TISLELIZUMAB for Hepatocellular carcinoma (HCC)

Inclusion criteria

• {"criterion_text":"- Age ≥18 years old,\n- Presence of measurable and evaluable disease according to RECIST v1.1\n- 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.\n- 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.\n- 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\n- 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 protein-based biomarker detection.\n- Patient affiliated to a social security regimen\n- Men and women patients must consent to not donate or bank sperm or ova during treatment and for 120 days after treatment stop\n- Patient presenting with histologically-proven Hepatocellular Carcinoma (HCC), or HCC defined by typical imaging findings (EASL criteria), if no biopsy could be performed safely.\n- Pretreated or not by tyrosine kinase inhibitors (e.g., sorafenib, lenvatinib, regorafenib, cabozantinib)\n- Child-Pugh B cirrhosis\n- ALBI (Albumin-Bilirubin) grade 1 or 2\n- BCLC (Barcelona Clinic Liver Cancer Group) B or C\n- Availability of biopsy specimen at study enrolment (with the exception of cases where biopsy could not be performed safely).\n- ECOG Performance status ≤2\n- Adequate organ function as indicated by the following laboratory values: a. 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 x 109/L  Platelets ≥ 50 x 109/L  Hemoglobin ≥90 g/L b. Serum creatinine ≤1.5 x upper limit of normal (ULN) or estimated Glomerular Filtration Rate ≥60 mL/min/1.73 m2 c. Liver function: ASAT and ALAT ≤5 ULN, albumin >2.0 g/dL"}

Exclusion criteria

• {"criterion_text":"- More than 50% of the liver is affected by the HCC (according to investigators evaluation)\n- Live vaccine within 4 weeks of first dose of study drug. Note: Seasonal vaccines for influenza are generally inactivated vaccines and Covid vaccination with non-live vaccine are allowed. Intranasal vaccines are live vaccines, and are not allowed.\n- Transplanted liver, or patient with intent for transplantation\n- Received locoregional therapy to the liver (TACE, transcatheter embolization, hepatic arterial infusion, radiation, radioembolization or ablation) in the 4 weeks before inclusion\n- Prior malignancy active within the previous 3 years of inclusion except for locally curable cancers considered cured or successfully resected, such as basal or squamous cell skin cancers, superficial bladder cancer, or gastric cancers, or carcinoma in situ of the prostate, cervix, or breast carcinomas. Any oncological concomitant treatment are not allowed during the treatment period.\n- Has received any herbal medicine used to control cancer with immunostimulant properties that may interfere with liver function within 14 days of the first study drug administration.\n- Pregnant woman or breast-feeding women or patient with no adequate contraception\n- Participation in another therapeutic trial within the 30 days prior to study inclusion\n- Patients deprived of their liberty or under protective custody or guardianship\n- Patients unable to adhere to the protocol for geographical, social, or psychological reasons\n- Patients eligible for treatment by TACE or SIRT are not allowed\n- Fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC\n- Previous treatment with immunotherapy (anti-PD-1, anti-PD-L1, or anti-CTLA-4 agents)\n- History of active autoimmune disease. Note: Patients with the following diseases are not excluded and may proceed to further screening: a. Type I diabetes, b. Hypothyroidism (provided it is managed with hormone replacement therapy only), c. Controlled celiac disease, d. Skin diseases not requiring systemic treatment (e.g., vitiligo, psoriasis, alopecia), e. Any other disease that is not expected to recur in the absence of external triggering factors\n- History of interstitial lung disease, non-infectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases\n- Any of the following cardiovascular risk factors: a. Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living, ≤ 28 days before first dose of study drug b. Pulmonary embolism ≤ 28 days before first dose of study drug c. Any history of acute myocardial infarction ≤ 6 months before first dose of study drug d. Any history of heart failure meeting New York Heart Association (NYHA) Classification III or IV ≤ 6 months before first dose of study drug e. Any event of ventricular arrhythmia ≥ Grade 2 in severity ≤ 6 months before first dose of study drug f. Any history of cerebrovascular accident ≤ 6 months before first dose of study drug g. Uncontrolled hypertension: systolic pressure ≥ 160 mmHg or diastolic pressure ≥ 100 mmHg despite anti-hypertension medications before first dose of drug h. Any episode of syncope or seizure before first dose of study drug\n- Patients with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers whose HBV DNA is > 500 IU/mL or patients with active hepatitis C virus (HCV) should be excluded. Note: Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B (HBV DNA < 500 IU/mL), and cured hepatitis C patients can be enrolled\n- Known primary immunodeficiency or active HIV\n- Immunosuppression, including subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg/day prednisone equivalent) ≤ 14 days before inclusion. Note: Patients who are currently or have previously been on any of the following steroid regimens are not excluded: a. Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent) b. Topical, ocular, intra-articular, intranasal, or inhaled corticosteroid with minimal systemic absorption c. Short course (≤ 7 days) of corticosteroid prescribed prophylactically (e.g., for contrast dye allergy) or for the treatment of a non-autoimmune condition (e.g., delayed-type hypersensitivity reaction caused by contact allergen)"}

Primary endpoints

• {"endpoint_text":"- The Objective Response Rate defined as the proportion of patients with Complete Response or Partial Response to treatment based on best overall response according to RECIST 1.1, recorded from treatment initiation to the end of treatment.","definition_or_measurement_approach":"Objective Response Rate (ORR) defined as the proportion of patients with Complete Response or Partial Response based on best overall response according to RECIST 1.1, recorded from treatment initiation to end of treatment."}

Secondary endpoints

• {"endpoint_text":"- Frequency of limiting toxicity (LT), defined as any adverse event related to the experimental drug, and leading to definitive treatment discontinuation according to the investigator, before the second injection","definition_or_measurement_approach":"Frequency of limiting toxicity (LT): any adverse event related to the experimental drug leading to definitive treatment discontinuation per investigator, measured before the second injection."}
• {"endpoint_text":"- Frequency of related and not related adverse events occurring during the treatment period and until 3 months after treatment discontinuation. Adverse events will be coded and categorized according MedDRA classification and CTCAE V5.0 grade for severity.","definition_or_measurement_approach":"Frequency of adverse events during treatment and until 3 months after discontinuation; events coded per MedDRA and graded by CTCAE v5.0."}
• {"endpoint_text":"- Objective Response Rate defined as the proportion of patients with Complete Response or Partial Response to treatment based on best overall response according to mRECIST and iRECIST recorded from treatment initiation to the end of treatment.","definition_or_measurement_approach":"ORR measured by best overall response according to mRECIST and iRECIST from treatment initiation to end of treatment."}
• {"endpoint_text":"- Overall survival, defined as the time between date of inclusion and death from any cause. Patients lost to follow-up will be censored at the date of last known to be alive.","definition_or_measurement_approach":"Overall survival (OS): time from inclusion to death from any cause; lost to follow-up censored at last known alive date."}
• {"endpoint_text":"- Progression-free survival, defined as the time between date of inclusion and disease progression or death, whichever occurs first. Disease progression will be evaluated 3 times according to RECIST v1.1, mRECIST and iRECIST, respectively. Patients lost to follow-up and patients who could benefit from secondary surgery for HCC will be censored at the date of last news and date of surgery, respectively.","definition_or_measurement_approach":"Progression-free survival (PFS): time from inclusion to disease progression (per RECIST v1.1, mRECIST, iRECIST) or death; specific censoring rules for lost to follow-up and secondary surgery."}
• {"endpoint_text":"- Time to progression is defined as the time between the date of inclusion and the date of radiological progression according RECIST v1.1. Death will be censored.","definition_or_measurement_approach":"Time to progression: time from inclusion to radiological progression per RECIST v1.1; death censored."}
• {"endpoint_text":"- Health Related Quality of Life according to EORTC QLQ-C30 and HCC-18","definition_or_measurement_approach":"Health-related quality of life measured using EORTC QLQ-C30 and HCC-18 questionnaires."}

France

Earliest CTIS Part Ii Submission Date

12-07-2024

Latest Decision Or Authorization Date

22-08-2025

Processing Time Days

406

Number Of Sites

12

Number Of Participants

50

Primary sponsor

Full Name

Unicancer

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France