Study of Tislelizumab (BGB-A317) Versus Placebo in Combination With Chemoradiotherapy in Participant With ESCC

Study Overview
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Brief Summary
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This is a phase 3, randomized, double-blind, placebo-controlled study to compare the efficacy and safety of BGB-A317 versus P placebo with chemoradiotherapy in participants with Localized Esophageal Squamous Cell Carcinoma.

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Tislelizumab (BGB-A317) Versus Placebo in Combination With Concurrent Chemoradiotherapy in Patients With Localized Esophageal Squamous Cell Carcinoma

Conditions
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Esophageal Squamous Cell Carcinoma (ESCC)

Intervention / Treatment
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* Drug: Tislelizumab
* Drug: Placebo
* Drug: Paclitaxel
* Drug: Cisplatin
* Radiation: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: 18 to 75 years on the day of signing the informed consent form Histologically confirmed diagnosis of localized ESCC Measurable and/or non-measurable disease defined per RECIST v1.1 Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1 Adequate organ function Key Exclusion Criteria: Indicators of severe malnutrition Clinically uncontrolled pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention within 2 weeks prior to randomization Known to be intolerable or resistant to treatment with the protocol-specified chemotherapy Received prior radiotherapy or therapies targeting PD-1, PD-L1, PD-L2 or other immune-oncology therapies Active autoimmune diseases or history of autoimmune diseases that may relapse NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tislelizumab + chemoradiotherapy<br>Tislelizumab once every 3-week cycle (Q3W) + paclitaxel on Day 1 of every cycle, for a total of 2 cycles + cisplatin on Day 1 to 3 of every cycle (3 weeks), for a total of 2 cycles + Radiotherapy | Drug: Tislelizumab<br>* Administrated at dose of 200 mg intravenously (IV)<br>* Other names: BGB-A317;Drug: Paclitaxel<br>* Administered as 135 mg/m² IV injection<br>Drug: Cisplatin<br>* Administered as 25 mg/m² IV injection<br>Radiation: Radiotherapy<br>* Administered at a total dose of 50.4 Gy in 28 fractions<br>|
| Placebo Comparator: Placebo combined + chemoradiotherapy<br>Placebo once every 3-week cycle (Q3W) + paclitaxel on Day 1 of every cycle, for a total of 2 cycles + cisplatin on Day 1 to 3 of every cycle (3 weeks), for a total of 2 cycles + Radiotherapy | Drug: Placebo<br>* Placebo to match tislelizumab<br>Drug: Paclitaxel<br>* Administered as 135 mg/m² IV injection<br>Drug: Cisplatin<br>* Administered as 25 mg/m² IV injection<br>Radiation: Radiotherapy<br>* Administered at a total dose of 50.4 Gy in 28 fractions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) |  | From date of randomization up to 4 years, approximately | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall response rate (ORR) |  | From date of randomization up to 4 years, approximately | 
| duration of response (DOR) |  | From first determination of an objective response up to 4 years, approximately | 
| overall survival (OS) |  | From date of randomization up to 4 years, approximately | 
| change from baseline in European Quality of Life-Core 30 Questionnaire index (EORTC QLQ-C30). | Scale consultant including to assess Global health status/Qol with range from minimum scores 1 as worse outcome and maximum scores 7 as higher values represent a better, Physical functioning, role functioning, Emotional functioning, Cognitive functioning, social functioning, fatigue, nausea and vomiting, pain dyspnoea, insomnia, appetite loss, constipation, diarrhea and finical difficulties with range from maximum scores 4 as worse outcome and from minimum scores 1 as higher values represent as better. | From date of randomization to end of treatment  2 years, | 
| change from baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire esophageal cancer module (EORTC QLQ-OES18). | Total 18 questions to assess your symptoms or problems during the past week with the range from minimum scores 1 as better outcome and maximum 4 as worst outcomes. includes whether any difficult to eat solids, liquids food or not， whether it is difficult to swallow ， whether the sense of smell and conversation are normal or not， whether have Symptoms include cough, indigestion or heartburn, acid reflux and pain or not . | From date of randomization to end of treatment,  2years | 
| The incidence and severity of treatment-emergent adverse events (TEAEs) graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events'. |  | From date of enrollment up to 4 years, approximately. |