Clinical trial
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
Name
BGB-A317-301
Description
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.
Trial arms
Trial start
2017-12-28
Estimated PCD
2022-07-11
Trial end
2023-12-14
Status
Completed
Phase
Early phase I
Treatment
Tislelizumab
200 mg once every 3 weeks (Q3W), intravenous dosing (IV)
Arms:
Arm A: Tislelizumab & Safety Run-In Substudy [Japan Only]
Other names:
BGB-A317
Sorafenib
400 mg twice daily (BID), oral dosing
Arms:
Arm B: Sorafenib
Other names:
Nexavar, BAY43-9006
Size
674
Primary endpoint
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.
Eligibility criteria
Key Inclusion Criteria:
1. Histologically confirmed diagnosis of HCC
2. 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
3. No prior systemic therapy for HCC (with the exception of HCC participants enrolled in the safety run-in substudy \[Japan only\])
4. Measurable disease
5. Child-Pugh score A
6. Easter Cooperative Oncology Group (ECOG) Performance Status ≤ 1
7. Adequate organ function
Key Exclusion Criteria:
1. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC histology
2. Tumor thrombus involving main trunk of portal vein or inferior vena cava
3. Loco-regional therapy to the liver within 28 days before randomization
4. Clinical evidence of portal hypertension with bleeding esophageal or gastric varices at Screening, or within 6 months before randomization
5. 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
6. Presence at Screening of active immune deficiency or autoimmune disease and/or prior history of any immune deficiency or autoimmune disease that may relapse
7. 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
8. History of interstitial lung disease or non-infectious pneumonitis, unless induced by radiation therapy
9. 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.
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 674, 'type': 'ACTUAL'}}
Updated at
2024-01-10
1 organization
2 products
2 abstracts
1 indication
Product
TislelizumabIndication
Hepatocellular CarcinomaProduct
SorafenibOrganization
BeiGeneAbstract
Tislelizumab (TIS) versus sorafenib (SOR) in first-line (1L) treatment of unresectable hepatocellular carcinoma (HCC): The RATIONALE-301 European/North American (EU/NA) subgroup.Org: BeiGene (Ridgefield Park) Co., Ltd., BeiGene (Beijing) Co., Ltd., Beijing, China, BeiGene Co., Ltd.,
Abstract
Impact of risk factors on overall survival (OS) in patients (pts) with unresectable hepatocellular carcinoma (HCC) treated with first-line (1L) tislelizumab (TIS).Org: BeiGene (USA) Co., Ltd., BeiGene (Beijing) Co., Ltd., Beijing, China, BeiGene Co., Ltd., Jiahui Cancer Center, Massachusetts General Hospital,