A Study to Evaluate LBL-007 in Combination With Tislelizumab Plus Chemotherapy in Participants With Unresectable Locally Advanced or Metastatic Esophageal Squamous Cell Carcinoma

Study Overview
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Brief Summary
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This is a randomized, open-label study to compare how well LBL-007 works in combination with tislelizumab and chemotherapy versus tislelizumab and chemotherapy when given as the first-line treatment in participants with inoperable locally advanced or metastatic esophageal squamous cell carcinoma (ESCC).

Official Title
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A Phase 2, Randomized, Active-Controlled, Open-Label Study to Evaluate the Efficacy and Safety of LBL-007 in Combination With Tislelizumab Plus Chemotherapy as First-Line Treatment in Patients With Unresectable Locally Advanced or Metastatic Esophageal Squamous Cell Carcinoma

Conditions
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Esophageal Cancer, Esophageal Squamous Cell Carcinoma, Esophageal Squamous Cell Carcinoma by AJCC V8 Stage

Intervention / Treatment
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* Drug: LBL-007
* Drug: Tislelizumab
* Drug: Chemotherapy Doublet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to provide written informed consent and can agree to comply with the study requirements. Participants with metastatic ESCC or unresectable, locally advanced ESCC. Histologically confirmed diagnosis of ESCC. Can provide a tumor sample. At least 1 measurable lesion as defined by RECIST v1.1. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1. Exclusion Criteria: Prior treatment for advanced or metastatic ESCC within the past 6 months Locally advanced ESCC that is either resectable or potentially curable with definitive chemoradiation treatment per local investigator Palliative radiation treatment for ESCC within the past 4 weeks Participants with an esophageal/bronchial or esophageal/aorta fistula Prior treatment with programmed cell death protein-1 (PD-1) or other immune-oncological drugs 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LBL-007<br>LBL-007 in combination with tislelizumab plus chemotherapy doublet. | Drug: LBL-007<br>* LBL-007 will be administered at a standard dose intravenously.<br>Drug: Tislelizumab<br>* Tislelizumab will be administered at a standard dose intravenously.<br>* Other names: BGB-A317;Drug: Chemotherapy Doublet<br>* Doublet 1: cisplatin + 5-fluorouracil Doublet 2: cisplatin + paclitaxel Choice of chemotherapy doublet will be determined by the investigator and will be administered at standard doses intravenously.<br>|
| Active Comparator: Tislelizumab and Chemotherapy<br>Tislelizumab plus chemotherapy doublet. | Drug: Tislelizumab<br>* Tislelizumab will be administered at a standard dose intravenously.<br>* Other names: BGB-A317;Drug: Chemotherapy Doublet<br>* Doublet 1: cisplatin + 5-fluorouracil Doublet 2: cisplatin + paclitaxel Choice of chemotherapy doublet will be determined by the investigator and will be administered at standard doses intravenously.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | Percentage of participants whose best overall response (BOR) is complete response (CR) or partial response (PR) as assessed by the investigator per Response Evaluation Criteria for Solid Tumors (RECIST) v1.1. | Approximately 14 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | 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 14 months | 
| Duration of Response (DOR) | Time from the first determination of an overall response until the first documentation of progression assessed by the investigator per RECIST v1.1 or death, whichever occurs first. | Approximately 14 months | 
| Disease Control Rate (DCR) | Percentage of participants whose BOR is CR, PR, and stable disease as assessed by the investigator per RECIST v1.1. | Approximately 14 months | 
| Number of Participants with Adverse Events (AEs) | Number of participants with AEs, including findings from physical examinations, electrocardiograms, and laboratory assessments according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0. | Approximately 14 months |