A Randomised, Double blind, Placebo controlled Phase 3 study comparing Efficacy and Safety of Tislelizumab plus Chemotherapy versus Placebo plus Chemotherapy in patients with Gastric Cancer

Phase 1

Conditions: Therapeutic area: Diseases [C] - Cancer [C04]
ocally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
MedDRA version: 20.0Level: LLTClassification code 10001158Term: Adenocarcinoma gastric stage IV with metastasesSystem Organ Class: 100000004864

Registration Number: EUCTR2018-000312-24-FR

Lead Sponsor: BeiGene, Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 720

Inclusion 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 lesion as defined 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.
7. ECOG PS = 1 within 7 days prior to randomization
8. Adequate organ function:
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) = 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. 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.
10. Non-sterile males must be willing to use a highly effective method of birth control.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 440
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 280

Exclusion Criteria

1. Patient has squamous cell or undifferentiated or other histological type GC
2. Active leptomeningeal disease or uncontrolled brain metastasis.
3. Active autoimmune diseases or history of autoimmune diseases that may relapse.
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.
5. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage within 7 days prior to randomization (The cytological confirmation of any effusion is permitted).
6. Have clinically significant bleeding from the gastrointestinal (GI) tract within 3 months prior to randomization
7. Have a history of GI perforation and/or fistulae within 6 months prior to randomization
8. Have a clinically significant bowel obstruction
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
11. With history of interstitial lung disease, non-infectious pneumonitis or uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, acute lung diseases, etc.
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. Patients with cardiovascular risk factors.
15. 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