AdvanTIG-203: Anti-PD-1 Monoclonal Antibody Tislelizumab (BGB-A317) Combined With or Without Anti-TIGIT Monoclonal Antibody Ociperlimab (BGB-A1217) in Participants With Recurrent or Metastatic Esophageal Squamous Cell Carcinoma

Study Overview
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Brief Summary
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A study of tislelizumab (BGB-A317) plus ociperlimab versus tislelizumab plus placebo as second-line treatment in participants with programmed cell death protein-ligand 1 (PD-L1) tumor area positivity (TAP) ≥ 10% unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma.

Official Title
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A Phase 2, Multicenter, Randomized, Placebo-Controlled Study to Compare the Efficacy of Anti-PD-1 Monoclonal Antibody Tislelizumab (BGB-A317) Plus Anti-TIGIT Monoclonal Antibody Ociperlimab (BGB-A1217) Versus Tislelizumab Plus Placebo as Second-Line Treatment in Patients With PD-L1 Tumor Area Positivity (TAP) ≥ 10% Unresectable, Locally Advanced, Recurrent or Metastatic Esophageal Squamous Cell Carcinoma

Conditions
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Esophageal Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Tislelizumab
* Drug: Ociperlimab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Histologically confirmed diagnosis of (esophageal squamous cell carcinoma) ESCC. Have PD during or after first-line of systemic treatment for unresectable, locally advanced, recurrent or metastatic ESCC. Have measurable disease as assessed by RECIST v1.1. Have confirmed PD-L1 TAP ≥ 10% in tumor tissues tested by the central lab. Eastern Cooperative Oncology Group Performance Status score of 0 or 1. Key Exclusion Criteria: Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains, or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways. Participants with evidence of fistula (either esophageal/bronchial or esophageal/aorta). Evidence of complete esophageal obstruction not amenable to treatment. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage (recurrence within 2 weeks after intervention). Has received any chemotherapy, immunotherapy (eg, interleukin, interferon, thymosin, etc) or any investigational therapies within 14 days or 5 half-lives (whichever is longer) before the first dose of study drug. Or has received palliative radiation treatment or other local regional therapies within 14 days before the first dose of study drug. 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: Arm A: Tislelizumab plus Ociperlimab<br>Participants will receive tislelizumab (200 milligrams [mg]) plus ociperlimab (900 mg) intravenously once every 3 weeks. | Drug: Tislelizumab<br>* Tislelizumab is a monoclonal antibody formulated for intravenous injection.<br>* Other names: BGB-A317;Drug: Ociperlimab<br>* Ociperlimab is a monoclonal antibody formulated for intravenous injection.<br>* Other names: BGB-A1217;|
| Placebo Comparator: Arm B: Tislelizumab plus Placebo<br>Participants will receive tislelizumab (200 mg) plus placebo intravenously once every 3 weeks. | Drug: Tislelizumab<br>* Tislelizumab is a monoclonal antibody formulated for intravenous injection.<br>* Other names: BGB-A317;Drug: Placebo<br>* Ociperlimab placebo injection is a sterile, preservative-free solution for infusion formulated in the same buffer as ociperlimab active drug.<br>* Other names: Ociperlimab placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) Assessed By The Investigator's Review Per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 | The objective response rate will be defined as the proportion of participants who have confirmed complete response (CR) or partial response (PR). | Approximately 17 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival will be defined as the time from the date of randomization until the date of death due to any cause in all randomized participants. | Approximately 32 months | 
| Progression-free Survival Assessed By The IRC And The Investigator Per RECIST v1.1 | Progression-free survival will be defined as the time from the date of randomization to the date of first documentation of PD assessed by both the IRC and the investigator per RECIST v1.1 or death, whichever occurs first. | Approximately 32 months | 
| Duration Of Response Assessed By The IRC And The Investigator Per RECIST v1.1 | Duration of response will be defined as the time from the first determination of an objective response until the first documentation of PD as assessed by both the IRC and the investigator per RECIST v1.1, or death, whichever comes first. | Approximately 32 months | 
| Disease Control Rate Assessed By The IRC And The Investigator Per RECIST v1.1 | Disease Control Rate will be defined as the proportion of participants who have confirmed CR, PR, and stable disease assessed by both the IRC and the investigator per RECIST v1. | Approximately 32 months | 
| Clinical Benefit Rate | The clinical benefit rate will be defined as the proportion of participants who achieve confirmed complete response, partial response, and durable stable disease (stable disease ≥ 24 weeks). | Approximately 32 months | 
| Health -related Quality Of Life (HRQoL): European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) | The HRQoL will be assessed by scores in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-30) : | 30 days (±7) after last dose | 
| HRQoL: Dysphagia, Eating, Reflux and Pain Scales of EORTC Quality of Life Oesophageal Cancer Questionnaires 18 (QLQ-OES18) | The HRQoL will be assessed by scores in the EORTC QLQ-OES18. | 30 days (±7) after last dose | 
| Incidence of Adverse Events And Serious Adverse Events |  | 90 days (±14) after last dose |