A Study of Tislelizumab Versus Sorafenib in Participants With Unresectable Hepatocellular Carcinoma (HCC)

BeiGene

Status and phase: Completed; Phase 3

Conditions: Hepatocellular Carcinoma (HCC)

Treatments: Drug: Sorafenib; Drug: Tislelizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03412773

CTR20170882 (Registry Identifier)

RATIONALE-301 (Other Identifier)

JapicCTI-194569 (Registry Identifier)

BGB-A317-301

2017-002423-19 (EudraCT Number)

Details and patient eligibility

About

This Phase 3 study was a global, multicenter trial that randomly assigned participants to either tislelizumab or sorafenib as a first-line treatment for adults with advanced liver cancer (hepatocellular carcinoma) that could not be surgically removed. Before enrolling Japanese participants in the main Phase 3 study, a preliminary assessment of safety and tolerability (the Safety Run-In Sub-study) was conducted in Japan.

Enrollment: 684 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Safety Run-In Sub-study Eligibility Criteria: The study included adult Japanese participants (≥ 20 years) with histologically confirmed hepatocellular carcinoma (HCC) at Barcelona Clinic Liver Cancer (BCLC) Stage C or B. Eligible participants had either received, were ineligible for, or declined standard treatment. Additional requirements were a Child-Pugh A classification within 7 days before enrollment, at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and an Eastern Cooperative Oncology Group (ECOG) Performance Status score of ≤ 1.

Main Study 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

Main Study 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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684 participants in 3 patient groups

Safety Run-In Sub-study

Experimental group

Description:

Japanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability.

Treatment:

Drug: Tislelizumab

Arm A: Tislelizumab

Experimental group

Description:

Participants received 200 mg of intravenous tislelizumab every 3 weeks until intolerable toxicity, withdrawal of consent, or the investigator determined no further benefit from the therapy.

Treatment:

Drug: Tislelizumab

Arm B: Sorafenib

Active Comparator group

Description:

Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.

Treatment:

Drug: Sorafenib