Testing Immunotherapy for Patients With Liver Cancer and Moderately Altered Liver Functions

NCT05622071 | Completed Phase 2 DMC

• 1 other identifier: UC-GIG-2003
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 10

Brief Summary

Liver cancer is the third leading cause of cancer-related deaths worldwide. The majority of primary liver cancers occur as hepatocellular carcinoma (HCC), the incidence of which is increasing in many parts of the world. The vast majority of HCC cases occur in the setting of liver cirrhosis, usually due to chronic viral infections with hepatitis C or hepatitis B, alcohol consumption, non-alcoholic fatty liver disease or diabetes. The degree of underlying liver disease, as well as the stage of the tumour and the general condition of the patients, should therefore be taken into account when deciding on the treatment of HCC. Most patients with HCC have advanced disease at the time of diagnosis, or have recurrent disease after potentially curative treatments. Tislelizumab showed enhanced cellular functional activities by blocking PD-1-mediated reverse signal transduction and activating human T cells and primary peripheral blood mononuclear cells in vitro. Based on this preliminary safety profile, and knowing that there is antitumour activity, we can offer tislelizumab as a single agent in patients with unresectable HCC. HESTIA study is a multicentric French national phase II trial assessing tislelizumab in monotherapy for patients with Hepatocellular Carcinoma Child-Pugh B and ALBI grade 1 or 2 liver function score. It is planned to include 50 patients in the study. All patients will be recruited in France. The study will be presented to eligible patients at participating centres and an information note will be provided. No advertising material is planned for this study. To be eligible, patients must meet all the following criteria to be ≥18 years old, with histologically proven Hepatocellular Carcinoma (HCC), pre-treated or not with a tyrosine kinase inhibitor and Child-Pugh B cirrhosis, ALBI (Albumin-Bilirubin) grade 1 or 2 and BCLC (Barcelona Clinic Liver Cancer Group) B or C and with no more than 50% liver invasion of tumour disease.

Conditions

Hepatocellular Carcinoma by BCLC Stage

Keywords

Hepatocellular Carcinoma; tislelizumab; monotherapy; Child-Pugh B; ALBI grade 1 or 2 liver function score

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  Objective response rate (ORR) is the percentage of patients with a best response during treatment being either complete response (CR) or partial response (PR).

  48 months

Secondary Outcomes (7)

• Frequency of limiting toxicity

  From inclusion, up to 6 months

• Frequency of related and not related adverse events

  From inclusion, up to 48 months

• Overall survival

  From inclusion to death from any cause, up to 52 months

• Progression-free survival

  From inclusion to disease progression or death, up to 52 months

• Time to progression

  From inclusion to radiographic disease progression, up to 52 months

Study Arms (1)

SINGLE ARM

EXPERIMENTAL

Tislelizumab 200 mg will be administered every 3 weeks IV. Treatment will be continued until progression or limiting toxicities, for a maximum duration of 2 years and with an average duration of 4 months

Drug: Tislelizumab

Interventions

Tislelizumab DRUG

Tislelizumab 200 mg will be administered every 3 weeks IV for a maximum of 2 years

Also known as: BGB-A317

SINGLE ARM

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years old
• Patient presenting with histologically-proven Hepatocellular Carcinoma (HCC), or HCC defined by typical imaging findings (EASL criteria), if no biopsy could be performed safely
• Pretreated or not by tyrosine kinase inhibitors (e.g., sorafenib, lenvatinib, regorafenib, cabozantinib)
• Child-Pugh B cirrhosis
• ALBI (Albumin-Bilirubin) grade 1 or 2
• BCLC (Barcelona Clinic Liver Cancer Group) B or C
• Availability of biopsy specimen at study enrolment (taken within 3 months of enrolment with the exception of cases where biopsy could not be performed safely)
• ECOG Performance status ≤2
• Adequate organ function as indicated by the following laboratory values:
• Patients must not have required a blood transfusion or growth factor support ≤14 days before sample collection at screening for the following:
• Absolute neutrophil count (ANC) ≥1.5 x 10⁹/L
• Platelets ≥75 x 10⁹/L
• Hemoglobin ≥90 g/L
• Serum creatinine ≤1.5 x upper limit of normal (ULN) or estimated Glomerular Filtration Rate ≥60 mL/min/1.73 m²
• Serum total bilirubin ≤3 mg/dL

You may not qualify if:

• More than 50% of the liver is affected by the HCC (according to investigators evaluation)
• Fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
• Previous treatment with immunotherapy (anti-PD-1, anti-PD-L1, or anti-CTLA-4 agents)
• History of active autoimmune disease. Note: Patients with the following diseases are not excluded and may proceed to further screening:
• Type I diabetes
• Hypothyroidism (provided it is managed with hormone replacement therapy only)
• Controlled celiac disease
• Skin diseases not requiring systemic treatment (e.g., vitiligo, psoriasis, alopecia)
• Any other disease that is not expected to recur in the absence of external triggering factors
• History of interstitial lung disease, non-infectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases
• Any of the following cardiovascular risk factors:
• Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living, ≤28 days before first dose of study drug
• Pulmonary embolism ≤28 days before first dose of study drug
• Any history of acute myocardial infarction ≤6 months before first dose of study drug
• Any history of heart failure meeting New York Heart Association (NYHA) Classification III or IV ≤6 months before first dose of study drug

Sponsors & Collaborators

• UNICANCER: lead

Study Sites (10)

CHU Angers

Angers, France

Location

Hôpital Avicenne

Bobigny, France

Location

CHU Beaujon

Clichy, France

Location

Hôpital Michallon

Grenoble, France

Location

CHU La Croix Rousse

Lyon, France

Location

Hôpital Saint Joseph

Marseille, France

Location

Institut Paoli Calmette

Marseille, France

Location

CHU Saint Eloi

Montpellier, France

Location

Centre Eugene Marquis

Rennes, France

Location

CHRU Strasbourg

Strasbourg, France

Location

Related Publications (1)

• Edeline J, Blanc JF. Difficulties for providing evidence in hepatocellular carcinoma with Child-Pugh B liver function. Liver Int. 2023 Feb;43(2):274-275. doi: 10.1111/liv.15495. No abstract available.

  PMID: 36680319 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

tislelizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Julien Edeline, MD PhD

  CLCC UNICANCER EUGENE MARQUIS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Tislelizumab will be administered every 3 weeks IV for a maximum of 2 years
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicentre, national, monotherapy, open-label, phase II single-arm study

Study Record Dates

• First Submitted: November 10, 2022
• First Posted: November 18, 2022
• Study Start: October 12, 2023
• Primary Completion: June 15, 2025
• Study Completion: September 4, 2025
• Last Updated: November 17, 2025

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (10)