Evaluate the Safety and Efficacy of Toripalimab Combined With Bevacizumab Versus Sorafenib Therapy for HCC

Trial number:
Trial phase:
Study type:
targeted, immunotherapy
Overall status:

Study start date

October, 2020

Scientific title

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


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.

Patients meeting all the following inclusion criteria can be enrolled in this study: 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. 2. Barcelona Clinic Liver Cancer (BCLC) stage Category B or C , and unsuitable for radical surgical and/or local therapy, or has progressed following surgical and/or local therapy. 3. No previous systemic therapy for HCC, mainly including systemic chemotherapy, anti-angiogenic drugs or other molecular targeted therapy, immunotherapy containing CTLA-4, PD-1/PD-L1 monoclonal antibody) for HCC. 4. Having ≥ 1 measurable lesion per RECISTv1.1. Requirement: the selected target lesion has not been treated locally before, or is located in the area of previous local therapy, but determined as PD through radiological examination. 5. Child-Pugh class A, with no history of hepatic encephalopathy. 6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) status of 0 or 1. 7. Predicted life expectancy ≥12 weeks. 8. Adequate hematologic and end-organ function 9. In case of HBsAg (+) and/or HBcAb (+), HBV DNA is required to be < 500 IU/mL, and it is required to continue the effective anti-HBV therapy that has been adopted in the full course, or start to use entecavir or tenofovir after screening in the full course during the study; Patients with anti-HCV antibody positive and HCV-RNA>103 copies/mL will be excluded; HBV/HCV co-infected patients, i.e., positive for both HbsAg and HCV-RNA, will be excluded. 10. 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. 11. Being voluntary to participate in the study, sufficiently informed consent and signature of written informed consent form, with good compliance. Patients can not be enrolled in the study if any one of the following criteria is fulfilled: 1. Known cholangiocellular carcinoma (ICC) or mixed cell carcinoma, sarcomatoid HCC and hepatic fibrolamellar carcinoma. 2. History of malignancy other than HCC within 5 years prior to screening, with the exception of cured localized malignancies including cervical carcinoma in situ, skin basal cell carcinoma and carcinoma in situ of prostate. 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, defined as reaching the following criteria: having clinical symptoms and physical examination identifies pleural effusion; Paracentesis and/or intracavitary administration are required for pleural effusion during 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, or history of active tuberculosis. 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.

Study design

Primary purpose: Treatment, Allocation: Randomized, Intervention model: Factorial Assignment, Masking: None (Open Label),


Advanced Hepatocellular Carcinoma (HCC)

Other study ID numbers



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