A Randomized, Open-label, Multi-center Phase III Clinical Study to Evaluate the Safety and Efficacy of Toripalimab (JS001) Combined With Bevacizumab Versus Sorafenib as First-line Therapy for Advanced Hepatocellular Carcinoma

JS001-035-III-HCC

This is a prospective, randomized, open-label, parallel-group, active controlled, multi-center phase III registration clinical study to observe, compare and evaluate the efficacy and safety of Toripalimab (hereafter referred to as JS001) combined with Bevacizumab versus Sorafenib as the first-line therapy for advanced HCC This study will enroll the patients with locally advanced or metastatic hepatocellular carcinoma who could not be radically cured and not receive any prior systemic therapy. The study will use PFS and OS as the co-primary endpoints, with approximately 280 patients planned to be enrolled.

2020-10-15

2023-10-31

2024-12-31

Active (not recruiting)

Early phase I

326

Inclusion Criteria: 1. Age of 18-75 years (inclusive), male or female. 2. Histological or cytological diagnosis of HCC or clinical diagnosis of HCC in cirrhotic patients per the American Association for the Study of Liver Diseases (AASLD) guideline. 3. Unresectable BCLC B/C 4. No previous systemic therapy for HCC, patients with prior adjuvant therapy alone who relapsed at 6 months or above after the last adjuvant therapy may be enrolled. 5. ≥ 1 measurable lesion per RECISTv1.1. 6. Child-Pugh class A, with no history of hepatic encephalopathy. 7. ECOG PS 0 or 1. 8. Predicted life expectancy ≥12 weeks. 9. adequate main organ functions 10. In case of HBsAg (+) and/or HBcAb (+), HBV DNA is required to be \< 2000 IU/mL. Patients with anti-HCV antibody positive and HCV- RNA\>1000 copies/mL will be excluded; HBV/HCV co-infected patients will be excluded. patients with a prior history of HCV infection who tested negative for HCV-RNA can be considered HCV uninfected. 11. Female subjects of childbearing potential must receive serum pregnancy test within 7 days before randomization and the result should be negative, and should be willing to adopt reliable and effective contraceptive methods during the trial and within 60 days after the last dose of study drug. The male patients whose partners are women of childbearing potential must agree to use reliable and effective contraceptive methods during the trial and within 60 days after the last dose of study drug. 12. Being voluntary to participate in the study, sufficiently informed consent and signature of written informed consent form, with good compliance. Exclusion Criteria： 1. Known ICC or mixed cell carcinoma, sarcomatoid HCC and hepatic fibrolamellar carcinoma. 2. History of malignancy other than HCC within 5 years prior to screening. 3. Hepatic surgery and/or local therapy or investigational treatment with for HCC within 4 weeks prior to randomization, or palliative radiotherapy for bone metastatic lesion within 2 weeks prior to randomization, or Chinese medicine preparation with anti-liver cancer effect within 2 weeks prior to randomization, and non-recovery (not recovered to ≤ NCI-CTCAE v5.0 grade 1) from side effects of any such treatment (except alopecia). 4. Prior other anti-PD-1 antibody therapy or other immunotherapy against PD- 1 / PD-L1. 5. Uncontrolled pericardial effusion, uncontrolled pleural effusion or clinically obvious moderate/severe pleural effusion at screening. 6. History of gastrointestinal hemorrhage within 6 months prior to randomization; the patients with portal hypertension need to receive gastroscopy to exclude the patients with "red sign", if they are considered by investigators to have high risk for hemorrhage (including moderate-to-severe esophageal and/or gastric varices with hemorrhagic risk, locally active peptic ulcer and persistent fecal occult blood (+)). The patient needs to be excluded if there is a history of "red sign" in gastroscopy. 7. Having ≥ grade 3 (NCI-CTC AE v5.0) gastrointestinal or non- gastrointestinal fistula at present. 8. Cancer thrombus in the main trunk of portal vein involving contralateral portal vein branch, or involving superior mesenteric vein. Cancer thrombus in inferior vena cava should be excluded. 9. Serious cardiovascular and cerebrovascular diseases 10. Having major bleeding and coagulation disorders or other obvious evidence on hemorrhagic tendency: 11. Medium to large surgical treatment within 4 weeks prior to randomization (except diagnostic biopsy). 12. Central nervous system metastases. 13. Serious, non-healing or dehiscing wound, active ulcer or untreated bone fracture. 14. Vaccination of live vaccine within 30 days prior to randomization. 15. Active autoimmune diseases requiring systemic treatment (i.e., immunomodulatory drug, corticosteroid or immunosuppressant) in the past 2 years; however, replacement therapy (e.g., thyroxine, insulin or physiological corticosteroid replacement therapy for renal or pituitary insufficiency), inhaled or topical corticosteroids will not be excluded. 16. History of clear interstitial lung disease or non-infectious pneumonia, unless induced by local radiotherapy; Presence of active tuberculosis during screening period or previous anti-tuberculosis treatment within one year prior to randomization. 17. Any serious acute and chronic infection requiring systemic antibacterial, antifungal or antiviral therapy at screening, not including viral hepatitis. 18. Known history of human immunodeficiency virus (HIV) infection. 19. Previously receiving allogeneic stem cell or solid organ transplantation. 20. Inability to swallow tablets, malabsorption syndrome or any condition that affects gastrointestinal absorption. 21. Known history of serious allergy to any monoclonal antibody, targeted anti- angiogenic drug. 22. Other unsuitable subjects as per the investigators.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'FACTORIAL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 326, 'type': 'ACTUAL'}}

2023-08-14