Efficacy and Safety of Tislelizumab (BGB-A317) as Neo-Adjuvant Treatment in Patients With Colorectal Cancer

Study Overview
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Brief Summary
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This study will evaluate the safety, and tolerability of neo-adjuvant treatment with tislelizumab in participants with early-stage (Stage II-III) Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) colorectal cancer.

Official Title
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A Single-Arm, Multicenter, Open-Label, Phase 2 Study to Investigate the Efficacy and Safety of Tislelizumab (BGB-A317) as Neo-Adjuvant Treatment in Patients With Early-Stage (Stage II-III) Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: Tislelizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ECOG Performance status of 0 or 1. Pathologically (histologically) confirmed diagnosis of potentially resectable Stage II or Stage III Colon/Rectal Cancer (CRC) with MSI-H confirmed by sponsor designated central laboratory or known MSI-H status by local laboratory. Participants should be eligible for an R0 resection with curative intent. Evaluable or measurable disease as assessed by the investigator per RECIST v1.1. Adequate hematologic and organ function, defined by protocol-specified laboratory test results, obtained within 7 days before first dose. Exclusion Criteria: Any prior therapy for current CRC, including chemotherapy or radiotherapy or immunotherapy. Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days before first dose. 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

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tislelizumab<br>Tislelizumab administered intravenously before surgery during the neo-adjuvant phase | Drug: Tislelizumab<br>* Administered intravenously<br>* Other names: BGB-A317;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major pathological response (MPR) rate | MPR rate is defined as the percentage of participants with ≤ 10% residual viable tumor in the resected primary tumor | approximately 16 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological complete response (pCR) rate | Percentage of participants with absence of residual tumor | approximately 16 months | 
| Event-free survival (EFS) | Time from first dose until disease progression | approximately 50 months | 
| 2-year/3-year EFS rate | Percentage of participants free from EFS events at 2 years and 3 years estimated using the Kaplan-Meier method. | approximately 50 months | 
| Proportion of participants expressing Potential Biomarkers in Blood | Potential biomarkers include immune cell infiltration, PD-L1 expression, tumor mutational burden (TMB) and DNA mutation, gene expression profile (GEP) | approximately 50 months | 
| Number of Participants With Clinically Significant Laboratory Values | Laboratory parameters include hematology , chemistry, coagulation and urinalysis | approximately 16 months | 
| Number of Participants With Clinically Significant Vital Signs | Vital signs include pulse rate and blood pressure | approximately 16 months | 
| Number of Participants With Clinically Significant Physical Examination Findings | A full physical examination includes head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal and musculoskeletal systems | approximately 16 months | 
| Number of Participants with Treatment-emergent Adverse Events (TEAEs) | Number of participants with one or more TEAE, including serious adverse events and immune-mediated adverse events, graded according to NCI-CTCAE Version 5.0. | approximately 16 months |