A Prospective, Non-interventional Study of Different First-line Immunotherapy in Advanced Hepatocellular Carcinoma Patients: Efficacy and Immune Microenvironment Dynamics
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
研究概览
简要总结
To evaluate the efficacy and immune microenvironment changes in advanced hepatocellular carcinoma (HCC) patients receiving different first-line immunotherapy.
详细描述
This is a prospective, non-interventional, observational study evaluating the efficacy and immune microenvironment changes in advanced hepatocellular carcinoma (HCC) patients receiving different first-line immunotherapy, including anti-PD1+anti-VEGF, anti-PD1+TKI and anti-PD1+anti-CTLA4. The primary endpoint is objective response rate (ORR), with secondary endpoints including disease control rate (DCR), duration of response (DOR), time to response (TTR), progression-free survival (PFS), overall survival (OS), and immune profiling of tumor tissue and peripheral blood before and after treatment.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years at time of study entry.
- •Barcelona Clinic Liver Cancer stage C, or stage B not amenable to curative or locoregional therapies.
- •HCC confirmed by radiology, histology or cytology.
- •No prior systemic therapy for HCC.
- •At least one measurable site of disease as defined by RECIST1.1criteria with spiral CT scan or MRI.
- •Child-Pugh scores 5-7, performance status (PS) ≤ 2 (ECOG scale).
- •Adequate organ function:
- •ANC ≥1.5 × 10⁹/L, platelets ≥100 × 10⁹/L, hemoglobin ≥9 g/dL.
- •Total bilirubin ≤1.5 × ULN, AST/ALT ≤3 × ULN (≤5 × ULN if liver metastases).
- •Creatinine ≤1.5 × ULN or CrCl ≥60 mL/min.
- •Willing to provide archival/fresh tumor tissue and peripheral blood samples.
- •Signed informed consent.
排除标准
- •Prior systemic therapy for HCC
- •Active autoimmune disease requiring immunosuppression.
- •Active infection requiring IV antibiotics.
- •HIV-positive or active HBV/HCV infection (HBsAg+ with HBV DNA ≥2000 IU/mL; HCV RNA+).
- •Symptomatic CNS metastases.
- •Pregnancy/lactation.
- •Any condition compromising protocol compliance or data interpretation per investigator.
研究组 & 干预措施
HCC cohort 3: O+Y
干预措施: Ipilimumab (Drug)
HCC cohort 1: Sintilimab plus bevacizumab biosimilar
干预措施: Sintilimab (Drug)
HCC cohort 1: Sintilimab plus bevacizumab biosimilar
干预措施: Bevacizumab Biosimilar (Drug)
HCC cohort 2: Camrelizumab plus Rivoceranib
干预措施: Camrelizumab (Drug)
HCC cohort 2: Camrelizumab plus Rivoceranib
干预措施: Rivoceranib (Drug)
HCC cohort 3: O+Y
干预措施: Nivolumab (Drug)
结局指标
主要结局
Objective Response Rate (ORR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
时间窗: max 24 months
ORR is defined as the percentage of participants who have a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters). Responses are according to RECIST 1.1 as assessed by investigator.
次要结局
- Disease control rate (DCR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1(max 24 months)
- Number of participants with treatment-related adverse events as assessed by CTCAE v5.0(max 42 months)
- Duration of Response (DOR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1(max 24 months)
- Time to Response (TTR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1(max 24 months)
- Progression Free Survival (PFS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1(max 24 months)
- Overall survival (OS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1(max 42 months)
- Translational study(max 24 months)