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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Gastric, or Gastroesophageal Junction Adenocarcinoma

Intervention / Treatment
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* Drug: Tislelizumab
* Drug: Placebo
* Drug: Cisplatin
* Drug: Oxaliplatin
* Drug: Capecitabine
* Drug: 5-FU


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Locally advanced unresectable or metastatic GC or GEJ carcinoma and have histologically confirmed adenocarcinoma 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. ECOG PS ≤ 1 within 7 days prior to randomization Adequate organ function as indicated by the following laboratory values ≤ days prior to randomization Key Exclusion Criteria: Has squamous cell or undifferentiated or other histological type GC Active leptomeningeal disease or uncontrolled brain metastasis Diagnosed with gastric or GEJ adenocarcinoma with positive HER2 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 NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tislelizumab (BGB-A317) + chemotherapy<br>Tislelizumab and chemotherapy. Oxaliplatin + capecitabine or cisplatin + 5-Fluorouracil regimens are used as the backbone chemotherapy. | Drug: Tislelizumab<br>* 200 mg IV on Day 1 during each 21-day cycle<br>* Other names: BGB-A317;Drug: Cisplatin<br>* 80 mg/m² IV on Day 1 during each 21-day cycle<br>Drug: Oxaliplatin<br>* 130 mg/m² IV on Day 1 during each 21-day cycle<br>Drug: Capecitabine<br>* 1000 mg/m² orally twice daily (BD) Days 1 through 14 (14 days total) during each 21-day cycle<br>Drug: 5-FU<br>* 800 mg/m²/day IV using continuous pumping system on Days 1 through 5 during each 21-day cycle<br>|
| Placebo Comparator: Placebo + chemotherapy<br>Placebo and chemotherapy. Oxaliplatin + capecitabine or cisplatin + 5-FU regimens are used as the backbone chemotherapy. | Drug: Placebo<br>* Placebo to match tislelizumab on Day 1 during each 21-day cycle<br>Drug: Cisplatin<br>* 80 mg/m² IV on Day 1 during each 21-day cycle<br>Drug: Oxaliplatin<br>* 130 mg/m² IV on Day 1 during each 21-day cycle<br>Drug: Capecitabine<br>* 1000 mg/m² orally twice daily (BD) Days 1 through 14 (14 days total) during each 21-day cycle<br>Drug: 5-FU<br>* 800 mg/m²/day IV using continuous pumping system on Days 1 through 5 during each 21-day cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | The time from the date of randomization to the date of death due to any cause | Up to 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | The time from the date of randomization to the date of the first objectively documented tumor progression | Up to 30 months | 
| Overall response rate (ORR) | The proportion of participants whose best overall response is complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors v1.1 | Up to 48 months | 
| Duration of response (DOR) | 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 | Baseline, at every cycle through cycle 6 (each cycle is 21 days), and then every other cycle for up to 48 months | 
| Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Gastric Cancer Module QLQ-STO22 (EORTC QLQ-STO22) |  | Baseline, at every cycle through cycle 6 (each cycle is 21 days), and then every other cycle for up to 48 months | 
| Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 Score (EORTC QLQ-30) |  | Baseline, at every cycle through cycle 6 (each cycle is 21 days), and then every other cycle for up to 48 months | 
| Change from baseline in European Quality of Life 5-Dimensions 5-Levels Health Questionnaire Score (EQ-5D-5L) |  | Baseline, at every cycle through cycle 6 (each cycle is 21 days), and then every other cycle for up to 48 months | 
| Number of participants experiencing Adverse Events (AEs) |  | Up to 48 months | 
| Number of participants experiencing Serious Adverse Events (SAEs) |  | Up to 48 months | 
| Disease control rate (DCR) | Proportion of complete response + partial response + stable disease | Up to 48 Months | 
| clinical benefit rate (CBR) | Proportion of complete response + partial response + durable stable disease | Up to 48 Months | 
| time to response (TTR) | Time from randomization to the first determination of an objective response | Up to 48 Months |