Phase 3 Study of Tislelizumab Versus Sorafenib in Participants With Unresectable HCC
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ClinicalTrials.gov Identifier: NCT03412773 |
Recruitment Status :
Active, not recruiting
First Posted : January 26, 2018
Last Update Posted : June 29, 2020
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Hepatocellular Carcinoma (HCC) | Drug: Tislelizumab Drug: Sorafenib | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 674 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | 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 |
Actual Study Start Date : | December 28, 2017 |
Estimated Primary Completion Date : | June 20, 2021 |
Estimated Study Completion Date : | May 2022 |

Arm | Intervention/treatment |
---|---|
Experimental: Arm A: Tislelizumab & Safety Run-In Substudy [Japan Only] |
Drug: Tislelizumab
200 mg once every 3 weeks (Q3W), intravenous dosing (IV)
Other Name: BGB-A317 |
Active Comparator: Arm B: Sorafenib |
Drug: Sorafenib
400 mg twice daily (BID), oral dosing
Other Names:
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- Overall Survival (OS) [ Time Frame: From date of randomization up to 4 years, approximately ]
- Safety Run-In Substudy[Japan only]: Percentage of participants with adverse events [ Time Frame: 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] [ Time Frame: From the date of enrollment up to 28 days [DLT period]. ]
- Safety Run-In Substudy[Japan only]: Maximum Concentration (Cmax) of Tislelizumab [ Time Frame: From first dose of study treatment up to 4 years, approximately. ]
- Safety Run-In Substudy[Japan only]: Trough Serum Concentration (Cmin) of tislelizumab [ Time Frame: From first dose of study treatment up to 4 years, approximately. ]
- Safety Run-In Substudy[Japan only]: Area Under the Curve (AUC) of tislelizumab [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: From date of enrollment up to 4 years, approximately. ]
- Objective Response Rate (ORR) [ Time Frame: From date of randomization up to 4 years, approximately ]
- Progression-free survival (PFS) [ Time Frame: From date of randomization up to 4 years, approximately ]
- Duration of Response (DOR) [ Time Frame: From first determination of an objective response up to 4 years, approximately ]
- Time to Progression (TTP) [ Time Frame: From date of randomization up to 4 years, approximately. ]
- Health-Related Quality of Life (HRQoL) [ Time Frame: From date of enrollment up to 4 years, approximately. ]
- Disease Control Rate (DCR) [ Time Frame: From first dose of study treatment up to 4 years, approximately ]
- Clinical Benefit Rate (CBR) [ Time Frame: From first dose of study treatment up to 4 years, approximately ]
- Percentage of participants with adverse events [ Time Frame: From date of screening up to 4 years, approximately. ]
- Safety Run-In Substudy[Japan only]: Objective Response Rate (ORR) [ Time Frame: From date of randomization up to 4 years, approximately. ]
- Safety Run-In Substudy[Japan only]: Progression-free survival (PFS) [ Time Frame: From date of randomization up 4 years, approximately ]
- Safety Run-In Substudy[Japan only]: Duration of Response (DOR) [ Time Frame: From date of randomization up 4 years, approximately ]
- Safety Run-In Substudy[Japan only]: Overall Survival (OS) [ Time Frame: From date of randomization up 4 years, approximately ]
- Safety Run-In Substudy[Japan only]: Anti-tislelizumab antibody [ Time Frame: From first dose of study treatment up 4 years, approximately ]
- Percentage of Participants With Clinically Significant Changes in Vital Signs Findings [ Time Frame: From date of enrollment up to 4 years, approximately ]
- Percentage of Participants With Clinically Significant Changes in Physical Examination Findings [ Time Frame: From date of enrollment up to 4 years, approximately ]
- Percentage of Participants With Clinically Significant Changes in Clinical Laboratory Results Findings [ Time Frame: From date of enrollment up to 4 years, approximately ]
- Percentage of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings [ Time Frame: From date of enrollment up to 4 years, approximately ]

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03412773

Study Director: | Yaxi Chen, MD | BeiGene |
Responsible Party: | BeiGene |
ClinicalTrials.gov Identifier: | NCT03412773 |
Other Study ID Numbers: |
BGB-A317-301 2017-002423-19 ( EudraCT Number ) CTR20170882 ( Registry Identifier: Center for drug evaluation, CFDA ) JapicCTI-194569 ( Registry Identifier: Japic ) |
First Posted: | January 26, 2018 Key Record Dates |
Last Update Posted: | June 29, 2020 |
Last Verified: | June 2020 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Advanced liver cancer RATIONALE-301 |
Carcinoma Carcinoma, Hepatocellular Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Adenocarcinoma Liver Neoplasms Digestive System Neoplasms |
Neoplasms by Site Digestive System Diseases Liver Diseases Sorafenib Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |