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NCT03419897

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

Completed Phase 2 Results posted Last updated 26 October 2024
What this trial tests

Phase 2 trial testing Tislelizumab in Hepatocellular Carcinoma (HCC) in 249 participants. Completed in 6 July 2022.

Timeline
9 April 2018
Primary endpoint
30 June 2021
6 July 2022

Quick facts

Lead sponsorBeiGene
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment249
Start date9 April 2018
Primary completion30 June 2021
Estimated completion6 July 2022
Sites54 locations across France, Italy, Taiwan, United Kingdom, Germany, Poland, China, Spain

Drugs / interventions tested

Conditions studied

Sponsor

BeiGene — full company profile →

Who can join

18 and older, any sex, with Hepatocellular Carcinoma (HCC). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Objective Response Rate (ORR) Assessed by Independent Review Committee (IRC) Primary · From date of first dose to primary analysis data cut-off date of 30-June-2021 (up to approximately 3 years and 3 months)

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.

GroupValue95% CI
Tislelizumab12.98.96 – 17.66
ORR Assessed by Investigator Secondary · From date of first dose to end of study (up to approximately 4 years and 3 months)

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.

GroupValue95% CI
Tislelizumab14.510.34 – 19.45
Duration of Response (DOR) Assessed by IRC Secondary · From date of first dose to end of study (up to approximately 4 years and 3 months)

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

GroupValue95% CI
TislelizumabNA14.6 – NA
DOR Event-Free Rate Assessed by IRC Secondary · From date of first dose to end of study (up to approximately 4 years and 3 months); Months 12 and 24 reported

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.

12 Months
GroupValue95% CI
Tislelizumab76.957.5 – 88.3
24 Months
GroupValue95% CI
Tislelizumab65.945.7 – 80.1
DOR Assessed by Investigator Secondary · From date of first dose to end of study (up to approximately 4 years and 3 months)

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

GroupValue95% CI
Tislelizumab21.411.1 – NA
DOR Event-Free Rate Assessed by Investigator Secondary · From date of first dose to end of study (up to approximately 4 years and 3 months); Months 12 and 24 reported

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.

12 Months
GroupValue95% CI
Tislelizumab68.149.8 – 80.9
24 Months
GroupValue95% CI
Tislelizumab47.430.1 – 62.8
Progression-free Survival (PFS) Assessed by IRC Secondary · From date of first dose to end of study (up to approximately 4 years and 3 months)

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

GroupValue95% CI
Tislelizumab2.71.4 – 2.8
PFS Assessed by Investigator Secondary · From date of first dose to end of study (up to approximately 4 years and 3 months)

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

GroupValue95% CI
Tislelizumab2.82.6 – 4.0
Overall Survival (OS) Secondary · From date of first dose to end of study (up to approximately 4 years and 3 months)

OS is defined as the time from first study drug administration to the date of death due to any cause

GroupValue95% CI
Tislelizumab13.210.8 – 15.2
Disease Control Rate (DCR) Assessed by IRC Secondary · From date of first dose to end of study (up to approximately 4 years and 3 months)

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

GroupValue95% CI
Tislelizumab53.046.61 – 59.34
DCR Assessed by Investigator Secondary · From date of first dose to end of study (up to approximately 4 years and 3 months)

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

GroupValue95% CI
Tislelizumab59.052.65 – 65.20
Clinical Benefit Rate (CBR) Assessed by IRC Secondary · From date of first dose to end of study (up to approximately 4 years and 3 months)

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

GroupValue95% CI
Tislelizumab22.517.46 – 28.19

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose to 30 days after last dose of study drug (up to approximately 4 years and 3 months). Reporting threshold: 3%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Tislelizumab
Serious: 94/249 (38%)
Deaths: 180/249

Serious adverse events (87 terms)

ReactionSystemTislelizumab
AscitesGastrointestinal disorders
Hepatic failureHepatobiliary disorders
PneumoniaInfections and infestations
Aspartate aminotransferase increasedInvestigations
Upper gastrointestinal haemorrhageGastrointestinal disorders
Hepatic function abnormalHepatobiliary disorders
Abdominal painGastrointestinal disorders
General physical health deteriorationGeneral disorders
SepsisInfections and infestations
Blood bilirubin increasedInvestigations
MyocarditisCardiac disorders
Abdominal pain upperGastrointestinal disorders
Duodenal ulcer haemorrhageGastrointestinal disorders
Chest painGeneral disorders
DeathGeneral disorders
Multiple organ dysfunction syndromeGeneral disorders
Immune-mediated hepatitisHepatobiliary disorders
Jaundice cholestaticHepatobiliary disorders
GastroenteritisInfections and infestations
Staphylococcal bacteraemiaInfections and infestations
Alanine aminotransferase increasedInvestigations
HyperglycaemiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
MyositisMusculoskeletal and connective tissue disorders
Haemorrhage intracranialNervous system disorders
Other adverse events (52 terms — click to expand)

ReactionSystemTislelizumab
Aspartate aminotransferase increasedInvestigations
Alanine aminotransferase increasedInvestigations
Blood bilirubin increasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
AstheniaGeneral disorders
PruritusSkin and subcutaneous tissue disorders
AnaemiaBlood and lymphatic system disorders
PyrexiaGeneral disorders
DiarrhoeaGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
FatigueGeneral disorders
Abdominal painGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
ConstipationGastrointestinal disorders
RashSkin and subcutaneous tissue disorders
HypothyroidismEndocrine disorders
Abdominal distensionGastrointestinal disorders
VomitingGastrointestinal disorders
Oedema peripheralGeneral disorders
Blood alkaline phosphatase increasedInvestigations
Platelet count decreasedInvestigations
Gamma-glutamyltransferase increasedInvestigations
AscitesGastrointestinal disorders
HypoalbuminaemiaMetabolism and nutrition disorders
Abdominal pain upperGastrointestinal disorders
White blood cell count decreasedInvestigations
InsomniaPsychiatric disorders
ThrombocytopeniaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
Weight decreasedInvestigations
HyperglycaemiaMetabolism and nutrition disorders
Blood creatine phosphokinase MB increasedInvestigations
HypertensionVascular disorders
HypokalaemiaMetabolism and nutrition disorders
MyalgiaMusculoskeletal and connective tissue disorders
Influenza like illnessGeneral disorders
Upper respiratory tract infectionInfections and infestations
Blood lactate dehydrogenase increasedInvestigations
Back painMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Ascites, Hepatic failure, Pneumonia, Aspartate aminotransferase increased, Upper gastrointestinal haemorrhage, Hepatic function abnormal, Abdominal pain, General physical health deterioration.

Data from ClinicalTrials.gov NCT03419897 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Current perspectives on the immunosuppressive tumor microenvironment in hepatocellular carcinoma: challenges and opportunities.
    Lu C, Rong D, Zhang B, Zheng W, et al · · 2019 · cited 327× · PMID 31464625 · DOI 10.1186/s12943-019-1047-6
  2. Antibodies to watch in 2022.
    Kaplon H, Chenoweth A, Crescioli S, Reichert JM. · · 2022 · cited 245× · PMID 35030985 · DOI 10.1080/19420862.2021.2014296
  3. Tislelizumab: A Modified Anti-tumor Programmed Death Receptor 1 Antibody.
    Zhang L, Geng Z, Hao B, Geng Q. · · 2022 · cited 66× · PMID 35926155 · DOI 10.1177/10732748221111296
  4. Tislelizumab in Patients with Previously Treated Advanced Hepatocellular Carcinoma (RATIONALE-208): A Multicenter, Non-Randomized, Open-Label, Phase 2 Trial.
    Ren Z, Ducreux M, Abou-Alfa GK, Merle P, et al · · 2023 · cited 60× · PMID 36872927 · DOI 10.1159/000527175
  5. Systemic Therapy for Hepatocellular Carcinoma: Current Updates and Outlook.
    Fan Y, Xue H, Zheng H. · · 2022 · cited 48× · PMID 35388357 · DOI 10.2147/jhc.s358082
  6. Overview of Immune Checkpoint Inhibitors Therapy for Hepatocellular Carcinoma, and The ITA.LI.CA Cohort Derived Estimate of Amenability Rate to Immune Checkpoint Inhibitors in Clinical Practice.
    Giannini EG, Aglitti A, Borzio M, Gambato M, et al · · 2019 · cited 43× · PMID 31671581 · DOI 10.3390/cancers11111689
  7. New landscapes and horizons in hepatocellular carcinoma therapy.
    Cervello M, Emma MR, Augello G, Cusimano A, et al · · 2020 · cited 37× · PMID 32018226 · DOI 10.18632/aging.102777
  8. Tumor Microenvironment Composition and Related Therapy in Hepatocellular Carcinoma.
    Li Z, Zhang Z, Fang L, Zhao J, et al · · 2023 · cited 29× · PMID 38022729 · DOI 10.2147/jhc.s436962

Verify or expand the search:

Other trials of Tislelizumab

Trials testing the same drug.

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Trials by the same sponsor.

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