Phase 3 Study of Tislelizumab Versus Sorafenib in Participants With Unresectable HCC

Study Overview
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Brief Summary
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This is a Phase 3, randomized, open-label, multicenter, global study designed to compare the efficacy and safety of tislelizumab versus sorafenib as a first-line systemic treatment in participants with unresectable hepatocellular carcinoma. This study also includes a substudy investigating the safety, tolerability, PK, and preliminary efficacy in HCC in Japanese participants. In Japan, preliminary safety and tolerability will be evaluated (Safety Run-In Substudy) before Japanese participants are recruited in this Phase 3 study.

Official Title
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RATIONALE-301: A Randomized, Open-label, Multicenter Phase 3 Study to Compare the Efficacy and Safety of BGB-A317 Versus Sorafenib as First-Line Treatment in Patients With Unresectable Hepatocellular Carcinoma

Conditions
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Hepatocellular Carcinoma (HCC)

Intervention / Treatment
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* Drug: Tislelizumab
* Drug: Sorafenib


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Histologically confirmed diagnosis of HCC Barcelona Clinic Liver Cancer (BCLC) Stage B or C disease not amenable to or progressing after loco-regional therapy and not amenable to a curative treatment approach No prior systemic therapy for HCC (with the exception of HCC participants enrolled in the safety run-in substudy [Japan only]) Measurable disease Child-Pugh score A Easter Cooperative Oncology Group (ECOG) Performance Status ≤ 1 Adequate organ function Key Exclusion Criteria: Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC histology Tumor thrombus involving main trunk of portal vein or inferior vena cava Loco-regional therapy to the liver within 28 days before randomization Clinical evidence of portal hypertension with bleeding esophageal or gastric varices at Screening, or within 6 months before randomization Bleeding or thrombotic disorder or any prescribed anticoagulant requiring therapeutic international normalized ratio monitoring (eg, warfarin or similar agents) at Screening, or within 6 months before randomization/enrollment Presence at Screening of active immune deficiency or autoimmune disease and/or prior history of any immune deficiency or autoimmune disease that may relapse Participant with any condition requiring systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication within 14 days before randomization History of interstitial lung disease or non-infectious pneumonitis, unless induced by radiation therapy QT interval corrected for heart rate (QTc) (corrected by Fridericia's method) > 450 msec at Screening 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: Arm A: Tislelizumab & Safety Run-In Substudy [Japan Only]<br> | Drug: Tislelizumab<br>* 200 mg once every 3 weeks (Q3W), intravenous dosing (IV)<br>* Other names: BGB-A317;|
| Active Comparator: Arm B: Sorafenib<br> | Drug: Sorafenib<br>* 400 mg twice daily (BID), oral dosing<br>* Other names: BAY43-9006;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) |  | From date of randomization up to 4 years, approximately | 
| Safety Run-In Substudy[Japan only]: Percentage of participants with adverse events |  | From date of enrollment up to 4 years, approximately. | 
| Safety Run-In Substudy[Japan only]: Percentage of participants with dose-limiting toxicities (DLT) [Determination of the pivotal Phase 3 dose of tislelizumab in Japanese participants] |  | From the date of enrollment up to 28 days [DLT period]. | 
| Safety Run-In Substudy[Japan only]: Maximum Concentration (Cmax) of Tislelizumab |  | From first dose of study treatment up to 4 years, approximately. | 
| Safety Run-In Substudy[Japan only]: Trough Serum Concentration (Cmin) of tislelizumab |  | From first dose of study treatment up to 4 years, approximately. | 
| Safety Run-In Substudy[Japan only]: Area Under the Curve (AUC) of tislelizumab |  | From first dose of study treatment up to 4 years, approximately. | 
| Safety Run-In Substudy[Japan only]:Anti-Drug Antibodies (ADA) against tislelizumab at Cmin |  | From first dose of study treatment up to 4 years, approximately. | 
| Safety Run-In Substudy[Japan only]: Percentage of Participants With Clinically Significant Changes in Vital Signs Findings |  | From date of enrollment up to 4 years, approximately. | 
| Safety Run-In Substudy[Japan only]: Percentage of Participants With Clinically Significant Changes in Physical Examination Findings |  | From date of enrollment up to 4 years, approximately. | 
| Safety Run-In Substudy[Japan only]: Percentage of Participants With Clinically Significant Changes in Clinical Laboratory Results Findings |  | From date of enrollment up to 4 years, approximately. | 
| Safety Run-In Substudy[Japan only]: Percentage of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings |  | From date of enrollment up to 4 years, approximately. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) |  | From date of randomization up to 4 years, approximately | 
| Progression-free survival (PFS) |  | From date of randomization up to 4 years, approximately | 
| Duration of Response (DOR) |  | From first determination of an objective response up to 4 years, approximately | 
| Time to Progression (TTP) |  | From date of randomization up to 4 years, approximately. | 
| Health-Related Quality of Life (HRQoL) |  | From date of enrollment up to 4 years, approximately. | 
| Disease Control Rate (DCR) |  | From first dose of study treatment up to 4 years, approximately | 
| Clinical Benefit Rate (CBR) |  | From first dose of study treatment up to 4 years, approximately | 
| Percentage of participants with adverse events |  | From date of screening up to 4 years, approximately. | 
| Safety Run-In Substudy[Japan only]: Objective Response Rate (ORR) |  | From date of randomization up to 4 years, approximately. | 
| Safety Run-In Substudy[Japan only]: Progression-free survival (PFS) |  | From date of randomization up 4 years, approximately | 
| Safety Run-In Substudy[Japan only]: Duration of Response (DOR) |  | From date of randomization up 4 years, approximately | 
| Safety Run-In Substudy[Japan only]: Overall Survival (OS) |  | From date of randomization up 4 years, approximately | 
| Safety Run-In Substudy[Japan only]: Anti-tislelizumab antibody |  | From first dose of study treatment up 4 years, approximately | 
| Percentage of Participants With Clinically Significant Changes in Vital Signs Findings |  | From date of enrollment up to 4 years, approximately | 
| Percentage of Participants With Clinically Significant Changes in Physical Examination Findings |  | From date of enrollment up to 4 years, approximately | 
| Percentage of Participants With Clinically Significant Changes in Clinical Laboratory Results Findings |  | From date of enrollment up to 4 years, approximately | 
| Percentage of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings |  | From date of enrollment up to 4 years, approximately | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced liver cancer, RATIONALE-301