifically targeting T-cell co-stimulation or checkpoint pathways
20. Have undergone major surgery within 28 days prior to randomization, except if the procedure is minimally invasive (for example, introduction of peripherally inserted central catheter [PICC])
21. Prior allogeneic stem cell transplantation or organ transplantation
22. A history of severe hypersensitivity reactions to other monoclonal antibodies or any components of study treatment
23. Known dihydropyrimidine dehydrogenase (DPD) deficiency
24. 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, specific laboratory abnormalities)
25. 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.
26. Underlying medical conditions or alcohol 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; or insufficient compliance during the study according to investigator’s judgement.
27. Have an estimated life expectancy < 3 months, in the judgment of the investigator.
1. Patient has squamous cell or undifferentiated or other histological type GC
2. Active leptomeningeal disease or uncontrolled brain 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 ≥ 4 weeks before randomization.
3. Active autoimmune diseases or history of autoimmune diseases that may relapse (Appendix 5).
NOTE: Patients with the following diseases are not excluded and may proceed to further screening:
a. Controlled 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
4. Any active malignancy ≤ 2 years before randomization, with the exception of the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast).
5. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage (at least once a week) and/or diuretics within 7 days prior to randomization (the cytological confirmation of any effusion is permitted).
6. Have clinically significant bleeding (CTCAE ≥ Grade 2) from the gastrointestinal (GI) tract within 1 month prior to randomization
7. Have a history of ≥ Grade 2 (CTCAE) GI perforation and/or fistulae (including prior gastric fistula operation) within 6 months prior to randomization
8. Have a clinically significant bowel obstruction (CTCAE ≥ Grade 2)
9. Diagnosed with gastric or GEJ adenocarcinoma with positive HER2
10. Any condition that requires systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before randomization
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 antiemetic therapy for specific chemotherapy) 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.
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
12. With severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection, etc.
13. A known history of HIV infection
14. Any of the following cardiovascular risk factors:
a. Cardiac chest pain, defined as moderate pain that limits instrumental activities of
daily living, ≤ 28 days before randomization
b. Symptomatic pulmonary embolism ≤ 28 days before randomization
c. Any history of acute myocardial infarction ≤ 6 months before randomization
d. Any history of heart failure meeting New York Heart Association Classification III or
IV (Appendix 6) ≤ 6 months before randomization
e. Any event of ventricular arrhythmia ≥ Grade 2 in severity ≤ 6 months before
randomization
BGB-A317-305 BeiGene
Protocol Amendment 2.0 03 April 2020
CONFIDENTIAL Page 59
f. Any history of cerebrovascular accident ≤ 6 months before randomization
15. Patients with weight loss ≥ 20% within 2 months prior to randomization and/or CTCAE
≥ Grade 2 anorexia within 7 days prior to randomization
16. Within 28 days or 5 half-lives (whichever is shorter but at least 14 days) prior to
randomization: any immunotherapy (eg, interleukin, interferon, thymoxin, etc) or any
investigational therapies; Within 28 days prior to randomization for investigational
devices.
17. Within 14 days prior to randomization: any Chinese herbal medicine or Chinese patent
medicines used to control cancer or boost immunity
18. Palliative radiation treatment within 14 days prior to randomization
19. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 or any other antibody or drug
specifically targeting T-cell co-stimulation or checkpoint pathways
20. Have undergone major surgery within 28 days prior to randomization, except if the procedure is minimally invasive (for example, introduction of peripherally inserted central catheter [PICC])
21. Prior allogeneic stem cell transplantation or organ transplantation
22. A history of severe hypersensitivity reactions to other monoclonal antibodies or any components of study treatment
23. Known dihydropyrimidine dehydrogenase (DPD) deficiency
24. 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, specific laboratory abnormalities)
25. 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.
26. Underlying medical conditions or alcohol 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; or insufficient compliance during the study according to investigator’s judgement.
27. Have an estimated life expectancy < 3 months, in the judgment of the investigator.
The Estimated Number of Participants
-
Taiwan
20 participants
-
Global
720 participants
