A Phase III, Multicenter, Randomized, Controlled, Open-label Clinical Study to Evaluate the Efficacy and Safety of JS207 in Combination With JS007 Versus Toripalimab in Combination With Bevacizumab as First-line Treatment for Advanced Hepatocellular Carcinoma
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 560
- 试验地点
- 2
- 主要终点
- Progression-Free Survival Assessed by Blinded Independent Central Review (BICR-PFS)
研究概览
简要总结
This is a multicenter, randomized, open-label, controlled Phase III clinical study designed to evaluate the efficacy and safety of JS207 in combination with JS007 versus toripalimab in combination with bevacizumab as first-line treatment in participants with advanced HCC.
All study participants have unresectable locally advanced, recurrent, or metastatic HCC and have not previously received systemic anti-tumor therapy for advanced disease.
Approximately 560 participants are planned to be enrolled in this study. The JS207 + JS007 group (experimental group) and the toripalimab + bevacizumab group (positive control group) are each planned to enroll 280 participants.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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-
- •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.
排除标准
- •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
- •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.
研究组 & 干预措施
Toripalimab plus bevacizumab
Drug:Toripalimab, intravenous infusion Drug:Bevacizumab, intravenous infusion
干预措施: Toripalimab (Drug)
Toripalimab plus bevacizumab
Drug:Toripalimab, intravenous infusion Drug:Bevacizumab, intravenous infusion
干预措施: Bevacizumab (Drug)
JS207 plus JS007
Drug:JS207, intravenous infusion Drug:JS007, intravenous infusion
干预措施: JS007 (Drug)
JS207 plus JS007
Drug:JS207, intravenous infusion Drug:JS007, intravenous infusion
干预措施: JS207 (Drug)
结局指标
主要结局
Progression-Free Survival Assessed by Blinded Independent Central Review (BICR-PFS)
时间窗: From randomization to disease progression or death, whichever occurs first; assessed up to 24 months.
Time from randomization to the first documented disease progression assessed by BICR per RECIST v1.1 or death from any cause, whichever occurs first. Tumor assessments use Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Assessments are performed every 6 weeks through Week 54 and every 9 weeks thereafter.
Overall Survival (OS)
时间窗: From randomization to death from any cause; assessed up to 66 months.
Time from randomization to death from any cause. After safety follow-up, survival status is assessed every 2 months until death, loss to follow-up, withdrawal of consent, or study termination.
次要结局
- Progression-Free Survival Assessed by the Investigator (INV-PFS)(From randomization to disease progression or death, whichever occurs first; assessed up to 24 months.)
- Objective Response Rate Assessed by BICR (ORR)(From randomization to the end of tumor assessment follow-up; assessed up to 24 months.)
- Objective Response Rate Assessed by the Investigator (ORR)(From randomization to the end of tumor assessment follow-up; assessed up to 24 months.)
- Disease Control Rate Assessed by BICR (DCR)(From randomization to the end of tumor assessment follow-up; assessed up to 24 months.)
- Disease Control Rate Assessed by the Investigator (DCR)(From randomization to the end of tumor assessment follow-up; assessed up to 24 months.)
- Duration of Response Assessed by BICR (DoR)(From first complete or partial response to progression or death, whichever occurs first; assessed up to 24 months.)
- Duration of Response Assessed by the Investigator (DoR)(From first complete or partial response to progression or death, whichever occurs first; assessed up to 24 months.)
- Number of Participants With Adverse Events(From informed consent through 90 days after the last dose or initiation of new anticancer therapy, whichever occurs first; Up to 28 months.)
- Number of Participants With Serious adverse events (SAEs)(From informed consent through 90 days after the last dose or initiation of new anticancer therapy, whichever occurs first; Up to 28 months.)
- Number of Participants With Immune-related AEs(From informed consent through 90 days after the last dose or initiation of new anticancer therapy, whichever occurs first; Up to 28 months.)