Clinical Trials /

Tislelizumab in Combination With Chemotherapy as First-Line Treatment in Adults With Inoperable, Locally Advanced or Metastatic Gastric, or Gastroesophageal Junction Carcinoma

NCT03777657

Description:

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.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Tislelizumab in Combination With Chemotherapy as First-Line Treatment in Adults With Inoperable, Locally Advanced or Metastatic Gastric, or Gastroesophageal Junction Carcinoma
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: BGB-A317-305
  • NCT ID: NCT03777657

Conditions

  • Gastric, or Gastroesophageal Junction Adenocarcinoma

Interventions

DrugSynonymsArms
Tislelizumab (BGB-A317) combined with oxaliplatin and capecitabine or Tislelizumab (BGB-A317) combined with Cisplatin and 5-FUTislelizumab (BGB-A317) + chemotherapy
Placebo combined with oxaliplatin and capecitabine or Placebo combined with Cisplatin and 5-FUPlacebo + chemotherapy

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Tislelizumab (BGB-A317) + chemotherapyExperimentalPatients received Tislelizumab and chemotherapy. Oxaliplatin + capecitabine or cisplatin + 5-Fluorouracil regimens are used as the backbone chemotherapy.
  • Tislelizumab (BGB-A317) combined with oxaliplatin and capecitabine or Tislelizumab (BGB-A317) combined with Cisplatin and 5-FU
Placebo + chemotherapyPlacebo ComparatorPatients receive placebo and chemotherapy. Oxaliplatin + capecitabine or cisplatin + 5-FU regimens are used as the backbone chemotherapy.
  • Placebo combined with oxaliplatin and capecitabine or Placebo combined with Cisplatin and 5-FU

Eligibility Criteria

        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 as indicated by the following laboratory values ≤ 7 days prior
             to randomization:

          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 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.

         10. 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.

        Exclusion Criteria:

          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.

          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 within 7 days prior to randomization (The cytological confirmation of any
             effusion is permitted).

          6. Diagnosed with gastric or GEJ adenocarcinoma with positive HER2

          7. Any condition that requires systemic treatment with either corticosteroids (> 10 mg
             daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days
             before randomization.

          8. 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

          9. With severe chronic or active infections requiring systemic antibacterial, antifungal
             or antiviral therapy, including tuberculosis infection, etc.

         10. A known history of HIV infection

         11. Patients with untreated chronic hepatitis B virus (HBV) or HBV carriers at screening
             or patients with active Hepatitis C virus (HCV) infection should be excluded.

         12. 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

         13. Prior allogeneic stem cell transplantation or organ transplantation

         14. A history of severe hypersensitivity reactions to other monoclonal antibodies or any
             components of study treatment

         15. Known dihydropyrimidine dehydrogenase (DPD) deficiency

         16. 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.

        NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival - defined as the time from the date of randomization to the date of the first objectively documented tumor progression
Time Frame:Up to 27 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall response rate - defined as the proportion of patients whose best overall response is complete response or partial response per Response Evaluation Criteria in Solid Tumors v1.1
Time Frame:Up to 43 months
Safety Issue:
Description:
Measure:Duration of response - defined as the time from the first determination of an objective response per Response Evaluation Criteria in Solid Tumors v1.1, until the first documentation of progression or death, whichever occurs first
Time Frame:Up to 43 months
Safety Issue:
Description:
Measure:Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Gastric Cancer Module (at Screening or baseline, at every cycle through Cycle 6, then every other cycle thereafter until PD, and at EOT)
Time Frame:Up to 43 months
Safety Issue:
Description:
Measure:Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 Score (at Screening or baseline, at every cycle through Cycle 6, then every other cycle thereafter until PD, and at EOT)
Time Frame:Up to 43 months
Safety Issue:
Description:
Measure:Change from baseline in European Quality of Life 5-Dimensions 5-Levels Health Questionnaire Score (at Screening or baseline, at every cycle through Cycle 6, then every other cycle thereafter until PD, and at EOT)
Time Frame:Up to 43 months
Safety Issue:
Description:
Measure:The incidence and severity of adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0
Time Frame:Up to 43 months
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:BeiGene

Last Updated