JS207 Plus JS007 Versus Toripalimab Plus Bevacizumab as First-Line Treatment for Advanced Liver Cancer

This is a multicenter, randomized, open-label, active-controlled Phase III study in participants with unresectable locally advanced, recurrent, or metastatic hepatocellular carcinoma.Tumor images will be assessed by investigator and blinded independent central review (BICR). Treatment will continue until protocol-defined discontinuation criteria are met, for a maximum of 2 years. Participants will undergo tumor assessments, safety assessments, and survival follow-up.

Anti-tumor activity will be assessed by determining best overall response (BOR), objective response rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (BICR-PFS and INV Safety will be assessed through AEs, laboratory variables, physical examination findings, vital signs, 12-lead electrocardiogram, echocardiography, and ECOG performance status. The severity of AEs will be graded per NCI-CTCAE v6.0.

Participants in the JS207 + JS007 group (experimental group) will undergo plasma concentration assessments and immunogenicity assessments for JS207 and JS007.

The EORTC QLQ-C30, EORTC QLQ-HCC18, and EQ-5D-5L questionnaires will be used to assess participants' health-related quality of life (HRQOL).

Inclusion criteria

• Voluntarily participate and sign a written informed consent form.
• Aged 18-75 years, regardless of sex.
• Histologically/cytologically confirmed HCC, or cirrhosis meeting the American Association for the Study of Liver Diseases (AASLD) clinical diagnostic criteria for HCC.
• No prior systemic therapy for HCC.
• At least one measurable lesion per RECIST v1.1 criteria.
• Child-Pugh liver function grade A or grade B with a score ≤7, and no history of hepatic encephalopathy.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-1.
• Expected survival ≥ 12 weeks.
• Adequate hematologic and end-organ function.
• Female participants of childbearing potential and male participants with female partners of childbearing potential must use a highly effective contraceptive method during the study and for at least 6 months after the last dose. Female participants of childbearing potential must have a negative blood HCG test within 7 days prior to study enrollment and must not be breastfeeding.

Exclusion criteria

• Concomitant with the following study disease states: Known intrahepatic cholangiocarcinoma (ICC) or mixed-type liver cancer, sarcomatoid hepatocellular carcinoma, and fibrolamellar carcinoma of the liver; Presence of HCC central nervous system metastasis.
• Prior treatment-related toxicity not recovered to ≤ CTCAE Grade 1.
• Severe infection at screening.
• Uncontrolled pericardial effusion, uncontrolled pleural effusion, or clinically apparent moderate or greater ascites at screening.

-≥ Grade 3 (NCI-CTCAE v6.0) gastrointestinal or non-gastrointestinal fistula at screening.

• Severe unhealed wounds, active ulcers, or untreated fractures at screening.
• Severe cardiovascular or cerebrovascular disease:
• History of gastrointestinal bleeding within 6 months prior to the first dose, or definite tendency for gastrointestinal bleeding.
• Other obvious bleeding tendency or evidence of major coagulation disorders:
• Active autoimmune disease requiring systemic treatment within 2 years prior to the first dose.
• Malignancy other than HCC within 5 years prior to the first dose.
• Confirmed or suspected moderate-to-severe pulmonary disease severely affecting pulmonary function.
• Active tuberculosis.
• Co-infection with hepatitis B and hepatitis C.
• Known history of human immunodeficiency virus (HIV) infection, prior allogeneic stem cell or solid organ transplantation, or other immunodeficiency.
• Known history of severe allergy to any monoclonal antibody.
• Other factors that, in the investigator's judgment, may affect study results or lead to forced premature termination of the study.