Study of Tislelizumab in Participants With Resectable 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 pathological complete response (pCR) in participants receiving tislelizumab plus chemotherapy/chemoradiotherapy as neoadjuvant treatment.

Official Title
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A Phase 2, Multicenter, Open-label, 2-Cohort Study to Investigate the Efficacy and Safety of PET Guided Neoadjuvant Treatment With Tislelizumab (BGB-A317) Plus Chemotherapy/Chemoradiotherapy in Patients With Resectable Esophageal Squamous Cell Carcinoma

Conditions
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Resectable Esophageal Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Tislelizumab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Eastern Cooperative Oncology Group Performance Status of 0 or 1. Histologically confirmed esophageal squamous cell carcinoma (ESCC). Stage cT1-2N+M0 and cT3NanyM0 (per The American Joint Committee on Cancer 8th Edition). Evaluation by the investigator to confirm eligibility for an R0 resection with curative intent. Adequate hematologic and organ function, defined by protocol-specified laboratory test results obtained within 14 days before first dose. Key Exclusion Criteria: Ineligible for treatment with any of the chemotherapy doublets of protocol-specified chemotherapy. Any prior therapy for current ESCC, including investigational agents, chemotherapy, radiotherapy, targeted therapy agents, or prior therapy with an anti-programmed cell death protein-1, anti-programmed cell death protein ligand-1, anti-programmed cell death protein ligand-2, or any other antibody or drug specifically targeting T-Cell co-stimulation or checkpoint pathways. History of fistula due to primary tumor invasion. Participants with high risk of fistula or sign of perforation evaluated by investigator. Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days before first dose. * Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent) and topical, ocular, intra-articular, intranasal, or inhaled corticosteroid with minimal systemic absorption, and short course (≤ 7 days) of corticosteroid prescribed prophylactically or for the treatment of a non-autoimmune condition are permitted. Active autoimmune diseases or history of autoimmune diseases that may relapse. * Controlled Type I diabetes, hypothyroidism only requiring hormone replacement, controlled celiac disease, skin diseases (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. History of interstitial lung disease, non-infectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases. With infections requiring systemic antibacterial, antifungal, or antiviral therapy, including tuberculosis infection. Severe infections within 4 weeks before first dose, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia. Receive therapeutic oral or intravenous antibiotics within 2 weeks before first dose. 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A (Responder)<br>Participants with a decrease in positron emission tomography (PET) Standardized Uptake Value (SUV)max ≥ 35% will receive 3 cycles of tislelizumab (200 milligrams [mg]/cycle) plus 2 cycles of chemotherapy doublet (cisplatin + paclitaxel) | Drug: Tislelizumab<br>* Administered intravenously as specified in the treatment arm.<br>* Other names: BGB-A317;|
| Experimental: Cohort B (Non-responder)<br>Participants with a decrease in PET SUVmax < 35% will receive 3 cycles of tislelizumab (200 mg/cycle) plus 2 cycles of investigator-chosen chemotherapy doublet (paclitaxel + cisplatin or 5-fluorouracil + cisplatin) plus concurrent radiotherapy (40 grays/20 fractions). | Drug: Tislelizumab<br>* Administered intravenously as specified in the treatment arm.<br>* Other names: BGB-A317;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pCR Rate | The pCR will be defined as the proportion of participants with absence of residual tumor in the resected primary tumor and all resected lymph nodes after completion of neoadjuvant treatment. | approximately 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| R0 Resection Rate | This will be defined as the proportion of participants with R0 resection. | approximately 5 years | 
| 1-year/3-year Disease-free Survival (DFS) Rate | The DFS will be defined as the proportion of participants free from disease events at 1st year and 3rd year after the first date of no disease. The DFS will be defined as the time from the first date of no disease (R0 resection as surgery outcome) to local or distant recurrence or death due to any cause, whichever occurs first. The DFS rate will be analyzed only for participants who undergo R0 resection. | approximately 5 years | 
| 1-year/3-year Event-free Survival (EFS) Rate | The EFS will be defined as the proportion of participants free from EFS events at 1st year and 3rd year after the first dose. The EFS will be defined as the time from the time of first dose until any of the following events, whichever occurs first: progression of disease that precludes definitive surgery, local or distant recurrence, or death due to any cause. | approximately 5 years | 
| Objective Response Rate (ORR) | The ORR will be defined as the proportion of participants who have a complete response or partial response before surgery as assessed by the investigator per RECIST v1.1 in all participants with measurable disease at baseline. | approximately 5 years | 
| Number Of Participants Experiencing Treatment-Emergent Adverse Events |  | approximately 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tislelizumab, PET, Chemotherapy, Chemoradiotherapy