Study of BGB-A317 in Participants With Previously Treated Unresectable HCC

Study Overview
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Brief Summary
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This study investigated the efficacy, safety, and pharmacokinetics of the anti-PD-1 monoclonal antibody BGB-A317 in participants with previously treated hepatocellular unresectable carcinoma.

Official Title
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A Phase 2, Open-label, Multicenter Study to Investigate the Efficacy, Safety, and Pharmacokinetics of the Anti-PD-1 Monoclonal Antibody BGB-A317 in Patients With Previously Treated Hepatocellular Unresectable Carcinoma

Conditions
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Hepatocellular Carcinoma (HCC)

Intervention / Treatment
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* Drug: Tislelizumab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Histologically confirmed HCC Participants with Barcelona Clinic Liver Cancer (BCLC) Stage C, or BCLC stage B not amenable to locoregional therapy or relapsed after locoregional therapy, and not amenable to a curative treatment approach Has received at least 1 line of systemic therapy for unresectable HCC Has at least 1 measurable lesion as defined per RECIST v1.1 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 Prior therapies targeting PD-1 or PD-L1 Has known brain or leptomeningeal metastasis Tumor thrombus involving main trunk of portal vein or inferior vena cava Loco-regional therapy to the liver within 4 weeks before enrollment Medical history of interstitial lung disease, non-infectious pneumonitis or uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, or acute lung diseases Has received: Within 28 days or 5 half-lives (whichever is shorter) of the first study drug administration: any chemotherapy, immunotherapy (eg, interleukin, interferon, thymoxin) or any investigational therapies Within 14 days of the first study drug administration: sorafenib, regorafenib, or any Chinese herbal medicine or Chinese patent medicines used to control cancer Active autoimmune diseases or history of autoimmune diseases 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 study drug administration 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tislelizumab<br>200 milligrams once every 3 weeks | Drug: Tislelizumab<br>* Administered intravenously<br>* Other names: BGB-A317;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) Assessed by Independent Review Committee (IRC) | ORR is defined as the percentage of participants with complete response (CR) and partial response (PR) as the best overall response, as determined by an IRC using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR is defined as disappearance of all target lesions and PR is defined as at least a 30% decrease in the sum of diameters of target lesions. | From date of first dose to primary analysis data cut-off date of 30-June-2021 (up to approximately 3 years and 3 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR Assessed by Investigator | ORR is defined as the percentage of participants with CR and PR as the best overall response, as determined by investigator assessment using RECIST v1.1. CR is defined as disappearance of all target lesions and PR is defined as at least a 30% decrease in the sum of diameters of target lesions. | From date of first dose to end of study (up to approximately 4 years and 3 months) | 
| Duration of Response (DOR) Assessed by IRC | DOR is defined as the time from the date that response criteria are first met to the date that progressive disease is objectively documented or death, whichever comes first, as assessed by the IRC using RECIST v1.1 | From date of first dose to end of study (up to approximately 4 years and 3 months) | 
| DOR Event-Free Rate Assessed by IRC | DOR is defined as the time from the date that response criteria are first met to the date that progressive disease is objectively documented or death, whichever comes first, as assessed by the IRC using RECIST v1.1. The Kaplan-Meier method was used to estimate the percentage of participants who were event-free for progression or death at 12 and 24 months with 95% confidence intervals estimated using Greenwood's formula. | From date of first dose to end of study (up to approximately 4 years and 3 months); Months 12 and 24 reported | 
| DOR Assessed by Investigator | DOR is defined as the time from the date that response criteria are first met to the date that progressive disease is objectively documented or death, whichever comes first, as assessed by the investigator using RECIST v1.1 | From date of first dose to end of study (up to approximately 4 years and 3 months) | 
| DOR Event-Free Rate Assessed by Investigator | DOR is defined as the time from the date that response criteria are first met to the date that progressive disease is objectively documented or death, whichever comes first, as assessed by the investigator using RECIST v1.1. The Kaplan-Meier method was used to estimate the percentage of participants who were event-free for progression or death at 12 and 24 months with 95% confidence intervals estimated using Greenwood's formula. | From date of first dose to end of study (up to approximately 4 years and 3 months); Months 12 and 24 reported | 
| Progression-free Survival (PFS) Assessed by IRC | PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as assessed by the IRC using RECIST v1.1 | From date of first dose to end of study (up to approximately 4 years and 3 months) | 
| PFS Assessed by Investigator | PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as assessed by the investigator using RECIST v1.1 | From date of first dose to end of study (up to approximately 4 years and 3 months) | 
| Overall Survival (OS) | OS is defined as the time from first study drug administration to the date of death due to any cause | From date of first dose to end of study (up to approximately 4 years and 3 months) | 
| Disease Control Rate (DCR) Assessed by IRC | DCR is defined as the percentage of participants whose best overall response is CR, PR, or stable disease (SD) as assessed by the IRC using RECIST v1.1 | From date of first dose to end of study (up to approximately 4 years and 3 months) | 
| DCR Assessed by Investigator | DCR is defined as the percentage of participants whose best overall response is CR, PR, or stable disease (SD) as assessed by the investigator using RECIST v1.1 | From date of first dose to end of study (up to approximately 4 years and 3 months) | 
| Clinical Benefit Rate (CBR) Assessed by IRC | CBR is defined as the percentage of participants who have CR, PR, or SD of ≥ 24 weeks in duration as assessed by the IRC using RECIST v1.1 | From date of first dose to end of study (up to approximately 4 years and 3 months) | 
| CBR Assessed by Investigator | CBR is defined as the percentage of participants who have CR, PR, or SD of ≥ 24 weeks in duration as assessed by the investigator using RECIST v1.1 | From date of first dose to end of study (up to approximately 4 years and 3 months) | 
| European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L) Visual Analogue Score (VAS) | Mean change from baseline in EQ-5D-5L VAS. The EQ-5D-5L measures health outcomes using a VAS to record a participant's self-rated health on a scale from 0 to 100, where 100 is 'the best health you can imagine' and 0 is 'the worst health you can imagine.' A higher score indicates better health outcomes. | Baseline to Cycle 6 Day 1 and Cycle 12 Day 1 (each cycle is 21 days) | 
| European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status | Mean change from baseline in EORTC QLQ-C30 Global Health Status/Quality of Life score. The EORTC QLQ-C30 v3.0 is a questionnaire that assesses quality of life of cancer patients. It includes global health status and quality of life questions related to overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. A higher score indicates better health outcomes. | Baseline to Cycle 6 Day 1 and Cycle 12 Day 1 (each cycle is 21 days) | 
| EORTC QLQ - Hepatocellular Carcinoma 18 Questions (HCC18): Index Scores | Mean change from baseline in EORTC QLQ HCC18 Index Scores. The EORTC QLQ HCC18 is a specific questionnaire module that assesses quality of life of cancer patients related to overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. A higher score indicates better health outcomes. | Baseline to Cycle 6 Day 1 and Cycle 12 Day 1 (each cycle is 21 days) | 
| Number of Participants With Adverse Events | Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), which includes laboratory tests, physical exams, electrocardiogram results and vital signs | From first dose up to 30 days after the last dose of study drug; up to approximately 4 years and 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced liver cancer, RATIONALE-208