A Multicentric 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
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.
• 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
‣ Liver function: ASAT and ALAT ≤5 ULN, albumin \>2.0 g/dL
⁃ Presence of measurable and evaluable disease according to RECIST v1.1
⁃ Women of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and ≥120 days after the last dose of tislelizumab, and have a negative urine or serum pregnancy test ≤7 days of first dose of study drug. In case of a urine pregnancy test, it must be a highly sensitive urine pregnancy test
⁃ Non-sterile males must be willing to use a highly effective method of birth control for the duration of the study and for ≥120 days after the last dose of tislelizumab. A sterile male is defined as one for whom azoospermia has been previously demonstrated in a semen sample examination as definitive evidence of infertility. Males with known low sperm counts (consistent with sub-fertility) are not to be considered sterile for purposes of this study
⁃ Patients must have provided consent for the study by signing and dating a written informed consent form prior to any study specific procedures, sampling, or analyses. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent
⁃ Patient consent to the use of their collected tumour specimen, as well as blood samples as detailed in the protocol for future scientific research which includes but not limited to DNA, RNA, and proteinbased biomarker detection
⁃ Patient affiliated to a social security regimen
⁃ Men and women patients must consent to not donate or bank sperm or ova during treatment and for 120 days after treatment stop