Patient selection
pleural effusion, bleeding, malignancy, basal cell carcinoma of the skin, HCC, fibrolamellar HCC, Cancer, ascites, toxicity, coronaropathy, sarcomatoid HCC, pericardial effusion, hepatitis, esophageal and/or gastric varices, infection, Left Ventricular Ejection Fraction, cardiac failure, chronic infection, proteinuria, BCLC, Tuberculosis, fistula, Active autoimmune disease, alopecia, unresectable disease, cholangiocarcinoma
CARCINOMATOUS MENINGITIS, BLEEDING, CENTRAL NERVOUS SYSTEM METASTASES, ENCEPHALOPATHY, HEPATOCELLULAR CARCINOMA, ONCOLOGY, CANCER, ASCITES, BREAST CANCER, RESPIRATORY FAILURE, HEPATITIS, ADVERSE EVENTS, BRAIN METASTASES, INFECTION, CARDIAC FAILURE, CHRONIC INFECTION, DISEASE, EVENT, TUBERCULOSIS, ALOPECIA, CHOLANGIOCARCINOMA, VARICES
The study population consists of patients with histologically confirmed HCC locally advanced, metastatic or unresectable. Patients should not have previously received systemic anti-cancer treatment.Patients should have an Eastern Cooperative Oncology Group-performance status (ECOG-PS) of 0 or 1, a Child–Pugh Class A status and adequate organ function.The main inclusion and exclusion criteria are listed in Table Main inclusion and exclusion criteria of the TERTIO trial 1. Age ≥ 18 years 2. Histologically confirmed hepatocellular carcinoma (HCC) 3. Locally advanced, metastatic, or unresectable disease 4. BCLC C stage or BCLC B stage not eligible to loco-regional therapy according to the Barcelona Clinic Liver Cancer (BCLC) staging system 5. Measurable disease defined according to RECIST v1.1 guidelines 6. Patient who had not previously received systemic anti-cancer treatment 7. Patients who have received previous chemoembolization, radioembolization and/or radiotherapy should have recovered from any treatment related toxicity, to a level of ≤ grade 1 (according to National Cancer Institute common terminology criteria for adverse events, version 5) with the exception of Grade 2 alopecia 8. ECOG-Performance status < 2 9. Child–Pugh Class A status 10. Documented virology status of hepatitis, as confirmed by screening HBV and HCV tests:- For patients with active HBV: HBV DNA < 500 IU/ml during screening, initiation of anti-HBV treatment at least 14 days prior to randomization and willingness to continue anti-HBV treatment during the study (per local standard of care)- Patients with HCV, either with resolved infection (as evidenced by detectable antibody) or chronic infection (as evidence by detectable HCV RNA), are eligible 11. Performance of an esophagogastroduodenoscopy and assessment and treatment of varices of all sizes per local standard of care prior to randomization 1. Patients previously exposed to anti-tumor immunotherapy as anti-PD-1, anti-PD-L1, or anti-CTLA4 agent or any immune therapy 2. Diagnosis of additional malignancy within 3 years prior to the inclusion with the exception of curatively treated basal cell carcinoma of the skin and/or curatively resected in situ cervical or breast cancer 3. Know fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC 4. Known active central nervous system metastases and/or carcinomatous meningitis. Subject with previously treated brain metastases and with radiological and clinical stability are allowed 5. History of encephalopathy 6. Prior bleeding event due to untreated or incompletely treated esophageal and/or gastric varices within 6 months prior to randomization 7. Uncontrolled pleural effusion, pericardial effusion, ascites or symptomatic fistula 8. Inadequate organ functions: known cardiac failure of unstable coronaropathy, respiratory failure, or uncontrolled infection or another life-risk condition 9. Patients with Left Ventricular Ejection Fraction (LEVF) < 40% 10. HIV positive (HIV 1/2 antibodies patients), or a known history of active Tuberculosis bacillus 11. Prior allogeneic bone marrow transplantation or prior solid organ transplantation 12. Active autoimmune disease that has required a systemic treatment in past 2 years (i.e. corticosteroids or immunosuppressive drugs) 13. Patients under chronic treatment with systemic corticoids or other immunosuppressive drugs (prednisone or prednisolone ≤ 10 mg/day is allowed) for a period of at least 4 weeks and whose treatment was not stopped 1 week prior to the start of the study treatment 14. Inadequate hematology function: Lymphocyte count at baseline < 800/mm 15. Inadequate hepatic function: bilirubin threefold ULN, AST/ALT fivefold ULN, International normalized thromboplastin time ratio > 2 16. Inadequate renal function: MDRD CrCl < 30 ml/min, proteinuria ≥ 1 g/24h 17. Others inadequate laboratory values: serum albumin < 28 g/L; troponin > ULN; BNP > ULN