| Eligibility |
Inclusion Criteria:After providing written consent before participation in the study,
patients must fulfill all of the following criteria. If a subject is found not to meet any
of the following criteria before the first dose of the therapy regimen, the subject will
not be started on the study treatment but will be withdrawn from the study.
1. Sex: Men and women
2. Age (at the time of informed consent): 18 years and older
3. Patients with unresectable advanced or recurrent gastric cancer (including
esophagogastric junction cancer) that has been istologically confirmed to be
adenocarcinoma and has not been treated with the first-line therapy with systemic
antitumor agents for advanced or recurrent gastric cancer (including esophagogastric
junction cancer).For patients who have received neoadjuvant or adjuvant chemotherapy
(including chemoradiotherapy) in combination with curative or endoscopic surgery (R0
resection confirmed), the chemotherapy in the last regimen must be completed by at
least 180 days before the date of recurrence.
4. Have at least one measurable lesion, as defined in the Response Evaluation Criteria in
Solid Tumors (RECIST) guidelines (version 1.1), on computed tomography (CT) or
magnetic resonance imaging (MRI) within 28 days before enrolled in the study
5. Able to provide tumor tissue specimens (archival or fresh biopsy specimens) for PD-L1
expression analysis. For patients who are unable to undergo another biopsy, archival
specimens may be used as an alternative.
6. ECOG PS score 0 or 1
7. Have a life expectancy of at least 3 months
8. Have latest laboratory data meeting the criteria below within 7 days before enrolled.
If the date of the laboratory tests at enrolled is not within 7 days before the first
dose of the therapy regimen, testing should be repeated within 7 days before the first
dose of the therapy regimen, and the latest laboratory data before the first dose of
the therapy regimen must be confirmed to meet the following criteria. Moreover,
laboratory data will not be valid if the patient has received a granulocyte colony
stimulating factor (G-CSF) or blood transfusion within 14 days before testing.
- White blood cells =3000 cells per µL, and neutrophil count =1000 cells per µL
- Platelets =70 000 per µL
- haemoglobin =80 g/L
- Aspartate aminotransferase (AST) and alanine aminotransferase =3 times the limit
of normal (ULN) or =5 times the ULN in patients with liver metastases
- Total bilirubin =1.5 times the ULN
- International Normalized Ratio (INR) =1.5
- Creatinine =1.5 times the ULN or creatinine clearance >30 mL/min
- albumin =3g/L
9. Women of childbearing potential (including women with chemical menopause or no
menstruation for other medical reasons) must agree to use contraception from the time
of informed consent until at least 5 months after the last dose of the therapy
regimen, whichever comes later. Also, women must agree not to breastfeed from the time
of informed consent until at least 5 months after the last dose of the therapy
regimen, whichever comes later.
10. Men must agree to use contraception from the start of the study treatment until at
least 7 months after the last dose of the therapy regimen.
Exclusion Criteria:Patients meeting any of the following criteria at assessment for
participation will be excluded from the study. If a randomized subject is found to meet any
of the following criteria before the first dose of the therapy regimen, the subject will
not be started on the study treatment but will be withdrawn from the study.
1. Patients with HER2-positive or indeterminate gastric cancer (Determination for
positive is made on the basis of the reference in each site. If there is no reference,
rough indication for positive is 3+ by immunohistochemistry [IHC], or 2+ by IHC and
positive by in situ hybridization [ISH]).
2. multiple cancers (with the exception of completely resected basal cell carcinoma,
stage I squamous cell carcinoma, carcinoma in situ, intramucosal carcinoma, and
superficial bladder cancer, and any other cancers that have not recurred for at least
5 years)
3. previous treatment with ICIs, chemotherapy or anti-angiogenic drug
4. interstitial lung disease or pulmonary fibrosis
5. Have concurrent autoimmune disease or a history of chronic or recurrent autoimmune
disease. Patients with Type 1 diabetes mellitus, hypothyroidism which is manageable by
hormone replacement or skin disorders not requiring systemic treatment (such as
vitiligo, psoriasis, or alopecia) are permitted to be enrolled.
6. Unable to take oral medicines
7. Have a current or past history of severe hypersensitivity to any other antibody
products
8. Have concurrent diverticulitis or symptomatic gastrointestinal ulcerative disease
9. Have experienced a transient ischemic attack, cerebrovascular accident, thrombosis or
thromboembolism (pulmonary arterial embolism or deep vein thrombosis) within 180 days
before enrolled
10. Have a history of uncontrollable or significant cardiovascular disease meeting any of
the following;
- myocardial infarction within 180 days before randomization
- uncontrollable angina pectoris within 180 days before randomization
- arrhythmia requiring treatment
11. Are receiving or require anticoagulant therapy (other than antiplatelet therapy
including low dose aspirin) for a disease
12. Have uncontrollable diabetes mellitus
13. Have systemic infection requiring treatment
14. Are contraindicated for oxaliplatin, capecitabine, tislelizumab, apatinib
15. Have received radiotherapy for gastric cancer within 28 days before randomization or
radiotherapy for bone metastases within 14 days before randomization
16. Have received any radiopharmaceuticals (except for examination or diagnostic use of
radiopharmaceuticals) within 56 days before randomization
17. Have a positive test result for human immunodeficiency virus-1 (HIV-1) antibody, human
immunodeficiency virus-2 (HIV-2) antibody, human T-lymphotropic virus-1 (HTLV-1)
antibody, hepatitis B surface protein (HBs) antigen, or hepatitis C virus (HCV)
antibody
18. Are pregnant or breastfeeding, or possibly pregnant
19. Have received any other unapproved drug (e.g., marketed drugs unapproved for gastric
cancer, investigational use of drugs, unapproved combined formulations, unapproved
dosage forms) within 28 days (or within 90 days for antibody products) before enrolled
20. With peripheral neuropathy of Grade =2
21. severe symptoms (including a rapid decline in ECOG performance; rapidly worsening
symptoms; requiring urgent medical intervention), or active systemic infection, blood
clotting disorder or other active major disease
22. Are incapable of providing consent for specific reasons, such as concurrent dementia
23. Are otherwise inappropriate for this study in the investigator's opinion.
24. Have received a live/attenuated vaccine within 28 days before randomization untreated
central nervous system metastases peripheral neuropathy (> grade 1), known history of
positive test for human immunodeficiency virus or known acquired immunodeficiency
syndrome, concurrent diverticulitis or symptomatic gastrointestinal ulcerative
disease, severe symptoms (including a rapid decline in ECOG performance; rapidly
worsening symptoms; requiring urgent medical intervention), or active systemic
infection, blood clotting disorder or other active major disease were excluded from
the trial.
|
