Tislelizumab in Combination With Chemotherapy as First-Line Treatment in Adults With Inoperable, Locally Advanced or Metastatic Gastric, or Gastroesophageal Junction Carcinoma
Trial Status: Active
This is a randomized (1:1), double-blind, placebo-controlled, Phase 3 study designed to compare the efficacy and safety of tislelizumab or placebo plus chemotherapy as first-line (1L) therapy for locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.
- Able to provide written informed consent and can understand and comply with the requirements of the study
- Adults (≥ 18 years of age or acceptable age according to local regulations, whichever is older) at the time of voluntarily signing informed consent
- Locally advanced unresectable or metastatic GC or GEJ carcinoma and have histologically confirmed adenocarcinoma
- At least 1 measurable lesion as defined per RECIST v1.1 as determined by investigator assessment.
- No previous systemic therapy for locally advanced unresectable or metastatic gastric/GEJ cancer. NOTE: Participants 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.
- Participants must be able to provide tumor tissues.
- ECOG PS ≤ 1 within 7 days prior to randomization
- Adequate organ function as indicated by the following laboratory values ≤ 7 days prior to randomization:
- 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 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.
- Non-sterile males must be willing to use a highly effective method of birth control 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.
- Has squamous cell or undifferentiated or other histological type GC
- Active leptomeningeal disease or uncontrolled brain metastasis. Participants 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.
- Active autoimmune diseases or history of autoimmune diseases that may relapse.
- 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).
- Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage within 7 days prior to randomization (The cytological confirmation of any effusion is permitted).
- Diagnosed with gastric or GEJ adenocarcinoma with positive HER2
- Any condition that requires systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before randomization.
- With history of interstitial lung disease, non-infectious pneumonitis or uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, acute lung diseases, etc. NOTE: Participants with radiation pneumonitis may be randomized if the radiation pneumonitis has been confirmed as stable (beyond acute phase) without any concerns about recurrence. Participants with severe but stable radiation-induced pneumonitis may be required to undergo routine pulmonary function studies
- With severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection, etc.
- A known history of HIV infection
- Participants with untreated chronic hepatitis B virus (HBV) or HBV carriers at screening or participants with active Hepatitis C virus (HCV) infection should be excluded.
- 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
- Prior allogeneic stem cell transplantation or organ transplantation
- A history of severe hypersensitivity reactions to other monoclonal antibodies or any components of study treatment
- Known dihydropyrimidine dehydrogenase (DPD) deficiency
- 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.
University of California Davis Comprehensive Cancer Center
Wayne State University / Karmanos Cancer Institute
University of New Mexico Cancer Center
Laura and Isaac Perlmutter Cancer Center at NYU Langone
Ohio State University Comprehensive Cancer Center
Fox Chase Cancer Center
Contact: systems coordinator
Thomas Jefferson University Hospital
Medical University of South Carolina
Trial Phase Phase III
Trial Type Treatment
- Primary ID BGB-A317-305
- Secondary IDs NCI-2018-03719, JapicCTI-194799, 2018-000312-24, CTR20181841
- Clinicaltrials.gov ID NCT03777657