Tislelizumab in Combination With TACE in Advanced Hepatocellular Carcinoma

Study Overview
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Brief Summary
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A multicentric, open-label, single-arm prospective study to assess the efficacy and safety of tislelizumab combined with TACE as first-line treatment in patients with unresectable BCLC stage C HCC.

Detailed Description
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This is a multicentric, open-label, single-arm prospective study to assess the efficacy and safety of tislelizumab combined with conventional transarterial chemoembolization(cTACE) as first-line treatment in BCLC stage C HCC patients without extrahepatic spread. The primary endpoint is time to progression (TTP).

Official Title
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A Multicentric, Open-Label Study to Evaluate Tislelizumab in Combination With Transarterial Chemoembolization as First-Line Treatment in Patients With Advanced Hepatocellular Carcinoma

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Tislelizumab in combination with cTACE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-70 years old on the day the patients voluntary to participate in the study and signing in ICF. Histological or clinical diagnosis of HCC. BCLC stage C patients ineligible for surgical resection or liver transplantation. No prior systemic therapy for HCC (including immunotherapy). Have at least one uni-dimensional lesion measurable by CT scan or magnetic resonance imaging per mRECIST. Child-Pugh A-B7. ECOG PS 0-1. Adequate hematological function (absolute neutrophil count ≥ 1.5 X 109/L, platelets count≥50 X109/L, and hemoglobin ≥85 g/L); Adequate hepatic function (both AST and ALT ≤ 3 ULN, serum total bilirubin ≤ 34.2 umol/L or 2mg/dl, serum albumin ≥ 29g/L); Adequate renal function (eGFR > 30 ml/min/1.73 m2) For patients with HBV or HCV infection, HBV DNA less than 500 IU/ml (2500 copies/ml) or HCV RNA detectable. life expectancy of more than 3 months. Patients must be able to understand and willing to sign a written informed consent document. Patients suitable for TACE therapy assessed by investigators. Exclusion Criteria: Tumor thrombus involving main trunk of portal vein or inferior vena cava. Prior local-regional therapy before beginning of study treatment (surgery or ablation allowed at BCLC stage 0-B) or radiotherapy on liver cancer. Disease history of grade 2 or more hepatic encephalopathy. Extrahepatic metastasis on baseline imaging. HIV infection or syphilis. Prior therapies with any anti-PD-1, anti-PD-L1, anti-PD-L2 or anti-CTLA-4 agents. Tumor diffuse.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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 in combination with cTACE<br>Tislelizumab in combination with on-demanded cTACE | Drug: Tislelizumab in combination with cTACE<br>* On-demanded cTACE in combined with tislelizumab (200mg q3w ivgtt on day 4 of each 21-day cycle)<br>* Other names: BGB-A317;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TTP assessed by independent review committee(IRC) | Defined as the time from the date of first cTACE to the date of first documentation of disease progression per mRECIST. When pseudoprogression is suspected by investigator, tumor response will be re-assessed per iRECIST to confirm (also applicable for secondary endpoint of efficacy). | up to 24 months after enrollment or study close | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TTP assessed by investigators | Defined as the time from the treatment initiation to the date of the first objectively documented tumor progression, assessed by investigators per mRECIST. | An expected average of 8 months | 
| PFS | Defined as the time from the treatment initiation to the date of the first objectively documented tumor progression or death, whichever occurs first, assessed by IRC and investigators, respectively, per mRECIST. | An expected average of 8 months | 
| ORR | Defined as the proportion of patients with a documented CR or PR, assessed by IRC and investigators, respectively, per mRECIST. | An expected average of 8 months | 
| DCR | Defined as the proportion of patients whose best overall response (BOR) is CR, PR, or SD, assessed by IRC and investigators, respectively, per mRECIST. | An expected average of 8 months | 
| DOR | Defined as the time from the first confirmation of objective remission (CR or PR) to the first recording of disease progression or death, whichever occurs first, assessed by IRC and investigators, respectively, per mRECIST. | An expected average of 8 months | 
| OS | Defined as the time from the treatment initiation to the date of death due to any cause. | An expected average of 24 months | 
| Safety | NCI-CTCAE v5.0. | up to 24 months after enrollment or study close | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TACE, tislelizumab