A Study of Tislelizumab (BGB-A317) in Combination With Chemotherapy as First Line Treatment in Participants With Advanced Esophageal Squamous Cell Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of tislelizumab as first line treatment in combination with chemotherapy in participants with advanced unresectable/metastatic esophageal squamous cell carcinoma (ESCC).

Official Title
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A Randomized, Placebo-Controlled, Double-Blind Phase 3 Study to Evaluate the Efficacy and Safety of Tislelizumab (BGB-A317) in Combination With Chemotherapy as First-Line Treatment in Patients With Unresectable, Locally Advanced Recurrent or Metastatic Esophageal Squamous Cell Carcinoma

Conditions
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Esophageal Squamous Cell Carcinoma (ESCC)

Intervention / Treatment
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* Drug: Cisplatin
* Drug: Oxaliplatin
* Drug: Fluorouracil (5-FU)
* Drug: Capecitabine
* Drug: Paclitaxel
* Drug: Tislelizumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Pathologically (histologically) confirmed diagnosis of ESCC Stage IV unresectable ESCC at first diagnosis OR unresectable, locally advanced recurrent or metastatic disease (per American Joint Committee on Cancer 7th Edition), if there is prior neoadjuvant/adjuvant therapy with platinum-based chemotherapy, a treatment-free interval of at least 6 months is required. Key Exclusion Criteria: Palliative radiation treatment for ESCC within 4 weeks of study treatment initiation Prior systemic therapy for unresectable, locally advanced recurrent or metastatic ESCC Received prior therapies targeting programmed cell death protein-1 (PD-1), programmed cell death protein ligand-1 (PD-L1) or PD-L2 Participants with evidence of fistula (either esophageal/bronchial or esophageal/aorta) Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention (clinically significant recurrence requiring an additional intervention within 2 weeks of intervention) Evidence of complete esophageal obstruction not amenable to treatment Unintentional weight loss ≥ 5% within one month prior to randomization or Nutritional Risk Index (NRI) < 83.5 per investigator's choice Locally advanced esophageal carcinoma that is resectable or potentially curable with radiation therapy per local investigator. Participants with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers whose HBV DNA is ≥ 500 IU/mL or participants with active hepatitis C virus (HCV) 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tislelizumab + Chemotherapy<br>Tislelizumab 200 milligrams (mg) administered intravenously (IV) on Day 1 of each cycle every 3 weeks (Q3W) plus one of the following until unacceptable toxicity, disease progression or withdrawal for other reasons; each cycle is 21 days Chemotherapy Doublet A: cisplatin 60-80 mg/m^2 or oxaliplatin 130 mg/m^2 administered IV on Day 1 of each cycle Q3W and 5-fluorouracil IV 750-800 mg/m^2 on Days 1 to 5 of each cycle Q3W; Chemotherapy Doublet B: cisplatin 60-80 mg/m^2 or oxaliplatin 130 mg/m^2 administered IV on Day 1 of each cycle Q3W and capecitabine orally 1000 mg/m^2 on Days 1 to 14 of each cycle, twice a day; or Chemotherapy Doublet C: cisplatin 60-80 mg/m^2 administered IV on Day 1 or 2 or oxaliplatin 130 mg/m^2 administered IV on Day 1 of each cycle Q3W and paclitaxel 175 mg/m^2 IV on Day 1 of each cycle Q3W; cisplatin may be given in 3 divided doses on Days 1, 2, and 3 depending on local guidelines | Drug: Cisplatin<br>* Administered IV<br>Drug: Oxaliplatin<br>* Administered IV<br>Drug: Fluorouracil (5-FU)<br>* Administered IV<br>Drug: Capecitabine<br>* Administered orally<br>Drug: Paclitaxel<br>* Administered IV<br>Drug: Tislelizumab<br>* Administered IV<br>* Other names: BGB-A317;|
| Active Comparator: Placebo + Chemotherapy<br>Matched placebo administered IV on Day 1 of each cycle every 3 weeks (Q3W) plus one of the following until unacceptable toxicity, disease progression or withdrawal for other reasons; each cycle is 21 days Chemotherapy Doublet A: cisplatin 60-80 mg/m^2 or oxaliplatin 130 mg/m^2 administered IV on Day 1 of each cycle Q3W and 5-fluorouracil IV 750-800 mg/m^2 on Days 1 to 5 of each cycle Q3W; Chemotherapy Doublet B: cisplatin 60-80 mg/m^2 or oxaliplatin 130 mg/m^2 administered IV on Day 1 of each cycle Q3W and capecitabine orally 1000 mg/m^2 on Days 1 to 14 of each cycle, twice a day; or Chemotherapy Doublet C: cisplatin 60-80 mg/m^2 administered IV on Day 1 or 2 or oxaliplatin 130 mg/m^2 administered IV on Day 1 of each cycle Q3W and paclitaxel 175 mg/m^2 IV on Day 1 of each cycle Q3W; cisplatin may be given in 3 divided doses on Days 1, 2, and 3 depending on local guidelines | Drug: Cisplatin<br>* Administered IV<br>Drug: Oxaliplatin<br>* Administered IV<br>Drug: Fluorouracil (5-FU)<br>* Administered IV<br>Drug: Capecitabine<br>* Administered orally<br>Drug: Paclitaxel<br>* Administered IV<br>Drug: Placebo<br>* Placebo to match Tislelizumab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is defined as the time from the date of randomization until the date of death due to any cause | Up to approximately 3 years and 2 months (as of primary analysis data cut-off date of 28FEB2022) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | PFS is defined as the time from the date of randomization to the date of first documentation of disease progression assessed by the investigator per RECIST v1.1 or death, whichever occurs first | Approximately 40 months from date of the first participant randomization | 
| Objective Response Rate (ORR) | ORR is defined as the proportion of participants whose best overall response (BOR) is complete response (CR) or partial response (PR) assessed by the investigator per RECIST v1.1 | Approximately 40 months from date of the first participant randomization | 
| Overall Survival (OS) in the PD-L1 Score ≥ 10% Subgroup | OS is defined as the time from the date of randomization until the date of death due to any cause | Approximately 40 months from date of the first participant randomization | 
| Duration of Response (DOR) | DOR is defined as the time from the first determination of an objective response until the first documentation of progression assessed by the investigator per RECIST v1.1 or death, whichever comes first | Approximately 40 months from date of the first participant randomization | 
| Health-Related Quality of Life (HRQoL) Assessment of the Participant's Overall Health Status Using European Quality of Life-Core 30 Questionnaire Index (EORTC QLQ-C30) |  | Approximately 40 months from date of the first participant randomization | 
| Health-Related Quality of Life (HRQoL) Assessment of the Participant's Overall Health Status Using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Esophageal Cancer Specific Module (EORTC QLQ-OES18) |  | Approximately 40 months from date of the first participant randomization | 
| Health-Related Quality of Life (HRQoL) Assessment of the Participant's Overall Health Status Using the Generic Health State Instrument European Quality of Life-5 Dimensions (EuroQol 5D EQ-5D-5L) |  | Approximately 40 months from date of the first participant randomization | 
| Number of Participants Experiencing Adverse Events (AEs) |  | Approximately 40 months from date of the first participant randomization |