Phase III Study of Toripalimab（JS001） Combined With Lenvatinib for Advanced HCC

Exclusion Criteria

• •1. Known cholangiocellular carcinoma (ICC) or mixed hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma and hepatic fibrolamellar carcinoma.
• •2. Malignant tumor except HCC within 5 years: however, localized tumor cured in the study is excluded,including cervical carcinoma in situ, skin basal cell carcinoma and carcinoma in situ of prostate.
• •3. Hepatic surgery and/or local therapy or treatment with investigational product for HCC within 4 weeks prior to randomization; palliative radiation therapy for bone metastatic lesion within 2 weeks prior to randomization; use of Chinese medicine preparations with anti-liver cancer effect within two weeks prior to randomization. Toxicity induced by previous therapy (except alopecia) not recovered to ≤ grade 1 (NCI-CTCAE v5.0).
• •4. Prior use of other anti-PD-1 antibody or other immunotherapy targeting PD-1/PD-L1.
• •5. Uncontrolled pericardial effusion, uncontrolled pleural effusion or clinically obvious moderate or severe peritoneal effusion at screening, defined as reaching the following criteria: having clinical symptoms and pleural and peritoneal effusion detected in physical examination at screening; or puncture for drainage required for pleural and peritoneal effusion and/or intracavitary administration during screening.
• •6. History of gastrointestinal hemorrhage within 6 months prior to randomization or clear tendency of gastrointestinal hemorrhage (including severe esophageal-gastric varices with hemorrhagic risk, locally active peptic ulcer, persistent fecal occult blood (+)).
• •7. Having ≥ grade 3 (NCI-CTCAE v5.0) gastrointestinal or non-gastrointestinal fistula at present.
• •8. Cancer thrombus invasion in the main trunk of portal vein (Vp4) (more than 1/2 of the lumen), inferior vena cava cancer thrombus or cardiac involvement in accordance with CT/MRI.
• •9. Serious cardiovascular and cerebrovascular diseases:
• •10. Other obvious hemorrhagic tendency or evidence on important coagulation disorder:
• •11. Medium to large surgical treatment within 4 weeks prior to randomization, not including diagnostic biopsy.
• •12. Know central nervous system metastasis; cranial and/or spinal MRI is needed for exclusion if central nervous system metastasis is suspected.
• •13. Serious, uncured wound, active ulcer or untreated bone fracture.
• •14. Vaccination of live vaccine within 30 days prior to randomization.
• •15. Presence of immunodeficiency or receiving long-term systemic steroid therapy within 7 days prior to randomization (daily dose \>10mg Prednisone or other equivalent glucocorticoid), or other immunosuppressive therapy.
• •16. Active autoimmune diseases requiring systemic treatment (i.e., immunomodulatory drug, corticosteroid or immunosuppressant) in the past two years; however, replacement therapy (e.g., thyroxine, insulin or physiological corticosteroid replacement therapy for renal or pituitary insufficiency) will not be considered as systemic therapy and is allowed to be used.
• •17. History of clear interstitial lung disease or non-infectious pneumonia, unless induced by local radiotherapy.
• •18. Active tuberculosis or received antituberculosis therapy within 1 year prior to randomization.
• •19. Any serious acute and chronic infection requiring systemic antibacterial, antifungal or antiviral therapy at screening, not including viral hepatitis.
• •20. Known history of human immunodeficiency virus (HIV) infection.
• •21. Previously receiving allogeneic stem cell or solid organ transplantation.
• •22. Inability to swallow tablets, malabsorption syndrome or any other condition that affects gastrointestinal absorption.
• •23. Known history of serious allergy to any monoclonal antibody, anti-angiogenesis drug.
• •24. Other participants who are unsuitable for inclusion as judged by the investigator."